myasthenia gravis winda

7/26/2019 Myasthenia Gravis Winda

1/18

MYASTHENIA GRAVIS

By :

Winda Diah Nugraheni

1102011293

Department of Neurology Pasar Rebo Proin!e "eneral #ospital

$e!turer %diser :

Dr& Donny #& #amid 'p'

RSUD PASAR REBO JAKARTA

FAKULTAS KEDOKTERAN

UNIVERSITAS YARSI

Definition


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(yasthenia grais )("*+ the most !ommon of the neuromus!ular ,un!tion disorders+

is an a!-uired+ predominantly antibody.mediated autoimmune disease& /n this disorder+

antibodies are targeted against the ni!otini! a!etyl!holine+ re!eptor )%hR* at the

neuromus!ular ,un!tion+ resulting in an oerall redu!tion in the number of %hRs and

damage to the postsynapti! membrane&

(yasthenia grais is a disorder of neuromus!ular transmission !hara!terised by

eaness and fatiguing of some or all msu!le groups& Weaness orsening on sustained

repeated eer!ise and relieed by rest& 4his !ondition is a !onse-uen!e of an autoimmune

destru!tion of the post synapti! reseptor for a!etyl!holine&

Anatomy an P!y"io#o$y Ne%&om%"'%#a& (%n'tion

4he neuromus!ular ,un!tion is the synapti! !onne!tion formed beteen a motorneuron aon and the mus!le fiber it innerates& 4he transmitter used at the neuromus!ular

,un!tion+ a!etyl!holine+ is stored in the presynapti! motor nere terminals& 4he post synapti!

mus!le membrane has many folds in hi!h re!eptors for a!etyl!holine are lo!ated& When a

motor nere a!tion potential rea!hes the presynapti! nere terminal+ there is resultant in!rease

in !al!ium !ondu!tan!e through oltage.gated !al!ium !hannels& 4his in!rease in intra!ellular

!al!ium leads to the fusion of a!etyl!holin.filled presynaptyi! esi!les ith the plasma

membrane of the motor nere terminal& %!etyl!holine is subse-uently released into the

synapti! !left by eo!ytosis&

4he a!etyl!holine diffuses a!ross the synapse and binds to the a!etyl!holine re!eptorson the postsynapti! mus!le membrane& 4he binding of a!etyl!holine to these re!eptors

fa!ilitates in!reased !ondu!tion of sodium and potassium& 4his leads to transient

depolari5ation of the post,un!tional mus!le membrane non as an end-plate potential. 4his

depolari5ation allos for the generation and propagation of a!tion potentials in the

postsynapti! mus!le !ell& 4hese pro!esses initiate a !hain of eents in the mus!le !ell that

!ulminates in mus!le !ontra!tion& Disorders of the neuromus!ular ,un!tion result from a

disruption of this series of eents&

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%dult %hR !omprises 6 subunits )2 alpha+ 1 beta+ 1 gamma+ and 1 delta*+ ea!h of hi!h is a

membrane.spanning protein mole!ule& 4hese subunits are homologous a!ross different

spe!ies+ suggesting that the en!oding genes eoled from a !ommon an!estral gene& 4he

subunits are arranged in a !ir!le+ forming a !entral opening that a!ts as an ion !hannel& When

an %h mole!ule binds to an %hR+ the %hR undergoes a 3.dimensional !onformational

!hange that opens the !hannel& 4he presynapti! terminal !ontains esi!les filled ith %h&

When an a!tion potential traels don a motor nere and rea!hes the nere terminal+ the

!ontents of these esi!les are released into the synapti! !left in a !al!ium.dependent manner&

