hereditary motor and sensory neuropathies

HEREDITARY MOTOR HEREDITARY MOTOR ANDAND

SENSORY SENSORY NEUROPATHIESNEUROPATHIES

Alireza Ashraf, M.D.Professor of Physical Medicine & Rehabilitation

Shiraz Medical school

CHARCOT-MARIE-TOOTH DISEASE ANDCHARCOT-MARIE-TOOTH DISEASE ANDRELATED DISORDERSRELATED DISORDERS

The various categories of CMT are subclassified The various categories of CMT are subclassified according to the nature of the according to the nature of the pathologypathology (demyelinating or axonal), (demyelinating or axonal),

mode of inheritancemode of inheritance (AD,AR or X-linked), (AD,AR or X-linked), age of onsetage of onset and the and the specific mutated gene.specific mutated gene.

CMT1CMT1 - - ADAD - - demyelinatingdemyelinating motor motor and sensory neuropathies.and sensory neuropathies.

CMT2CMT2 - -ADAD - - axonalaxonal motor and sensory motor and sensory neuropathies.neuropathies.

In contrast to In contrast to CMT1 CMT1 and and CMT2CMT2, which , which begin in childhood or early adult life, begin in childhood or early adult life, CMT3CMT3 begins in infancybegins in infancy and is and is associated with severe associated with severe demyelination/hypomyelination.demyelination/hypomyelination.

Charcot-Marie-Tooth Disease Type ICharcot-Marie-Tooth Disease Type I

CMT1CMT1 :The most common . :The most common . The ratio of The ratio of CMT1CMT1 to to CMT2CMT2 is approximately is approximately 2:12:1.. CMT1 usually manifests in the first to third CMT1 usually manifests in the first to third

decades, decades,

Most patients have Most patients have pes cavuspes cavus or or equinovarusequinovarus, , hammertoes hammertoes and and exuberant callousexuberant callous formation, formation, which lead to which lead to foot painfoot pain. .

The distal leg weakness leads to The distal leg weakness leads to a a compensatory gaitcompensatory gait,, which which places undue stress on the places undue stress on the lumbosacral region. Thus, some lumbosacral region. Thus, some patients are initially evaluated patients are initially evaluated for for back painback pain………………….………………….

Charcot-Marie-Tooth Disease Type Charcot-Marie-Tooth Disease Type II

Recurrent Recurrent ankle sprainsankle sprains..

Some patients note frequent stubbing of Some patients note frequent stubbing of toes during ambulation.toes during ambulation.

patients typically patients typically do not complain about do not complain about significant sensation loss in the distal significant sensation loss in the distal regions of the feet or handsregions of the feet or hands..

there is an absence of paresthesias or other there is an absence of paresthesias or other "positive" phenomena, which can be helpful "positive" phenomena, which can be helpful in distinguishing CMT from acquired forms of in distinguishing CMT from acquired forms of neuropathy. neuropathy.

some patients complain of some patients complain of severe cramps.severe cramps.



Physical examination reveals Physical examination reveals considerable muscle considerable muscle atrophyatrophy and and weaknessweakness in the distal compared to in the distal compared to proximal limb regions.proximal limb regions.

As an As an alternative name toalternative name to this disorder this disorder

implies, "implies, "peroneal muscular atrophyperoneal muscular atrophy,","

Rare patients have asymmetric Rare patients have asymmetric pseudohypertrophy of the calves.pseudohypertrophy of the calves.

This distal muscle atrophy resulted in the This distal muscle atrophy resulted in the original describers of the disease to original describers of the disease to compare the patients' legs to “compare the patients' legs to “inverted inverted champagne bottle legschampagne bottle legs." ."

Intrinsic foot muscle wastingIntrinsic foot muscle wasting is also is also prominent.prominent.

Weakness of the anterior compartment Weakness of the anterior compartment muscles of the distal lower limbs causes muscles of the distal lower limbs causes footdrop. footdrop.

steppage gaitsteppage gait : :excessive degree of hip and excessive degree of hip and knee flexionknee flexion . .

Symmetric distal atrophy and weakness of Symmetric distal atrophy and weakness of the the upper limbsupper limbs is also evident in is also evident in two-two-thirds of patientsthirds of patients. .

Severe Severe claw deformitiesclaw deformities of the of the hand hand intrinsicsintrinsics can be seen in some can be seen in some individuals.individuals.

Despite the lack of sensory Despite the lack of sensory symptoms, symptoms, diminished sensation to diminished sensation to all modalitiesall modalities is apparent on is apparent on examination. examination.

Sensory lossSensory loss is more apparent in is more apparent in the the lower limbs than the upper limbs.lower limbs than the upper limbs.

DTRsDTRs are usually markedly are usually markedly depressed or absent at the depressed or absent at the ankles and progressively ankles and progressively diminish over the course of years diminish over the course of years in the more proximal lower limb in the more proximal lower limb regions and then upper limbs.regions and then upper limbs.

Careful inspection of the peripheral Careful inspection of the peripheral nerves, especially posterior to the nerves, especially posterior to the ear and arm regions, may ear and arm regions, may demonstrate demonstrate neural hypertrophyneural hypertrophy and and firmnessfirmness compared to normal in compared to normal in about about 25% of patients25% of patients . .

Importantly, rare patients have Importantly, rare patients have developed developed compression of the spinal compression of the spinal cordcord and and cauda equinacauda equina due to marked due to marked hypertrophy of nerve roots. hypertrophy of nerve roots.

Approximately one-third of patients Approximately one-third of patients with CMT1 have an with CMT1 have an essential tremoressential tremor. .

These patients were previously referred These patients were previously referred to as having to as having Roussy-Levy syndromeRoussy-Levy syndrome. .

However, this term has become However, this term has become outdated as advances in the molecular outdated as advances in the molecular genetics have demonstrated that such genetics have demonstrated that such tremorstremors can be seen in can be seen in all subtypes of all subtypes of CMT1CMT1 as well as some patients with as well as some patients with CMT2CMT2..

HistopathologyHistopathologyHistopathologyHistopathology The gross appearance of the peripheral nerve The gross appearance of the peripheral nerve

reveals an reveals an overall increase in the fascicle sizeoverall increase in the fascicle size leading to the so-called "leading to the so-called "hypertrophic neuropathyhypertrophic neuropathy" " designation. designation.

There is a There is a predilection for the loss of the relatively predilection for the loss of the relatively larger diameterlarger diameter fibers. fibers.

In addition, there is a In addition, there is a decrease in axon caliberdecrease in axon caliber and and an an increase in the density of neurofilamentsincrease in the density of neurofilaments within within these "atrophic" axons.these "atrophic" axons.

