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3 22222222222222222222222222222222222222 Yacute 1

4 a a R 222222222222222222222 Yacute 4

a 222222222222222222222222222222222222222222222 Yacute 8 0 22222222222222222222222222222222222222222222222222222222222

1 22222222222222222222222222222222222222222222222222222

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a 22222222222222222222222222222222222222222222222 17

0 2222222222222222222222222222222222222222222222222222

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7 a 22222222222222222222222222222222222222222222222222 25

0 2222222222222222222222222222222222222222222222222222

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25 28

8 a middot 22222222222222222222222222222222222222222222 32

a 222222222222222222222222222222222222222222222222222 35 a L 2222222222222222222222 37

a 2222222222222222222222222222222222222222222222 41

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ȑȱƢicircłŐĤǾȠǺɛɪȺɯıȟįǺmicroiacuteɪɅȽǺżǺocircicircǺıĦɱıparaǺċijɱijǩğČŔȴƢ

icircłŐȏǺUgraveaumlƛOacuteȴWŴȞȑȱƛOacuteɡɲȻɲȭƛOacutepėǺıparaƝɡɲȻɲɱLJIJpėǺagraveƿ

ȝċijɱȿȵǺmicroiacuteǕčŔȟȹɘɍɯɅȴńőȏǺȔȲȯȴƭȨȆȕƛijȼȶɏɩȶɯȭmicroiacuteǕȼȶ

ɏɩȶɯŔȴmiddotȑȱȍțȞȮȖșǺɛɪȺɯıȟƛijǺǕǺatildeȤȌȕłŐȞƦĠȑȱȍțȴb

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ugraveǼȝampƌƆĝȉƎ9ȎȲǺyenȟżƞǪȞȌȕTȰšȩȉƸȏșȄȱǻ ȍȟǽɛɪȺɯıƛijȼȶɏɩȶɯ 2017ǾȠɛɪȺɯıƛijȴǐțȏȝȄƁJȌȞmiddotȑȱȬ

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plusmnűȉȮȰUgraveȋagraveƿȝƛijȴUȌȱȍțȉȚȊȱucircȉsȆȱȍțȉaumlpoundȎȲȱǻ

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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bullqĔɈɔȨəċȎŠfrac14ȉȏʼnČucircɚĶŴȍ7DzǪUgraveOgraveeumlȊǽȈą$UgraveOgraveɚņŅƗethUgraveOgraveɚņigraveUgraveOgraveǵEacuteăȉǯȞǫƛ

bullqĔɈɔȨəċȎŠfrac14aocircȏ džƷƾ ȎŠfrac14aocirc ƦơƛƧǵŌĖȍ3ăǻȟȈǰȞǫƛ

bullą$UgraveOgraveȉȏƏŸ ƼǁƸ umlcedilŦą$ƝǎǓǐǐǞǜǓǘǗƛǠǏǓǑǒǝǏǎƛǓǖNjǑǏƯƛƳdžƸƞƛ ǵEacuteăȉǯȞǫƛbullņŅƗethUgraveOgraveȉȏņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊĹȷȥŒĕǵEacuteăȉǯȝǪƦƩƢƨƢƨ ŒĕȎUgraveǵɈɔȨəċŠfrac14aocircȎȇȊȌȆȈǰȞǫƛ

bullņigraveUgraveOgraveȉȏUEumlNEumlmiddotƇɜǙǏǛǓǘǎǓǍƛǜǢǗǍǒǛǘǗǘǞǜƛǎǓǜǍǒNjǛǑǏƯƛƿǂƳɝǵuacuteĖ řȉǯȝǪɈɔȨəċȎŠfrac14aocircȎȇȊȌȆȈǰȞǫƛ

bullqĔɈɔȨəċȎLċ_ɚĻċEumlƀȍțȆȈą$UgraveOgraveɚņŅƗethUgraveOgraveɚņigraveUgraveOgraveȎȏĈȌȞǹȊȍiacuteǿȞǫȖȃǪqĔɈɔȨəċȍƓǽȃħĶĊǵǯȝǪż2ǵŻŘȉǯȞǫƛ

ETHǶĢΞΰ͵εǰUmiddotUmiddot7MM1MV1˻Umiddot7κMM2-ǺʬmiddotMM2-ʅ

ĀmiddotMV2VV1VV2λ Creutzfeldt-Jakob ǰκCreutzfeldt-Jakob disease CJDλ[ɻ

-23ŤŹeƏ7ETHǶĢΞΰ͵εǰΝΈͰΞƧǛȐκreg-1λUmiddot7˻Umiddot7ɢĀDZǘηɢĀȷˈηƏƅκǧIηɛɚƽηɛƲλĬăǪʒŠ˱ǩī

ǥƢƦɟAacuteIacuteȎ4UgraveȍdzǸȞqĔɈɔȨəċȎȰɇȷȤɈaringyumlƛ

ƛ

ƛ

ƛ

ƛ

ƛ

ƛ

ƛ

ƛ

ƛ

ƛ

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ƛ

2 -

ɜƦɝƛ ʼnČucircƛ

ŤŹETHǶĢΞΰ͵εǰɢĀIȐ 4-6ɢĀIɈǰŶˣΞΰ͵εǰΈͰΞ

Ǫ 4 13 Umiddot7κMM1MV1λ

Umiddot7˅ɹĢʙȉƗə˲UgravekΦ͵ͺγθΓƒ˽˲UgraveatildeɛAEligʟƟɹ˲Ugrave5

ȯ 3-7 ζŲțăǑpǑʋɤ 3 4ɛƲ PSD

13 ˻Umiddot7κMM2-ǺʬmiddotMM2-ʅĀmiddotVV1VV2λ MM2-ǺʬmiddotυMM2-ǺʬmiddotAEligɹAEligʚƚƗə˲UgraveĺDZǘȬȓDZǘ

Atildeɂē˅ɹĢȷˈȐ 3 7 8ȯ 1-2yacutețăƟɹ˲UgraveǑpǑʋɤɈǰŶˣ 247 ζŲƑ˟

MM2-ʅĀmiddotυMM2-ʅĀmiddot 3 9 10ȅɣđȓȷ˲UgraveʙȉƗə˲UgraveȬȓDZǘȐ

AtildeɈǰŶˣ 185 ζŲ˟ǑpǑʋɤDZ7 κVV1VV2λυVV1frac12Țɂē˅ɹĢdFmiddotʙȉDZDZǘ

˚1ʱĘBΦ͵ͺγθΓVV2AEligʟĢƟɹġˁ˅ɹĢʙȉDZΦ͵ͺγθΓ 13ƙɛƲ PSD

ɜƧɝƛ UgraveOgraveeumlɜą$UgraveOgraveǪņŅƗethUgraveOgraveǪņigraveUgraveOgraveɝƛ

ETHǶĢΞΰ͵εǰƏƅƱǧIƏƅɛɚƽƏƅɛƲƏƅńETHǶĢ CJD

ΈͰΞƏƅĬăǪƳī 13 ǧIƏƅˏ MRI DWIʒŠųǡreg-211-14ɻȐŻƔdžt DWIʒ

Šə FLAIRǧI 15ǧIĴʃȐǯĤǯĤ˞_

˔ʂ 16

DWIAumlɛǺʬκˀuacuteʀśĴλordmāƇκǗɀŻ1dyˏλǪuacute

Atilde 14

ǥƢƧɟ)- 1 2 )3 ƛ

)- 1 V UV b S 1 V RT b S RV

PJacM Q a )- W 1 V b S W b SME PJac W 1

V b S W b S UV b S W )- PJac

2 )3 M WI

ƛ

2 ( -

13 ɛɚƽƏƅ 14-3-3 ɷǸɾlǹʒŠordmdž˾ǽk 2CJD ĤɎ

ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

qĔɈɔȨəċĽsup1ƛ

Ugraveşsup1ƛƛ ƪƦƤƪƫƛ ƛ ƪƧƤƪƫƛ ƛ ƪƭƤƫƬƛ ƛ ƫƩƤƫƬƛ ƦƥƮƤƦƧƨƛ ƦƦƫƤƦƧƨƛ

ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

ƛ

MŞƛ ƮƦƜƛ ƮƨƜƛ ƭƬƜƛ ƮƫƜƛ ƭƮƜƛ ƮƩƜƛ

ƼƼƛ ƮƥƜƛ ƮƬƜƛ ƮƥƜƛ ƮƨƜƛ ƮƥƜƛ ƮƪƜƛ

ƼDžƛ ƭƭƜƛ ƭƧƜƛ ƭƭƜƛ ƦƥƥƜƛ ƭƭƜƛ ƮƪƜƛ

DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

uacuteĈƛ ƮƭƜƛ ƪƫƜƛ ƦƥƥƜƛ ƬƪƜƛ ƮƮƜƛ ƫƪƜƛ

13 ɛƲƏƅ Steinhoff 26ɛƲ PSDʔordmdžȐǶDZťŶ 45 ˮĢȐȷˈ 90 ˮĢȐfrac12PSD ZǞǛ CJD ΝΈͰΞɈǰˣŶˣ

Ǫ

ɜƨɝƛ Šfrac14aocircƛ

WHOʒŠordmdž 2κɻ-1λήθγΘʒŠordmdžκɻ-4λȐ 11ǞplusmnŤŹ CJDθΠͰίε WHO ʒŠordmdžņǡκɻ-1λκǧIƏƅɛɚƽƏƅƏƅƔ

džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

A Φ͵ͺγθΓ B ʅʆǪuacuteatildeɛAEligʟ C ˚1ʱ˲Ugrave˚1Acircʱ˲Ugrave D ǑpǑʋ

3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

ήθγΘκEuroCJDλordmdžɛɚƽ 14-3-3ɷǸ˩ μμ ήθγΘκEuroCJDλǧIʒŠŮOtildeordmdž MRI ŀřĉʟǧIκDWIλ FLAIR ǧIaeligǘƇηɼƦAumlɛǺʬsup1 2 ζĴʙ

2 ) -

ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

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Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

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224-233

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surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

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patients in Germany J Neurol 2014 261 1811-1817

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disease in Germany J Clin Psychiatry 2015 76 1209-1215

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sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

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mimicking fatal familial insomnia Neurology 1999 52 1757-1763

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662-669

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źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

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Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

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differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

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sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

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ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

ƛ

bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

ĶŴǵsup1ȊŽǰ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċ ɜ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ

ƶǂǂɝǪŚ_qĔ ƲƹƳ ȍȈĝȌȋŊħĶČucircǵĘįȇŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛ

ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

bullhsup1ȎŶnfĈǵĠȜȟȈǰȞǵǪAacuteIacuteȉȏ DžƦƭƥƸǪƼƧƨƧǁǪƴƧƥƥƺǪƿƦƥƧƻ ȉigtȡȘȞǫƛbullȒȇDZȏǪNtildeōŶȉǯȞǵǪDžƦƭƥƸǪƼƧƨƧǁ ȏȔȊȢȋxAgraveĔČǵȌǷqĔ ƲƹƳ

ȊǽȈĔČǿȞȃȘŶnUgraveOgraveȡǽȌǸȟȐŠfrac14ȏȇǴȌǰǫƛ

bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

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ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

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-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

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ˌċĆuacuteƄɩ1JĢˌċĆƻʿǛAacuteǪȜǪŤŹ

ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

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ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

LJƦƩƪǜǝǘǙƛƝţĠČƞơƛƧnjǙƢǎǏǕƛNjǝƛƦƬƭljƦƮƪǜǝǘǙNJƛƝśŊħĶȾɐɛɗɂȸɛƞƛƪ

2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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2 -

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ƶǂǂƛ

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ƦƭƥƛƠƛ

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ƦƭƥƯƛDžNjǕƛ ǩƛ ƸǕǏƛ

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ƶǂǂǪƲƹƳȌȋ

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

( )- 1

2 -

ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

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ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

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7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

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6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

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18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

1 ǢźŬɮIcircοĤɎηUacuteţszligęǟȑ)ǹŕōκȣςˏΞΰ͵εǰν0οΙΏηΞΰ͵εǰοȣ21ȡλοǠnH

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CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

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DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

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RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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2 ) -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

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4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

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5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

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Źˍ2004yacute 11Ų 2007yacute 3ŲǰmiddotǪΞΰ͵εǰ 11DZ7szlig PPSɛtimesVĻɹś7˟ŶǠIumlƗəǹcopyĖȐDZ7 5ƛograve

15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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WHO World Health Organization

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

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ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

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ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

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DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

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Ǫ

ɜƨɝƛ Šfrac14aocircƛ

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džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

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3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

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ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

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Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

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supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

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sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

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Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

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ƝƩƞƛ ȂȎƛ ƛ

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ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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2 -

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ƝƦƞƛDžƦƭƥƸ fĈ ƲƹƳƛ

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

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ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

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ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

2 ȍOuml7κprobableλυɢĀDZǘΞΰ͵εɷǸˌIcircAacuteǪȍOuml7ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

3 Ǭ7κpossibleλυUacuteţƢ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴ+Ξΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

DZǘETHǶĢ CJDUmiddot7ġˁ˅ɹĢuumlacuteǶDZyacute 586ơɬŹˍUacuteţƢȍʙ7ȯ 54ǗOtildesup2sup1DAtilde 1 4ɛƲ

PSD ȯ 92ˏ MRI ȯ 94ɛɚƽ 14-3-3 ɷǸȯ 87ˮĢRT-QUICƱˮĢǛȯ 85ųǡ 4

ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

P105L AacuteǪ GSS Źˍfrac12AacuteǪuumlacuteǶDZyacute 44 ơɬyacute˻uacuteɂē˅ɹ7Atilde 4 25 26AEligʟDZǘDzĢszligǴʙ7AtildeűʻΘθεΒ΄Χ

7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

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28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

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bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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2 -

1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

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ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

ƛ

MŞƛ ƮƦƜƛ ƮƨƜƛ ƭƬƜƛ ƮƫƜƛ ƭƮƜƛ ƮƩƜƛ

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uacuteĈƛ ƮƭƜƛ ƪƫƜƛ ƦƥƥƜƛ ƬƪƜƛ ƮƮƜƛ ƫƪƜƛ

13 ɛƲƏƅ Steinhoff 26ɛƲ PSDʔordmdžȐǶDZťŶ 45 ˮĢȐȷˈ 90 ˮĢȐfrac12PSD ZǞǛ CJD ΝΈͰΞɈǰˣŶˣ

Ǫ

ɜƨɝƛ Šfrac14aocircƛ

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džtɹ 27-29λ

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A Φ͵ͺγθΓ B ʅʆǪuacuteatildeɛAEligʟ C ˚1ʱ˲Ugrave˚1Acircʱ˲Ugrave D ǑpǑʋ

3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

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2 ) -

ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

D178N-129M FFIǰIȐD178N-129V CJD

ˌċĆuacuteƄɩ1JĢˌċĆƻʿǛAacuteǪȜǪŤŹ

ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

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ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

LJƦƩƪǜǝǘǙƛƝţĠČƞơƛƧnjǙƢǎǏǕƛNjǝƛƦƬƭljƦƮƪǜǝǘǙNJƛƝśŊħĶȾɐɛɗɂȸɛƞƛƪ

2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

2 - -

ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ʒŠĚʂuumlacuteɈǰŶˣ 4-5 yacute˟^ŶʙȉDZʒŠĒęǟǹ

ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

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2 -

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ƦƭƥƛƠƛ

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ƦƭƥƯƛDžNjǕƛ ǩƛ ƸǕǏƛ

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ƾǠǏǗơƛƦƮƭƮƛƦƪƛ

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ŊħĶƄwǪƛ

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

( )- 1

2 -

ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

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ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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PSD ȯ 92ˏ MRI ȯ 94ɛɚƽ 14-3-3 ɷǸȯ 87ˮĢRT-QUICƱˮĢǛȯ 85ųǡ 4

ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

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7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

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EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

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Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

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ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

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bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

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bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

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2 ) -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

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Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

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Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

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4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

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5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

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13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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Engl J Med 1985 313 734-738

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cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

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variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

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of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

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incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

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17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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2 -

1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

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Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

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Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

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mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

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9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

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18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

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21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

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D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

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bull ǎƲƹƳ Ȏij ƧƤƨ ȏ ƲƹƳ_ȉǯȞǵǪaumlȝȎij ƦƤƨ ȏǪɈɓɛȬ_ȊVȐȟȞƊ_ȉǪŲŕǵaringŮĖųǷǪĔČAcircEumlȍȏņigraveȍUEumlNEumlmiddotƇɜǙǏǛǓǘǎǓǍƛǜǢǗǍǒǛǘǗǘǞǜƛǎǓǜǍǒNjǛǑǏƯƛ

ƿǂƳɝǵĀǽȌǰǹȊȍiacuteǿȞɜŗǧƢƧɝǫƛ

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IumlplusmnmacrǶDZȍʙwĢ CJD dCJD vCJD

ƝƦƞƛ ģňĪOslash ƲƹƳƛ ƛ

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ƝƧƞƛ fĈ_ ƲƹƳƛ

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2 - -

sign7ˋě˧

ŗǧƢƨƣƛ fĈ_ ƲƹƳ Šfrac14aocircɜdžƷƾƛƧƥƥƦɝƩƛ

I A B 6 C 9 D E Creutzfeldt-Jakob

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III A PSD B MRI

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definite probable

possible

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EacuteăȉǯȞǫƛ

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ǧƢƦɟǟƲƹƳ Ȏ ƼǁƸƛǃƧ Ŧą$ƛ

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ɜŏ] ƲƹƳ ȰɛɉȤɓəȲɑȾȹȻ ƳƣưƣƛƲǘǕǕǓǏ eȎǺB

ȍțȞɝ

ƛ

2 -

ŗǧƢƩɟfĈ_ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċȎŠfrac14aocircɜƴDŽƛƧƥƥƭɝƭƛ

A ĚŻ ȷˈ 6 ζŲ˅ɹĢȬȓηȓȷDZB ɧƏƅǯĤOtilde

ΙΏǣżpara1αΩεȌɠșƎƮǵƢ

ˌĢˊĢƺȽǘɛDZOtilde

B ɢĀDZB 5DZBauml 4ʙ

ǶDZ^ŶȬȓDZǘκĺOacuteǑˤęɣˡEacuteĪλ

łȼdzǪuacuteĬʆκɎλ

AEligʟ

Φ͵ͺγθΓβΏΒ

ʙȉDZ

C ƏƅĴʃ ȍOtildeʒŠ

AumlɛatildeɛƺȽǘAacutet florid plaque +ǪuacuteΞΰ͵εɷǸƭȇʙ ƏƅĴʃ

ɛƲŶĢŶĢŗ˷κPSDλ˫Ģ ˏ MRIFʅĀƀ ĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢ

D ǭNtildeǹĴʃ ǭNtildeǹˤ˃ȐΙΏΙΏœκʸɸλ

E ʒŠ ȍOuml7 Ɲdifiniteƞ

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A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

