HEREDITARY MOTOR AND SENSORY NEUROPATHIES

1
HEREDITARY MOTOR ANDSENSORY NEUROPATHIES
Alireza Ashraf, M.D.Professor of Physical
Medicine Rehabilitation
Shiraz Medical school
2
CHARCOT-MARIE-TOOTH DISEASE ANDRELATED DISORDERS

• The various categories of CMT are subclassified
  according to the nature of the pathology
  (demyelinating or axonal),
• mode of inheritance (AD,AR or X-linked),
• age of onset and the specific mutated
  gene.
• CMT1 - AD - demyelinating motor and sensory
  neuropathies.

3

• CMT2 -AD - axonal motor and sensory neuropathies.
• In contrast to CMT1 and CMT2, which begin in
  childhood or early adult life, CMT3 begins in
  infancy and is associated with severe
  demyelination/hypomyelination.

4
Charcot-Marie-Tooth Disease Type I

• CMT1 The most common .
• The ratio of CMT1 to CMT2 is approximately 21.
• CMT1 usually manifests in the first to third
  decades,
• Most patients have pes cavus or equinovarus,
  hammertoes and exuberant callous formation, which
  lead to foot pain.

5

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

6
Charcot-Marie-Tooth Disease Type I

• Recurrent ankle sprains.
• Some patients note frequent stubbing of toes
  during ambulation.
• patients typically do not complain about
  significant sensation loss in the distal regions
  of the feet or hands.
• there is an absence of paresthesias or other
  "positive" phenomena, which can be helpful in
  distinguishing CMT from acquired forms of
  neuropathy.
• some patients complain of severe cramps.

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Charcot-Marie-Tooth Disease Type I

• Physical examination reveals considerable muscle
  atrophy and weakness in the distal compared to
  proximal limb regions.
• As an alternative name to this disorder implies,
  "peroneal muscular atrophy,"
• Rare patients have asymmetric pseudohypertrophy
  of the calves.
• This distal muscle atrophy resulted in the
  original describers of the disease to compare the
  patients' legs to inverted champagne bottle
  legs."

9

• Intrinsic foot muscle wasting is also prominent.
• Weakness of the anterior compartment muscles of
  the distal lower limbs causes footdrop.
• steppage gait excessive degree of hip and knee
  flexion .
• Symmetric distal atrophy and weakness of the
  upper limbs is also evident in two-thirds of
  patients.

10

• Severe claw deformities of the hand intrinsics
  can be seen in some individuals.
• Despite the lack of sensory symptoms, diminished
  sensation to all modalities is apparent on
  examination.
• Sensory loss is more apparent in the lower limbs
  than the upper limbs.

11

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

12

• Careful inspection of the peripheral nerves,
  especially posterior to the ear and arm regions,
  may demonstrate neural hypertrophy and firmness
  compared to normal in about 25 of patients .
• Importantly, rare patients have developed
  compression of the spinal cord and cauda equina
  due to marked hypertrophy of nerve roots.

13

• Approximately one-third of patients with CMT1
  have an essential tremor.
• These patients were previously referred to as
  having Roussy-Levy syndrome.
• However, this term has become outdated as
  advances in the molecular genetics have
  demonstrated that such tremors can be seen in all
  subtypes of CMT1 as well as some patients with
  CMT2.

14
Histopathology

• The gross appearance of the peripheral nerve
  reveals an overall increase in the fascicle size
  leading to the so-called "hypertrophic
  neuropathy" designation.
• There is a predilection for the loss of the
  relatively larger diameter fibers.
• In addition, there is a decrease in axon caliber
  and an increase in the density of neurofilaments
  within these "atrophic" axons.
• Schwann cell proliferation due to repeated bouts
  of demyelination and remyelination results in the
  formation of so-called onion bulbs.

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• Demyelination, neuronal loss, and axonal atrophy
  are slightly more prominent distally.
• The mean internode length is reduced compared to
  normal.
• The spinal cord is also affected with loss of
  myelinated libers in the fasciculus gracilis as
  noted at the cervical levels.

16

• Patients with CMT1 may be born with normal or
  only minimally slowed nerve conduction
  velocities.
• These velocities rapidly decline such that by the
  time the child is 3-5 years of age, a maximal
  reduction is achieved that changes little over
  the course of the patient's life.
• The CMAP amplitudes also continue to diminish
  over time, indicative of axon loss.

17

• Distal motor latencies at birth are commonly
  borderline abnormal.
• These latencies continue to increase until
  approximately the age of 10 years, at which time
  there is little further prolongation of the
  distal latencies.
• .