4he released %h mole!ules diffuse a!ross the synapse and bind to the %hRs at the peas of

the folds on the postsynapti! membrane&

4his binding !auses the ion !hannels in the %hR to open briefly+ alloing sodium

ions into the interior of the mus!le !ell and thereby bringing about partial depolari5ation of

the postsynapti! membrane and generation of an e!itatory postsynapti! potential )7P'P*& /f

the number of open sodium !hannels rea!hes a threshold alue+ a self.propagating mus!le

a!tion potential is generated in the postsynapti! membrane&

E)iemio#o$y

4he prealen!e of autoimmune (" is estimated at 1 !ase in 10+000820+000 people&

Women are affe!ted more often in the se!ond and third de!ades of life+ and men more often in

the fifth and sith de!ades& %sso!iated autoimmune diseases are present in approimately 6

of patients+ and !omorbid thyroid disease o!!urs in more than 10&

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ertain epidemiologic features of the disease are of !lini!al interest& /ts prealen!e is

ariously estimated to be from 3 to ; per million of the population and the annual

in!iden!e rate+ approimately 1 per 300+000& 4he disease may begin at any age+ but onset in

the first de!ade is relatiely rare )only 10 per!ent of !ases o!!ur under the age of 10 years*&

4he pea age of onset is beteen 20 and 30 years in omen and beteen 60 and f patients ith thymomas+ the ma,ority

are older )60 to #.

leen*& With feer re!eptor sites aailable+ your mus!les re!eie feer nere signals+ resulting

in eaness&

%ntibodies may also blo! the fun!tion of a protein !alled a mus!le.spe!ifi! re!eptor tyrosine

inase )4/7.roh.seen A/7.nays*& 4his protein is inoled in forming the nere.mus!ular

,un!tion& When antibodies blo! the fun!tion of this protein+ it may lead to myastheniagrais& Resear!h !ontinues to study ho the antibodies inhibiting this protein are related to

the deelopment of myasthenia grais&

T!ym%" $#an

Resear!hers beliee that the thymus gland+ a part of your immune system situated in the

upper !hest beneath your breastbone+ may trigger or maintain the produ!tion of the antibodies

that blo! a!etyl!holine&

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$arge in infan!y+ the thymus is small in healthy adults& /n some adults ith myasthenia

grais+ hoeer+ the thymus is abnormally large& 'ome people ith myasthenia grais also

hae tumors of the thymus )thymomas*& =sually+ thymomas aren@t !an!erous )malignant*&

Ot!e& 'a%"e"

'ome people may hae myasthenia grais that isn@t !aused by antibodies blo!ing

a!etyl!holine or the mus!le.spe!ifi! re!eptor tyrosine inase& 4his type of myasthenia grais

is !alled antibody.negatie myasthenia grais& %ntibodies against another protein+ !alled

lipoprotein.related protein + may play a part in the deelopment of this !ondition&

"eneti! fa!tors also may be asso!iated ith myasthenia grais&

Rarely+ mothers ith myasthenia grais hae !hildren ho are born ith myasthenia grais

)neonatal myasthenia grais*& /f treated promptly+ !hildren generally re!oer ithin to

months after birth&

'ome !hildren are born ith a rare+ hereditary form of myasthenia+ !alled !ongenital

myastheni! syndrome&

Fa'to&" t!at 'an *o&"en mya"t!enia $&a+i"

atigue

/llness

'tress

'ome medi!ations C su!h as beta blo!ers+ -uinidine glu!onate+ -uinidine sulfate+

-uinine )uala-uin*+ phenytoin )Dilantin*+ !ertain anestheti!s and some antibioti!s

Pat!o$ene"i"

(yastheni! eaness and fatigue are due to the failure of effe!tie neuromus!ular

transmission on the postsynapti! side& 4he greatly redu!ed number of re!eptors and the

!ompetitie a!tiity of anti.%hR antibodies produ!e end.plate potentials of insuffi!ient

amplitude to generate a!tion potentials in some nere fibers& By the !umulation of blo!ed

transmission at many end plates+ there results a redu!tion in the !ontra!tile poer of the

mus!le& 4his defi!ien!y is refle!ted first in the o!ular and !ranial mus!les+ the ones that are

both the most !ontinuously a!tie mus!les and hae the feest %hR per motor unit& atigue

is understandable as the result of the normal de!line in the amount of %h released ith ea!h

su!!essie impulse&

#o the antibodies a!t at the re!eptor surfa!e of the end plate has also been

inestigated+ but the matter is !omple& Neuromus!ular transmission is probably impaired in

seeral ays: )1* 4he antibodies may blo! the binding of %h to the %hR& )2* 'erum /g"