Schwann cell Schwann cell proliferationproliferation due to repeated bouts of due to repeated bouts of demyelination and remyelination results in the demyelination and remyelination results in the formation of so-called onion bulbs.formation of so-called onion bulbs.

DemyelinationDemyelination, , neuronal lossneuronal loss, and , and axonalaxonal atrophyatrophy are slightly more are slightly more prominent distally. prominent distally.

The The mean internode lengthmean internode length is reduced is reduced compared to normal.compared to normal.

The spinal cord is also affected with loss The spinal cord is also affected with loss of myelinated libers in the of myelinated libers in the fasciculus fasciculus gracilisgracilis as noted at the cervical levels. as noted at the cervical levels.

Patients with Patients with CMT1CMT1 may be born with may be born with normal or only minimally slowed nerve normal or only minimally slowed nerve conduction velocitiesconduction velocities. .

These velocities rapidly decline such These velocities rapidly decline such that by the time the child that by the time the child is is 3-53-5 years years of of age, a maximal reduction is achieved age, a maximal reduction is achieved that changes little over the course of that changes little over the course of the patient's life. the patient's life.

The The CMAPCMAP amplitudes also continue to amplitudes also continue to diminish over time, indicative of diminish over time, indicative of axon axon loss.loss.

Distal motor latencies at birth are Distal motor latencies at birth are commonly commonly borderline abnormalborderline abnormal. .

These latencies continue to increase These latencies continue to increase until approximately the until approximately the age of 10 age of 10 yearsyears, at which time there is , at which time there is little little further prolongationfurther prolongation of the distal of the distal latencieslatencies..

..

Sensory Conduction Sensory Conduction StudiesStudies

The sensory nerve conduction studies in The sensory nerve conduction studies in both the upper and lower limbs are usually both the upper and lower limbs are usually markedly abnormalmarkedly abnormal in most patients with in most patients with CMT1.CMT1.

SNAPsSNAPs are are unobtainable or very low in unobtainable or very low in amplitudeamplitude. .

In addition, the In addition, the distal latencies of distal latencies of obtainable responsesobtainable responses are are markedly markedly prolongedprolonged and nerve conduction velocities and nerve conduction velocities are commonly less than are commonly less than 60%60% of normal of normal..

Motor Nerve Conduction StudiesMotor Nerve Conduction Studies

The CMAPs may be absent when recordings are The CMAPs may be absent when recordings are attempted from severe wasted attempted from severe wasted extensor digitorum extensor digitorum brevisbrevis ( (EDBEDB)and )and abductor hallucisabductor hallucis ( (AHAH) muscles.) muscles.

It may be necessary to perform motor conduction It may be necessary to perform motor conduction studies in the lower limb by recording from the studies in the lower limb by recording from the tibialis tibialis anterioranterior muscle. muscle.

When responses can be detected from either the EDB When responses can be detected from either the EDB or AH, the or AH, the CMAP amplitudesCMAP amplitudes are frequently reduced. are frequently reduced.

CMAP amplitudesCMAP amplitudes are only are only slightly decreasedslightly decreased early in the disease course early in the disease course in the upper limbsin the upper limbs..

Distal motor latenciesDistal motor latencies are considerably are considerably prolonged in prolonged in both the upper and lower limbs. both the upper and lower limbs.

When stimulating at distal and proximal sites, When stimulating at distal and proximal sites, there is there is no evidence of no evidence of conduction blockconduction block or or temporal dispersiontemporal dispersion. .

The most dramatic finding is a The most dramatic finding is a greater than 60% reduction in nerve greater than 60% reduction in nerve conduction velocityconduction velocity compared to expected normal values. compared to expected normal values.

Values in the Values in the 25 m/s range25 m/s range are characteristic for are characteristic for patients with patients with CMT I A.CMT I A.

Patients with point mutations in Patients with point mutations in PMP-22 PMP-22 gene gene have even slower conduction velocities have even slower conduction velocities approaching that seen in approaching that seen in CMT3CMT3 ( (10 m/s or less10 m/s or less).).

There is There is little little correlation between the correlation between the patients clinical patients clinical symptoms and the degree to which nerve conductions symptoms and the degree to which nerve conductions are affected.are affected.

NCVs can be NCVs can be quite profoundly affected during early quite profoundly affected during early childhood,childhood, when there is little in the way of clinical when there is little in the way of clinical deficits…deficits…

It appears that It appears that weaknessweakness is more related is more related to the degree to the degree of of axon lossaxon loss, rather than the extent of demyelination , rather than the extent of demyelination and slowing of nerve conductionand slowing of nerve conduction………………..………………..

As noted above, patients with CMT1 As noted above, patients with CMT1 do do not usually demonstrate not usually demonstrate conduction conduction blockblock or or temporal dispersiontemporal dispersion..

This contrasts with the presence of This contrasts with the presence of conduction block or temporal conduction block or temporal dispersion in patients with acquired dispersion in patients with acquired forms of demyelinating neuropathy forms of demyelinating neuropathy (e.g., (e.g., Guillain-Barre svndromeGuillain-Barre svndrome and and chronic inflammatory demyelinating chronic inflammatory demyelinating neuropathyneuropathy). ).

A nerve commonly forgotten is the A nerve commonly forgotten is the phrenic nerve.phrenic nerve.

Patients with CMTI can have Patients with CMTI can have significantly significantly prolonged phrenicprolonged phrenic CMAP CMAP latencies.“latencies.“

CMTI patients can have CMTI patients can have reduced reduced pulmonary function secondary to pulmonary function secondary to diaphragmatic and intercostal muscle diaphragmatic and intercostal muscle weakness weakness due to denervation. due to denervation.

F-waves latencies are F-waves latencies are usually absentusually absent but when but when obtainable are obtainable are extremely prolongedextremely prolonged. .

Of note, when calculating, proximal conduction Of note, when calculating, proximal conduction velocities using F-waves, the obtained values velocities using F-waves, the obtained values are are almost but not quite as slowed as the distal limb almost but not quite as slowed as the distal limb valuesvalues. .

Slowing of Slowing of facial nervefacial nerve conduction conduction is commonly is commonly found in found in CMTICMTI. .

This is reflected as a significant prolongation in the This is reflected as a significant prolongation in the facial nerve's motor latency often approaching facial nerve's motor latency often approaching 1414 msms (normal < (normal < 4.04.0 MS). MS).

The The blink reflexblink reflex can also be markedly can also be markedly abnormal in that the abnormal in that the R1 responseR1 response may be as may be as long as long as 2626 ms (normal < ms (normal < 1313 ms). ms).