Ǭ7ƛ Ɲpossibleƞ A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫Ģ

ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

ƟƟƛ ŰǪiexclOtildeĂUgraveȏshymǽȌǰǫȃȄǪʼnČǵ ǟƲƹƳ ȍMŋǽɞƏŸ ƼǁƸ ȉŚIumlƘKȡţȘȌǰȉ

EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

2 -

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ƝƦƞƛ łAringɚĘĖƛ

Ξΰ͵εǰˋ˔DZă[Ξΰ͵εǰǰmiddotǪAtildeč

ȓȷDZB˅ɹǟǣɍszlig˔DZă

ʔͼθαIumlplusmnǯĤɣǒƢʟƅƮǵˢǶ˔DZăʔĚ

macrǠnHȁ˶ǰszligȧƐκ˶ǰƱordm˶ǰwǵʫlIJaăλΞΰ͵εǰ

˔DZă[ Barthel Index1ǡκɻ-1λŹˍΞΰ͵εǰɣǒƢʟƅȊȟκJapanese Consortium of Prion Disease JACOPλ Medical Research Council Prion Disease Rating Scale MRC Scale26ǡκɻ-2λŹȝǞplusmnfrac12˔DZăʔͼθαʽ

ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

9 99

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(

9 9 9

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() 9 9() 9

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9

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ƝƧƞƛ ŜŤɚȧɄȺəȲƛ

Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

ǗOtildeŪǏ˔DZăʔͼθα6ǡǞOumlǹ

ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

2 ( -

ǞplusmnmacrǠnHȁ˶ǰszligȧƐņǡΞΰ͵εǰ˔DZăʔ Barthel Index1 ʐŤuacuteǠƵp4ʔͼθαʗĊͼθαɲ

ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

1ǞplusmnͼθαɛzΰΖΚΰθέεʔŃƔɄǡ 2

Barthel Index ʔǏ 0 Ǐ 100 Ǐ[divide100 ǏEuacuteǘĭɧǹ 80

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

ʗĊΞΰ͵εǰZǞȓȷĘB 8ͶͿΰθ[ʍ 26˾ǽ]ʐ˾ǽ 0 = 1 = ʵăκǬλ2 = ˔ăκŧλ 3ƥ˯ʔ

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ī˔ʂ˾ǽȣǏ˾ǽǏś˒[˔

ǏȣǏ]ʐ˾ǽDZǘ˅ɹǽȠʔ

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λǠ

JACOP 6ǡ MRC Scale ʐŤuacuteǠƵp4ʔͼθαʗĊΞΰ͵εǰǗĘǹʋʚƗəʙȉƗəʔkǏǗĘǹǑpǑ

ʋǘĭʔŤuacuteǠƵp4ˤͶͿΰθ 7˾ǽʋʚηʙȉƗəηƚɛƗəͶ

Ϳΰθ 4 ˾ǽʍ 11 ˾ǽIJʑpoundVUcircě 25 ƥ˯ʔ0 1Ǐʔ˾ǽ0 1 2 3 4Ǐʔ˾ǽĕǏ 0Ǐκű˔DZλ 20Ǐ[

divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ɈɔȨəċȎeacuteĒȏOacuteƕǪVRıāȚŌĖȮȣǵiquestǻȟȞȎȗȉǪĊȎeacuteēǯȞǰȏŲŕųȡȘǼǽȃĊƔeacuteĒȏ ƧƥƦƧ ƂȍǪfrac12ȃȌ9ETHĖő5ȎĔřȏȌǰǫǹȟȖȉȍŕ

ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

ƞuacutemiddotΞΰ͵εɷǸκcellular prion protein PrPCλLjĢǪuacutemiddotΞΰ͵εɷǸ

κscrapie prion protein PrPScλƒ˂Aacutet˦Ugrave4ǡPrPScX˵ĺaʥ=˅

4ǡȳɗAacuteĢĺa4ǡųɵǖͺΰθΒεͻɢĀȊȟɹ

ΑͺΰεKżļΥίΰɵPrPC PrPScʴŋ PrPScɳȞ˦UgraveoƂ

frac12Ξΰ͵εǰɢĀȊȟɹ 1ɮmacrɹ PRION-1 studyĊ^OtildeίεΉΧtʕŠƮǵɊ˻ƮǵɊ[Ƨʶʕɹ 2űȵǹ 107

7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

ˣʈYacuteŶˣ78 7κ73ιλʈYacuteŶˣƣǠIumlǛΑͺΰεVŴɊ˻VŴɊˢEumlŪ˔DZăɾƞɹɎocircɓƗə˲Ugrave 20 7

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ɵf28Creutzfeldt-JakobǰκCreutzfeldt-Jakob disease CJDλĤɎszligʨ13Oumlɵ

15Ξί΅ΣĻ 3ʙȉƗəƏƅ 2ɊˣųīocircǠĒocirc

ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

ƂPPSɛtimesVłȼĻƱɮmacrAacuteǪmiddot CJDκvariant CJD vCJDλszlig^ɹ 4

Źˍ2004yacute 11Ų 2007yacute 3ŲǰmiddotǪΞΰ͵εǰ 11DZ7szlig PPSɛtimesVĻɹś7˟ŶǠIumlƗəǹcopyĖȐDZ7 5ƛograve

15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

2 -

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˅ 6ĬƄpǖOumlΐͰͺΰεǶDZˆąoƂǠIumlŶˣą˟ΐͰ

ͺΰεǰǹ PrPSc ȸΞΰ͵εĬƄĺaoƂŶĐɢĀȊȟ

ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

[ƏʎȸƂΐͰͺΰε 100mg ĻOacuteQɹǠIumlŶˣą˟oƂʙ 7

DZǘ˅ɹȷŐnot˶frac34ȷɖȨȷȨƆɹAtilde

ǠĒŖcurrenŧȍͳΚΎε

CJD ȷˈʙΦ͵ͺγθΓszligǺʬĢǺʬĢΦ͵ͺγθΓƮǵͺγΑΆΘΧΗαΞγ˓6ǡ 8ŧȍͳΚΎε

1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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2 ) -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

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4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

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5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

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Źˍ2004yacute 11Ų 2007yacute 3ŲǰmiddotǪΞΰ͵εǰ 11DZ7szlig PPSɛtimesVĻɹś7˟ŶǠIumlƗəǹcopyĖȐDZ7 5ƛograve

15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

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Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

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źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

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Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

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Neurobiol 2006 26 45-52

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differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

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diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

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sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

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CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

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ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

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ƛ

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ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

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ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

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ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

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DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

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Ǫ

ɜƨɝƛ Šfrac14aocircƛ

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džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

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3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

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ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

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Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

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supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

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sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

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Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

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ƝƩƞƛ ȂȎƛ ƛ

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ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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2 -

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ƝƦƞƛDžƦƭƥƸ fĈ ƲƹƳƛ

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

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ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

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ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

2 ȍOuml7κprobableλυɢĀDZǘΞΰ͵εɷǸˌIcircAacuteǪȍOuml7ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

3 Ǭ7κpossibleλυUacuteţƢ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴ+Ξΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

DZǘETHǶĢ CJDUmiddot7ġˁ˅ɹĢuumlacuteǶDZyacute 586ơɬŹˍUacuteţƢȍʙ7ȯ 54ǗOtildesup2sup1DAtilde 1 4ɛƲ

PSD ȯ 92ˏ MRI ȯ 94ɛɚƽ 14-3-3 ɷǸȯ 87ˮĢRT-QUICƱˮĢǛȯ 85ųǡ 4

ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

P105L AacuteǪ GSS Źˍfrac12AacuteǪuumlacuteǶDZyacute 44 ơɬyacute˻uacuteɂē˅ɹ7Atilde 4 25 26AEligʟDZǘDzĢszligǴʙ7AtildeűʻΘθεΒ΄Χ

7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

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28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

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bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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PPS pentosan polysulfate

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RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

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- 1 Colby DW Prusiner SB Prions Cold Spring Harb Perspect Biol 2011 3 a006833 Review

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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bullhsup1ȎŶnfĈǵĠȜȟȈǰȞǵǪAacuteIacuteȉȏ DžƦƭƥƸǪƼƧƨƧǁǪƴƧƥƥƺǪƿƦƥƧƻ ȉigtȡȘȞǫƛbullȒȇDZȏǪNtildeōŶȉǯȞǵǪDžƦƭƥƸǪƼƧƨƧǁ ȏȔȊȢȋxAgraveĔČǵȌǷqĔ ƲƹƳ

ȊǽȈĔČǿȞȃȘŶnUgraveOgraveȡǽȌǸȟȐŠfrac14ȏȇǴȌǰǫƛ

bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

ˌĢΞΰ͵εǰƞuacutemiddot PrPκcellular prion protein PrPCλθΐ PrPˌIcircAacuteǪ

ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

ȓȷDZǘǽȠ FFIAuml_κɻ-1λɢĀǰmiddotordfˌIcircAacuteǪǞplusmn 30ȜǏAacuteǪΐε 51 91 8ΦΕ˓ɆʼκΰΛθΏλˏ- 15ȜƙAEligηŅPfrac12 1-3κreg-1λăƓȜǪ 4ŹˍˌĢ

CJDV180Iκΐε 180ΗΰεͰγͰεɇŋλM232RκΨΊ͵ΒεαΒελE200KκͻαΈΦε˓ΰελ GSS P102LκΞγΰεͰγͰελAumlˏ[~κreg

-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

D178N-129M FFIǰIȐD178N-129V CJD

ˌċĆuacuteƄɩ1JĢˌċĆƻʿǛAacuteǪȜǪŤŹ

ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

ǁƦƩƭƷơƛǀƦƫƥǜǝǘǙơƛƳƦƬƭƽƢƦƧƮDžơƛDžƦƭƥƸơƛǃƦƭƨươƛǃƦƭƭươƛǃƦƮƨƸơƛƴƦƮƫƺơƛƴƧƥƥƺƢƦƧƮƼơƛƴƧƥƥƺƢƦƧƮDžơƛDžƧƥƨƸơƛ

ǁƧƥƭƷơƛDžƧƦƥƸơƛƴƧƦƦǀơƛƼƧƨƧǁơƛƲǘǎǘǗƪƦƢƮƦƛǓǗǜƛ

ƝƧƞƛƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċƛ ƝƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƛǎǓǜǏNjǜǏƯƛƶǂǂƞƛ

ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

LJƦƩƪǜǝǘǙƛƝţĠČƞơƛƧnjǙƢǎǏǕƛNjǝƛƦƬƭljƦƮƪǜǝǘǙNJƛƝśŊħĶȾɐɛɗɂȸɛƞƛƪ

2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

frac34ǵaacuteh_Ǫfrac34ǵȌċĖfĈȡĥǽjoǵȠǵ]ȍhǰfĈǫƛ

ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

uumlacuteǶDZyacuteȯ 77ơʐ˙i˲UgraveAEligʚAEligɹƚɛƗə˲UgraveǶDZAtildeɂē˅ɹĢ^ŶΦ͵ͺγθΓatildeɛAEligʟʅʆ˲Ugrave

AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

2 - -

ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

ɞaacuteǰǹaacuteƧʶǹťŶʙŪ CJDƓDZBȐ7

ƻʿǛatildeɛAEligʟDZʙȉDZUacuteţƢɑǬłˌIcircƏƅ

ʒŠĚʂuumlacuteɈǰŶˣ 4-5 yacute˟^ŶʙȉDZʒŠĒęǟǹ

ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

8

bullŶɈɔȨəċȏŶ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċ ɜ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ ǎǓǜǏNjǜǏƯƛ ƲƹƳ ɝ Ǫ

ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ ƶǂǂɝǪŋatildexAgrave

ĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ȍƓǻȟȞǫƛ

bullIacuteŷȎŶɈɔȨəċȉȏxAgraveacircǵȌǰȷȤɈǵhǰȎȉŠfrac14ȍȏŶnUgraveĴǵƍȉǯȝǪLfĈȎƐȏ DžƦƭƥƸǪƿƦƥƧƻǪƴƧƥƥƺǪƼƧƨƧǁǪƳƦƬƭƽ Ȏƌȍhǰǫƛ

bull DžƦƭƥƸ Ț ƴƧƥƥƺ ȉȏƏŸ ƼǁƸƛ umlcedilŦą$ƝǎǓǐǐǞǜǓǘǗƛǠǏǓǑǒǝǏǎƛǓǖNjǑǏƯƛƳdžƸƞȉǪiņėŪȚaOcircȍƘKfȡţȘȞǹȊǵhǷǪƿƦƥƧƻ Ț ƴƧƥƥƺ ȉȏxAgraveacircȡQȘȃiacutentildeǰċacircȎľG

ȚǪņŅƗethUgraveOgraveȍdzǸȞ ƦƩƢƨƢƨ ŒĕǪņŅƗethȎĈ_ɈɔȨəŒĕƘdeuml

ɜǛǏNjǕƢǝǓǖǏƛǚǞNjǔǓǗǑƢǓǗǎǞǍǏǎƛǍǘǗǟǏǛǜǓǘǗƯƛǁǃƢǀDŽƸƲɝUgraveOgraveȌȋǵEacuteăȉǯȞǫƛ

bull ƿƦƥƪƻȚ ƳƦƬƭƽȎ ƵƵƸ ȉȏuacuteĖȌʼnČucircȍiacuteǽǪƿƦƥƪƻ ȉȏɂɛȪəȶȾȳɍȡȊǿȞČșǰȞǹȊȡćǿȞǫDžƦƭƥƸ ȏuacuteĖȌɤɥɣą$ǴȜż2ǽDZȞcMǵǯȞǵǪƼƧƨƧǁ ȏ

ŶnUgraveĴȡǽȌǰȊqĔ ƲƹƳ ȊȎż2ȏȉǶȌǰǫƛ

bullůǪŊħĶƄwǪIgravetimesħĶƄwȡČucircȊǿȞŶɈɔȨəċǵbTǻȟȈǰȞǫƛ

ɢĀǰmiddotˌĢ CJDGSSFFI [ɻ-2P102L AacuteǪ CJD ƓDZǘ

frac34GSS 2 3V180IM232RˌĢΞΰ͵εǰUacuteţƢʒŠˌIcircƏȲĚ 4ʾΞΰ͵εɷǸκprion protein PrPλˌ

IcircǪuacuteȓȷDZBΞΰ͵εǰʒŠ˱ƳīĚʂ

ŹˍAtildeǰmiddotʊʝˌĢ CJD ʒŠordmdž CJD UacuteţƢų

CJD PRNPˌIcircAacuteǪųDZ7ɢĀDZǘETHǶĢ CJD dž

2 -

ŗǦƢƧƣƛ Lʼnċ_ȊbTǻȟȈǰȞŶnfĈƛ

ʼnċā$ƛ ȯȼəƛ ȣɌɀźĺmacrƛ ȯȼə ƦƧƮƛ raquouumlƛ

ƶǂǂƛ

ƦƥƧƛ ǙǛǘǕǓǗǏƛ ǩƛ ǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƷǜǓNjǘơƛƦƮƭƮƛƪƛ

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ƦƦƬƛ NjǕNjǗǓǗǏƛ ǩƛ ǟNjǕǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ǃǛNjǗǍǒNjǗǝơƛƦƮƭƮƛƬƛ

ƲƹƳƛ

ƦƬƭƛ NjǜǙNjǛǝNjǝǏƛ ǩƛ NjǜǙNjǛNjǑǓǗǏƛ ǟNjǕǓǗǏƛ ƶNjǖnjǏǝǝǓơƛƦƮƮƪƛƭƛ ƛ

Ʀƭƥƛ ǟNjǕǓǗǏƛ ǩƛ ǓǜǘǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƺǓǝNjǖǘǝǘơƛƦƮƮƨƛƮƛ

ƦƭƥƛƠƛ

ƧƨƧƛ

ƦƭƥƯƛDžNjǕƛ ǩƛ ƸǕǏƛ

ƧƨƧƯƛƼǏǝƛ ǩƛ ưǛǑƛǖǏǝǒǓǘǗǓǗǏƛ ƷǓǝǘǜǒǓơƛƦƮƮƨƛƦƥƛ

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ƶǘǕǎǑNjnjǏǛơƛƦƮƭƮƛƦƦƛ

ƧƦƥƛ ǟNjǕǓǗǏƛ ǩƛ ǓǜǘǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƿǘǍǍǒǓNjǛǓơƛƦƮƮƨƛƦƧƛ

ƧƨƧƛ ǖǏǝǒǓǘǗǓǗǏƛ ǩƛ NjǛǑǓǗǓǗǏƛ ǗǘǝƛǜǝNjǝǏǎƛ ƺǓǝNjǖǘǝǘơƛƦƮƮƨƛƮƛ

ƶǂǂǪƲƹƳȌȋ

hƛ ƛ

ȯȼə ƪƦƢƮƦ Ǝ`ȎɊɈȸȼFŹ0Ÿȓ

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ƶǘǕǎǐNjǛnjơƛƦƮƮƨƛƦƩƛ

ƾǠǏǗơƛƦƮƭƮƛƦƪƛ

ƶǘǕǎǐNjǛnjơƛƦƮƮƦƛƦƫƛ

ǟNjǗƛƶǘǘǕơƛƦƮƮƪƛƦƬƛ

ƱǏǍǔƛƧƥƥƦƛƦƭƛ

ƵƵƸƛ ƦƬƭƛ NjǜǙNjǛǝNjǝǏƛ ǩƛ NjǜǙNjǛNjǑǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƼǏǎǘǛǓơƛƦƮƮƧƛƦƮƛ

ŊħĶƄwǪƛ

IgravetimesħĶƄwƛ

Ʀƫƨƛ ǝǢǛǘǍǓǗǏƛǩƛǘǝǒǏǛǜƛ ǟNjǕǓǗǏƛ ƼǏNjǎơƛƧƥƦƨƛƧƥƛ

ƦƬƭƛ ƧƢnjǙƛǎǏǕǏǝǓǘǗƛƝƲǃƞƛ ƛ ƼNjǝǜǞǣǘǗǘơƛƧƥƦƨƛƧƦƛ

ƝƦƞƛDžƦƭƥƸ fĈ ƲƹƳƛ

ˏ MRIųǡDWIQ7ĒɱęLJdĒ˩Qsup1AumlɛǺʬΰΣεǘordmāƇoacuteocircAumlɛǺʬQ1ƹɝǘɝɜIreg1-3uumlacuteǶDZyacute 765 ơǶDZ^ǶDZǘʐ˙i˲Ugraveɂē˅ɹ

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

( )- 1

2 -

ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

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RT-QUICƱˮĢǛȯ 88ųǡGSSʒŠordmdžɻ1-3Ȑ

ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

2 ȍOuml7κprobableλυɢĀDZǘΞΰ͵εɷǸˌIcircAacuteǪȍOuml7ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

3 Ǭ7κpossibleλυUacuteţƢ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴ+Ξΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

DZǘETHǶĢ CJDUmiddot7ġˁ˅ɹĢuumlacuteǶDZyacute 586ơɬŹˍUacuteţƢȍʙ7ȯ 54ǗOtildesup2sup1DAtilde 1 4ɛƲ