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Sensory Conduction Studies

• The sensory nerve conduction studies in both the
  upper and lower limbs are usually markedly
  abnormal in most patients with CMT1.
• SNAPs are unobtainable or very low in amplitude.
  
• In addition, the distal latencies of obtainable
  responses are markedly prolonged and nerve
  conduction velocities are commonly less than 60
  of normal.

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Motor Nerve Conduction Studies

• The CMAPs may be absent when recordings are
  attempted from severe wasted extensor digitorum
  brevis (EDB)and abductor hallucis (AH) muscles.
• It may be necessary to perform motor conduction
  studies in the lower limb by recording from the
  tibialis anterior muscle.
• When responses can be detected from either the
  EDB or AH, the CMAP amplitudes are frequently
  reduced.

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• CMAP amplitudes are only slightly decreased early
  in the disease course in the upper limbs.
• Distal motor latencies are considerably prolonged
  in both the upper and lower limbs.
• When stimulating at distal and proximal sites,
  there is no evidence of conduction block or
  temporal dispersion.
• The most dramatic finding is a greater than 60
  reduction in nerve conduction velocity compared
  to expected normal values.

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• Values in the 25 m/s range are characteristic for
  patients with CMT I A.
• Patients with point mutations in PMP-22 gene have
  even slower conduction velocities approaching
  that seen in CMT3 (10 m/s or less).

22

• There is little correlation between the patients
  clinical symptoms and the degree to which nerve
  conductions are affected.
• NCVs can be quite profoundly affected during
  early childhood, when there is little in the way
  of clinical deficits
• It appears that weakness is more related to the
  degree of axon loss, rather than the extent of
  demyelination and slowing of nerve
  conduction..

23

• As noted above, patients with CMT1 do not usually
  demonstrate conduction block or temporal
  dispersion.
• This contrasts with the presence of conduction
  block or temporal dispersion in patients with
  acquired forms of demyelinating neuropathy (e.g.,
  Guillain-Barre svndrome and chronic inflammatory
  demyelinating neuropathy).

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• A nerve commonly forgotten is the phrenic nerve.
• Patients with CMTI can have significantly
  prolonged phrenic CMAP latencies.
• CMTI patients can have reduced pulmonary
  function secondary to diaphragmatic and
  intercostal muscle weakness due to denervation.

25

• F-waves latencies are usually absent but when
  obtainable are extremely prolonged.
• Of note, when calculating, proximal conduction
  velocities using F-waves, the obtained values are
  almost but not quite as slowed as the distal limb
  values.
• Slowing of facial nerve conduction is commonly
  found in CMTI.
• This is reflected as a significant prolongation
  in the facial nerve's motor latency often
  approaching 14 ms (normal lt 4.0 MS).

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• The blink reflex can also be markedly abnormal in
  that the R1 response may be as long as 26 ms
  (normal lt 13 ms).
• A reduction in the R1 to facial nerve latency
  ratio (R/D ratio) can be found in most patients
  indicating that the facial nerve (motor) latency
  is prolonged out of proportion to the trigeminal
  (sensory) latency.
• Alternatively, the motor nerves may be slightly
  more severely affected than sensory nerves in
  regards to conduction velocities.

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Somatosensory evoked

• These evoked potential studies have demonstrated
  slowing of spinal and cortical conducting
  pathways when central conduction times are
  calculated.
• The slowing is less dramatic than that seen
  peripherally
• Visual evoked potentials also reveal similar
  slowing of the optic pathways.

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Needle electromyography

• If the CMAP is absent. e.g.. in the EDB or AH,
  one can anticipate a significant reduction or
  even absence of insertional activity .
• Some patients may reveal evidence of very small
  amplitude (50 ?V or less) sustained positive
  sharp waves and fibrillation potentials despite
  little activity during, needle insertion.
• If these patients are followed over time,
  eventually complete electrical silence can be
  noted in these muscles.

29

• The documentation of Psw and Fib potentials is
  quite common in the distal muscles of both the
  upper and lower limbs in CMT1.
• Occasionally, other forms of spontaneous
  electrical activity can be seen, such as complex
  repetitive discharges and fasciculation
  potentials.
• The tibialis anterior muscle is perhaps the best
  muscle to demonstrate spontaneous activity, even
  in patients with advanced disease.

30

• The MUAPs fire at high rates and in reduced
  numbers (reduced recruitment).
• The MUAPs are typically of long duration, high
  amplitude, and polyphasic.