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from myastheni! patients has been shon to indu!e a to. to threefold in!rease in the

degradation rate of %hR& 4his may be the result of the !apa!ity of antibodies to !ross.lin

the re!eptors+ hi!h are gathered into !lusters in the mus!le membrane and then internali5ed

by a pro!ess of endo!ytosis and degraded& )3* %ntibodies may !ause a !omplement.mediated

destru!tion of the postsynapti! folds& 4he latter to me!hanisms ould be epe!ted to redu!ethe number of %hR at the synapse&

%n immune pro!ess atta!s the neuromus!ular ,un!tion& %ntibodies bind to the

re!eptor sites resulting in their destru!tion )!omplement mediated*& 4hese antibodies are

referred to as %!etyl!holine Re!eptor %ntibodies )%!hR antibodies* an are demostrated by

radioimmunoassay in the serum of 90 of patients& /n human myasthenia grais+ a redu!tion

of a!etyl!holine re!eptor sites has been demonstrated in the postsynapti! folds& Redu!ed

re!eptor synthesis and in!reased reseptor destru!tion+ as ell as the blo!ing if re!eptor

response to a!etyl!holine& %ll seem responsible for the disorder&

%ntibodies to epitopes other than the %hR hae been identified in patients ith ("&

4hese in!lude antibodies to another postsynapti! neuromus!ular ,un!tion protein+ mus!le.

spe!ifi! inase )(u'A*+ found in about 0 of (" patients ho do not hae %hR

antibodies& (u'A antibodies hae been shon to disrupt neuromus!ular ,un!tion fun!tion by

adersely affe!ting the maintenan!e of %hR !lustering at the mus!le endplate+ thus leading

to redu!ed numbers of fun!tional %hRs& /n patients ho hae neither %hR nor (u'A

antibodies+ so.!alled seronegatie ("+ antibodies to striated mus!le proteins+ su!h as titin

and the ryanodine re!eptor+ are sometimes dete!ted& /t is un!lear ho these other antibodies

lead to !lini!al disease&

4hymi! lymphofolli!ular hypeplasia o!!urs in E0 of (" patients& 4hymoma+ an

epithelial tumor of the thymus+ o!!urs in 10 of patients ith ("& 4he antibody produ!tion

is a 4.!ell.mediated pro!ess thought to be asso!iated ith thymi! dysfun!tion&

,#a""ifi'ation

4o fa!ilitate !lini!al staging of therapy and prognosis+ the folloing !lassifi!ation+ introdu!ed

by >sserman+ remains useful )the relatie in!iden!e of ea!h type is indi!ated and Fdrug

responseG refers to treatment ith an anti!holinesterase*:

/& >!ular myasthenia )16 to 20 per!ent*

//&A. (ild generali5ed myasthenia ith slo progressionH no !risesH drug.responsie )30

per!ent*

B. (oderately seere generali5ed myastheniaH seere seletal and bulbar inolement

but no !risesH drug response less than satisfa!tory )26 per!ent*

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///& %!ute fulminant myastheniaH rapid progression of seere symptoms ith respiratory

!rises and poor drug response+ high in!iden!e of thymomaH high mortality )16

per!ent*&

/I& $ate seere myastheniaH symptoms same as ///+ but resulting from steady progression

oer 2 years from !lass / to !lass // )10 per!ent*&

Dia$no"i"

,#ini'a# Manife"tation"

(" is !lini!ally !hara!teri5ed by flu!tuating+ fatigable eaness of !ommonly used

mus!les& #allmar features in!lude ptosis+ diplopia+ dysarthria+ dysphagia+ and respiratory

and limb mus!le eaness& %bout half of patients present ith o!ular findings& 4he o!ular

mus!le eaness is usually bilateral and asymmetri! and results in diplopia+ ptosis+ or both&