PSD ȯ 92ˏ MRI ȯ 94ɛɚƽ 14-3-3 ɷǸȯ 87ˮĢRT-QUICƱˮĢǛȯ 85ųǡ 4

ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

ETHǶĢ CJD Umiddot7ġˁ˅ɹ7 MM2 ǺʬmiddotƓɂē˅ɹ7κETHǶĢ

CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

P105L AacuteǪ GSS Źˍfrac12AacuteǪuumlacuteǶDZyacute 44 ơɬyacute˻uacuteɂē˅ɹ7Atilde 4 25 26AEligʟDZǘDzĢszligǴʙ7AtildeűʻΘθεΒ΄Χ

7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

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2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

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6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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ǶDZ^ŶȬȓDZǘκĺOacuteǑˤęɣˡEacuteĪλ

łȼdzǪuacuteĬʆκɎλ

AEligʟ

Φ͵ͺγθΓβΏΒ

ʙȉDZ

C ƏƅĴʃ ȍOtildeʒŠ

AumlɛatildeɛƺȽǘAacutet florid plaque +ǪuacuteΞΰ͵εɷǸƭȇʙ ƏƅĴʃ

ɛƲŶĢŶĢŗ˷κPSDλ˫Ģ ˏ MRIFʅĀƀ ĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢ

D ǭNtildeǹĴʃ ǭNtildeǹˤ˃ȐΙΏΙΏœκʸɸλ

E ʒŠ ȍOuml7 Ɲdifiniteƞ

A ĚŻ C ƏƅĴʃȍOtildeʒŠDŽ ȍOuml7ƛ Ɲprobableƞ

A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫ĢˏMRIFʅĀƀDŽ

A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

Ǭ7ƛ Ɲpossibleƞ A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫Ģ

ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

ƟƟƛ ŰǪiexclOtildeĂUgraveȏshymǽȌǰǫȃȄǪʼnČǵ ǟƲƹƳ ȍMŋǽɞƏŸ ƼǁƸ ȉŚIumlƘKȡţȘȌǰȉ

EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

2 -

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ƝƦƞƛ łAringɚĘĖƛ

Ξΰ͵εǰˋ˔DZă[Ξΰ͵εǰǰmiddotǪAtildeč

ȓȷDZB˅ɹǟǣɍszlig˔DZă

ʔͼθαIumlplusmnǯĤɣǒƢʟƅƮǵˢǶ˔DZăʔĚ

macrǠnHȁ˶ǰszligȧƐκ˶ǰƱordm˶ǰwǵʫlIJaăλΞΰ͵εǰ

˔DZă[ Barthel Index1ǡκɻ-1λŹˍΞΰ͵εǰɣǒƢʟƅȊȟκJapanese Consortium of Prion Disease JACOPλ Medical Research Council Prion Disease Rating Scale MRC Scale26ǡκɻ-2λŹȝǞplusmnfrac12˔DZăʔͼθαʽ

ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

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ƝƧƞƛ ŜŤɚȧɄȺəȲƛ

Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

ǗOtildeŪǏ˔DZăʔͼθα6ǡǞOumlǹ

ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

2 ( -

ǞplusmnmacrǠnHȁ˶ǰszligȧƐņǡΞΰ͵εǰ˔DZăʔ Barthel Index1 ʐŤuacuteǠƵp4ʔͼθαʗĊͼθαɲ

ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

1ǞplusmnͼθαɛzΰΖΚΰθέεʔŃƔɄǡ 2

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ǏĤɎɣȠ40 Ǐɲ9IumlǹΞΰ͵εǰDZǘ˅ɹ˄|-ʔǏśǂaumlĪŹǯĤ Barthel

Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

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ī˔ʂ˾ǽȣǏ˾ǽǏś˒[˔

ǏȣǏ]ʐ˾ǽDZǘ˅ɹǽȠʔ

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λǠ

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ʋǘĭʔŤuacuteǠƵp4ˤͶͿΰθ 7˾ǽʋʚηʙȉƗəηƚɛƗəͶ

Ϳΰθ 4 ˾ǽʍ 11 ˾ǽIJʑpoundVUcircě 25 ƥ˯ʔ0 1Ǐʔ˾ǽ0 1 2 3 4Ǐʔ˾ǽĕǏ 0Ǐκű˔DZλ 20Ǐ[

divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ΑͺΰεKżļΥίΰɵPrPC PrPScʴŋ PrPScɳȞ˦UgraveoƂ

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Źˍ2004yacute 11Ų 2007yacute 3ŲǰmiddotǪΞΰ͵εǰ 11DZ7szlig PPSɛtimesVĻɹś7˟ŶǠIumlƗəǹcopyĖȐDZ7 5ƛograve

15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

2 -

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ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

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ǠĒŖcurrenŧȍͳΚΎε

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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ɡŠĒĀcȎltĒĽȍzǽȈɢƛ

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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džtɹ 27-29λ

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

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Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

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diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

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Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

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differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

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supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

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periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

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Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

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Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

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bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

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ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

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ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

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ƛ

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ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

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ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

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via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

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creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

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of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

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incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

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Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

ĶŴǵsup1ȊŽǰ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċ ɜ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ

ƶǂǂɝǪŚ_qĔ ƲƹƳ ȍȈĝȌȋŊħĶČucircǵĘįȇŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛ

ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

bullhsup1ȎŶnfĈǵĠȜȟȈǰȞǵǪAacuteIacuteȉȏ DžƦƭƥƸǪƼƧƨƧǁǪƴƧƥƥƺǪƿƦƥƧƻ ȉigtȡȘȞǫƛbullȒȇDZȏǪNtildeōŶȉǯȞǵǪDžƦƭƥƸǪƼƧƨƧǁ ȏȔȊȢȋxAgraveĔČǵȌǷqĔ ƲƹƳ

ȊǽȈĔČǿȞȃȘŶnUgraveOgraveȡǽȌǸȟȐŠfrac14ȏȇǴȌǰǫƛ

bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

ˌĢΞΰ͵εǰƞuacutemiddot PrPκcellular prion protein PrPCλθΐ PrPˌIcircAacuteǪ

ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

ȓȷDZǘǽȠ FFIAuml_κɻ-1λɢĀǰmiddotordfˌIcircAacuteǪǞplusmn 30ȜǏAacuteǪΐε 51 91 8ΦΕ˓ɆʼκΰΛθΏλˏ- 15ȜƙAEligηŅPfrac12 1-3κreg-1λăƓȜǪ 4ŹˍˌĢ

CJDV180Iκΐε 180ΗΰεͰγͰεɇŋλM232RκΨΊ͵ΒεαΒελE200KκͻαΈΦε˓ΰελ GSS P102LκΞγΰεͰγͰελAumlˏ[~κreg

-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

D178N-129M FFIǰIȐD178N-129V CJD

ˌċĆuacuteƄɩ1JĢˌċĆƻʿǛAacuteǪȜǪŤŹ

ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

ǁƦƩƭƷơƛǀƦƫƥǜǝǘǙơƛƳƦƬƭƽƢƦƧƮDžơƛDžƦƭƥƸơƛǃƦƭƨươƛǃƦƭƭươƛǃƦƮƨƸơƛƴƦƮƫƺơƛƴƧƥƥƺƢƦƧƮƼơƛƴƧƥƥƺƢƦƧƮDžơƛDžƧƥƨƸơƛ

ǁƧƥƭƷơƛDžƧƦƥƸơƛƴƧƦƦǀơƛƼƧƨƧǁơƛƲǘǎǘǗƪƦƢƮƦƛǓǗǜƛ

ƝƧƞƛƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċƛ ƝƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƛǎǓǜǏNjǜǏƯƛƶǂǂƞƛ

ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

LJƦƩƪǜǝǘǙƛƝţĠČƞơƛƧnjǙƢǎǏǕƛNjǝƛƦƬƭljƦƮƪǜǝǘǙNJƛƝśŊħĶȾɐɛɗɂȸɛƞƛƪ

2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

frac34ǵaacuteh_Ǫfrac34ǵȌċĖfĈȡĥǽjoǵȠǵ]ȍhǰfĈǫƛ

ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

uumlacuteǶDZyacuteȯ 77ơʐ˙i˲UgraveAEligʚAEligɹƚɛƗə˲UgraveǶDZAtildeɂē˅ɹĢ^ŶΦ͵ͺγθΓatildeɛAEligʟʅʆ˲Ugrave

AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

2 - -

ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

ɞaacuteǰǹaacuteƧʶǹťŶʙŪ CJDƓDZBȐ7

ƻʿǛatildeɛAEligʟDZʙȉDZUacuteţƢɑǬłˌIcircƏƅ

ʒŠĚʂuumlacuteɈǰŶˣ 4-5 yacute˟^ŶʙȉDZʒŠĒęǟǹ

ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

8

bullŶɈɔȨəċȏŶ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċ ɜ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ ǎǓǜǏNjǜǏƯƛ ƲƹƳ ɝ Ǫ

ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ ƶǂǂɝǪŋatildexAgrave

ĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ȍƓǻȟȞǫƛ

bullIacuteŷȎŶɈɔȨəċȉȏxAgraveacircǵȌǰȷȤɈǵhǰȎȉŠfrac14ȍȏŶnUgraveĴǵƍȉǯȝǪLfĈȎƐȏ DžƦƭƥƸǪƿƦƥƧƻǪƴƧƥƥƺǪƼƧƨƧǁǪƳƦƬƭƽ Ȏƌȍhǰǫƛ

bull DžƦƭƥƸ Ț ƴƧƥƥƺ ȉȏƏŸ ƼǁƸƛ umlcedilŦą$ƝǎǓǐǐǞǜǓǘǗƛǠǏǓǑǒǝǏǎƛǓǖNjǑǏƯƛƳdžƸƞȉǪiņėŪȚaOcircȍƘKfȡţȘȞǹȊǵhǷǪƿƦƥƧƻ Ț ƴƧƥƥƺ ȉȏxAgraveacircȡQȘȃiacutentildeǰċacircȎľG

ȚǪņŅƗethUgraveOgraveȍdzǸȞ ƦƩƢƨƢƨ ŒĕǪņŅƗethȎĈ_ɈɔȨəŒĕƘdeuml

ɜǛǏNjǕƢǝǓǖǏƛǚǞNjǔǓǗǑƢǓǗǎǞǍǏǎƛǍǘǗǟǏǛǜǓǘǗƯƛǁǃƢǀDŽƸƲɝUgraveOgraveȌȋǵEacuteăȉǯȞǫƛ

bull ƿƦƥƪƻȚ ƳƦƬƭƽȎ ƵƵƸ ȉȏuacuteĖȌʼnČucircȍiacuteǽǪƿƦƥƪƻ ȉȏɂɛȪəȶȾȳɍȡȊǿȞČșǰȞǹȊȡćǿȞǫDžƦƭƥƸ ȏuacuteĖȌɤɥɣą$ǴȜż2ǽDZȞcMǵǯȞǵǪƼƧƨƧǁ ȏ

ŶnUgraveĴȡǽȌǰȊqĔ ƲƹƳ ȊȎż2ȏȉǶȌǰǫƛ

bullůǪŊħĶƄwǪIgravetimesħĶƄwȡČucircȊǿȞŶɈɔȨəċǵbTǻȟȈǰȞǫƛ

ɢĀǰmiddotˌĢ CJDGSSFFI [ɻ-2P102L AacuteǪ CJD ƓDZǘ

frac34GSS 2 3V180IM232RˌĢΞΰ͵εǰUacuteţƢʒŠˌIcircƏȲĚ 4ʾΞΰ͵εɷǸκprion protein PrPλˌ

IcircǪuacuteȓȷDZBΞΰ͵εǰʒŠ˱ƳīĚʂ

ŹˍAtildeǰmiddotʊʝˌĢ CJD ʒŠordmdž CJD UacuteţƢų

CJD PRNPˌIcircAacuteǪųDZ7ɢĀDZǘETHǶĢ CJD dž

2 -

ŗǦƢƧƣƛ Lʼnċ_ȊbTǻȟȈǰȞŶnfĈƛ

ʼnċā$ƛ ȯȼəƛ ȣɌɀźĺmacrƛ ȯȼə ƦƧƮƛ raquouumlƛ

ƶǂǂƛ

ƦƥƧƛ ǙǛǘǕǓǗǏƛ ǩƛ ǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƷǜǓNjǘơƛƦƮƭƮƛƪƛ

Ʀƥƪƛ ǙǛǘǕǓǗǏƛ ǩƛ ǕǏǞǍǓǗǏƛ ǟNjǕǓǗǏƛ ƺǓǝNjǖǘǝǘơƛƦƮƮƨƛƫƛ

ƦƦƬƛ NjǕNjǗǓǗǏƛ ǩƛ ǟNjǕǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ǃǛNjǗǍǒNjǗǝơƛƦƮƭƮƛƬƛ

ƲƹƳƛ

ƦƬƭƛ NjǜǙNjǛǝNjǝǏƛ ǩƛ NjǜǙNjǛNjǑǓǗǏƛ ǟNjǕǓǗǏƛ ƶNjǖnjǏǝǝǓơƛƦƮƮƪƛƭƛ ƛ

Ʀƭƥƛ ǟNjǕǓǗǏƛ ǩƛ ǓǜǘǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƺǓǝNjǖǘǝǘơƛƦƮƮƨƛƮƛ

ƦƭƥƛƠƛ

ƧƨƧƛ

ƦƭƥƯƛDžNjǕƛ ǩƛ ƸǕǏƛ

ƧƨƧƯƛƼǏǝƛ ǩƛ ưǛǑƛǖǏǝǒǓǘǗǓǗǏƛ ƷǓǝǘǜǒǓơƛƦƮƮƨƛƦƥƛ

Ƨƥƥƛ ǑǕǞǝNjǖNjǝǏƛ ǩƛ ǕǢǜǓǗǏƛǟNjǕǓǗǏƛǘǛƛǖǏǝǒǓǘǗǓǗǏƛ

ƶǘǕǎǑNjnjǏǛơƛƦƮƭƮƛƦƦƛ

ƧƦƥƛ ǟNjǕǓǗǏƛ ǩƛ ǓǜǘǕǏǞǍǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƿǘǍǍǒǓNjǛǓơƛƦƮƮƨƛƦƧƛ

ƧƨƧƛ ǖǏǝǒǓǘǗǓǗǏƛ ǩƛ NjǛǑǓǗǓǗǏƛ ǗǘǝƛǜǝNjǝǏǎƛ ƺǓǝNjǖǘǝǘơƛƦƮƮƨƛƮƛ

ƶǂǂǪƲƹƳȌȋ

hƛ ƛ

ȯȼə ƪƦƢƮƦ Ǝ`ȎɊɈȸȼFŹ0Ÿȓ

Ȏ ƭƛƢƛƬƧ ȣɌɀźordfǪƦƫ ȣɌɀźszligkƛ

ƻNjǙǕNjǗǍǒǏơƛƦƮƮƪƛƦƨƛ

ƶǘǕǎǐNjǛnjơƛƦƮƮƨƛƦƩƛ

ƾǠǏǗơƛƦƮƭƮƛƦƪƛ

ƶǘǕǎǐNjǛnjơƛƦƮƮƦƛƦƫƛ

ǟNjǗƛƶǘǘǕơƛƦƮƮƪƛƦƬƛ

ƱǏǍǔƛƧƥƥƦƛƦƭƛ

ƵƵƸƛ ƦƬƭƛ NjǜǙNjǛǝNjǝǏƛ ǩƛ NjǜǙNjǛNjǑǓǗǏƛ ǖǏǝǒǓǘǗǓǗǏƛ ƼǏǎǘǛǓơƛƦƮƮƧƛƦƮƛ

ŊħĶƄwǪƛ

IgravetimesħĶƄwƛ

Ʀƫƨƛ ǝǢǛǘǍǓǗǏƛǩƛǘǝǒǏǛǜƛ ǟNjǕǓǗǏƛ ƼǏNjǎơƛƧƥƦƨƛƧƥƛ

ƦƬƭƛ ƧƢnjǙƛǎǏǕǏǝǓǘǗƛƝƲǃƞƛ ƛ ƼNjǝǜǞǣǘǗǘơƛƧƥƦƨƛƧƦƛ

ƝƦƞƛDžƦƭƥƸ fĈ ƲƹƳƛ

ˏ MRIųǡDWIQ7ĒɱęLJdĒ˩Qsup1AumlɛǺʬΰΣεǘordmāƇoacuteocircAumlɛǺʬQ1ƹɝǘɝɜIreg1-3uumlacuteǶDZyacute 765 ơǶDZ^ǶDZǘʐ˙i˲Ugraveɂē˅ɹ

UacuteţƢųMRI ŔďDZ7Alzheimer ǰʒŠɛƲŶĢŶĢŗ˷κperiodic synchronous discharge PSDλȯ 9ɛɚƽ 14-3-3ɷ

Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

( )- 1

2 -

ƝƧƞƛƿƦƥƧƻ fĈ ƶǂǂƛ

ˏ MRI ^ŶAacutetʙaumlųǡuumlacuteǶDZyacute 537 ơɬǗOtildesup2sup1DǶDZGƻʿǛpoundʒ˔ʂ 4ɚatildeɛ

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ɔǪuacuteĬʆDZ7 23CJDǰmiddotfrac34ǜUacuteȮVGSSǰmiddotCJDǰmiddotƿplusmnɛƲ PSDȯ 23ιɛɚƽ 14-3-3ɷǸȯ 25ˮĢ

RT-QUICƱˮĢǛȯ 88ųǡGSSʒŠordmdžɻ1-3Ȑ

ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

2 ȍOuml7κprobableλυɢĀDZǘΞΰ͵εɷǸˌIcircAacuteǪȍOuml7ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

3 Ǭ7κpossibleλυUacuteţƢ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴ+Ξΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

DZǘETHǶĢ CJDUmiddot7ġˁ˅ɹĢuumlacuteǶDZyacute 586ơɬŹˍUacuteţƢȍʙ7ȯ 54ǗOtildesup2sup1DAtilde 1 4ɛƲ

PSD ȯ 92ˏ MRI ȯ 94ɛɚƽ 14-3-3 ɷǸȯ 87ˮĢRT-QUICƱˮĢǛȯ 85ųǡ 4

ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

ETHǶĢ CJD Umiddot7ġˁ˅ɹ7 MM2 ǺʬmiddotƓɂē˅ɹ7κETHǶĢ

CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

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2 -

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6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

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cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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ƛ

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

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2 ( -

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

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ŤŹETHǶĢΞΰ͵εǰɢĀIȐ 4-6ɢĀIɈǰŶˣΞΰ͵εǰΈͰΞ

Ǫ 4 13 Umiddot7κMM1MV1λ

Umiddot7˅ɹĢʙȉƗə˲UgravekΦ͵ͺγθΓƒ˽˲UgraveatildeɛAEligʟƟɹ˲Ugrave5

ȯ 3-7 ζŲțăǑpǑʋɤ 3 4ɛƲ PSD

13 ˻Umiddot7κMM2-ǺʬmiddotMM2-ʅĀmiddotVV1VV2λ MM2-ǺʬmiddotυMM2-ǺʬmiddotAEligɹAEligʚƚƗə˲UgraveĺDZǘȬȓDZǘ