31

• The lack of appreciable peripheral sprouting in
  sensory nerves often results in a complete
  absence of SNAPs.
• In motor nerves, the larger size of the recorded
  potential combined with the motor nerve's ability
  to peripherally sprout and reinnervate denervated
  muscle fibers staves off a complete absence of
  CMAPs for a longer period compared to the SNAPs.
• Macro-EMG studies reveal extensive collateral
  reinnvervation in CMT1 compared to CMT2.

32
Charcot-Marie-Tooth Disease Type 2 (CMT2)

• CMT2 refers to the autosomal dominant
  neuronal" hereditary motor and sensory
  neuropathies.
• CMT2A and CMT2B (CMT2A/B) are the most common
  subtypes of CMT2 and are discussed together.
• The clinical features of CMT2A/B are rather
  similar to CMT1 with several important
  exceptions.
• The peak age of symptom onset in CMT2A/B is
  usually in the second decade with some patients
  becoming symptomatic only in their seventh
  decade.

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• Also, there is a distinct absence of enlarged
  nerves in CMT2,
• Patients with CMT2A/B tend to have less severe
  involvement of the intrinsic hand muscles and
  tremor is not as common as seen in CMT1.
• There is more significant atrophy of the distal
  lower limbs and weakness of the posterior tibial
  and calf muscles (in addition to atrophy and
  weakness of the anterior lateral compartment
  muscles) in CMT2A/B corripared to CMT1.
• Complete lack of deep tendon reflexes is found in
  only a small percentage of patients with CMT2A/B,
  while it is common in CMT 1

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• Ankle reflexes are usually absent in both types
  of disease.
• About 50-70 of patients with CMT1 have
  significant reductions in light touch, pain,
  joint position and vibration sense, while
  approximately 20-50 of patients with CMT2A/B
  have similar findings.
• Severe mutilating neuropathic ulcerations similar
  to those typically seen in hereditary sensory and
  autonomic neuropathy type I (HSAN 1) have been
  demonstrated in some patients with CMT2B.

35

• Pes cavus and hammer toe deformities are less
  common in CMT2A1B than in CMT1..
• CMT2A/B needs to be distinguished from
  chronic idiopathic axonal neuropathy (CIAP).
  .
• Although there is electrophysiologic evidence of
  motor involvement in CIAP, sensory symptoms
  dominate the clinical picture.
• This contrasts with CMT2A/B, in which motor
  symptoms and signs are the major features..

36
CMT2C

• The distinguishing feature of CMT2C is vocal cord
  paralysis.
• The age of onset is variable and symptoms can
  begin in infancy, manifesting with breathing
  difficulties and stridor.
• More common is the insidious onset of laryngeal
  weakness causing progressive hoarseness.
• The diaphragm and intercostal muscles are often
  weak leading to reduced respiratory function.

37
CMT2C

• Atrophy of the distal limbs is common, and
  patients can develop proximal and distal weakness
  of the arms and legs.
• There is mild sensory loss to all modalities and
  deep tendon reflexes are reduced.
• Pes cavus can be appreciated in some patients,
  but such foot deformities are not as common as
  seen in CMTI, CMT2A, or CMT2B.
• Similar cases have been reported as hereditary
  distal spinal muscular atrophy with vocal cord
  paralysis.

38
CMT2D

• UnIike CMT2A and CMT2B, weakness and atrophy of
  the hands are more severe than in the distal
  legs.
• Deep tendon reflexes are generally absent in the
  arms and reduced in the legs.
• Pes cavus, hammertoes, and scoliosis are variably
  present.
• Enlarged palpable nerves are not appreciated.
• This disorder is allelic to distal spinal
  muscular atrophy type 5.

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CMT2 E

• Distal sensory loss, hypo- or areflexia, and pes
  cavus deformities were common.
• Some patients exhibited hyperkeratosis of the
  hands and feet.

40

• Sensory nerve conduction studies reveal reduced
  or absent SNAP amplitudes in both the upper and
  lower limbs.
• Conduction velocities are comparatively well
  preserved and always greater than 70 of the
  lower limit of normal.
• The distal sensory latencies are either normal or
  only mildly prolonged.

41

• The motor conduction studies demonstrate normal
  or only mildly reduced nerve conduction
  velocities (usually in excess of 70 of the lower
  limit of normal).
• The distal motor latencies are normal or only
  mildly prolonged.
• The CMAPs are often preserved in the upper
  limbs
• however, the peroneal and posterior tibial CMAPs
  are absent or reduced in size.