Notably+ the pupil is spared& 7entually+ almost all patients ith (" deelop o!ular

symptoms+ and in some the disease is limited to the etrao!ular mus!les&

Within the first year of disease onset+ up to E6 of patients deelop generali5ed

symptoms& Bulbar symptoms are !ommon and in!lude dysarthria+ dysphagia+ fa!ial

eaness+ and eaness of masti!ation& Be!ause of palatal eaness+ patients often hae

nasal spee!h and !an regurgitate li-uids through the nose& Bulbar manifestations are often the

most disabling symptoms& $imb and trun eaness is !ommon in a proimal greater than

distal distribution& re-uently+ the arms are more affe!ted than the legs& 4he -uadri!eps+tri!eps+ and ne! etensor mus!les appear to be preferentially inoled& % hallmar of

myastheni! eaness is its flu!tuating and fatigable nature& /t may in!rease throughout the

day+ orsen ith sustained a!tiity+ and improe ith rest&

4he most serious of the symptoms is respiratory !ompromise !aused by eaness of

diaphragmati! and inter!ostal mus!les& 4hese respiratory symptoms+ in !on,un!tion ith

seere bulbar symptoms+ !an !ulminate in so.!alled myastheniccrisis+ defined as respiratory

failure re-uiring me!hani!al entilation& 4his !ompli!ation o!!urs in about 16820 of

patients ith (" and may be pre!ipitated by infe!tion or aspiration&

P!y"i'a# E-amination

1& ranial nere signs and symptoms:

. >!ular inolement produ!es ptosis and mus!le paresis&

. Weaness of ,a mus!les allos the mouth to hang open

. Weaness of fa!ial mus!les results in epressionless appearan!e

. >n smiling+ bu!!inator eaness produ!es a !hara!teristi!s smile )myasthenia

snarl*

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2. Bulbar inolement may result in:

. Dysarthri!+ dysphoni! spee!h and dysphagia

. Nasal regurgitation of fluids or nasal -uality to spee!h

3& 4he demonstration of fatiguing is important in rea!hing diagnosis and monitoring

response to treatment:

atiguing of other bulbar mus!les may be demonstrated by:. Bloing out !hees against pressure

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. ounting as far as possible in one breathe

4he tongue o!!asionally shos the !hara!teristi! triple grooed appearan!e ith to pateral

and !entral furro&

& $imb and trun signs and symptoms

Weaness of ne! mus!les may result in lolling of the head& Proimal limb mus!les are

preferentially affe!ted& atigue may be demonstrated by moement against a !onstant

resistan!e&

. $imb reflees are often hypera!tie and fatigue on repeated testing&

. (us!le asting o!!urs in 16 of !ases&

. 'tress+ infe!tion and pregnan!y and drugs that alter neuromus!ular transmission

all ea!erbate the eaness&

Dia$no"ti' St%ie"

./ Ten"i#on 0e&o)!oni%m1 te"t

4his test ealuates the response to a short.a!ting !holinesterase inhibitor& 4he

eaminer must identify a !lini!al feature )most often ptosis* to obsere& >ne

milligram of edrophonium is gien intraenously as a test dose& /f no aderse effe!ts

are noted+ a 3.mg dose is gien& % !lini!al response should be seen ithin 308


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proteins ryanodine and titin& >f note+ the absolute titers of these antibodies do not

!orrelate ell ith disease !ourse or seerity&

4/ E#e't&oia$no"ti' "t%ie"

Routine nere !ondu!tion studies and ele!tromyography usually do not

identify dysfun!tion of the neuromus!ular ,un!tion& 'lo repetitie nere stimulationis the most !ommonly used test to ealuate for ("& /n this test+ a nere is stimulated


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or generali5ed ("+ the differential diagnosis in!ludes $ambert.7aton myastheni!

syndrome+ botulism+ and myopathy& or o!ular myasthenia+ alternatie diagnoses in!lude

progressie eternal ophthalmoplegia+ thyroid disease+ and o!ulopharyngeal mus!ular

dystrophy& (otor neuron disease+ brainstem stroe+ diphtheria+ and botulism must be

!onsidered in patients ith bulbar predominant myasthenia grais&

Distinguishfrom:

.4he patient ho !omplains of fatiguing easil . neuroti!+ hysteri!al or d!pr!ss!d indiidual&