A A reduction in the reduction in the R1 to facial nerve latency R1 to facial nerve latency ratioratio (R/D ratio) can be found in most patients (R/D ratio) can be found in most patients indicating that the indicating that the facial nerve (motor) facial nerve (motor) latency is prolonged out of proportion to the latency is prolonged out of proportion to the trigeminal (sensory) latencytrigeminal (sensory) latency. .

Alternatively, the motor nerves may be Alternatively, the motor nerves may be slightly more severely affected than sensory slightly more severely affected than sensory nerves in regards to conduction velocities.nerves in regards to conduction velocities.

Somatosensory evokedSomatosensory evoked

These evoked potential studies have These evoked potential studies have demonstrated demonstrated slowing of spinal and slowing of spinal and cortical conducting pathwayscortical conducting pathways when when central conduction times are central conduction times are calculated. calculated.

The slowing is The slowing is less dramatic than that less dramatic than that seen peripherallyseen peripherally

Visual evoked potentialsVisual evoked potentials also reveal also reveal similar slowing of the optic pathways.similar slowing of the optic pathways.

Needle electromyographyNeedle electromyography

If the CMAP is absent. e.g.. in the EDB or AH, If the CMAP is absent. e.g.. in the EDB or AH, one can anticipate a one can anticipate a significant reductionsignificant reduction or or even even absence of insertional activityabsence of insertional activity . .

Some patients may reveal evidence of very Some patients may reveal evidence of very small amplitude (small amplitude (50 50 ЧЧV or lessV or less) sustained ) sustained positive sharp waves and fibrillation positive sharp waves and fibrillation potentials despite little activity during, potentials despite little activity during, needle insertion.needle insertion.

If these patients are followed over time, If these patients are followed over time,

eventually eventually complete electrical silencecomplete electrical silence can can be noted in these muscles.be noted in these muscles.

The documentation of The documentation of PswPsw and and Fib Fib potentials potentials is quite common in the distal muscles of both is quite common in the distal muscles of both the upper and lower limbs in the upper and lower limbs in CMT1CMT1. .

Occasionally, other forms of spontaneous Occasionally, other forms of spontaneous electrical activity can be seen, such as electrical activity can be seen, such as complex repetitive dischargescomplex repetitive discharges and and fasciculationfasciculation potentials. potentials.

The The tibialis anterior muscletibialis anterior muscle is perhaps the is perhaps the best muscle to demonstrate spontaneous best muscle to demonstrate spontaneous activity, even in patients with advanced activity, even in patients with advanced diseasedisease..

The MUAPs fire at high rates The MUAPs fire at high rates and in reduced numbers and in reduced numbers (reduced recruitment(reduced recruitment). ).

The MUAPs are typically of The MUAPs are typically of long long durationduration, , high amplitudehigh amplitude, and , and polyphasic. polyphasic.

The lack of appreciable The lack of appreciable peripheral sproutingperipheral sprouting in in sensory nerves often results in a sensory nerves often results in a complete complete absence of SNAPsabsence of SNAPs..

In motor nerves, the larger size of the In motor nerves, the larger size of the recorded potential combined with the motor recorded potential combined with the motor nerve's ability to peripherally sprout and nerve's ability to peripherally sprout and reinnervate denervated muscle fibers staves reinnervate denervated muscle fibers staves off a complete absence of CMAPs for a longer off a complete absence of CMAPs for a longer period compared to the SNAPs. period compared to the SNAPs.

Macro-EMGMacro-EMG studies reveal extensive collateral studies reveal extensive collateral reinnvervation in CMT1 compared to CMT2.reinnvervation in CMT1 compared to CMT2.

Charcot-Marie-Tooth Disease Type Charcot-Marie-Tooth Disease Type 2 (CMT2)2 (CMT2)

CMT2 refers to the CMT2 refers to the autosomal dominantautosomal dominant neuronal" neuronal" hereditary motor and sensory neuropathieshereditary motor and sensory neuropathies. .

CMT2A and CMT2BCMT2A and CMT2B ( (CMT2A/BCMT2A/B) are the most common ) are the most common subtypes of CMT2 and are discussed together. subtypes of CMT2 and are discussed together.

The clinical features ofThe clinical features of CMT2A/B CMT2A/B are rather similar to are rather similar to CMT1 CMT1 with several important exceptionswith several important exceptions. .

The peak age of symptom onset in The peak age of symptom onset in CMT2A/BCMT2A/B is usually in the is usually in the second decade with some patients becoming symptomatic second decade with some patients becoming symptomatic only in their seventh decade. only in their seventh decade.

Also, there is a Also, there is a distinct absence of enlarged nervesdistinct absence of enlarged nerves in in CMT2CMT2, ,

Patients with Patients with CMT2A/BCMT2A/B tend to have tend to have less severe involvement of less severe involvement of the intrinsic hand muscles and tremorthe intrinsic hand muscles and tremor is not as common as is not as common as seen in CMT1. seen in CMT1.

There is more There is more significant atrophysignificant atrophy of the distal lower limbs and of the distal lower limbs and weakness of the posterior tibial and calf muscles (in addition to weakness of the posterior tibial and calf muscles (in addition to atrophy and weakness of the anterior lateral compartment atrophy and weakness of the anterior lateral compartment muscles) in muscles) in CMT2A/BCMT2A/B corripared to corripared to CMT1CMT1. .

Complete lack of deep tendon reflexesComplete lack of deep tendon reflexes is found in only a small is found in only a small percentage of patients with percentage of patients with CMT2A/BCMT2A/B, while it is common in, while it is common in CMTCMT 11

Ankle reflexesAnkle reflexes are usually absent in both types of disease. are usually absent in both types of disease. About About 50-70%50-70% of patients with CMT1 have significant of patients with CMT1 have significant

reductions in reductions in light touchlight touch, , painpain, , joint positionjoint position and and vibration vibration sensesense, while approximately , while approximately 20-50%20-50% of patients with of patients with CMT2A/B have similar findingsCMT2A/B have similar findings. .

Severe mutilating Severe mutilating neuropathic ulcerationsneuropathic ulcerations similar to those similar to those typically seen in hereditary sensory and autonomic typically seen in hereditary sensory and autonomic neuropathy type I (HSAN 1) have been demonstrated in neuropathy type I (HSAN 1) have been demonstrated in some patients with some patients with CMT2BCMT2B.‘.‘

Pes cavusPes cavus and and hammer toehammer toe deformities are less common in deformities are less common in CMT2A1B than in CMT1…………………..CMT2A1B than in CMT1…………………..