Atildeɂē˅ɹĢȷˈȐ 3 7 8ȯ 1-2yacutețăƟɹ˲UgraveǑpǑʋɤɈǰŶˣ 247 ζŲƑ˟

MM2-ʅĀmiddotυMM2-ʅĀmiddot 3 9 10ȅɣđȓȷ˲UgraveʙȉƗə˲UgraveȬȓDZǘȐ

AtildeɈǰŶˣ 185 ζŲ˟ǑpǑʋɤDZ7 κVV1VV2λυVV1frac12Țɂē˅ɹĢdFmiddotʙȉDZDZǘ

˚1ʱĘBΦ͵ͺγθΓVV2AEligʟĢƟɹġˁ˅ɹĢʙȉDZΦ͵ͺγθΓ 13ƙɛƲ PSD

ɜƧɝƛ UgraveOgraveeumlɜą$UgraveOgraveǪņŅƗethUgraveOgraveǪņigraveUgraveOgraveɝƛ

ETHǶĢΞΰ͵εǰƏƅƱǧIƏƅɛɚƽƏƅɛƲƏƅńETHǶĢ CJD

ΈͰΞƏƅĬăǪƳī 13 ǧIƏƅˏ MRI DWIʒŠųǡreg-211-14ɻȐŻƔdžt DWIʒ

Šə FLAIRǧI 15ǧIĴʃȐǯĤǯĤ˞_

˔ʂ 16

DWIAumlɛǺʬκˀuacuteʀśĴλordmāƇκǗɀŻ1dyˏλǪuacute

Atilde 14

ǥƢƧɟ)- 1 2 )3 ƛ

)- 1 V UV b S 1 V RT b S RV

PJacM Q a )- W 1 V b S W b SME PJac W 1

V b S W b S UV b S W )- PJac

2 )3 M WI

ƛ

2 ( -

13 ɛɚƽƏƅ 14-3-3 ɷǸɾlǹʒŠordmdž˾ǽk 2CJD ĤɎ

ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

qĔɈɔȨəċĽsup1ƛ

Ugraveşsup1ƛƛ ƪƦƤƪƫƛ ƛ ƪƧƤƪƫƛ ƛ ƪƭƤƫƬƛ ƛ ƫƩƤƫƬƛ ƦƥƮƤƦƧƨƛ ƦƦƫƤƦƧƨƛ

ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

ƛ

MŞƛ ƮƦƜƛ ƮƨƜƛ ƭƬƜƛ ƮƫƜƛ ƭƮƜƛ ƮƩƜƛ

ƼƼƛ ƮƥƜƛ ƮƬƜƛ ƮƥƜƛ ƮƨƜƛ ƮƥƜƛ ƮƪƜƛ

ƼDžƛ ƭƭƜƛ ƭƧƜƛ ƭƭƜƛ ƦƥƥƜƛ ƭƭƜƛ ƮƪƜƛ

DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

uacuteĈƛ ƮƭƜƛ ƪƫƜƛ ƦƥƥƜƛ ƬƪƜƛ ƮƮƜƛ ƫƪƜƛ

13 ɛƲƏƅ Steinhoff 26ɛƲ PSDʔordmdžȐǶDZťŶ 45 ˮĢȐȷˈ 90 ˮĢȐfrac12PSD ZǞǛ CJD ΝΈͰΞɈǰˣŶˣ

Ǫ

ɜƨɝƛ Šfrac14aocircƛ

WHOʒŠordmdž 2κɻ-1λήθγΘʒŠordmdžκɻ-4λȐ 11ǞplusmnŤŹ CJDθΠͰίε WHO ʒŠordmdžņǡκɻ-1λκǧIƏƅɛɚƽƏƅƏƅƔ

džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

A Φ͵ͺγθΓ B ʅʆǪuacuteatildeɛAEligʟ C ˚1ʱ˲Ugrave˚1Acircʱ˲Ugrave D ǑpǑʋ

3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

ήθγΘκEuroCJDλordmdžɛɚƽ 14-3-3ɷǸ˩ μμ ήθγΘκEuroCJDλǧIʒŠŮOtildeordmdž MRI ŀřĉʟǧIκDWIλ FLAIR ǧIaeligǘƇηɼƦAumlɛǺʬsup1 2 ζĴʙ

2 ) -

ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

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differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

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sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

ƛ

bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

ĶŴǵsup1ȊŽǰ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċ ɜ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ

ƶǂǂɝǪŚ_qĔ ƲƹƳ ȍȈĝȌȋŊħĶČucircǵĘįȇŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛ

ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

bullhsup1ȎŶnfĈǵĠȜȟȈǰȞǵǪAacuteIacuteȉȏ DžƦƭƥƸǪƼƧƨƧǁǪƴƧƥƥƺǪƿƦƥƧƻ ȉigtȡȘȞǫƛbullȒȇDZȏǪNtildeōŶȉǯȞǵǪDžƦƭƥƸǪƼƧƨƧǁ ȏȔȊȢȋxAgraveĔČǵȌǷqĔ ƲƹƳ

ȊǽȈĔČǿȞȃȘŶnUgraveOgraveȡǽȌǸȟȐŠfrac14ȏȇǴȌǰǫƛ

bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

ˌĢΞΰ͵εǰƞuacutemiddot PrPκcellular prion protein PrPCλθΐ PrPˌIcircAacuteǪ

ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

ȓȷDZǘǽȠ FFIAuml_κɻ-1λɢĀǰmiddotordfˌIcircAacuteǪǞplusmn 30ȜǏAacuteǪΐε 51 91 8ΦΕ˓ɆʼκΰΛθΏλˏ- 15ȜƙAEligηŅPfrac12 1-3κreg-1λăƓȜǪ 4ŹˍˌĢ

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-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

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ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

ǁƦƩƭƷơƛǀƦƫƥǜǝǘǙơƛƳƦƬƭƽƢƦƧƮDžơƛDžƦƭƥƸơƛǃƦƭƨươƛǃƦƭƭươƛǃƦƮƨƸơƛƴƦƮƫƺơƛƴƧƥƥƺƢƦƧƮƼơƛƴƧƥƥƺƢƦƧƮDžơƛDžƧƥƨƸơƛ

ǁƧƥƭƷơƛDžƧƦƥƸơƛƴƧƦƦǀơƛƼƧƨƧǁơƛƲǘǎǘǗƪƦƢƮƦƛǓǗǜƛ

ƝƧƞƛƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċƛ ƝƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƛǎǓǜǏNjǜǏƯƛƶǂǂƞƛ

ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

LJƦƩƪǜǝǘǙƛƝţĠČƞơƛƧnjǙƢǎǏǕƛNjǝƛƦƬƭljƦƮƪǜǝǘǙNJƛƝśŊħĶȾɐɛɗɂȸɛƞƛƪ

2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

frac34ǵaacuteh_Ǫfrac34ǵȌċĖfĈȡĥǽjoǵȠǵ]ȍhǰfĈǫƛ

ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

uumlacuteǶDZyacuteȯ 77ơʐ˙i˲UgraveAEligʚAEligɹƚɛƗə˲UgraveǶDZAtildeɂē˅ɹĢ^ŶΦ͵ͺγθΓatildeɛAEligʟʅʆ˲Ugrave

AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

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ƝƦƞƛDžƦƭƥƸ fĈ ƲƹƳƛ

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1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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Ɲƪƞƛ ȂȎƛ

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7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

1 ǢźŬɮIcircοĤɎηUacuteţszligęǟȑ)ǹŕōκȣςˏΞΰ͵εǰν0οΙΏηΞΰ͵εǰοȣ21ȡλοǠnH

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

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RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

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mimicking fatal familial insomnia Neurology 1999 52 1757-1763

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662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

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early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

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patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

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Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

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6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

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17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

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20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

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21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

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D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

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3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

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CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

1 Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

2 WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

3 ǠnHȁǗOtildeǯĤszligȧȊȟƐοˆǶĢͱͰαĬƄDZʟƅȊȟǝοͺγͰΌΜͲαΏηΫΝǰʒǵΥΒά

ακŖʌǔλο2002

4 Iwasaki Y Mimuro M Yoshida M Sobue G Hashizume Y Clinical diagnosis of Creutzfeldt-Jakob disease

Accuracy based on analysis of autopsy-confirmed cases J Neurol Sci 2009 277119-123

5 Iwasaki Y Yoshida M Hashizume Y Kitamoto T Sobue G Clinicopathologic characteristics of sporadic Japanese

Creutzfeldt-Jakob disease classified according to prion protein gene polymorphism and prion protein type Acta

Neuropathol 2006 112 561-571

6 Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

7 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

8 Iwasaki Y Mimuro M Yoshida M Kitamoto T Hashizume Y Survival to akinetic mutism state in Japanese cases of

MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians Eur J Neurol 2011 18 999-1002

9 Iwasaki Y Akagi A Mimuro M Kitamoto T Yoshida M Factors influencing the survival period in Japanese

patients with sporadic Creutzfeldt-Jakob disease J Neurol Sci 2015 357 63-68

2 -

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bullņigraveUgraveOgraveȉȏUEumlNEumlmiddotƇɜǙǏǛǓǘǎǓǍƛǜǢǗǍǒǛǘǗǘǞǜƛǎǓǜǍǒNjǛǑǏƯƛƿǂƳɝǵuacuteĖ řȉǯȝǪɈɔȨəċȎŠfrac14aocircȎȇȊȌȆȈǰȞǫƛ

bullqĔɈɔȨəċȎLċ_ɚĻċEumlƀȍțȆȈą$UgraveOgraveɚņŅƗethUgraveOgraveɚņigraveUgraveOgraveȎȏĈȌȞǹȊȍiacuteǿȞǫȖȃǪqĔɈɔȨəċȍƓǽȃħĶĊǵǯȝǪż2ǵŻŘȉǯȞǫƛ

ETHǶĢΞΰ͵εǰUmiddotUmiddot7MM1MV1˻Umiddot7κMM2-ǺʬmiddotMM2-ʅ

ĀmiddotMV2VV1VV2λ Creutzfeldt-Jakob ǰκCreutzfeldt-Jakob disease CJDλ[ɻ

-23ŤŹeƏ7ETHǶĢΞΰ͵εǰΝΈͰΞƧǛȐκreg-1λUmiddot7˻Umiddot7ɢĀDZǘηɢĀȷˈηƏƅκǧIηɛɚƽηɛƲλĬăǪʒŠ˱ǩī

ǥƢƦɟAacuteIacuteȎ4UgraveȍdzǸȞqĔɈɔȨəċȎȰɇȷȤɈaringyumlƛ

ƛ

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ŤŹETHǶĢΞΰ͵εǰɢĀIȐ 4-6ɢĀIɈǰŶˣΞΰ͵εǰΈͰΞ

Ǫ 4 13 Umiddot7κMM1MV1λ

Umiddot7˅ɹĢʙȉƗə˲UgravekΦ͵ͺγθΓƒ˽˲UgraveatildeɛAEligʟƟɹ˲Ugrave5

ȯ 3-7 ζŲțăǑpǑʋɤ 3 4ɛƲ PSD

13 ˻Umiddot7κMM2-ǺʬmiddotMM2-ʅĀmiddotVV1VV2λ MM2-ǺʬmiddotυMM2-ǺʬmiddotAEligɹAEligʚƚƗə˲UgraveĺDZǘȬȓDZǘ

Atildeɂē˅ɹĢȷˈȐ 3 7 8ȯ 1-2yacutețăƟɹ˲UgraveǑpǑʋɤɈǰŶˣ 247 ζŲƑ˟

MM2-ʅĀmiddotυMM2-ʅĀmiddot 3 9 10ȅɣđȓȷ˲UgraveʙȉƗə˲UgraveȬȓDZǘȐ

AtildeɈǰŶˣ 185 ζŲ˟ǑpǑʋɤDZ7 κVV1VV2λυVV1frac12Țɂē˅ɹĢdFmiddotʙȉDZDZǘ

˚1ʱĘBΦ͵ͺγθΓVV2AEligʟĢƟɹġˁ˅ɹĢʙȉDZΦ͵ͺγθΓ 13ƙɛƲ PSD

ɜƧɝƛ UgraveOgraveeumlɜą$UgraveOgraveǪņŅƗethUgraveOgraveǪņigraveUgraveOgraveɝƛ

ETHǶĢΞΰ͵εǰƏƅƱǧIƏƅɛɚƽƏƅɛƲƏƅńETHǶĢ CJD

ΈͰΞƏƅĬăǪƳī 13 ǧIƏƅˏ MRI DWIʒŠųǡreg-211-14ɻȐŻƔdžt DWIʒ

Šə FLAIRǧI 15ǧIĴʃȐǯĤǯĤ˞_

˔ʂ 16

DWIAumlɛǺʬκˀuacuteʀśĴλordmāƇκǗɀŻ1dyˏλǪuacute

Atilde 14

ǥƢƧɟ)- 1 2 )3 ƛ

)- 1 V UV b S 1 V RT b S RV

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2 )3 M WI

ƛ

2 ( -

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ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

qĔɈɔȨəċĽsup1ƛ

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ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

ƛ

MŞƛ ƮƦƜƛ ƮƨƜƛ ƭƬƜƛ ƮƫƜƛ ƭƮƜƛ ƮƩƜƛ

ƼƼƛ ƮƥƜƛ ƮƬƜƛ ƮƥƜƛ ƮƨƜƛ ƮƥƜƛ ƮƪƜƛ

ƼDžƛ ƭƭƜƛ ƭƧƜƛ ƭƭƜƛ ƦƥƥƜƛ ƭƭƜƛ ƮƪƜƛ

DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

uacuteĈƛ ƮƭƜƛ ƪƫƜƛ ƦƥƥƜƛ ƬƪƜƛ ƮƮƜƛ ƫƪƜƛ

13 ɛƲƏƅ Steinhoff 26ɛƲ PSDʔordmdžȐǶDZťŶ 45 ˮĢȐȷˈ 90 ˮĢȐfrac12PSD ZǞǛ CJD ΝΈͰΞɈǰˣŶˣ

Ǫ

ɜƨɝƛ Šfrac14aocircƛ

WHOʒŠordmdž 2κɻ-1λήθγΘʒŠordmdžκɻ-4λȐ 11ǞplusmnŤŹ CJDθΠͰίε WHO ʒŠordmdžņǡκɻ-1λκǧIƏƅɛɚƽƏƅƏƅƔ

džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

A Φ͵ͺγθΓ B ʅʆǪuacuteatildeɛAEligʟ C ˚1ʱ˲Ugrave˚1Acircʱ˲Ugrave D ǑpǑʋ

3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

ήθγΘκEuroCJDλordmdžɛɚƽ 14-3-3ɷǸ˩ μμ ήθγΘκEuroCJDλǧIʒŠŮOtildeordmdž MRI ŀřĉʟǧIκDWIλ FLAIR ǧIaeligǘƇηɼƦAumlɛǺʬsup1 2 ζĴʙ

2 ) -

ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

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Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

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224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

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662-669

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Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

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sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

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disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

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differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

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diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

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sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

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bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

ĶŴǵsup1ȊŽǰ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċ ɜ ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛ

ƶǂǂɝǪŚ_qĔ ƲƹƳ ȍȈĝȌȋŊħĶČucircǵĘįȇŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛ

ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

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ȊǽȈĔČǿȞȃȘŶnUgraveOgraveȡǽȌǸȟȐŠfrac14ȏȇǴȌǰǫƛ

bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

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-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

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ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

ŵ

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ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ƛ ƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

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ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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Ǹȯ 80ˮĢǛRT-QUICƱˮĢǛȯ 62 22

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

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18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

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21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

1 ǢźŬɮIcircοĤɎηUacuteţszligęǟȑ)ǹŕōκȣςˏΞΰ͵εǰν0οΙΏηΞΰ͵εǰοȣ21ȡλοǠnH

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

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Ǫ

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džtɹ 27-29λ

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ήθγΘκEuroCJDλordmdžɛɚƽ 14-3-3ɷǸ˩ μμ ήθγΘκEuroCJDλǧIʒŠŮOtildeordmdž MRI ŀřĉʟǧIκDWIλ FLAIR ǧIaeligǘƇηɼƦAumlɛǺʬsup1 2 ζĴʙ

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ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

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Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

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4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

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5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

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cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

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variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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ƝƦƞƛ ģňĪOslash ƲƹƳƛ ƛ

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ŗǧƢƨƣƛ fĈ_ ƲƹƳ Šfrac14aocircɜdžƷƾƛƧƥƥƦɝƩƛ

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ƛ

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ΙΏǣżpara1αΩεȌɠșƎƮǵƢ

ˌĢˊĢƺȽǘɛDZOtilde

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

ǗOtildeŪǏ˔DZăʔͼθα6ǡǞOumlǹ

ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

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ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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džtɹ 27-29λ

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ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

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Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

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5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

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20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

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23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

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25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

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2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 ( -

13 ɛɚƽƏƅ 14-3-3 ɷǸɾlǹʒŠordmdž˾ǽk 2CJD ĤɎ

ɛɚƽ 14-3-3ɷǸȿΈͱɷǸʒŠųo 17-23ɈǰŶˣ 18 CJDΝΈͰΞ 1914-3-3 ɷǸȿΈͱɷǸĬăǪCJD AcircǯĤ 14-3-3 ɷǸȿΈͱɷǸˮĢȐ 22 23ǪuacutemiddotΞΰ͵εɷǸĬăiquestucircƱCJDĤɎɛɚƽ

ǪuacutemiddotΞΰ͵εɷǸƏZIJj 24 25ʒŠųoĢȐκɻ-3λ

ŗǥƢƨɟqĔɈɔȨəċȍdzǸȞņŅƗethȎ ƦƩƢƨƢƨ ŒĕȊ ǁǃƢǀDŽƸƲ eumlȍțȞƛĈ_ɈɔȨəŒĕȎƃyumlȎUgraveş

ƛ ƛnotĴĖUgraveşƛ ĤšĖUgraveşƛ ĹŞƛ

ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ ǁǃƢǀǞƸƲƛ ƛ ƦƩƢƨƢƨ Œĕƛ

qĔɈɔȨəċĽsup1ƛ

Ugraveşsup1ƛƛ ƪƦƤƪƫƛ ƛ ƪƧƤƪƫƛ ƛ ƪƭƤƫƬƛ ƛ ƫƩƤƫƬƛ ƦƥƮƤƦƧƨƛ ƦƦƫƤƦƧƨƛ

ȯəȻɗɛɕƛ ƛ ƦƤƪƧƛ ƛ ƧƨƤƪƧƛ ƛ ƥƤƪƦƛ ƛ ƦƨƤƪƦƛ ƛ ƦƤƦƥƨƛ ƛ ƨƫƤƦƥƨƛ

ƛ

MŞƛ ƮƦƜƛ ƮƨƜƛ ƭƬƜƛ ƮƫƜƛ ƭƮƜƛ ƮƩƜƛ

ƼƼƛ ƮƥƜƛ ƮƬƜƛ ƮƥƜƛ ƮƨƜƛ ƮƥƜƛ ƮƪƜƛ

ƼDžƛ ƭƭƜƛ ƭƧƜƛ ƭƭƜƛ ƦƥƥƜƛ ƭƭƜƛ ƮƪƜƛ

DžDžƛ ƦƥƥƜƛ ƦƥƥƜƛ ƮƧƜƛ ƦƥƥƜƛ ƮƪƜƛ ƦƥƥƜƛ

uacuteĈƛ ƮƭƜƛ ƪƫƜƛ ƦƥƥƜƛ ƬƪƜƛ ƮƮƜƛ ƫƪƜƛ

13 ɛƲƏƅ Steinhoff 26ɛƲ PSDʔordmdžȐǶDZťŶ 45 ˮĢȐȷˈ 90 ˮĢȐfrac12PSD ZǞǛ CJD ΝΈͰΞɈǰˣŶˣ