.4he patient ith progressie ophthalmoplegia+ e&g6 mito!hrondrial myopathy+

o!ulopharangeal dystrophy&

.4he patient ith rnultipl! s!lerosis . diplnpia+ dysarthria and fatigue ith a relapsing and

remitting !ourse&

.4he patient ith the $arnbert.7aton myastheni! syndrome

T&eatment

4he treatment of this disease inoles the !areful use of to groups of drugsC

anti!holinesterases and immunosuppressants thyme!tomy+ and+ in spe!ial !ir!umstan!es+

plasma e!hange and intraenous immune globulin&

A/ Sym)tomati' T&eatment

Anticholinesterase Drugs

4he to drugs that hae gien the best results in ameliorating myastheni! eaness

are neostigmine )Prostigmin* and pyridostigmine )(estinon*+ the latter being preferred by

most !lini!ians and patients& 4he usual dose of pyridostigmine is 30 to 90 mg gien eery < h

)typi!ally a


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or mild !ases ithout thymi! tumor+ for patients in partial remission after

thyme!tomy+ and for purely o!ular myasthenia+ the use of anti!holinesterase drugs may be the

only form of therapy ne!essary for some period of time )o!ular myasthenia often responds

ell to small doses of !orti!osteroids as noted further on*& %lthough these drugs seldom

reliee symptoms !ompletely )the response of o!ular symptoms is typi!ally in!omplete*+

most su!h patients are able to remain fun!tional&

/f the response to anti!holinesterase drugs is poor and progressiely larger doses are

not relieing symptoms+ there is alaysnthe danger of a so.!alled cholinergic crisis& /n our

on eperien!e ith more than


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daily* alone or in !ombinationith a5athioprine )see later* are also often ade-uate to !ontrol

o!ular myasthenia& #oeer+ one must be prepared to !ontend ith the side effe!ts of long.

term !orti!osteroid therapy+ and e hesitate to undertae su!h a program in !hildren or

patients ith seere diabetes or other diseases that are liely to be aggraated&

4he usual form of !orti!osteroid therapy is prednisone )or !orresponding doses of

prednisolone*+ beginning ith 16 to 20 mgJday and in!reasing the dose gradually until a

satisfa!tory !lini!al response is obtained+ or until a daily dose of 60 to n!e the

maimal effe!t from prednisone has been attained+ the dosage !an be redu!ed gradually oer

months to the loest point at hi!h it is still effe!tie& 4he usual pra!ti!e has been to then

institute an alternate.day s!hedule+ hi!h diminishes the side effe!ts& >ur patients hae done

better ith a modest differen!e in dose from one day to the net+ rather than omitting a doseentirely on alternate days& Potassium supplements and anta!ids should be pres!ribed liberally

if needed+ as ith any !hroni! !orti!osteroid regime& %t the outset of steroid therapy+

anti!holinesterase drugs are gien simultaneouslyH as the patient improes+ the dosage of the

latter may be ad,usted donard&

Azathioprine (Imuran) and Other Immunosuppressive Drugs

Azathioprine is a useful ad,un!t to steroids and !an be effe!tie alone in patients ho !annot

tolerate or fail to respond to prednisone& /t has been possible to manage the disease

reasonably ell in a fe patients ith a5athioprine alone& 4reatment begins ith 60 mg )1tablet* ti!e daily for a fe daysH if this is tolerated+ the dosage is raised to 2 to 3 mgJg per

day )160 to 260 mg daily*& 4he number of positie responses is mu!h the same as ith

prednisone& #oeer+ improement o!!urs mu!h more sloly ith a5athioprine+ and a

signifi!ant response may not be eident for many months to a year )Witte et al*& $ier

fun!tion tests and blood !ell !ount should be !he!ed regularly& 4he (yasthenia "rais

lini!al 'tudy "roup found that the most seere forms of the disease+ parti!ularly those

resistant to prednisone or a5athioprine alone+ benefit from the !ombination of the to

medi!ations& (any neurologists+ in!luding the present authors+ begin by pres!ribing both

medi!ations early in the illness ith the plan of redu!ing the !orti!osteroid dose in the third

or fourth month&

Mycophenolate )ellept* is !urrently being used as an ad,un!t to !orti!osteroids and has

been benefi!ial in seeral small trials& 4he !lini!al improement suggested by these studies

has generally o!!urred sooner than it does ith a5athioprine& Diarrhea as the main aderse

effe!t& >ur initial impression is that my!ophenolate may be preferable to most of the

ad,un!tie medi!ations and+ in some milder !ases+ may be effe!tie alone&

Cyclophosphamide+ administered in intraenous pulses+ has been used by De eo and

!oorersH they ere able to remoe 6 of their 12 patients from steroids but the appropriate

use of this potent agent is not !lear and e hae resorted to it infre-uently& Dra!hman and