CMT2A/B needs to be distinguished from chronic idiopathic CMT2A/B needs to be distinguished from chronic idiopathic axonal neuropathy (axonal neuropathy (CIAPCIAP). ………………….). ………………….

Although there is electrophysiologic evidence of motor Although there is electrophysiologic evidence of motor involvement in CIAP, involvement in CIAP, sensory symptoms dominate the clinical sensory symptoms dominate the clinical picture………………………………………….picture………………………………………….

This contrasts with CMT2A/B, in which This contrasts with CMT2A/B, in which motor symptoms and motor symptoms and signssigns are the major features…………….. are the major features……………..

CMT2CCMT2C

The distinguishing feature of CMT2C is The distinguishing feature of CMT2C is vocal vocal cord paralysiscord paralysis. .

The age of onset is variable and symptoms can The age of onset is variable and symptoms can begin in infancy,begin in infancy, manifesting with manifesting with breathing breathing difficultiesdifficulties and and stridor. stridor.

More common is the More common is the insidious onsetinsidious onset of of laryngeal laryngeal weaknessweakness causing progressive hoarseness. causing progressive hoarseness.

TheThe diaphragm diaphragm and and intercostal musclesintercostal muscles are are often weak leading to reduced respiratory often weak leading to reduced respiratory function. function.

CMT2CCMT2C Atrophy of the distal limbs is common, and Atrophy of the distal limbs is common, and

patients can develop proximal and distal patients can develop proximal and distal weakness of the arms and legs.weakness of the arms and legs.

There is There is mildmild sensory loss to sensory loss to all modalitiesall modalities and and deep tendon reflexes are reduceddeep tendon reflexes are reduced..

Pes cavus can be appreciated in some Pes cavus can be appreciated in some patients, but such foot deformities are not patients, but such foot deformities are not as common as seen in as common as seen in CMTICMTI, , CMT2ACMT2A, or , or CMT2BCMT2B. .

Similar cases have been reported as Similar cases have been reported as hereditary distal hereditary distal spinal muscular atrophyspinal muscular atrophy with vocal cord paralysis.with vocal cord paralysis.

CMT2DCMT2D UnIike UnIike CMT2ACMT2A and and CMT2BCMT2B, , weakness and weakness and

atrophy of the hands are more severe than in atrophy of the hands are more severe than in the distal legsthe distal legs..

Deep tendon reflexes are generally absent in Deep tendon reflexes are generally absent in

the arms and reduced in the legs. the arms and reduced in the legs.

Pes cavus, hammertoes, and Pes cavus, hammertoes, and scoliosisscoliosis are are variably present. variably present.

Enlarged palpable nerves are not appreciated. Enlarged palpable nerves are not appreciated.

This disorder is allelic to distal This disorder is allelic to distal spinal muscular spinal muscular atrophy type 5.atrophy type 5.

CMT2 ECMT2 E

Distal sensory loss, hypo- or Distal sensory loss, hypo- or areflexia, and pes cavus areflexia, and pes cavus deformities were common.deformities were common.

Some patients exhibited Some patients exhibited hyperkeratosishyperkeratosis of the hands and of the hands and feet.feet.

Sensory nerve conduction studies reveal Sensory nerve conduction studies reveal reduced or absent reduced or absent SNAPSNAP amplitudes in amplitudes in both the upper and lower limbs.both the upper and lower limbs.

Conduction velocities are comparatively Conduction velocities are comparatively well preserved and always greater than well preserved and always greater than 70% of the lower limit of normal70% of the lower limit of normal. .

The The distal sensory latenciesdistal sensory latencies are either are either normal or only mildly prolonged.normal or only mildly prolonged.

The motor conduction studies demonstrate The motor conduction studies demonstrate normal or only mildly reduced nerve normal or only mildly reduced nerve conduction velocities (conduction velocities (usually in excess of 70% usually in excess of 70% of the lower limit of normalof the lower limit of normal).).

The distal motor latencies are normal or only The distal motor latencies are normal or only mildly prolonged.mildly prolonged.

TheThe CMAPs CMAPs are often preserved in the are often preserved in the upper upper limbs; limbs;

however, the peroneal and posterior tibial however, the peroneal and posterior tibial CMAPsCMAPs are absent or reduced in size are absent or reduced in size..

The MUAPs can be The MUAPs can be increased in amplitudeincreased in amplitude and and durationduration

The recruitment may be reduced in some persons. The recruitment may be reduced in some persons.

Occasional Occasional fasciculationfasciculation and and fibrillationfibrillation potentials potentials can be observed. can be observed.

Complex repetitive dischargesComplex repetitive discharges can also be can also be documented in some patients.documented in some patients.

A few patients withA few patients with CMT2 CMT2 have been reported to have been reported to have have neuromyotonianeuromyotonia in that it is abolished with in that it is abolished with peripheral peripheral

neuromuscular blockade.neuromuscular blockade.

HNPPHNPP

Tomaculous neuropathyTomaculous neuropathy Pmp-22Pmp-22 ADAD MEDIANMEDIAN,,ULNARULNAR,,RADIALRADIAL,,PERONEPERONE

ALAL&&BRACHIAL PLEXUSBRACHIAL PLEXUS DTRDTR((diminisheddiminished)) HAMMERTOESHAMMERTOES PES CAVUSPES CAVUS

EDXEDX

CONDUCTION BLOCKCONDUCTION BLOCK TEMPORAL DISPERSIONTEMPORAL DISPERSION Fib Fib &&PswPsw FasciculationFasciculation CRDCRD Reduced recruitmentReduced recruitment PolyphasicPolyphasic Larg amp Larg amp &&Long durationLong duration

CMT 3CMT 3 Dejerine SottasDejerine Sottas Infancy-early childhoodInfancy-early childhood Congenital hypomyelination Congenital hypomyelination

neuropathyneuropathy Pmp-22Pmp-22 , ,EGR-2EGR-2 HypotoniaHypotonia--Respiratory distressRespiratory distress--

arthrogryposisarthrogryposis--Swallowing difficultiesSwallowing difficulties--Peripheral nerve enlargementPeripheral nerve enlargement--AtaxiaAtaxia--Hearing lossHearing loss--Abnormal pupillary Abnormal pupillary reactionreaction--Pes cavusPes cavus--KyphoscoliosisKyphoscoliosis

Elevated Elevated CSF.CSF.