Ǫ

ɜƨɝƛ Šfrac14aocircƛ

WHOʒŠordmdž 2κɻ-1λήθγΘʒŠordmdžκɻ-4λȐ 11ǞplusmnŤŹ CJDθΠͰίε WHO ʒŠordmdžņǡκɻ-1λκǧIƏƅɛɚƽƏƅƏƅƔ

džtɹ 27-29λ

ŗǥƢƩɟɒɛɗȹɂɜƴǞǛǘƲƹƳɝȍdzǸȞqĔ ƲƹƳ ȎŠfrac14aocircƛ ƝLjǏǛǛƛǏǝƛNjǕƛƦƦƞƛ

1 ġˁ˅ɹĢʙȉƗə˲Ugrave 2 ɢĀDZǘ

A Φ͵ͺγθΓ B ʅʆǪuacuteatildeɛAEligʟ C ˚1ʱ˲Ugrave˚1Acircʱ˲Ugrave D ǑpǑʋ

3 ɛƲŶĢŶĢŗ˷κPSDλȐ 4 MRIŀřĉʟǧIκDWIλ FLAIRǧIaeligǘƇηɼƦʙ

definite CJD ɛȶɅ CJDǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZETHǶĢ CJD ɥǰǟIł probable CJD ǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ0 2˾ǽˮĢȐauml 1˾ǽȐ possible CJD 2˾ǽˮĢȐQɢĀȷˈ 2yacuteŸDŽ μ ήθγΘκEuroCJDλETHǶĢ CJDʒŠordmdžMRIƏƅŀřĉʟǧIκDWIλ FLAIRǧIɢĀƏƅ˾ǽʒŠordmdžǧIƔdžtŔIŢƱʄOtilde

ήθγΘκEuroCJDλordmdžɛɚƽ 14-3-3ɷǸ˩ μμ ήθγΘκEuroCJDλǧIʒŠŮOtildeordmdž MRI ŀřĉʟǧIκDWIλ FLAIR ǧIaeligǘƇηɼƦAumlɛǺʬsup1 2 ζĴʙ

2 ) -

ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

ƛ

bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

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ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

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bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

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Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

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ƝƩƞƛ ȂȎƛ ƛ

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ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

uumlacuteǶDZyacuteȯ 77ơʐ˙i˲UgraveAEligʚAEligɹƚɛƗə˲UgraveǶDZAtildeɂē˅ɹĢ^ŶΦ͵ͺγθΓatildeɛAEligʟʅʆ˲Ugrave

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ƛ ƛ

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ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

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8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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ɜƩɝƛ Ccedilȍƛ

űʻǧIƏƅηɛɚƽƏƅΞΰ͵εǰ˞_ǯĤIumlplusmnŧ˞

_ǯĤƖŹɛDZ˓ȱɛDZLewy atilde1middotʙȉDZʥǪuacuteDZɣotildeNǭĢɛǎńɢĀĘBȷˈƏƅĴʃȥǩī 16 30-36κreg-3λ

Masters CL Harris JO Gajdusek DC Gibbs CJ Jr Bernoulli C Asher DM Creutzfeldt-Jakob disease patterns of

worldwide occurrence and the significance of familial and sporadic clustering Ann Neurol 1979 5 177-188

WHO WHO Manual for Strengthening Diagnosis and Surveillance of Creutzfeldt-Jakob Disease World Health

Organization Geneva 1998

Parchi P Giese A Capellari S Brown P Schulz-Schaeffer W Windl O et al Classification of sporadic

Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects Ann Neurol 1999 46

224-233

Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

Krasnianski A Kaune J Jung K Kretzschmar HA Zerr I First symptom and initial diagnosis in sporadic CJD

patients in Germany J Neurol 2014 261 1811-1817

Krasnianski A Bohling GT Harden M Zerr I Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob

disease in Germany J Clin Psychiatry 2015 76 1209-1215

Hamaguchi T Kitamoto T Sato T Mizusawa H Nakamura Y Noguchi M et al Clinical diagnosis of MM2-type

sporadic Creutzfeldt-Jakob disease Neurology 2005 64 643-648

Krasnianski A Meissner B Schulz-Schaeffer W Kallenberg K Bartl M Heinemann U et al Clinical features and

diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease Arch Neurol 2006 63 876-880

Parchi P Capellari S Chin S Schwarz HB Schecter NP Butts JD et al A subtype of sporadic prion disease

mimicking fatal familial insomnia Neurology 1999 52 1757-1763

Moda F Suardi S Di Fede G Indaco A Limido L Vimercati C et al MM2-thalamic Creutzfeldt-Jakob Disease

neuropathological biochemical and transmission studies identify a distinctive prion strain Brain Pathol 2012 22

662-669

Zerr I Kallenberg K Summers DM Romero C et al Updated clinical diagnostic criteria for sporadic

Creutzfeldt-Jakob disease Brain 132 2659-68 2009

Shiga Y Miyazawa K Sato S Fukushima R Shibuya S Sato Y et al Diffusion-weighted MRI abnormalities as an

early diagnostic marker for Creutzfeldt-Jakob disease Neurology 2004 63 443-449

Meissner B Kallenberg K Sanchez-Juan P Collie D Summers DM Almonti S et al MRI lesion profiles in

sporadic Creutzfeldt-Jakob disease Neurology 2009 72 1994-2001

Caobelli F Cobelli M Pizzocaro C Pavia M Magnaldi S Guerra UP The role of neuroimaging in evaluating

patients affected by Creutzfeldt-Jakob disease a systematic review of the literature J Neuroimaging 2015 25 2-13

Fujita K Harada M Sasaki M Yuasa T Sakai K Hamaguchi T Sanjo N Shiga Y Satoh K Atarashi R Shirabe S

Nagata K Maeda T Murayama S Izumi Y Kaji R Yamada M Mizusawa H Multicentre multiobserver study of

diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob

disease a reliability and agreement study BMJ Open 2012 2 e000649

źžCIcirc Ǎ˕Ĝc ǸɶƱIcirc žƪūIcirc ntildeƞˉ ȫǢ ʛ Periodic synchronous discharge

Creutzfeldt-Jakobǰ˞_ʂƖŹɛDZ 17 ɢĀȓȷNtilde 2013 53 716-720

Satoh K Shirabe S Eguchi H Tsujino A Eguchi K Satoh A et al 14-3-3 protein total tau and phosphorylated tau

in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan Cell Mol

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

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Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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Ɲƪƞƛ ȂȎƛ

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7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

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28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

ƞuacutemiddotΞΰ͵εɷǸκcellular prion protein PrPCλLjĢǪuacutemiddotΞΰ͵εɷǸ

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4ǡȳɗAacuteĢĺa4ǡųɵǖͺΰθΒεͻɢĀȊȟɹ

ΑͺΰεKżļΥίΰɵPrPC PrPScʴŋ PrPScɳȞ˦UgraveoƂ

frac12Ξΰ͵εǰɢĀȊȟɹ 1ɮmacrɹ PRION-1 studyĊ^OtildeίεΉΧtʕŠƮǵɊ˻ƮǵɊ[Ƨʶʕɹ 2űȵǹ 107

7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

ˣʈYacuteŶˣ78 7κ73ιλʈYacuteŶˣƣǠIumlǛΑͺΰεVŴɊ˻VŴɊˢEumlŪ˔DZăɾƞɹɎocircɓƗə˲Ugrave 20 7

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15Ξί΅ΣĻ 3ʙȉƗəƏƅ 2ɊˣųīocircǠĒocirc

ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

2 -

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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980-8575 Oslashcedilȃouml˹ɱvũˬǦ 2-1 TELυ022-717-8147 FAXυ022-717-8148

E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

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WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

Neurobiol 2006 26 45-52

Zerr I Bodemer M Gefeller O Otto M Poser S Wiltfang J et al Detection of 14-3-3 protein in the cerebrospinal

fluid supports the diagnosis of Creutzfeldt-Jakob disease Ann Neurol 1998 43 32-40

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Sanchez-Juan P Green A Ladogana A Cuadrado-Corrales N Saacuteanchez-Valle R Mitrovaacutea E et al CSF tests in the

differential diagnosis of Creutzfeldt-Jakob disease Neurology 2006 67 637-643

Satoh K Shirabe S Tsujino A Eguchi H Motomura M Honda H et al Total tau protein in cerebrospinal fluid and

diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease Dement Geriatr Cogn Disord

2007 24207-212

Stoeck K Sanchez-Juan P Gawinecka J Green A Ladogana A Pocchiari M et al Cerebrospinal fluid biomarker

supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias a longitudinal multicentre study over 10

years Brain 2012 135 3051-3061

Coulthart MB Jansen GH Olsen E Godal DL Connolly T Choi BC et al Diagnostic accuracy of cerebrospinal

fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada a 6-year prospective study BMC Neurol

2011 10 133

Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D et al Ultrasensitive human prion detection in

cerebrospinal fluid by real-time quaking-induced conversion Nat Med 2011 17 175-178

Peden AH McGuire LI Appleford NE Mallinson G Wilham JM Orruacute CD et al Sensitive and specific detection of

sporadic Creutzfeldt-Jakob disease brain prion protein using real-time quaking-induced conversion J Gen Virol

2011 93 438-449

Steinhoff BJ Racker S Herrendorf G Poser S Grosche S Zerr I Kretzschmar H et al Accuracy and reliability of

periodic sharp wave complexes in Creutzfeldt-Jakob disease Arch Neurol 1996 53 162-166

Fujita K Yuasa T Takahashi Y Tanaka K Iwasaki Y Matsui N et al Differentiation between anti-NMDAR

antibody-positive Creutzfeldt-Jakob disease and immune-mediated encephalitis Clin Exp Neuroimmunol 2014 5

246

Cramm M Schmitz M Karch A Mitrova E Kuhn F Schroeder B et al Stability and reproducibility underscore

utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease Mol Neurobiol 2016 53 1896-18904

Schmitz M Ebert E Stoeck K Karch A Collins S Calero M et al Validation of 14-3-3 protein as a marker in

sporadic Creutzfeldt-Jakob disease diagnostic Mol Neurobiol 2016 53 2189-2199

0˕Ą Ʃ˕ʣO ˟ethiexclş raquoVˮ 13eacuteK Ȗecirc et al CJD ˞_ʂɸȭɛDZ7

ɢĀȓȷNtilde 2015 55 285

Ƙigraveˎ ǢJ źĎOcirc Ɓ Ȓ ŷźŭAring gt j et al Creutzfeldt-JakobǰɢĀȷˈ

Ȑ Basedowǰ+ƖŹɛDZ 17 BRAIN NERVE 2008 60559-565

Aumliuml ǟ EcircntildeȰIcirc ȳntildeģIcirc ɶAumlƕ ƍ ˅ɶMˎ ͺγͰΌΜͲαΏΫΝǰCJD˞_Ħ

ĢΰεΘɝordfġĢɛǎ7 ɢĀȓȷNtilde 2015 55 210

ƲAtilde˕ŚIcirc ɶƞŧ Nj`Ĉ ȷˈ Creutzfeldt-JakobǰDZBγͰΐųo

ɣotildeNǭĢʹɃȮɛǎ 70ơǥĢ7 ȓȷVȗ 2014 81 216-220

ɶǢƸ ǃƶČ Ɩthorn` ǢĩIcirc eumlicirc ˺ žaringIcirc et al ļ NMDA Ucirc1ļ1ˮĢ

Creutzfeldt-JakobǰNǭˤ˃ɛǎ˞_ ȓȷNǭNtilde 2013 18 109

KUumlɉ ȢVŬIcirc sup2 ˊ ɪcedilǀȔ $sup2 ɏ 0rİ et al ^ŶƖŹɛDZ˞_not˶

CJD 17 ɢĀȓȷNtilde 2007 47 196

ȫǢ ʛ ƖŹɛDZ [IcircȬȓwNtilde 2013 13178-184

2 -

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bullŶɈɔȨəċȊȏǪɈɔȨəŒĕɜǙǛǓǘǗƛ ǙǛǘǝǏǓǗƯƛ ƿǛƿɝȡȯɛȼǿȞɈɔȨəŒĕŶnȎfĈȍțȝĂǾȞɈɔȨəċȉǪȌʼnČȍțȝqĔ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċɜƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛ

ǎǓǜǏNjǜǏƯƛ ƲƹƳɝȍƓȎČȡSǿȞŶ ƲƹƳǪŅƗ|ņfČȚčzƙďȌȋȍƓǽ

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ƶǂǂɝǪŚ_qĔ ƲƹƳ ȍȈĝȌȋŊħĶČucircǵĘįȇŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛ

ǐNjǖǓǕǓNjǕƛ ǓǗǜǘǖǗǓNjƯƛ ƵƵƸƞǪȂȎȍi2ǻȟȞǫIgravetimesħĶƄwȡĥǿfĈșǯȝʼnȲɊȬȻɓɍȏ

ƊȍccedilȉǯȞǫƛ

bullhsup1ȎŶnfĈǵĠȜȟȈǰȞǵǪAacuteIacuteȉȏ DžƦƭƥƸǪƼƧƨƧǁǪƴƧƥƥƺǪƿƦƥƧƻ ȉigtȡȘȞǫƛbullȒȇDZȏǪNtildeōŶȉǯȞǵǪDžƦƭƥƸǪƼƧƨƧǁ ȏȔȊȢȋxAgraveĔČǵȌǷqĔ ƲƹƳ

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bullŶɈɔȨəċșNtildeȏǯȞȃȘǪqĔ ƲƹƳ ȊNUumlȌiacuteǵŘȉǯȞǫ

ˌĢΞΰ͵εǰƞuacutemiddot PrPκcellular prion protein PrPCλθΐ PrPˌIcircAacuteǪ

ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

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-2λΐε 129 AtildemiddotΨΊ͵ΒεMAtildeβαAacuteǪAtildeΗΰεVβαAacuteǪǠɢĀIAumlAacuteƳīĚʂ7

D178N-129M FFIǰIȐD178N-129V CJD

ˌċĆuacuteƄɩ1JĢˌċĆƻʿǛAacuteǪȜǪŤŹ

ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

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ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

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ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

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ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

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5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

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6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

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dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

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20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

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mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

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28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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2 -

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1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

2 -

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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ȊȟǝθΧΡθΉͱεγθΐəλhttpprionuminjpguidelineindexhtml

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l

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GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

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CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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ǠΞΰ͵εǰɢĀDZBETHǶĢ CJD DZBˌĢ CJDɚatildeɛAacuteĢDZDzĢszligǴȷˈśyacute˟ GSSʅĀmiddotETHǶĢ CJD ȅɣđ

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D178N-129M FFIǰIȐD178N-129V CJD

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ă V180I M232R UacuteţVǶDZɎldquoETHǶĢrdquoǶDZ

ˌIcircAacuteǪǪɢĀηǰǟIETHǶ7Q7ˌIcircƏƅɹ

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ŗǦƢƦɟŶɈɔȨəċȎʼnċ_ȊȂȎCYȊȌȞȌŶnfĈƛ

ƝƦƞƛ Ŷ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċƛ ƝǑǏǗǏǝǓǍƛƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnjƛǎǓǜǏNjǜǏƯƛǑƲƹƳƞƛ

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ƿƦƥƧƻơƛƿƦƥƪƻơƛƶƦƦƩDžơƛưƦƦƬDžơƛƶƦƨƦDžơƛƼƦƭƬǁơƛƷƦƭƬǁơƛƵƦƮƭǂơƛƳƧƥƧƽơƛǀƧƦƧƿơƛǀƧƦƬǁơƛƲǘǎǘǗƪƦƢƮƦǓǗǜƛ

Ɲƨƞƛ ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ ƛ

ƳƦƬƭƽƢƦƧƮƼƛ

ƝƩƞƛ ȂȎƛ ƛ

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2 -

ɟȠǵ]Ȋagrave~ȉȎŶɈɔȨəċȎŶnfĈȎƐƛ

ƛ

ǦƢƧɟɈɔȨəŒĕȎȱȦɛɋȊŶnh_ȌȜȑȍȌċĖfĈƛ

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ɜƦɝƛ DžƦƭƥƸ fĈ ƲƹƳƛ

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AlzheimerǰʜʒƳīĚʂ 6

ƛ ƛ

2 - -

ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

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bullIacuteŷȎŶɈɔȨəċȉȏxAgraveacircǵȌǰȷȤɈǵhǰȎȉŠfrac14ȍȏŶnUgraveĴǵƍȉǯȝǪLfĈȎƐȏ DžƦƭƥƸǪƿƦƥƧƻǪƴƧƥƥƺǪƼƧƨƧǁǪƳƦƬƭƽ Ȏƌȍhǰǫƛ

bull DžƦƭƥƸ Ț ƴƧƥƥƺ ȉȏƏŸ ƼǁƸƛ umlcedilŦą$ƝǎǓǐǐǞǜǓǘǗƛǠǏǓǑǒǝǏǎƛǓǖNjǑǏƯƛƳdžƸƞȉǪiņėŪȚaOcircȍƘKfȡţȘȞǹȊǵhǷǪƿƦƥƧƻ Ț ƴƧƥƥƺ ȉȏxAgraveacircȡQȘȃiacutentildeǰċacircȎľG

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ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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CJD ˾Ǔλ4 24UacuteţƢˌIcircƏȲĚ 1 4

Ɲƪƞƛ ȂȎƛ

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7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫ĢˏMRIFʅĀƀDŽ

A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

Ǭ7ƛ Ɲpossibleƞ A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫Ģ

ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

ƟƟƛ ŰǪiexclOtildeĂUgraveȏshymǽȌǰǫȃȄǪʼnČǵ ǟƲƹƳ ȍMŋǽɞƏŸ ƼǁƸ ȉŚIumlƘKȡţȘȌǰȉ

EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

2 -

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ƝƦƞƛ łAringɚĘĖƛ

Ξΰ͵εǰˋ˔DZă[Ξΰ͵εǰǰmiddotǪAtildeč

ȓȷDZB˅ɹǟǣɍszlig˔DZă

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macrǠnHȁ˶ǰszligȧƐκ˶ǰƱordm˶ǰwǵʫlIJaăλΞΰ͵εǰ