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• The MUAPs can be increased in amplitude and
  duration
• The recruitment may be reduced in some persons.
• Occasional fasciculation and fibrillation
  potentials can be observed.
• Complex repetitive discharges can also be
  documented in some patients.
• A few patients with CMT2 have been reported to
  have neuromyotonia in that it is abolished with
  peripheral
• neuromuscular blockade.

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HNPP

• Tomaculous neuropathy
• Pmp-22
• AD
• MEDIAN,ULNAR,RADIAL,PERONEALBRACHIAL PLEXUS
• DTR(diminished)
• HAMMERTOES
• PES CAVUS

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EDX

• CONDUCTION BLOCK
• TEMPORAL DISPERSION
• Fib Psw
• Fasciculation
• CRD
• Reduced recruitment
• Polyphasic
• Larg amp Long duration

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CMT 3

• Dejerine Sottas
• Infancy-early childhood
• Congenital hypomyelination neuropathy
• Pmp-22 ,EGR-2
• Hypotonia-Respiratory distress-arthrogryposis-Swal
  lowing difficulties-Peripheral nerve
  enlargement-Ataxia-Hearing loss-Abnormal
  pupillary reaction-Pes cavus-Kyphoscoliosis
• Elevated CSF.

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EDX

• NCVs are 5-10 m/s or less.
• Proximal musclesincreased IA,Psw,Fib
• Distal musclesReduced IA,Little in the way of
  sustained Fib Psw
• Near the terminal stage of the disease,low-amplitu
  de MUAP with long or short durations may be
  documented

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CMT 4A

• FIRST 2 YEARS OF LIFE
• MILD SENSORY LOSS
• SCOLIOSIS

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CMT 4B

• FLOPPY AT BIRTH
• DTRabsent
• TOMACULAE

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CMT 4C

• Delay in walking until 18-24 months
• Deformities in the feet and spine by 5 years of
  age
• Sensory loss
• DTRabsent
• HYPERTROPHY OF NERVES

50
CMT 4D

• HEREDITARY MOTOR AND SENSORY NEUROPATHY WITH
  DEAFNESS-LOM
• (HMSN-L)

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CMT 4E

• PMP-22,,,,EGR-2
• Same as CMT 3..

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CMT 4F

• ATAXIA
• KYPHOSCOLIOSIS..
• PES CAVUS

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LAB

• CSF protein is reportedly normal in CMT4A and CMT
  4C
• Elevated in some reported cases of CMT4B

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EDX

• NCVs are markedly in CMT4A,4B 4F
• CMT 4A,4B 4Fless than 20 m/s
• CMT 4C 24 m/s
• Fib,Psw,polyphasic decreased recruitment

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CMT X

• Similar to CMT 1
• MEN
• Foot drop,pes cavus,hammertoes claw-hand
• DTRDiminished
• Unlike CMT1,the nerves are not profoundly
  hypertrophic

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EDX

• SAME AS CMT1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
• BUT NCVs IN MEN WITH CMTX ARE
  APPROXIMATELY 10 m/s FASTER THAN THOSE
  RECORDED IN Pt WITH CMT1..

57
CMT 2X

• Axonal motor-sensory neuropathy
• Deafness
• MR
• First few years of life

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HMSN-L

• AR
• Demyelinating neuropathy
• First decade gait difficulties due to distal leg
  weakness
• Second decade hands
• Third decade hearing loss

59
EDX

• BAVP reveal both peripheral and central slowing
  of auditory conduction..
• VEP is normal

60
HMSNP

• AD
• Same as Kennedy
• Muscle cramp
• 30 y/o
• Fasciculations in trunk and limbs
• Mild facial weakness
• Neck Flx Ext are spared
• Tongue,Dysphagia Dysarthria
• Tremor
• DM 2
• Decreased vibratory and position

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LAB

• CK is often elevated
• DM 2
• HLP.

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EDX

• SNAPs are markedly reduced in amp or
  absent..
• CMAP amps are moderately decreased
• Distal motor and sensory latencies are
  preserved..
• Fasciculation,Fib,Psw,Polyphasic Decreased
  recruitment

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HNA

• AD,Axonal
• Pain,weakness sensory loss
• Childhood
• Parsonage-Turner Sx
• Multifocal sensory neuropathy(Wartenbergs
  migrant neuropathy)
• Hypotelorism,Epicanthal fold,Cleft
  palate,Syndactylly,Micrognathia Facial asymmetry

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EDX

• Distal latencies and conduction velocities of the
  CMAP and SNAPs are relatively preserved
• Fib,Psw,Decreased recruitment Polyphasic
  ..