EDXEDX

NCVs are NCVs are 5-105-10 m/s or less m/s or less.. ProximalProximal muscles muscles::increased increased

IAIA,,PswPsw,,FibFib DistalDistal muscles muscles::Reduced IAReduced IA,,Little Little

in the way of sustained Fib in the way of sustained Fib &&PswPsw Near the terminal stage of the Near the terminal stage of the

diseasedisease,,low-amplitude MUAP with low-amplitude MUAP with long long oror short durations may be short durations may be documenteddocumented

CMT 4ACMT 4A

FIRST FIRST 22 YEARS OF LIFE YEARS OF LIFE MILD SENSORY LOSSMILD SENSORY LOSS SCOLIOSISSCOLIOSIS

CMT 4BCMT 4B

FLOPPY AT BIRTHFLOPPY AT BIRTH DTRDTR::absentabsent TOMACULAETOMACULAE

CMT 4CCMT 4C

Delay in walking until Delay in walking until 18-2418-24 monthsmonths

Deformities in the feet and spine Deformities in the feet and spine by by 55 years of age years of age

Sensory lossSensory loss DTRDTR::absentabsent HYPERTROPHY OF NERVESHYPERTROPHY OF NERVES

CMT 4DCMT 4D

HEREDITARY MOTOR AND HEREDITARY MOTOR AND SENSORY NEUROPATHY WITH SENSORY NEUROPATHY WITH DEAFNESSDEAFNESS-LOM-LOM

((HMSN-LHMSN-L))

CMT 4ECMT 4E

PMP-22PMP-22,,,,,,,,EGR-EGR-22…………………………………………………………

Same as CMT Same as CMT 33……………………………..……………………………..

CMT 4FCMT 4F

ATAXIAATAXIA………………………………………………………………………………

KYPHOSCOLIOSISKYPHOSCOLIOSIS………………………………………………....

PES PES CAVUSCAVUS……………………………………………………………………

LABLAB

CSF protein is reportedly normal CSF protein is reportedly normal in in CMT4ACMT4A and and CMT 4CCMT 4C

Elevated in some reported cases Elevated in some reported cases of of CMT4BCMT4B

EDXEDX

NCVs are markedly in NCVs are markedly in CMT4ACMT4A,,4B4B &&4F4F

CMT CMT 4A4A,,4B4B & &4F4F::less than less than 2020 m/s m/s CMT CMT 4C4C :24:24 m/s m/s Fib,Psw,polyphasic &decreased Fib,Psw,polyphasic &decreased

recruitmentrecruitment

CMT XCMT X

Similar to CMT 1Similar to CMT 1 MENMEN Foot dropFoot drop,,pes cavuspes cavus,,hammertoes hammertoes

&&claw-handclaw-hand DTR:DiminishedDTR:Diminished Unlike CMT1,the nerves are not Unlike CMT1,the nerves are not

profoundly hypertrophicprofoundly hypertrophic

EDXEDX

SAME AS SAME AS CMT1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,CMT1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

BUT NCVs IN MEN WITH BUT NCVs IN MEN WITH CMTX CMTX ARE APPROXIMATELY ARE APPROXIMATELY 10 m/s10 m/s FASTER THAN THOSE FASTER THAN THOSE RECORDED IN Pt WITH RECORDED IN Pt WITH CMT1…………..CMT1…………..

CMT 2XCMT 2X

Axonal motor-sensory Axonal motor-sensory neuropathyneuropathy

DeafnessDeafness MRMR First few years of lifeFirst few years of life

HMSN-LHMSN-L

ARAR Demyelinating neuropathyDemyelinating neuropathy First decadeFirst decade: gait difficulties due : gait difficulties due

to distal leg weaknessto distal leg weakness Second decadeSecond decade: hands: hands Third decadeThird decade: hearing loss: hearing loss

EDXEDX

BAVPBAVP reveal both peripheral and reveal both peripheral and central slowing of auditory central slowing of auditory conductionconduction…..…..

VEPVEP is normal is normal……………………

HMSNPHMSNP ADAD Same as Kennedy Same as Kennedy Muscle crampMuscle cramp 30 y/o30 y/o Fasciculations in trunk and limbsFasciculations in trunk and limbs Mild facial weaknessMild facial weakness Neck Flx Neck Flx &&Ext are sparedExt are spared TongueTongue,,Dysphagia Dysphagia && Dysarthria Dysarthria TremorTremor DM 2DM 2 Decreased vibratory Decreased vibratory and positionand position

LABLAB

CK is often CK is often elevatedelevated………………………………………………

DM 2DM 2…………………………………………………………………………………… HLPHLP………………………………………….………………………………………….

EDXEDX

SNAPsSNAPs are markedly reduced in are markedly reduced in amp or absentamp or absent……………………..……………………..

CMAPCMAP amps are moderately amps are moderately decreaseddecreased

Distal motor and sensory Distal motor and sensory latencies are preservedlatencies are preserved……..……..

FasciculationFasciculation,,FibFib,,PswPsw,,Polyphasic Polyphasic &&Decreased recruitmentDecreased recruitment…………………………

HNAHNA

AD,AxonalAD,Axonal PainPain,,weakness weakness &&sensory losssensory loss ChildhoodChildhood Parsonage-Turner SxParsonage-Turner Sx Multifocal sensory Multifocal sensory

neuropathy(neuropathy(Wartenberg’sWartenberg’s migrant migrant neuropathyneuropathy))

HypotelorismHypotelorism,,Epicanthal foldEpicanthal fold,,Cleft Cleft palatepalate,,SyndactyllySyndactylly,,Micrognathia Micrognathia && Facial asymmetryFacial asymmetry

EDXEDX

Distal latencies and conduction Distal latencies and conduction velocities of the velocities of the CMAP CMAP and and SNAPsSNAPs are relatively preserved are relatively preserved

FibFib,,PswPsw,,Decreased recruitmentDecreased recruitment&& PolyphasicPolyphasic……………………………..……………………………..