˔DZă[ Barthel Index1ǡκɻ-1λŹˍΞΰ͵εǰɣǒƢʟƅȊȟκJapanese Consortium of Prion Disease JACOPλ Medical Research Council Prion Disease Rating Scale MRC Scale26ǡκɻ-2λŹȝǞplusmnfrac12˔DZăʔͼθαʽ

ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

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Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

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ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

2 ( -

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ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

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Ϳΰθ 4 ˾ǽʍ 11 ˾ǽIJʑpoundVUcircě 25 ƥ˯ʔ0 1Ǐʔ˾ǽ0 1 2 3 4Ǐʔ˾ǽĕǏ 0Ǐκű˔DZλ 20Ǐ[

divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

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2 -

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2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

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17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

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26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

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28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

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6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

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9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

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of kuru in the native population N Engl J Med 1957 257 974-978

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1966 209 794-796

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incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

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17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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ΙΏǣżpara1αΩεȌɠșƎƮǵƢ

ˌĢˊĢƺȽǘɛDZOtilde

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

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ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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l

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CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 - -

ɜƧɝƛ ƿƦƥƧƻ fĈ ƶǂǂƛ

ǶDZyacuteuumlacute 55 ơȯ 90Ɵɹ˲UgraveatildeɛDZǘǶDZ 2-3 yacuteˣ˅ɹĒʙȉDZΦ͵ͺγθΓkAtildeű^ɚatildeɛAacuteĢDZʜʒ 7ɔǪuacuteĬʆ

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ΜʹγθΞAumlΞΰ͵εǰθΠͰίεĬƄ˥ˤʟƅȊȟǝˌ

Ͷͱε΅ΰεͻě

ƩNjɮƴκɁ˵λυΞΰ͵εǰˆǶĢͱͰαĬƄDZ ǠnHȁ˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰ

ˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ˗ZǔŽ2010

Mead S Prion disease genetics Eur J Hum Genet 2006 14 273-281

Mastrianni JA The genetics of prion diseases Genet Med 2010 12 187-195

Kovacs GG Puopolo M Ladogana A Pocchiari M Budka H van Duijn C et al Genetic prion disease the

EUROCJD experience Hum Genet 2005 118 166-174

Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et la A novel familial prion disease causing

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20 e67-e69

Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4 e004968

Higuma m Sanjyo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological

features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8

e60003

2 -

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9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

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5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

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20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

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23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

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25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

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2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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ƦƬƭƛ NjǜǙNjǛǝNjǝǏƛ ǩƛ NjǜǙNjǛNjǑǓǗǏƛ ǟNjǕǓǗǏƛ ƶNjǖnjǏǝǝǓơƛƦƮƮƪƛƭƛ ƛ

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ƾǠǏǗơƛƦƮƭƮƛƦƪƛ

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ƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛ ċɜƶǏǛǜǝǖNjǗǗƢǂǝǛǤǞǜǜǕǏǛƢǂǍǒǏǓǗǔǏǛƯƛƶǂǂɝ

1 ȍOuml7κdefiniteλυ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴΞΰ͵εɷǸˌIcircAacuteǪʙɛȶɅ GSS ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

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3 Ǭ7κpossibleλυUacuteţƢ˅ɹĢʙȉDZatildeɛDZǘDzĢszligǴ+Ξΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

ƝƨƞƛƴƧƥƥƺ fĈ ƲƹƳƛ

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ƝƩƞƛƼƧƨƧǁ fĈ ƲƹƳƛ

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Ɲƪƞƛ ȂȎƛ

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7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

8 ȍOuml7κprobableλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε 129 MetMetǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

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8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

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8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

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DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

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PrPc cellular prion protein

PrPSc scrapie prion protein

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RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

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2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

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3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

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mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

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5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

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20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

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21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

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24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

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8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

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8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

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Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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ˏ MRI ^ŶAacutetʙaumlųǡuumlacuteǶDZyacute 537 ơɬǗOtildesup2sup1DǶDZGƻʿǛpoundʒ˔ʂ 4ɚatildeɛ

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7AtildeəĢŃőˏ MRIɛƲ PSDˮĢǛ 0ω15țăʒŠųǡ

D178N-129MM FFID178N-129MV ETHǶĢ CJD Umiddot7Ěv_7ƳīĚʂ 27 28ǶDZyacuteuumlacute 523 ơFFI ʒŠordmdžɻ1-4Ȑ

D ŋatildexAgraveĝČƛ ƝǐNjǝNjǕƛǐNjǖǓǕǓNjǕƛǓǗǜǘǖǗǓNjƯƛƵƵƸƞƛ

7 ȍOuml7κdefiniteλυɢĀǹ˅ɹĢȅʙȉDZĬȓȷɦEgraveǘĭΦ͵ͺγθΓatildeɛAEligʟ˚1ʱĘBǑpĢǑʋ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircΐε 178 AacuteǪųΐε129 MetMet ɛȶɅ FFI ǗĘǹǰǟĴʃʓŧͱͲΈεΝγΏƱNǭȶɅNtildeǹƏƅǪuacuteΞΰ͵εɷǸƏZ

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9 Ǭ7κpossibleλυɢĀǹ FFI ȈȀDZǘΞΰ͵εɷǸˌIcircAacuteǪǰǟĴʃηǪuacuteΞΰ͵εɷǸʓŧĕ

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

1 Nozaki I Hamaguchi T Sanjo N Noguchi-Shinohara M Sakai K Nakamura Y et al Prospective 10-year

surveillance of human prion diseases in Japan Brain 2010 133 3043-3057

2 Webb TE Poulter M Beck J Uphill J Adamson G Campbell T et al Phenotypic heterogeneity and genetic

modification of P102L inherited prion disease in an international series Brain 2008 131 2632-2646

3 Wadsworth JDF Joiner S Linehan JM Cooper S Powell C Mallinson G et al Phenotypic heterogeneity in

inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and

mutant prion protein Brain 2006 129 1557-1569

4 Higuma M Sanjo N Satoh K Shiga Y Sakai K Nozaki I et al Relationships between clinicopathological features

and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases PLoS One 2013 8 e60003

5 Hsiao K Baker HF Crow TJ Poulter M Owen F Terwilliger JD et al Linkage of a prion protein missense variant

to Gerstmann-Straumlussler syndrome Nature 1989 338 342-345

6 Kitamoto T Amano N Terao Y Nakazato Y Isshiki T Mizutani T et al A new inherited prion disease (PrP-P105L

mutation) showing spastic paraparesis Ann Neurol 1993 34 808-813

7 Tranchant C Doh-Ura K Steinmetz G Chevalier Y Kitamoto T Tateishi J et al Mutation of codon 117 of the

prion gene in Gerstmann-Straussler-Scheinker disease Rev Neurol 1991 147 274-278

8 Gambetti P Parchi P Petersen RB Chen SG Lugaresi E Fatal familial insomnia and familial Creutzfeldt-Jakob

disease clinical pathological and molecular features Brain Pathol 1995 5 43-51

9 Kitamoto T Ohta M Doh-ura K Hitoshi S Terao Y Tateishi J Novel missense variants of prion protein in

Creutzfeldt-Jakob disease or Gerstmann-Straumlussler syndrome Biochem Biophys Res Commun 1993 191 709-714

10 Hitoshi S Nagura H Yamanouchi H Kitamoto T Double mutations at codon 180 and codon 232 of the PRNP gene

in an apparently sporadic case of Creutzfeldt-Jakob disease J Neurol Sci 1993 120 208-212

11 Goldgaber D Goldfarb LG Brown P Asher DM Brown WT Lin S et al Mutations in familial Creutzfeldt-Jakob

disease and Gerstmann- Straumlussler -Scheinkers syndrome Exp Neurol 1989 106 204-206

12 Pocchiari M Salvatore M Cutruzzola F Genuardi M Allocatelli CT Masullo C et al A new point mutation of the

prion protein gene in Creutzfeldt-Jakob disease Ann Neurol 1993 34 802-807

13 Laplanche JL Delasnerie-Laupretre N Brandel JP Dussaucy M Chatelain J Launay JM Two novel insertions in

the prion protein gene in patients with late-onset dementia Hum Mol Genet 1995 4 1109-1111

14 Goldfarb LG Brown P Little BW Cervenakova L Kenney K Gibbs CJ Jr et al A new (two-repeat) octapeptide

coding insert mutation in Creutzfeldt-Jakob disease Neurology 1993 43 2392-2394

15 Owen F Poulter M Lofthouse R Collinge J Crow TJ Risby D et al Insertion in prion protein gene in familial

Creutzfeldt-Jakob disease Lancet 1989 1 51-52

16 Goldfarb LG Brown P McCombie WR Goldgaber D Swergold GD Wills PR et al Transmissible familial

Creutzfeldt-Jakob disease associated with five seven and eight extra octapeptide coding repeats in the PRNP gene

Proc Natl Acad Sci USA 1991 88 10926-10930

17 van Gool WA Hensels GW Hoogerwaard EM Wiezer JH Wesseling P Bolhuis PA Hypokinesia and presenile

dementia in a Dutch family with a novel insertion in the prion protein gene Brain 1995 118 1565-1571

18 Beck JA Mead S Campbell TA Dickinson A Wientjens DPMW Croes EA et al Two-octapeptide repeat deletion

of prion protein associated with rapidly progressive dementia Neurology 2001 57 354-356

19 Medori R Tritschler HJ LeBlanc A Villare F Manetto V Chen HY et al Fatal familial insomnia a prion disease

with a mutation at codon 178 of the prion protein gene N Engl J Med 1992 326 444-449

20 Mead S Gandhi S Beck J Caine D Gajulapalli D Carswell C et al A novel prion disease associated with diarrhea

and autonomic neuropathy N Engl J Med 2013 369 1904-1914

21 Matsuzono K Ikeda Y Liu W Kurata T Deguchi S Deguchi K et al A novel familial prion disease causing

2 ( -

pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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A ĚŻ C ƏƅĴʃȍOtildeʒŠDŽ ȍOuml7ƛ Ɲprobableƞ

A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫ĢˏMRIFʅĀƀDŽ

A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

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ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

ƟƟƛ ŰǪiexclOtildeĂUgraveȏshymǽȌǰǫȃȄǪʼnČǵ ǟƲƹƳ ȍMŋǽɞƏŸ ƼǁƸ ȉŚIumlƘKȡţȘȌǰȉ

EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

2 -

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ƝƦƞƛ łAringɚĘĖƛ

Ξΰ͵εǰˋ˔DZă[Ξΰ͵εǰǰmiddotǪAtildeč

ȓȷDZB˅ɹǟǣɍszlig˔DZă

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macrǠnHȁ˶ǰszligȧƐκ˶ǰƱordm˶ǰwǵʫlIJaăλΞΰ͵εǰ

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ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

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Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

ǗOtildeŪǏ˔DZăʔͼθα6ǡǞOumlǹ

ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

2 ( -

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ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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pan-autonomic-sensory neuropathy and cognitive impairment Eur J Neurol 2013 20e67-69

22 Qina T Sanjo N Hizume M Higuma M Tomita M Atarashi R et al Clinical features of genetic Creutzfeldt-Jakob

disease with V180I mutation in the prion protein gene BMJ Open 2014 4e004968

23 Yamada M Tomimitsu H Yokota T Tomi H Sunohara N Mukoyama M et al Involvement of the spinal posterior

horn in Gerstmann-Straumlussler-Scheinker disease (PrP P102L) Neurology 1999 52 260

24 Shiga Y Satoh K Kitamoto T Kanno S Nakashima I Sato S et al Two different clinical phenotypes of

Creutzfeldt-Jakob disease with a M232R substitution J Neurol 2007 254 1509-1517

25 Iwasaki Y Kizawa M Hori N Kitamoto T Sobue G A case of Gerstmann-Straumlussler-Scheinker syndrome with the

P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis Clin

Neurol Neurosurg 2009 111 606-609

26 Yamada M Itoh Y Inaba A Wada Y Takashima M Satoh S et al An inherited prion disease with a PrP P105L

mutation clinicopathologic and PrP heterogeneity Neurology 1999 53 181-188

27 Zarranz JJ Digon A Atares B Rodriguez-Martinez AB Arce A Carrera N et al Phenotypic variability in familial

prion diseases due to the D178N mutation J Neurol Neurosurg Psychiatry 2005 76 1491-1496

28 Taniwaki Y Hara H Doh-Ura K Murakami I Tashiro H Yamasaki T et al Familial Creutzfeldt-Jakob disease with

D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia J Neurol Neurosurg Psychiatry

2000 68 388

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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bull ǎƲƹƳ Ȏij ƧƤƨ ȏ ƲƹƳ_ȉǯȞǵǪaumlȝȎij ƦƤƨ ȏǪɈɓɛȬ_ȊVȐȟȞƊ_ȉǪŲŕǵaringŮĖųǷǪĔČAcircEumlȍȏņigraveȍUEumlNEumlmiddotƇɜǙǏǛǓǘǎǓǍƛǜǢǗǍǒǛǘǗǘǞǜƛǎǓǜǍǒNjǛǑǏƯƛ

ƿǂƳɝǵĀǽȌǰǹȊȍiacuteǿȞɜŗǧƢƧɝǫƛ

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IumlplusmnmacrǶDZȍʙwĢ CJD dCJD vCJD

ƝƦƞƛ ģňĪOslash ƲƹƳƛ ƛ

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ƝƧƞƛ fĈ_ ƲƹƳƛ

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2 - -

sign7ˋě˧

ŗǧƢƨƣƛ fĈ_ ƲƹƳ Šfrac14aocircɜdžƷƾƛƧƥƥƦɝƩƛ

I A B 6 C 9 D E Creutzfeldt-Jakob

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III A PSD B MRI

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definite probable

possible

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EacuteăȉǯȞǫƛ

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ɜŏ] ƲƹƳ ȰɛɉȤɓəȲɑȾȹȻ ƳƣưƣƛƲǘǕǕǓǏ eȎǺB

ȍțȞɝ

ƛ

2 -

ŗǧƢƩɟfĈ_ ƲǛǏǞǝǣǐǏǕǎǝƢƹNjǔǘnj ċȎŠfrac14aocircɜƴDŽƛƧƥƥƭɝƭƛ

A ĚŻ ȷˈ 6 ζŲ˅ɹĢȬȓηȓȷDZB ɧƏƅǯĤOtilde

ΙΏǣżpara1αΩεȌɠșƎƮǵƢ

ˌĢˊĢƺȽǘɛDZOtilde

B ɢĀDZB 5DZBauml 4ʙ

ǶDZ^ŶȬȓDZǘκĺOacuteǑˤęɣˡEacuteĪλ

łȼdzǪuacuteĬʆκɎλ

AEligʟ

Φ͵ͺγθΓβΏΒ

ʙȉDZ

C ƏƅĴʃ ȍOtildeʒŠ

AumlɛatildeɛƺȽǘAacutet florid plaque +ǪuacuteΞΰ͵εɷǸƭȇʙ ƏƅĴʃ

ɛƲŶĢŶĢŗ˷κPSDλ˫Ģ ˏ MRIFʅĀƀ ĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢ

D ǭNtildeǹĴʃ ǭNtildeǹˤ˃ȐΙΏΙΏœκʸɸλ

E ʒŠ ȍOuml7 Ɲdifiniteƞ

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A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

Ǭ7ƛ Ɲpossibleƞ A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫Ģ

ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

ƟƟƛ ŰǪiexclOtildeĂUgraveȏshymǽȌǰǫȃȄǪʼnČǵ ǟƲƹƳ ȍMŋǽɞƏŸ ƼǁƸ ȉŚIumlƘKȡţȘȌǰȉ

EacuteăȉǯȞǫƛ

1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

2 -

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ƝƦƞƛ łAringɚĘĖƛ

Ξΰ͵εǰˋ˔DZă[Ξΰ͵εǰǰmiddotǪAtildeč

ȓȷDZB˅ɹǟǣɍszlig˔DZă

ʔͼθαIumlplusmnǯĤɣǒƢʟƅƮǵˢǶ˔DZăʔĚ

macrǠnHȁ˶ǰszligȧƐκ˶ǰƱordm˶ǰwǵʫlIJaăλΞΰ͵εǰ

˔DZă[ Barthel Index1ǡκɻ-1λŹˍΞΰ͵εǰɣǒƢʟƅȊȟκJapanese Consortium of Prion Disease JACOPλ Medical Research Council Prion Disease Rating Scale MRC Scale26ǡκɻ-2λŹȝǞplusmnfrac12˔DZăʔͼθαʽ

ŗǨƢƦɟƱNjǛǝǒǏǕƛƸǗǎǏǡƛ

9 99

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(

9 9 9

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() 9 9() 9

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9

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ƝƧƞƛ ŜŤɚȧɄȺəȲƛ

Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

ăġˁ˅ɹĢɂē˅ɹĢ[ə˔DZă[

ǗOtildeŪǏ˔DZăʔͼθα6ǡǞOumlǹ

ɧǹǯĤ˔DZăʔͼθα˲UgraveăηDZBʔŤ

uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

2 ( -

ǞplusmnmacrǠnHȁ˶ǰszligȧƐņǡΞΰ͵εǰ˔DZăʔ Barthel Index1 ʐŤuacuteǠƵp4ʔͼθαʗĊͼθαɲ

ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

1ǞplusmnͼθαɛzΰΖΚΰθέεʔŃƔɄǡ 2

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

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ī˔ʂ˾ǽȣǏ˾ǽǏś˒[˔

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λǠ

JACOP 6ǡ MRC Scale ʐŤuacuteǠƵp4ʔͼθαʗĊΞΰ͵εǰǗĘǹʋʚƗəʙȉƗəʔkǏǗĘǹǑpǑ

ʋǘĭʔŤuacuteǠƵp4ˤͶͿΰθ 7˾ǽʋʚηʙȉƗəηƚɛƗəͶ

Ϳΰθ 4 ˾ǽʍ 11 ˾ǽIJʑpoundVUcircě 25 ƥ˯ʔ0 1Ǐʔ˾ǽ0 1 2 3 4Ǐʔ˾ǽĕǏ 0Ǐκű˔DZλ 20Ǐ[

divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ɈɔȨəċȎeacuteĒȏOacuteƕǪVRıāȚŌĖȮȣǵiquestǻȟȞȎȗȉǪĊȎeacuteēǯȞǰȏŲŕųȡȘǼǽȃĊƔeacuteĒȏ ƧƥƦƧ ƂȍǪfrac12ȃȌ9ETHĖő5ȎĔřȏȌǰǫǹȟȖȉȍŕ

ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

bull ȪȽȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈĊƔ9ETHȏPtĖȉǯȞǫȖȃŀƄwȎĀǵhǷǪshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɆɕɅɕȸəȏAtildeȜǴȌĊƔ9ETHȏţȘȜȟȀǪIacuteŷȍdzǸȞăĶƖșȌǷshymȏǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

bull ɊəȻȰəĢźņv-copyķbrvbareumlȍțȞĊƔ9ETHȏšAtildeǻȟȈdzȜȀǪgĨĖcentpoundȡŘǿȞȃȘshymǻȟȌǰɜshymȭɖɛȼ ƧƳɝǫƛ

bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

ƞuacutemiddotΞΰ͵εɷǸκcellular prion protein PrPCλLjĢǪuacutemiddotΞΰ͵εɷǸ

κscrapie prion protein PrPScλƒ˂Aacutet˦Ugrave4ǡPrPScX˵ĺaʥ=˅

4ǡȳɗAacuteĢĺa4ǡųɵǖͺΰθΒεͻɢĀȊȟɹ

ΑͺΰεKżļΥίΰɵPrPC PrPScʴŋ PrPScɳȞ˦UgraveoƂ

frac12Ξΰ͵εǰɢĀȊȟɹ 1ɮmacrɹ PRION-1 studyĊ^OtildeίεΉΧtʕŠƮǵɊ˻ƮǵɊ[Ƨʶʕɹ 2űȵǹ 107

7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

ˣʈYacuteŶˣ78 7κ73ιλʈYacuteŶˣƣǠIumlǛΑͺΰεVŴɊ˻VŴɊˢEumlŪ˔DZăɾƞɹɎocircɓƗə˲Ugrave 20 7

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ɵf28Creutzfeldt-JakobǰκCreutzfeldt-Jakob disease CJDλĤɎszligʨ13Oumlɵ

15Ξί΅ΣĻ 3ʙȉƗəƏƅ 2ɊˣųīocircǠĒocirc

ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

ƂPPSɛtimesVłȼĻƱɮmacrAacuteǪmiddot CJDκvariant CJD vCJDλszlig^ɹ 4

Źˍ2004yacute 11Ų 2007yacute 3ŲǰmiddotǪΞΰ͵εǰ 11DZ7szlig PPSɛtimesVĻɹś7˟ŶǠIumlƗəǹcopyĖȐDZ7 5ƛograve

15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

2 -

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˅ 6ĬƄpǖOumlΐͰͺΰεǶDZˆąoƂǠIumlŶˣą˟ΐͰ

ͺΰεǰǹ PrPSc ȸΞΰ͵εĬƄĺaoƂŶĐɢĀȊȟ

ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

[ƏʎȸƂΐͰͺΰε 100mg ĻOacuteQɹǠIumlŶˣą˟oƂʙ 7

DZǘ˅ɹȷŐnot˶frac34ȷɖȨȷȨƆɹAtilde

ǠĒŖcurrenŧȍͳΚΎε

CJD ȷˈʙΦ͵ͺγθΓszligǺʬĢǺʬĢΦ͵ͺγθΓƮǵͺγΑΆΘΧΗαΞγ˓6ǡ 8ŧȍͳΚΎε

1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

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bull ȼȪȱȰȤȬɔəĶIǯȞǰȏĶıbrvbarȍƁǽȈǪĀ^ȖȉĊƔ9ETHȏĤţǻȟȈdzȜȀǪIacuteŷȍdzǸȞăĶƖșȌǷs(ǵAtildeȉǯȞɜshymȭɖɛȼ ƧƳɝǫƛ

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

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1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

1 Duffy P Wolf J Collins G DeVoe AG Streeten B Cowen D Possible person-to-person transmission of

Creutzfeldt-Jakob disease N Engl J Med 1974 290 692-693

2 Heckmann JG Lang CJ Petruch F Druschky A Erb C Brown P et al Transmission of Creutzfeldt-Jakob disease

via a corneal transplant J Neurol Neurosurg Psychiatry 1997 63 388-390

3 Nevin S McMenemey WH Behrman S Jones DP Subacute spongiform encephalopathya subacute form of

encephalopathy attributable to vascular dysfunction (spongiform cerebral atrophy) Brain 1960 83 519-564

4 Bernoulli C Siegfried J Baumgartner G Regli F Rabinowicz T Gajdusek DC et al Danger of accidental

person-to-person transmission of Creutzfeldt-Jakob disease by surgery Lancet 1977 1 478-479

5 Koch TK Berg BO De Armond SJ Gravina RF Creutzfeldt-Jakob disease in a young adult with idiopathic

hypopituitarism Possible relation to the administration of cadaveric human growth hormone N Engl J Med 1985

13 731-733

6 Gibbs CJ Jr Joy A Heffner R Franko M Miyazaki M Asher DM et al Clinical and pathological features and

laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone N

Engl J Med 1985 313 734-738

7 Powell-Jackson J Weller RO Kennedy P Preece MA Whitcombe EM Newsom-Davis J Creutzfeldt-Jakob

disease after administration of human growth hormone Lancet 1985 2 244-246

8 Hoshi K Yoshino H Urata J Nakamura Y Yanagawa H Sato T Creutzfeldt-Jakob disease associated with

cadaveric dura mater grafts in Japan Neurology 2000 55 718-721

9 Hamaguchi T Sakai K Noguchi-Shinohara M Nozaki I Takumi I Sanjo N et al Insight into the frequent

occurrence of dura mater graft-associated Creutzfeldt-Jakob disease in Japan J Neurol Neurosurg Psychiatry 2013

84 1171-1175

10 Kobayashi A Asano M Mohri S Kitamoto T Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease

creates a new prion strain J Biol Chem 2007 282 30022-30028

11 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

12 Heath CA Cooper SA Murray K Lowman A Henry C MacLeod MA et al Validation of diagnostic criteria for

variant Creutzfeldt-Jakob disease Ann Neurol 2010 67 761-770

13 Lukic A Beck J Joiner S Fearnley J Sturman S Brandner S et al Heterozygosity at polymorphic codon 219 in

variant Creutzfeldt-Jakob disease Arch Neurol 2010 67 1021-1023

14 Gajdusek DC Zigas V Degenerative disease of the central nervous system in New Guinea the endemic occurrence

of kuru in the native population N Engl J Med 1957 257 974-978

15 Gajdusek DC Gibbs CJ Alpers M Experimental transmission of a Kuru-like syndrome to chimpanzees Nature

1966 209 794-796

16 Collinge J Whitfield J McKintosh E Frosh A Mead S Hill AF et al A clinical study of kuru patients with long

incubation periods at the end of the epidemic in Papua New Guinea Philos Trans R Soc Lond B Biol Sci 2008 363

3725-3739

17 Parchi P Cescatti M Notari S Schulz-Schaeffer WJ Capellari S Giese A Zou WQ Kretzschmar H Ghetti B

Brown Pƛ Agent strain variation in human prion disease insights from a molecular and pathological review of the

National Institutes of Health series of experimentally transmitted disease Brain 2010 1333030-3042

18 Cervenaacutekovaacute L Goldfarb LG Garruto R Lee HS Gajdusek DC Brown P Phenotype-genotype studies in kuru

implications for new variant Creutzfeldt-Jakob disease Proc Natl Acad Sci USA 1998 95 13239-13241

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

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6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

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8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

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8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

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Ϳΰθ 4 ˾ǽʍ 11 ˾ǽIJʑpoundVUcircě 25 ƥ˯ʔ0 1Ǐʔ˾ǽ0 1 2 3 4Ǐʔ˾ǽĕǏ 0Ǐκű˔DZλ 20Ǐ[

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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7Ξΰ͵εǰĤɎszligʨǰmiddot 457ETHǶĢ27wĢ187AacuteǪmiddot427UacuteţĢΞΰ͵εǰΑͺΰεƮǵɊ 38 7˻ƮǵɊ 69 7ƮǵƱ 1 Ť 300mg 2 yacute

ˣʈYacuteŶˣ78 7κ73ιλʈYacuteŶˣƣǠIumlǛΑͺΰεVŴɊ˻VŴɊˢEumlŪ˔DZăɾƞɹɎocircɓƗə˲Ugrave 20 7

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 - -

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ƛ

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A ĚŻ ȷˈ 6 ζŲ˅ɹĢȬȓηȓȷDZB ɧƏƅǯĤOtilde

ΙΏǣżpara1αΩεȌɠșƎƮǵƢ

ˌĢˊĢƺȽǘɛDZOtilde

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A ĚŻDŽC ƏƅĴʃĵƉǠƏǪuacuteΞΰ͵εɷǸˮĢȍʙ

Ǭ7ƛ Ɲpossibleƞ A ĚŻ B ɢĀDZBDŽC ƏƅĴʃɛƲ PSD˫Ģ

ƟƛǟƲƹƳ ȎĔČEumlȍȏǪīȍ ƿǂƳ ȡţȘȞǹȊǵǯȞǫƛ

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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ƝƦƞƛ łAringɚĘĖƛ

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Ξΰ͵εǰ˅ɹAtildeͼθDZǘġnjiquestĦǑpǑʋǘĭ

˪˔DZă[IJȠ˔DZă[˅ɹˁ

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uacuteǠƵp4κactivities of daily living ADLλʔǠƵʬκquality of life QOLλʔ

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ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

ʗĊΞΰ͵εǰZǞȓȷĘB 8ͶͿΰθ[ʍ 26˾ǽ]ʐ˾ǽ 0 = 1 = ʵăκǬλ2 = ˔ăκŧλ 3ƥ˯ʔ

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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1 Noguchi-Shinohara M Hamaguchi T Kitamoto T Sato T Nakamura Y Mizusawa H et al Clinical features and

diagnosis of dura mater graft associated Creutzfeldt-Jakob disease Neurology 2007 69 360-367

2 Yamada M Noguchi-Shinohara M Hamaguchi T Nozaki I Kitamoto T Sato T et al Dura mater graft-associated

Creutzfeldt-Jakob disease in Japan clinicopathological and molecular characterization of the two distinct subtypes

Neuropathology 2009 29 609-618

3 Will RG Ward HJ Clinical features of variant Creutzfeldt-Jakob disease Curr Top Microbiol Immunol 2004 284

121-132

4 World Health Organization The revision of the surveillance case definition for variant CJD 1 ed Geneva

Switzerland WHO 2001

5 Yamada M The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram

Lancet 2006 367 874

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

6 World Health Organization Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)

httpwwwwhointzoonosesdiseasesCreutzfeldt pdf

7 Llewelyn CA Hewitt PE Knight RS Amar K Cousens S Mackenzie J et al Possible transmission of variant

Creutzfeldt-Jakob disease by blood transfusion Lancet 2004 363 417-421

8 2008426EC Commission Decision of 28 April 2008 amending Decision 2002253EC laying down case

definitions for reporting communicable diseases to the Community network under Decision No 211998EC of the

European Parliament and of the Council (notified under document number C(2008) 1589) [cited 2012 May 14]

Available from httpeur-lexeuropaeuLexUriServLexUriServdouri=OJL2008159004601ENHTML

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

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Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

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Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

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1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ĶŴȍĀǿȞɌȨȬɗɛȿȲȍzǽȈȏǪŌȍȬɗȽȵɂɍȚɁɕɈɗźǵăǻȟȈǰȞǵǪAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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dCJD dura mater graft associated Creutzfeldt-Jakob disease

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DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

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RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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ǞplusmnmacrǠnHȁ˶ǰszligȧƐņǡΞΰ͵εǰ˔DZăʔ Barthel Index1 ʐŤuacuteǠƵp4ʔͼθαʗĊͼθαɲ

ɲɎȪltɣȠăŃƔΰΖΚΰθέεoƂʔųǡ

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Indexˤ˃Əʎfrac12 Ξΰ͵εǰǗt˔DZăʔͼθαCreutzfeldt-Jacob disease Neurological

Symptoms CJD-NSscale 4ű^ʐ˲UgraveăηDZBʔͼθα

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ī˔ʂ˾ǽȣǏ˾ǽǏś˒[˔

ǏȣǏ]ʐ˾ǽDZǘ˅ɹǽȠʔ

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λǠ

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divideǞŪǏΞΰ͵εǰʔűˋ˔DZăͼθαɍ

1 Mahoney FI Barthel DW Functional evaluation the Barthel Index Md State Med J 1965 14 61-65

2 Thompson AG Lowe J Fox Z Lukic A Porter MC Ford L et al The Medical Research Council prion disease

rating scale a new outcome measure for prion disease therapeutic trials developed and validated using systematic

observational studies Brain 2013 136 1116-1127

3 Harrison JK McArthur KS Quinn TJ Assessment scales in stroke clinimetric and clinical considerations Clin

Interv Aging 2013 8 201-211

4 Cohen OS Prohovnik I Korczyn AD Ephraty L Nitsan Z Tsabari R et al The Creutzfeldt-Jakob disease (CJD)

neurological status scale a new tool for evaluation of disease severity and progression Acta Neurol Scand 2011

124 368-374

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bull ɈɔȨəċȎeacuteĒȏOacuteƕǪVRıāȚŌĖȮȣǵiquestǻȟȞȎȗȉǪĊȎeacuteēǯȞǰȏŲŕųȡȘǼǽȃĊƔeacuteĒȏ ƧƥƦƧ ƂȍǪfrac12ȃȌ9ETHĖő5ȎĔřȏȌǰǫǹȟȖȉȍŕ

ȠȟȃʼnġĮǴȜȎȧɄȺəȲȡĥǿǫƛ

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bull ĶIsup3Gǵ[ƆȊȌȆȃcMȏǪŌȍĶƚŁıȌȋȍțȆȈĶıOacuteƕǵŕȠȟȞǵǪȂȎ9ETHȍȇǰȈAtildeĤȌȧɄȺəȲȏȌǰɜshymȭɖɛȼ ƧƲɝǫƛ

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ΡεΏεΤΰαΜͲθΏ pentosan polysulfate PPS13 ΟΘΰεȋ˓tAtildeȭˣʬĢɟɘǎˤȩǎƮǵǡpǖĬƄOumlĬƄdĒɛtimesVĻǶDZˆąo

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15 DZ7ɹvCJD ĤɎǠIumlŶˣεΏγξα vCJD Ɋŧ˟˅ɹ˥ʓŧ

2 -

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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l

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Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

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BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

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ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

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szligĬį

UacuteţǘưszligęǟǹˋěŪˣťΛθΐĤɎDZǘ˅ɹǠęǟǹOacuteOtildeǘĭ

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ǵmiddotwǵƗˤʴ˨ŊƊszligįDŽ oslashaumlǯĤĨfrac12ʰ˶ʊǯĤΨͶΒ΄ΧƿOacute

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ȑ)shyDʃʅɀszligğ

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ĤɎĒUacuteţƾędzħbrvbar

RV

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2 - -

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ɡ]ȚBĂ8ěȍzǽȈɢƛ

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D S

3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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Ξΰ͵εǰˆǶĢͱͰαĬƄDZο˗Zǔφ2010οpp213-219ο

2 ǢźŬɮIcircοCǟǹpoundęǟŕōκȣ 11ȡλ Ξΰ͵εǰĬƄ˥ͷͰΐίͰεκ2008yacuteǔλνǠnHȗNtildeȊ

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ȊȟǝθΧΡθΉͱεγθΐəλhttpprionuminjpguidelineindexhtml

3 ǢźŬɮIcirc Ξΰ͵εǰĤɎUacuteţŢͶͱε΅ΰεͻŤŹɢĀ 2007 65 1447-1453

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˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 17 yacuteăȿŁη[ĿȊ

ȟfrac12ŰκȊȟɻɎ ƩNjɮƴλ 2006 pp99-111

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httpprionuminjpsurveyindexhtml

Ξΰ͵εǰǧIʒŠŕōɹ

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e

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

ΏίͰͺΰεȮtǖ PrPSc ȸΦγͰΐƒ˂OacuteOtildetΞγθΆ[ʊ=

˅ 6ĬƄpǖOumlΐͰͺΰεǶDZˆąoƂǠIumlŶˣą˟ΐͰ

ͺΰεǰǹ PrPSc ȸΞΰ͵εĬƄĺaoƂŶĐɢĀȊȟ

ɹΜίεͰΈΰȊȟ 121 7Ξΰ͵εǰĤɎίεΉΧĻɊΞί΅ΣɊ

[ƏʎȸƂΐͰͺΰε 100mg ĻOacuteQɹǠIumlŶˣą˟oƂʙ 7

DZǘ˅ɹȷŐnot˶frac34ȷɖȨȷȨƆɹAtilde

ǠĒŖcurrenŧȍͳΚΎε

CJD ȷˈʙΦ͵ͺγθΓszligǺʬĢǺʬĢΦ͵ͺγθΓƮǵͺγΑΆΘΧΗαΞγ˓6ǡ 8ŧȍͳΚΎε

1 eacuteǢˊAring frac14ƷMɉ microɋAring iacute˴AgraveοͺγͰΌΜͲαΏηΫΝǰszlig Qinacrine Ʈǵ ǠnHȗNtilde

Ȋȟʫɾl˗ ˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 15 yacute

ăȿŁη[ĿȊȟfrac12Ű 2004 pp113-124

2 Collinge J Gorham M Hudson F et al Safety and efficacy of quinacrine in human prion disease (PRION-1 study)

a patient-preference trial Lancet Neurol 2009 8 334ndash344

3 Otto M Cepek L Ratzka P Doehlinger S Boekhoff I Wiltfang J et al Efficacy of flupirtine on cognitive function

in patients with CJD A double-blind study Neurology 2004 62 714-718

4 Todd NV Morrow J Doh-ura K Dealler S OHare S Farling P et al Cerebroventricular infusion of pentosan

polysulphate in human variant Creutzfeldt-Jakob disease J Infect 2005 50 394-396

5 Tsuboi Y Doh-Ura K Yamada Tet al Continuous intraventricular infusion of pentosan polysulfate clinical trial

against prion diseases Neuropathology 2009 29 632-636

6 De Luigi A Colombo L Diomede L Tettamanti M Welaratne A Giaccone G et al The efficacy of tetracyclines in

peripheral and intracerebral prion infection PLoS One 2008 3 e1888

7 Haiumlk S Marcon G Mallet A et al Doxycycline in Creutzfeldt-Jakob disease a phase 2 randomized double-blind

placebo-controlled trial Lancet Neurol 2014 13 150-158

8 Kojovic M Cordivari C Bhatia K Myoclonus disorders a practical approach for diagnosis and treatment Ther Adv

Neurol Disord 2011 4 47-62

2 -

S

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bullĽɚxAgraveȍdzǰȈyenDZȇucircǵĉȠȟȞȊǶȏǪIJħĨltȍĚŧǿȞǹȊǵEcircȖǽǰǫƛ

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Ūˣȷˈɣ[iOumlƨłŜǟi

łɧǹęǟǹˋě 2-3yacuteĊ^AumlğƿȼƾbǯĤǽdĥɭĔ

ęǟŕōǽƔęǟǹpoundʵǂʊƼΞΰ͵εǰǾ˼ĤɎUacuteţƨł

ǟʊęǟǹˋěˈțʃOgrave˱ĤɎUacuteţʋɱȄŒɐG

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ġǰƨPĚʂƨłŜǟŪˣĚʂųǡ

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2 -

D a 1 2 4

RV

ǒǶDZġˁǰǘ˅ɹȬȓDZǘʙȉDZszligȬȓǹέͺpŎ

ędz

ƈŹǹƮǵƱszligȻŵĬ

ǶDZʒŠŪˣAtildeǘưĹŌDZǘĦtʒŠĒƮǰʻacircżĤɎƣʺȉȬȓǹέͺʒŠ

szligĬį

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ǰǘ˅ɹUacuteţĤɎīĠǫˀszligęǟǹɭdz Ξΰ͵εǰˤȉʦǟʊx[ʋ˶wǵΈΜʋpszligɫȠįDŽĬ