!olleagues and others des!ribe a regimen of highdose !y!lophosphamide )60 mgJgJd for

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!onse!utie days* folloed by granulo!yte.stimulating fa!tor to FrebootG the immune system

in refra!tory !ases& 4his approa!h has riss but may be ,ustified if all other measures hae

failed in seere instan!es of the disease& $ier fun!tion and hite blood !ell !ount should be

monitored regularly& 4he !lini!al effe!ts of the immunosuppressie agent cyclosporine are

mu!h lie those of a5athioprine but be!ome eident more rapidly+ in a matter of a month orto )4indall et al*& /t is gien in to diided doses daily+ to a total of about < mgJg but not

often used !urrently be!ause of serious side effe!ts )hypertension+ nephrotoi!ity* and its

high !ost& Be!ause of the su!!ess of alternatie regimens+ e hae had o!!asion oer the

years to use !y!losporine only on!e for myasthenia&

Plasma Exchange and Intravenous Immune Globulin

or seere myasthenia that is refra!tory to treatment ith anti!holinesterase drugs and

prednisone+ or during an a!ute orsening+ one must resort to other measures& 'triing

temporary remissions )2 to ; ees* may be obtained by the use of plasma echange& 4his

form of treatment may be lifesaing during a myastheni! !risis+ as noted later& /t is also useful

before and after thyme!tomy and at the start of immunosuppressie drug therapy& 4he

number and olume of e!hanges re-uired in these !ir!umstan!es is somehat arbitrary+ but

they tend to be less than those re-uired for "B'H seeral e!hanges of 2 to 3&6 $ ea!h

)totaling approimately 126 m$Jg*+ performed oer a ee+ usually suffi!e& 4he remoed

plasma is repla!ed ith albumin and saline& /t has been estimated that a 2.$ e!hange ill

remoe ;0 per!ent of !ir!ulating antibodies and that this ill be refle!ted in redu!ed %h

antibody leels in 3 to 6 days& #oeer+ there is only an approimate !orrelation beteen a

redu!tion in the titer of anti.%hR antibody and the degree of !lini!al improement& /n a

!risis re-uiring plasma e!hanges and me!hani!al entilation+ it has been our pra!ti!e to

dis!ontinue or !urtail the use of anti!holinesterase drugs and resume them as the patient is

being eaned from the entilator& %lso+ it may be that sensitiity to these drugs may be

enhan!ed in the hours after an e!hange+ so that their dosages must be ad,usted a!!ordingly&

Plasma e!hange is also helpful in limiting the aforementioned eaness that is often

indu!ed by the institution of high.dose !orti!osteroids&

% small number of patients respond so ell to plasma e!hange and find the side

effe!ts of steroids so intolerable that they !hoose to be maintained ith to to three

e!hanges eery seeral ees or months& /mmunoadsorption+ a te!hni-ue similar to plasma

e!hange that remoes antibodies and immune !omplees by running blood oer a

tryptophan !olumn+ is less !umbersome than !onentional plasma e!hange and has been

effe!tie+ but eperien!e ith this pro!edure is limited&

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!ntravenous immune glo"ulin is similarly useful in the shortterm !ontrol of a!utely orsening

myasthenia& 4he usual dose is 2 gJg gien in diided doses oer 3 to 6 days& 'eeral small

series suggest that the effe!t is e-uialent to a series of plasma e!hanges& #oeer+ neither

plasma e!hange nor immune globulin has been sub,e!ted to systemati! study or !omparison+

and it should be emphasi5ed that hile these measures are inaluable in deteriorated patients

or those in !risis+ they offer only short.term benefit and are not used regularly in the

treatment of most patients&

T!yme'tomy

or patients ith a neoplasti! thymoma+ surgi!al remoal of the tumor is ne!essary to

preent tumor spread& or patients ithout thymoma+ thyme!tomy in!reases the lielihood of

remission& Data on the effi!a!y of thyme!tomy are !onfounded by fa!tors su!h as ariable

surgi!al te!hni-ue and la! of !ontrolled trials& /n most eperien!ed !enters+ hoeer+

perioperatie morbidity and mortality are ery lo and are outeighed by the !han!es for

improement in most !ases& 4here is !ontroersy about predi!tors of out!ome+ but thymuspathology+ age+ or disease seerity does not reliably predi!t remission& =nless there are