HSAN1HSAN1

ADAD 2nd-4th2nd-4th Decades Decades Slowly progressiveSlowly progressive Small myelinated Small myelinated && unmyelinated unmyelinated NumbnessNumbness::--,,lancinating lancinating

painpain,,burningburning,,achingaching Bladder dysfunctionBladder dysfunction,,reduced sweating reduced sweating PainPain,,temperaturetemperature,DTR,DTR absent at absent at ANKLESANKLES Pes cavusPes cavus,,HammertoeHammertoe

LABLAB

CSFCSF normal normal Increased Increased IgAIgA

EDXEDX

Normal or only mildly reduced Normal or only mildly reduced CMAPCMAPs and s and SNAPSNAPs amplitudess amplitudes

Near nerve recordingsNear nerve recordings::reduced reduced amp of amp of A deltaA delta and and C-fibersC-fibers

Abnormal Abnormal QSTQST SSRSSR:absent:absent

HSAN 2HSAN 2 InfancyInfancy ARAR Severe loss of sensation to all Severe loss of sensation to all

modalitiesmodalities((particularly touch particularly touch pressurepressure//vibrationvibration))

WhitlowWhitlow Lancinating painsLancinating pains::negneg RombergRomberg Impaired sweatingImpaired sweating,,bladder dysfunction bladder dysfunction

&&impotenceimpotence Postural hypotensionPostural hypotension::negneg ScoliosisScoliosis

PATHOLOGYPATHOLOGY

Virtual absence of Virtual absence of large large myelinated fibersmyelinated fibers

Mild loss of Mild loss of small myelinatedsmall myelinated and and unmyelinatedunmyelinated fibers fibers

EDXEDX

Absent Absent SNAPSNAP Normal or only mildly reduced Normal or only mildly reduced

CMAPsCMAPs amp amp Abnormal Abnormal QST(QST(particularly particularly

vibrationvibration)) EMGEMG::Reduced recruitment,long Reduced recruitment,long

durationduration

polyphasicpolyphasic,,FibFib&&PswPsw

HSAN 3HSAN 3

Riley-dayRiley-day Sx Sx;;Familial dysautonomiaFamilial dysautonomia ARAR InfancyInfancy Poor suckPoor suck AlacrimaAlacrima,,Blothy skinBlothy skin,,Fluctuations in Fluctuations in

body temperature and blood body temperature and blood pressurepressure,,VomitingVomiting,,Imfections of Imfections of lungslungs,,Esophageal and Esophageal and gastrointestinal dysmotilitygastrointestinal dysmotility,,Sweating Sweating excessiveexcessive,,Delay in normal Delay in normal developmentdevelopment

SeizuresSeizures Intelligence is normalIntelligence is normal Impairment in Impairment in

positionposition,,vibrationvibration,,painpain,,taste taste && corneal reflexescorneal reflexes

Tonic pupilsTonic pupils Postural hypotensionPostural hypotension MMTMMT:: nl but nl but DTR DTR::absentabsent Short stature Short stature && scoliosis scoliosis

PATHOLOGYPATHOLOGY

Marked reduction of Marked reduction of small small myelinatedmyelinated and and unmyelinatedunmyelinated fibers and to a fibers and to a lesser extent large lesser extent large myelinated fibersmyelinated fibers

EDXEDX

Decreased Decreased SNAPSNAP amp,mild amp,mild slowing of slowing of CMAPCMAP velocities velocities

Abnormal Abnormal QSTQST Normal Normal SSRSSR

HSAN 4HSAN 4

ARAR ANHYDROSISANHYDROSIS SELF MUTILATIONSELF MUTILATION POSTURAL HYPOTENSINPOSTURAL HYPOTENSIN PAIN PAIN & & TEMPERATURETEMPERATURE VIBRATORY VIBRATORY ::LESS AFFECTEDLESS AFFECTED

EDXEDX

There can be slight reductions in There can be slight reductions in CMAPsCMAPs & & SNAPsSNAPs amplitudes and amplitudes and conduction velocities,but not as conduction velocities,but not as severe as that seen in HSAN2 or severe as that seen in HSAN2 or HSAN3HSAN3…………………………

SSRSSR:unobtainable :unobtainable

HSAN 5HSAN 5

Fail to recognize or react to Fail to recognize or react to PAINFUL PAINFUL stimuli despite having stimuli despite having normal sensitivity to other normal sensitivity to other sensory modalities…..sensory modalities…..

EDXEDX

NCSNCS,,EMGEMG,,SSRSSR,,QSTQST&&SEPSEP::normalnormal WITHDRAWAL TO WITHDRAWAL TO

PAINPAIN::abnormalabnormal

FAPFAP AXONALAXONAL TransthyretinTransthyretin,,apolipoprotein A1 apolipoprotein A1 &&gelsolingelsolin Small myelinated Small myelinated && unmyelinated fibers unmyelinated fibers SNAPSNAP::Diminished in amp &normal or Diminished in amp &normal or

mildly prolonged in latencymildly prolonged in latency CMAPCMAP::Motor are less severely affectedMotor are less severely affected CTSCTS Fib Fib && Psw Psw,,PPPPPP,,Long duration Long duration &&Large AmpLarge Amp QSTQST::Cold Cold & & heatheat ….. …..No vibrationNo vibration

PORTUGUESEPORTUGUESE

NumbnessNumbness,,PainPain,,Temperature Temperature && Lancinating pains in feetLancinating pains in feet

CTSCTS::negneg ImpotenceImpotence,,constipationconstipation,,persistent persistent

diarrheadiarrhea Cranial neuropathyCranial neuropathy LiverLiver,,kidneykidney,,heart heart &&corneacornea ArrhytmiaArrhytmia DieDie::50 years50 years

INDIANAINDIANA//SWISSSWISS

Nephropathy Nephropathy && cardiomyopathy:negcardiomyopathy:neg

ImpotenceImpotence CTSCTS Mild sensorimotor Mild sensorimotor

polyneuropathypolyneuropathy SurvivalSurvival::LongLong

VAN ALLENVAN ALLEN

Numbness and painfull Numbness and painfull dysesthesiasdysesthesias

Muscle weakness and atrophyMuscle weakness and atrophy DiarrheaDiarrhea,,Constipation Constipation &&

GastroparesisGastroparesis Hypertension Hypertension & & renal failurerenal failure

FINNISHFINNISH

Mild generalized sensorimotor Mild generalized sensorimotor polyneuropathypolyneuropathy

Corneal dystrophy Corneal dystrophy Cranial neuropathyCranial neuropathy

LIPID METABOLISM LIPID METABOLISM DISORDERSDISORDERS

METACHROMATIC LEUKODYSTROPHYMETACHROMATIC LEUKODYSTROPHY KRABBE’S DISEASEKRABBE’S DISEASE FABRY’S DISEASEFABRY’S DISEASE ADRENOLEUKODYSTROPHYADRENOLEUKODYSTROPHY REFSUM’S DISEASEREFSUM’S DISEASE TANGIER DISEASETANGIER DISEASE CEREBROTENDINOUS CEREBROTENDINOUS

XANTHOMATOSISXANTHOMATOSIS

MLDMLD LATE INFANTILELATE INFANTILE((11--44)) JUVENILEJUVENILE((33--2121)) ADULT ONSETADULT ONSET((after 21after 21)) ARAR

Late infantileLate infantile: : Difficulty Difficulty ambulatingambulating,,muscle crampsmuscle cramps,,limb limb painpain,,weaknessweakness,,hypotoniahypotonia,,hyporehyporeflexia.slurred flexia.slurred speechspeech,,seizureseizure,,quadripareticquadriparetic,,spaspastic stic &&blindblind

Adult –onset: Adult –onset: Progressive Progressive psychosis,dementiapsychosis,dementia,,spasticity,vispasticity,visual impairmentsual impairment,,urinary urinary incontinenceincontinence,,cerebellar cerebellar dysfunction dysfunction && extrapyramidal extrapyramidal signs…….signs…….