65
HSAN1

• AD
• 2nd-4th Decades
• Slowly progressive
• Small myelinated unmyelinated
• Numbness-,lancinating pain,burning,aching
• Bladder dysfunction,reduced sweating
• Pain,temperature,DTR absent at ANKLES
• Pes cavus,Hammertoe

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LAB

• CSF normal
• Increased IgA

67
EDX

• Normal or only mildly reduced CMAPs and SNAPs
  amplitudes
• Near nerve recordingsreduced amp of A delta and
  C-fibers
• Abnormal QST
• SSRabsent

68
HSAN 2

• Infancy
• AR
• Severe loss of sensation to all
  modalities(particularly touch pressure/vibration)
• Whitlow
• Lancinating painsneg
• Romberg
• Impaired sweating,bladder dysfunction impotence
• Postural hypotensionneg
• Scoliosis

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PATHOLOGY

• Virtual absence of large myelinated fibers
• Mild loss of small myelinated and unmyelinated
  fibers

70
EDX

• Absent SNAP
• Normal or only mildly reduced CMAPs amp
• Abnormal QST(particularly vibration)
• EMGReduced recruitment,long duration
• polyphasic,FibPsw

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HSAN 3

• Riley-day SxFamilial dysautonomia
• AR
• Infancy
• Poor suck
• Alacrima,Blothy skin,Fluctuations in body
  temperature and blood pressure,Vomiting,Imfections
  of lungs,Esophageal and gastrointestinal
  dysmotility,Sweating excessive,Delay in normal
  development

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• Seizures
• Intelligence is normal
• Impairment in position,vibration,pain,taste
  corneal reflexes
• Tonic pupils
• Postural hypotension
• MMT nl but DTRabsent
• Short stature scoliosis

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PATHOLOGY

• Marked reduction of small myelinated and
  unmyelinated fibers and to a lesser extent large
  myelinated fibers

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EDX

• Decreased SNAP amp,mild slowing of CMAP
  velocities
• Abnormal QST
• Normal SSR

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HSAN 4

• AR
• ANHYDROSIS
• SELF MUTILATION
• POSTURAL HYPOTENSIN
• PAIN TEMPERATURE
• VIBRATORY LESS AFFECTED

76
EDX

• There can be slight reductions in CMAPs SNAPs
  amplitudes and conduction velocities,but not as
  severe as that seen in HSAN2 or HSAN3
• SSRunobtainable

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HSAN 5

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

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EDX

• NCS,EMG,SSR,QSTSEPnormal
• WITHDRAWAL TO PAINabnormal

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FAP

• AXONAL
• Transthyretin,apolipoprotein A1 gelsolin
• Small myelinated unmyelinated fibers
• SNAPDiminished in amp normal or mildly
  prolonged in latency
• CMAPMotor are less severely affected
• CTS
• Fib Psw,PPP,Long duration Large Amp
• QSTCold heat ..No vibration

80
PORTUGUESE

• Numbness,Pain,Temperature Lancinating pains in
  feet
• CTSneg
• Impotence,constipation,persistent diarrhea
• Cranial neuropathy
• Liver,kidney,heart cornea
• Arrhytmia
• Die50 years

81
INDIANA/SWISS

• Nephropathy cardiomyopathyneg
• Impotence
• CTS
• Mild sensorimotor polyneuropathy
• SurvivalLong

82
VAN ALLEN

• Numbness and painfull dysesthesias
• Muscle weakness and atrophy
• Diarrhea,Constipation Gastroparesis
• Hypertension renal failure

83
FINNISH

• Mild generalized sensorimotor polyneuropathy
• Corneal dystrophy
• Cranial neuropathy

84
LIPID METABOLISM DISORDERS

• METACHROMATIC LEUKODYSTROPHY
• KRABBES DISEASE
• FABRYS DISEASE
• ADRENOLEUKODYSTROPHY
• REFSUMS DISEASE
• TANGIER DISEASE
• CEREBROTENDINOUS XANTHOMATOSIS

85
MLD

• LATE INFANTILE(1-4)
• JUVENILE(3-21)
• ADULT ONSET(after 21)
• AR

86

• Late infantile Difficulty ambulating,muscle
  cramps,limb pain,weakness,hypotonia,hyporeflexia.s
  lurred speech,seizure,quadriparetic,spastic blind

87

• Adult onset Progressive psychosis,dementia,spast
  icity,visual impairment,urinary
  incontinence,cerebellar dysfunction
  extrapyramidal signs.