ęǟǹ3ɽǘĭwǵɎshyszligƓDŽǠfrac34ʃĉğɫȠ

ǵmiddotwǵƗˤʴ˨ŊƊszligįDŽ oslashaumlǯĤĨfrac12ʰ˶ʊǯĤΨͶΒ΄ΧƿOacute

ŧȍordfɫȠχχƨł

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ĢΞΰ͵εǰUacuteţˌę˒

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ĤɎĒUacuteţƾędzħbrvbar

RV

bullΞΰ͵εǰĬƄĢszligOacutebull țăĬƄĢOacuteƿbullʧĬƄˤOacutebullĬƄ˥ĤɎǪķĝĬbullwǵɎshyĬƄĢˤˈhěʜʊDʃćʮğɫȠĝĬ

bullʜʊDʃshyszligĤɎǘư͵θΞεʖΏβ

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2 - -

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II ǰ˨Q1ǰƨszligǟʊƾˈhĬƄ˥Uacuteţʳ1ǹηȬȓǹʩĿiquestȶ

IIIʒŠǰ˨űŶP˨ǑǟĒĨfrac12Sųi

ɡ]ȚBĂ8ěȍzǽȈɢƛ

IVPǰ˨iquestƜ

V Ȝaă`ǡ˱ǰǘAacutetġˁĶȼˁɹƜ

VIwugraveȂʧugraveszligěOtildeβΠαɤĨfrac12Ŋ8Řɕɹ

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

1 ǢźŬɮIcircοĤɎηUacuteţszligęǟȑ)ǹŕōκȣςˏΞΰ͵εǰν0οΙΏηΞΰ͵εǰοȣ21ȡλοǠnH

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2 ǢźŬɮIcircοCǟǹpoundęǟŕōκȣ 11ȡλ Ξΰ͵εǰĬƄ˥ͷͰΐίͰεκ2008yacuteǔλνǠnHȗNtildeȊ

ȟʫɾl˗η˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝκampȊȟ

2 ( -

Ɏ ƩNjɮƴɁ˵ʪampɎ eumlɋλο2008 pp123-140κΞΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅ

ȊȟǝθΧΡθΉͱεγθΐəλhttpprionuminjpguidelineindexhtml

3 ǢźŬɮIcirc Ξΰ͵εǰĤɎUacuteţŢͶͱε΅ΰεͻŤŹɢĀ 2007 65 1447-1453

4 ǢźŬɮIcirc Ξΰ͵εǰĤɎηUacuteţęǟȑ)ǹΤθΏΧszligɍYacute ǠnHȗNtildeȊȟʫɾl˗

˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 17 yacuteăȿŁη[ĿȊ

ȟfrac12ŰκȊȟɻɎ ƩNjɮƴλ 2006 pp99-111

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ȣ 11ȡ Cǟǹpoundęǟŕō ȣ 12ȡ ȑ)ǹpound

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l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 -

S

bull ɈɔȨəċȎțDZȍiǶȌ[ƆȍęƋǽȃ13ǬǵǪȝǪXǪŎǪsȌȋȡsectǷȎȏŊoumlȌǹȊȉǯȞȊāŜǿȞǹȊǵŻŘȉǯȞǫ

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bullĽɚxAgraveȍdzǰȈyenDZȇucircǵĉȠȟȞȊǶȏǪIJħĨltȍĚŧǿȞǹȊǵEcircȖǽǰǫƛ

ɜƦɝƛ 13ǬǵAumlƀȡǴǸȈŊŬȎ6ȉāĖȍucircecircȍŵǽȈǰǷŴĬȡāŜǽřrȞ 1-4ƛ

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Ūˣȷˈɣ[iOumlƨłŜǟi

łɧǹęǟǹˋě 2-3yacuteĊ^AumlğƿȼƾbǯĤǽdĥɭĔ

ęǟŕōǽƔęǟǹpoundʵǂʊƼΞΰ͵εǰǾ˼ĤɎUacuteţƨł

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2 -

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RV

ǒǶDZġˁǰǘ˅ɹȬȓDZǘʙȉDZszligȬȓǹέͺpŎ

ędz

ƈŹǹƮǵƱszligȻŵĬ

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szligĬį

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ęǟǹ3ɽǘĭwǵɎshyszligƓDŽǠfrac34ʃĉğɫȠ

ǵmiddotwǵƗˤʴ˨ŊƊszligįDŽ oslashaumlǯĤĨfrac12ʰ˶ʊǯĤΨͶΒ΄ΧƿOacute

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ĤɎĒUacuteţƾędzħbrvbar

RV

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bullʜʊDʃshyszligĤɎǘư͵θΞεʖΏβ

bullǘưȉʇţshyĽĬƄĢOacuteszligĤɎUacuteţƨ6ʝŧszligΏβ

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ǘưƓęǟǘưwǵɎɧǹʃǘưȉĤɎUacuteţ

szligǟʊƾĤɎUacuteţɣʳǘưǘưȉɣ[

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2 - -

D b RT aT 1 2 4

ɡŠĒĀcȎltĒĽȍzǽȈɢƛ

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ɡ]ȚBĂ8ěȍzǽȈɢƛ

IVPǰ˨iquestƜ

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ɜƧɝƛ bregȎampuȏāmicroplusmnȊȌȞ 1-4

ǘưǘưĹŌĬƨłɰȇ

AtildeĔΞίͰΗθfrac34ĴŪˣǯĤˤƞȍx[Ĩfrac12˳

ʋɱAumlęǟŕōʒŠĊ^ȄǸʝŧ

Pfrac34ăʖ˰ŪȍʙĚʂě2

ăʝŧǬpoundszligTHORNȦŵĊɎlaquo1ΫΝǰΤθΏΔΏδ

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ųǡκɻ-3λ

D S

3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

4 ˶ǰĨfrac12΅εΈθǯĤĨfrac12θΧΡθ Ξΰ͵εǰκςλͺγͰΌΜͲαΏηΫΝǰκCJDλ httpwwwnanbyouorjpentry80

Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

Ξΰ͵εǰκτλɥƣĢUacuteţĢȅDZκFFIλ httpwwwnanbyouorjpentry51

5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

1 ǢźŬɮIcircοĤɎηUacuteţszligęǟȑ)ǹŕōκȣςˏΞΰ͵εǰν0οΙΏηΞΰ͵εǰοȣ21ȡλοǠnH

ȗNtildeȊȟʫɾl˗˶ƮĢǯĤMŴȊȟƐΞΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝκɁλο

Ξΰ͵εǰˆǶĢͱͰαĬƄDZο˗Zǔφ2010οpp213-219ο

2 ǢźŬɮIcircοCǟǹpoundęǟŕōκȣ 11ȡλ Ξΰ͵εǰĬƄ˥ͷͰΐίͰεκ2008yacuteǔλνǠnHȗNtildeȊ

ȟʫɾl˗η˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝκampȊȟ

2 ( -

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PPS pentosan polysulfate

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GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 - -

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3 Ξΰ͵εǰȊȟǝθΧΡθ httpprionuminjpindexhtml

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Ξΰ͵εǰκσλͽαΏΥεηΏγͰίθηΪͰεͶθǰκGSSλ httpwwwnanbyouorjpentry88

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5 Ξΰ͵εǰĤɎUacuteţŢΞΰ͵εǰΰͺOacuteŢͶͱε΅ΰεͻ κΞΰ͵εǰȊȟǝθΧΡθVλ httpprionuminjpprioncounselinghtml

6 ΫΝǰΤθΏΔΏδθͺκŤŹĊɎlaquo1λ httpwwwcjdnetjp

7 CJD Support NetworkκɮmacrĊɎlaquo1λ httpwwwcjdsupportnet

8 Creutzfeldt-Jakob Disease FoundationκȫmacrĊɎlaquo1λ httpwwwcjdfoundationorg

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Ξΰ͵εǰˆǶĢͱͰαĬƄDZο˗Zǔφ2010οpp213-219ο

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ȟʫɾl˗η˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝκampȊȟ

2 ( -

Ɏ ƩNjɮƴɁ˵ʪampɎ eumlɋλο2008 pp123-140κΞΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅ

ȊȟǝθΧΡθΉͱεγθΐəλhttpprionuminjpguidelineindexhtml

3 ǢźŬɮIcirc Ξΰ͵εǰĤɎUacuteţŢͶͱε΅ΰεͻŤŹɢĀ 2007 65 1447-1453

4 ǢźŬɮIcirc Ξΰ͵εǰĤɎηUacuteţęǟȑ)ǹΤθΏΧszligɍYacute ǠnHȗNtildeȊȟʫɾl˗

˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 17 yacuteăȿŁη[ĿȊ

ȟfrac12ŰκȊȟɻɎ ƩNjɮƴλ 2006 pp99-111

2 ( -

Ξΰ͵εǰĬƄ˥Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ Ξ ΰ ͵ ε ǰ Ĭ Ƅ ˥ ͷ Ͱ ΐ ί Ͱ ε κ 2008 yacute ă ǔ λ R ˢ

κhttpprionuminjpguidelineindexhtmlλͷͰΐίͰεordmĬƄ˥ɹňCcedil ŹͷͰΐίͰεΞΰ͵εǰĬƄ˥ͷͰΐίͰεκ2008yacuteăǔλǽƚȴ

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ȣ 6ȡ ɛȓȷAcircȗĶɺ ȣ 7ȡ ƠȗƮǵ ȣ 8ȡ ȆȗƮǵ

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w

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113-8655 ŽˑŝvŹː 7-3-1

TELυ03-5800-8848Ǿˀ FAXυ03-5800-8849

httpprionuminjpsurveyindexhtml

Ξΰ͵εǰǧIʒŠŕōɹ

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TELυ019-651-5111 36603733 FAXυ019-622-1091 ˃ȹL υ ėiacuteAumlNtildeAumlNtilde˨ ΟαΗͰ͵ͰͳεȊȟˏ ŗaacuteɀȗNtilde[˕ŗaacuteɀʒŠȗ 770-8503 ėiacuteȃėiacuteoumlɴŹǦ 3-18-15

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httpwwwmednagasaki-uacjpmmicmbprionindexhtml

Ξΰ͵εɷǸˌIcircƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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e

WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 ( -

Ɏ ƩNjɮƴɁ˵ʪampɎ eumlɋλο2008 pp123-140κΞΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅ

ȊȟǝθΧΡθΉͱεγθΐəλhttpprionuminjpguidelineindexhtml

3 ǢźŬɮIcirc Ξΰ͵εǰĤɎUacuteţŢͶͱε΅ΰεͻŤŹɢĀ 2007 65 1447-1453

4 ǢźŬɮIcirc Ξΰ͵εǰĤɎηUacuteţęǟȑ)ǹΤθΏΧszligɍYacute ǠnHȗNtildeȊȟʫɾl˗

˶ƮĢǯĤMŴȊȟƐ Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟ uumlIJ 17 yacuteăȿŁη[ĿȊ

ȟfrac12ŰκȊȟɻɎ ƩNjɮƴλ 2006 pp99-111

2 ( -

Ξΰ͵εǰĬƄ˥Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ Ξ ΰ ͵ ε ǰ Ĭ Ƅ ˥ ͷ Ͱ ΐ ί Ͱ ε κ 2008 yacute ă ǔ λ R ˢ

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Ξΰ͵εǰĬƄ˥ͷͰΐίͰεκ2008yacuteăǔλ

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ȣ 6ȡ ɛȓȷAcircȗĶɺ ȣ 7ȡ ƠȗƮǵ ȣ 8ȡ ȆȗƮǵ

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ȣ 11ȡ Cǟǹpoundęǟŕō ȣ 12ȡ ȑ)ǹpound

˛ ΖͰΰͺĶĸǡĶɺumlT) CJDƚĬƄ˥ CJDƚĬƄ˥ˤszligȧƏʎ)

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ͷͰΐίͰεȜͷͰΐίͰεűšȊȟIJƂŊ8

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w

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httpprionuminjpsurveyindexhtml

Ξΰ͵εǰǧIʒŠŕōɹ

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TELυ019-651-5111 36603733 FAXυ019-622-1091 ˃ȹL υ ėiacuteAumlNtildeAumlNtilde˨ ΟαΗͰ͵ͰͳεȊȟˏ ŗaacuteɀȗNtilde[˕ŗaacuteɀʒŠȗ 770-8503 ėiacuteȃėiacuteoumlɴŹǦ 3-18-15

TELυ088-633-9283 FAXυ088-633-7174

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e E13 04 ) ɛɚƽƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ˟icircAumlNtildewNtildeˏ ĬƄ[IcircʊſNtildeŘtimes

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httpwwwmednagasaki-uacjpmmicmbprionindexhtml

Ξΰ͵εɷǸˌIcircƏƅΞΰ͵εǰʒŠŕō

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

e

WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 ( -

Ξΰ͵εǰĬƄ˥Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝ Ξ ΰ ͵ ε ǰ Ĭ Ƅ ˥ ͷ Ͱ ΐ ί Ͱ ε κ 2008 yacute ă ǔ λ R ˢ

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ȣ 1ȡ ȿʢ ȣ 2ȡ ˻ʁǹwǵɹǐȂʧͼ ȣ 3ȡ Ξΰ͵εljɯ

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Ξΰ͵εǰˆǶĢͱͰαĬƄDZˤʟƅȊȟǝΞΰ͵εǰθΠͰίεĬ

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187-8551 ŽˑatildeuumloumlatildentildeŽǦ4-1-1

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ǵɹǐɹwǵumlT6ǡwǵɹǐɹDZ7Ƿ˛ĒȷˈǼʅ

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113-8655 ŽˑŝvŹː 7-3-1

TELυ03-5800-8848Ǿˀ FAXυ03-5800-8849

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Ξΰ͵εǰǧIʒŠŕōɹ

˃ȹL υ eumlĶwȗAumlNtilde wƠɵȿȊȟĴ ʯȎfrac34MRIʒŠηǰĭȊȟˏˠ 020-8505 eumlĶȃǻecircoumlV1319-1

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TELυ088-633-9283 FAXυ088-633-7174

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˃ȹL υ ˟icircAumlNtildewNtildeˏ ĬƄ[IcircʊſNtildeŘtimes

852-8523 ˟icircȃ˟icircoumlsup3Ź1-12-4 ˟icircAumlNtildewNtildeˏ ordmȏƌ8F TELυ095-819-7059 FAXυ095-819-7060 E-mail nagasakiprionyahoocojp

httpwwwmednagasaki-uacjpmmicmbprionindexhtml

Ξΰ͵εɷǸˌIcircƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

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Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

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ǵɹǐɹwǵumlT6ǡwǵɹǐɹDZ7Ƿ˛ĒȷˈǼʅ

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113-8655 ŽˑŝvŹː 7-3-1

TELυ03-5800-8848Ǿˀ FAXυ03-5800-8849

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Ξΰ͵εǰǧIʒŠŕōɹ

˃ȹL υ eumlĶwȗAumlNtilde wƠɵȿȊȟĴ ʯȎfrac34MRIʒŠηǰĭȊȟˏˠ 020-8505 eumlĶȃǻecircoumlV1319-1

TELυ019-651-5111 36603733 FAXυ019-622-1091 ˃ȹL υ ėiacuteAumlNtildeAumlNtilde˨ ΟαΗͰ͵ͰͳεȊȟˏ ŗaacuteɀȗNtilde[˕ŗaacuteɀʒŠȗ 770-8503 ėiacuteȃėiacuteoumlɴŹǦ 3-18-15

TELυ088-633-9283 FAXυ088-633-7174

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˃ȹL υ ˟icircAumlNtildewNtildeˏ ĬƄ[IcircʊſNtildeŘtimes

852-8523 ˟icircȃ˟icircoumlsup3Ź1-12-4 ˟icircAumlNtildewNtildeˏ ordmȏƌ8F TELυ095-819-7059 FAXυ095-819-7060 E-mail nagasakiprionyahoocojp

httpwwwmednagasaki-uacjpmmicmbprionindexhtml

Ξΰ͵εɷǸˌIcircƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

980-8575 Oslashcedilȃouml˹ɱvũˬǦ 2-1 TELυ022-717-8147 FAXυ022-717-8148

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WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 ( -

e E13 04 ) ɛɚƽƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ˟icircAumlNtildewNtildeˏ ĬƄ[IcircʊſNtildeŘtimes

852-8523 ˟icircȃ˟icircoumlsup3Ź1-12-4 ˟icircAumlNtildewNtildeˏ ordmȏƌ8F TELυ095-819-7059 FAXυ095-819-7060 E-mail nagasakiprionyahoocojp

httpwwwmednagasaki-uacjpmmicmbprionindexhtml

Ξΰ͵εɷǸˌIcircƏƅΞΰ͵εǰʒŠŕō

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

980-8575 Oslashcedilȃouml˹ɱvũˬǦ 2-1 TELυ022-717-8147 FAXυ022-717-8148

E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

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WȸɛȶɅͱͳΈεΝγΏƱǪuacuteΞΰ͵εɷǸųǑmiddotʒŠɹ

˃ȹL υ ŽuAumlNtildeAumlNtilde˨wNtildeȮȊȟȗ ǰĭȓȷNtilde[˕

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E-mail kitamotomedtohokuacjp httpwwwprionmedtohokuacjpgeneticanalysishtml

l

Ξΰ͵εǰυhttpwwwnanbyouorjpentry3665

Ξΰ͵εǰκλͺγͰΌΜͲαΏηΫΝǰκCJDλ CJDǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry80

CJDʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry240 CJD FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry385

Ξΰ͵εǰκλͽαΏΥεηΏγͰίθηΪͰεͶθǰGSSGSSǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry88 GSSʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry247

GSS FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry386

Ξΰ͵εǰκλɥƣĢUacuteţĢȅDZFFIFFIǰƨʊʝκɧ`ǡɎλυhttpwwwnanbyouorjpentry51 FFIʒŠϊƮǵѢκwǵĔɎλυhttpwwwnanbyouorjpentry213

FFI FAQκʬpoundcopyȦλυhttpwwwnanbyouorjpentry387

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C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization

2 (( -

C

BSE bovine spongiform encephalopathy

CJD Creutzfeldt-Jakob disease Creutzfeldt-Jakob

CWD chronic wasting disease

dCJD dura mater graft associated Creutzfeldt-Jakob disease

Creutzfeldt-Jakob

DWI diffusion weighted image

FFI fatal familial insomnia

GSS Gerstmann-Straumlussler-Scheinker disease Gerstmann-Straumlussler-Scheinker

PPS pentosan polysulfate

PrP prion protein

PrPc cellular prion protein

PrPSc scrapie prion protein

PSD periodic synchronous discharge

RT-QUIC real-time quaking-induced conversion

TSE transmissible spongiform encephalopathies

vCJD variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob

WHO World Health Organization