LABLAB

Csf proteinCsf protein:: elevated elevated Arylsulfatase Arylsulfatase

AA((PROSAPOSINPROSAPOSIN):):decreaseddecreased

EDXEDX

SNAPs:SNAPs:mildly to moderately mildly to moderately prolonged latencies,markedly prolonged latencies,markedly reduced in amplitude.reduced in amplitude.

CMAPs:CMAPs: mildly to moderately mildly to moderately prolonged latencies,mildly to prolonged latencies,mildly to moderately reduced in amplitude.moderately reduced in amplitude.

Conduction block Conduction block && dispersiondispersion::negneg

TREATMENTTREATMENT

BONE MARROW BONE MARROW TRANSPLANTATIONTRANSPLANTATION

KRABBE’SKRABBE’S

Early infantileEarly infantile Late infantile or juvenileLate infantile or juvenile AdultAdult ARAR

Early infantileEarly infantile::

First First 66 months months

HypersensitivityHypersensitivity,,recurrent recurrent vomitingvomiting,,seizureseizure,,MRMR,,spasticityspasticity,,ddeafeaf,, blind…. blind….

deathdeath::2 years2 years

LABLAB

B-Galactosidase B-Galactosidase activityactivity::decreaseddecreased

CSF ProteinCSF Protein::50% increased50% increased

EDXEDX

SNAPs:SNAPs:mildly to moderately mildly to moderately prolonged latencies,markedly prolonged latencies,markedly reduced in amplitude.reduced in amplitude.

CMAPs:CMAPs: mildly to moderately mildly to moderately prolonged latencies,mildly to prolonged latencies,mildly to moderately reduced in amplitude.moderately reduced in amplitude.

Conduction block Conduction block && dispersiondispersion::negneg

TREATMENTTREATMENT


FABRY’S DISEASEFABRY’S DISEASE

Angiokeratoma corporis diffusumAngiokeratoma corporis diffusum XX--linkedlinked Burning Burning && stabbing pain stabbing pain AngiokeratomaAngiokeratoma::umbilicusumbilicus,,scrotumscrotum,,inging

uinaluinal&&perineumperineum AngiectasiasAngiectasias::oral oral

mucosa,conjunctiva& nailbedmucosa,conjunctiva& nailbed AtherosclerosisAtherosclerosis::HTNHTN,,RFRF,,CVDCVD,,StrokeStroke DeathDeath::Fifth decadeFifth decade

LABLAB

A-Galactosidase A-Galactosidase activityactivity::decreaseddecreased

Accumulation of CERAMIDEAccumulation of CERAMIDE

EDX & EMGEDX & EMG

NORMALNORMAL

ALDALD//AMNAMN

XX--linkedlinked Young maleYoung male Progressive dementiaProgressive dementia,,SeizureSeizure, ,

SpasticitySpasticity,,

Blindness Blindness && hearing loss hearing loss

90 %90 % adrenal insufficiency adrenal insufficiency

LABLAB

VLCFA VLCFA : : increasedincreased C22C22((docosanoic-erusicdocosanoic-erusic)) ::

decreaseddecreased

EDXEDX

ALDALD:Normal:Normal AMNAMN:associated with a :associated with a

superimposed sensorimotor superimposed sensorimotor polyneuropathypolyneuropathy

SEPSEP:abnormal:abnormal VEPVEP:normal:normal Conduction blockConduction block :neg :neg

EMGEMG

Increased IAIncreased IA, , PswPsw, , Fib Fib &&Fasciculation Fasciculation :: neg neg

Alternation in voluntary Alternation in voluntary MUAPMUAP characteristicscharacteristics

TREATMENTTREATMENT

Diets low in Diets low in VLCFAsVLCFAs and and supplemented with supplemented with LORENZO’ oilLORENZO’ oil (erucic (erucic andand olecic olecic acids)acids)


REFSUM’S DISEASEREFSUM’S DISEASE

ARAR Phytanic acidPhytanic acid

1-1-Peripheral neuropathyPeripheral neuropathy

2-2-Elevated CSF proteinElevated CSF protein

3-3-Cerebellar dysfunctionCerebellar dysfunction

4-4-Retinitis pigmentosaRetinitis pigmentosa

Cardiac Cardiac Hearing lossHearing loss AnosmiaAnosmia IchthyosisIchthyosis Bilateral drop footBilateral drop foot Paresthesia Paresthesia && pain pain Vibration Vibration &&position position DTRDTR::ReducedReduced Hypertrophic nerveHypertrophic nerve

LABLAB

Phytanic acid Phytanic acid ::elevatedelevated CSF protein CSF protein :: elevated elevated

EDX&EMGEDX&EMG

SNAPsSNAPs are pften reduced in Amp are pften reduced in Amp && prolonged latencies prolonged latencies……

Motor Motor NCVsNCVs can range from can range from 7 7 to to 30 30 m/sm/s

while in some cases are only while in some cases are only slightly slower than normalslightly slower than normal………………

CMAPsCMAPs can be normal or can be normal or moderately reducedmoderately reduced………..………..