!ontraindi!ations+ thyme!tomy should be !onsidered for patients of any age ith ("& 4he

pro!edure appears to be most effe!tie hen performed during the first 2 years of disease&

(edi!al treatment of (" prior to surgery de!reases the perioperatie morbidity& Preoperatie

intraenous immunoglobulin )/I/"* or plasmapheresis is often used to stabili5e patients ith

generali5ed ("&

4here is debate about the best surgi!al pro!edure+ and proto!ols hae in!luded

etensie trans.sternal and trans!eri!al approa!hes+ as ell as+ more re!ently+ endos!opi!

te!hni-ues and !ombination approa!hes& /t has been suggested that more etensie rese!tion

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re-uired for re!oery& /t is generally best to ait 2 or 3 ees before !ommitting a patient to

tra!heostomy&

When eaning from the entilator is anti!ipated+ anti!holinesterase agents are

reintrodu!ed sloly+ and treatment ith !orti!osteroids !an be instituted if ne!essary& #ral

doses of $% mg pyridostigmineor &' mg neostigmine are roughly e(uivalent to %.' to & mg

neostigmine intravenously and &.' to ) mg intramuscularly& 4he management of the !riti!ally

ill patient ith myasthenia has been reieed in the monograph by Ropper and !olleagues&

(ost patients ith myastheni! !risis ill tae seeral ees to re!oer+ and a fe of

our patients hae remained entilatordependent for months& /n the etensie eperien!e from

olumbia. Presbyterian+ half of patients !ould be safely etubated ithin 2 ees and three.

-uarters by a month& 4here ere E deaths among 63 patients+ refle!ting the graity of this

syndrome een in the modern era of intensie !are& %tele!tasis+ seere anemia+ !ongestie

heart failure+ and !lostridial diarrhea )asso!iated ith antibioti! use* portend a prolonged

period of generali5ed eaness and intubation& rom time to time one en!ounters a patient in

hom respiration and ambulation do not improe for many months after a myastheni! !risis&

/n our eperien!e+ these hae been middle.aged or older patients+ usually omen+ in hom

an element of hyperthyroidism or hypothyroidism may hae been operatie& 4hey be!ome

asted as the proimal limb and aial mus!les+ in!luding the diaphragm+ fail to re!oer their

poer+ een though the o!ular and oropharyngeal mus!les improe& 4he role of

!orti!osteroids in produ!ing a !on!omitant proimal myopathy is a fre-uent -uestion that !an

be soled by !areful 7(" eamination&

4he only re!ourse in !ases of long.standing and seere myasthenia is to !ontinue anaerage dose of !orti!osteroids and anti!holinesterase medi!ations ith intermittent trials of

immune globulin or plasma e!hanges& 4his is also a situation in hi!h high.dose

!y!lophosphamide folloed by granulo!yte.stimulating fa!tor as mentioned earlier may

result in slo improement&

DAFTAR PUSTAKA

./ Patterson+ '&A&+ et al.(yasthenia "rais and >ther Disorders of the Neuromus!ular

Kun!tion& /n: Brust K&&(& )ed*& urrent Diagnosis L 4reatment Neurology& 'e!ond

7dition& 4he (!"ra.#ill ompanies+ /n!& Ne ?or& 2012& P: 361.36E&

17


18/18

2/ Ropper %& and Bron R& %dams and Ii!torMs Prin!iples of Neurology& 7ighth

7dition& 4he (!"ra.#ill ompanies+ /n!& Ne ?or& 2006& P: 1260.126E&

4/ $indsay A&W&+ et al.Neurology and Neurosurgery /llustrated& ifth 7dition& hur!hill

$iingstone& P:

myasthenia gravis winda

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