TREATMENTTREATMENT

FishoilsFishoils, , dairy productsdairy products, , ruminant fats ruminant fats &&plasma plasma exchange :exchange :eliminationelimination

TANGIER DISEASETANGIER DISEASE ARAR Deficiency of Deficiency of HDL HDL1-1-Asymmetric peripheral polyneuropathyAsymmetric peripheral polyneuropathy2-2-Symmetric polyneuropathy Symmetric polyneuropathy 3-3-Pseudo-syringomyeliaPseudo-syringomyelia**Diminished vibrationDiminished vibration,,proprioceptionproprioception,,pain pain

&&temperaturetemperature……**Reduction DTRReduction DTR**Lymph nodes enlargement Lymph nodes enlargement & &

splenomegalysplenomegaly

LABLAB

Serum HDL Serum HDL ::reducedreduced Serum triacylglycerol Serum triacylglycerol ::

elevatedelevated

EDX & EMGEDX & EMG

1-1-MILDMILD 2-2-NORMALNORMAL 3-3-SEVERESEVERE,motor NCVs are ,motor NCVs are

reduced by about reduced by about 50%50% in upper in upper and and 20-30%20-30% in lower limbs………… in lower limbs…………Increased IAIncreased IA,,FibFib,,PswPsw,,PPPPPP,,Large Large Amp Amp && Long duration Long duration

CHOLESTANOLOSISCHOLESTANOLOSIS

Progressive dementiaProgressive dementia SpasticitySpasticity AtaxiaAtaxia Mild sensory neuropathy Mild sensory neuropathy CataractsCataracts Xanthomas on tendons and skin .Xanthomas on tendons and skin . Premature atherosclerosisPremature atherosclerosis

Serum Cholestanol Serum Cholestanol ::increasedincreased

TheThe sural sural nerve SNAPs can be nerve SNAPs can be absent or demonstrate a reduction absent or demonstrate a reduction in amplitude and prolongation in in amplitude and prolongation in latency or slowing in conduction latency or slowing in conduction velocity…velocity…

The The medianmedian and and ulnarulnar motor nerve motor nerve conduction velocities are normal or conduction velocities are normal or only slightly slow with normal or only slightly slow with normal or only mildly prolonged distal only mildly prolonged distal latencies……..latencies……..

TREATMENTTREATMENT

Chenodeoxycholic acidChenodeoxycholic acid

HEREDITARY ATAXIASHEREDITARY ATAXIAS

FRIEDREICHFRIEDREICH’’S ATAXIAS ATAXIA VITAMIN VITAMIN EE DEFICIENCY DEFICIENCY ABETALIPOPROTEINEMIAABETALIPOPROTEINEMIA ATAXIAATAXIA--TELANGIECTASIATELANGIECTASIA SPINOCEREBELLAR ATAXIASSPINOCEREBELLAR ATAXIAS MARINESCOMARINESCO--SJOGREN SJOGREN

SYNDROMESYNDROME

FRIEDREICHFRIEDREICH

ARAR Gait ataxiaGait ataxia ClumsinessClumsiness TrippingTripping ScoliosisScoliosis TremorTremor Cardiac symptomsCardiac symptoms

DysarthriaDysarthria DeafnessDeafness Optic atrophyOptic atrophy Pes cavusPes cavus Finger to nose ataxiaFinger to nose ataxia DysdiadochokinesisDysdiadochokinesis Distal weaknessDistal weakness Heel-shin ataxiaHeel-shin ataxia Reduction in vibration,position & painReduction in vibration,position & pain DTRDTR Extensor plantar responseExtensor plantar response DementiaDementia Wheelchair :Wheelchair :1616 Death : Death : 3737

LABLAB

MRIMRI :Cervical spinal cord may :Cervical spinal cord may reveal atrophyreveal atrophy

ECGECG :low voltage QRS & deep Q :low voltage QRS & deep Q waveswaves

EDX EDX

SNAPSNAP:: absent or profound reduction absent or profound reduction Blink reflexBlink reflex ::normalnormal H-reflexH-reflex ::absentabsent SEPSEP :: Reduced Reduced VEPVEP :: Reduced Reduced BAEPBAEP ::ReducedReduced Magnetic stimulation studiesMagnetic stimulation studies ::Slowing Slowing

of central conduction motor pathwaysof central conduction motor pathways CMAPCMAP :: Less affected than SNAP Less affected than SNAP

EMGEMG

Normal Normal Fib Fib && Psw Psw

Vit E DEFFICIENCYVit E DEFFICIENCY

ARAR AtaxiaAtaxia,,disdiadochokinesisdisdiadochokinesis,,dysarthridysarthri

aa,, clumsiness clumsiness,,rombergromberg,,reduced reduced vibration vibration && proprioception proprioception,,pes pes cavus cavus && scoliosis scoliosis

Plantar responses extensor Plantar responses extensor DTRDTR :: reduced reduced Reduced pain & touch & Reduced pain & touch &

temperaturetemperature,,ptosisptosis,,ophthalmoplegiophthalmoplegia and retinal pigmentationa and retinal pigmentation::NegativeNegative

LABLAB

Normal LDLNormal LDL,,HDLHDL,,TGTG,,VLDL VLDL && Vit Vit A,D,KA,D,K

Reduced Vit E Reduced Vit E

EDX & EMGEDX & EMG

Reduced or absent SNAPsReduced or absent SNAPs SEPSEP: reduced: reduced((centralcentral)) Neurogenic type Neurogenic type MUAPMUAP

parametersparameters A rare patient myopathic A rare patient myopathic MUAPMUAP

parametersparameters

TREATMENTTREATMENT

Vit E Vit E 400400 mg twice a day and is mg twice a day and is increased up to increased up to 100100 mg/kg/day mg/kg/day

Injection of Vit E Injection of Vit E 100100mg/weekmg/week

ABETALIPOPROTEINEMIAABETALIPOPROTEINEMIA

Bassen diseaseBassen disease AtaxiaAtaxia,,,,,,,,,,steatorrheasteatorrhea,,,,,,,,,,,,retinitis retinitis

pigmentosapigmentosa,,,,,,,,,,,,lossloss of sensation in distal of sensation in distal of upper and lower limbsof upper and lower limbs

Low weight and statureLow weight and stature,,reduced reduced DTRDTR,,flexor plantar responsesflexor plantar responses,,reduced in reduced in vibration and vibration and proprioceptionproprioception,,disdiadochokinesisdisdiadochokinesis,,romberombergrg,,ophthalmoplegiaophthalmoplegia,,reduced touch and reduced touch and painpain

Pes cavusPes cavus,,hammer toeshammer toes,,tremortremor

LABLAB

AcanthocyteAcanthocyte Reduced Reduced

LDLLDL,,VLDLVLDL,,HDLHDL,,TGTG,,Vit A,D,KVit A,D,K

EDX EDX

SNAPSNAP:: absent or profound reduction absent or profound reduction Blink reflexBlink reflex ::normalnormal H-reflexH-reflex ::absentabsent SEPSEP :: Reduced Reduced VEPVEP :: Reduced Reduced BAEPBAEP :normal:normal Magnetic stimulation studiesMagnetic stimulation studies ::Slowing Slowing

of central conduction motor pathwaysof central conduction motor pathways CMAPCMAP :: Less affected than SNAP Less affected than SNAP

TREATMENTTREATMENT

REPLACEMENT OF FAT REPLACEMENT OF FAT SOLUBLE VITAMINSSOLUBLE VITAMINS

hereditary motor and sensory neuropathies

Documents