88
LAB

• Csf protein elevated
• Arylsulfatase A(PROSAPOSIN)decreased

89
EDX

• SNAPsmildly to moderately prolonged
  latencies,markedly reduced in amplitude.
• CMAPs mildly to moderately prolonged
  latencies,mildly to moderately reduced in
  amplitude.
• Conduction block dispersionneg

90
TREATMENT

• BONE MARROW TRANSPLANTATION

91
KRABBES

• Early infantile
• Late infantile or juvenile
• Adult
• AR

92

• Early infantile
• First 6 months
• Hypersensitivity,recurrent vomiting,seizure,MR,
  spasticity,deaf, blind.
• death2 years

93
LAB

• B-Galactosidase activitydecreased
• CSF Protein50 increased

94
EDX

• SNAPsmildly to moderately prolonged
  latencies,markedly reduced in amplitude.
• CMAPs mildly to moderately prolonged
  latencies,mildly to moderately reduced in
  amplitude.
• Conduction block dispersionneg

95
TREATMENT

• BONE MARROW TRANSPLANTATION

96
FABRYS DISEASE

• Angiokeratoma corporis diffusum
• X-linked
• Burning stabbing pain
• Angiokeratomaumbilicus,scrotum,inguinalperineum
• Angiectasiasoral mucosa,conjunctiva nailbed
• AtherosclerosisHTN,RF,CVD,Stroke
• DeathFifth decade

97
LAB

• A-Galactosidase activitydecreased
• Accumulation of CERAMIDE

98
EDX EMG

• NORMAL

99
ALD/AMN

• X-linked
• Young male
• Progressive dementia,Seizure, Spasticity,
• Blindness hearing loss
• 90 adrenal insufficiency

100
LAB

• VLCFA increased
• C22(docosanoic-erusic) decreased

101
EDX

• ALDNormal
• AMNassociated with a superimposed sensorimotor
  polyneuropathy
• SEPabnormal
• VEPnormal
• Conduction block neg

102
EMG

• Increased IA, Psw, Fib Fasciculation neg
• Alternation in voluntary MUAP characteristics

103
TREATMENT

• Diets low in VLCFAs and supplemented with
  LORENZO oil (erucic and olecic acids)
• BONE MARROW TRANSPLANTATION

104
REFSUMS DISEASE

• AR
• Phytanic acid
• 1-Peripheral neuropathy
• 2-Elevated CSF protein
• 3-Cerebellar dysfunction
• 4-Retinitis pigmentosa

105

• Cardiac
• Hearing loss
• Anosmia
• Ichthyosis
• Bilateral drop foot
• Paresthesia pain
• Vibration position
• DTRReduced
• Hypertrophic nerve

106
LAB

• Phytanic acid elevated
• CSF protein elevated

107
EDXEMG

• SNAPs are pften reduced in Amp prolonged
  latencies
• Motor NCVs can range from 7 to 30 m/s
• while in some cases are only slightly slower
  than normal
• CMAPs can be normal or moderately reduced..

108
TREATMENT

• Fishoils, dairy products, ruminant fats
  plasma exchange elimination

109
TANGIER DISEASE

• AR
• Deficiency of HDL
• 1-Asymmetric peripheral polyneuropathy
• 2-Symmetric polyneuropathy
• 3-Pseudo-syringomyelia
• Diminished vibration,proprioception,pain
  temperature
• Reduction DTR
• Lymph nodes enlargement splenomegaly

110
LAB

• Serum HDL reduced
• Serum triacylglycerol elevated

111
EDX EMG

• 1-MILD
• 2-NORMAL
• 3-SEVERE,motor NCVs are reduced by about 50 in
  upper and 20-30 in lower limbsIncreased
  IA,Fib,Psw,PPP,Large Amp Long duration

112
CHOLESTANOLOSIS

• Progressive dementia
• Spasticity
• Ataxia
• Mild sensory neuropathy
• Cataracts
• Xanthomas on tendons and skin .
• Premature atherosclerosis

113

• Serum Cholestanol increased

114

• The sural nerve SNAPs can be absent or
  demonstrate a reduction in amplitude and
  prolongation in latency or slowing in conduction
  velocity
• The median and ulnar motor nerve conduction
  velocities are normal or only slightly slow with
  normal or only mildly prolonged distal
  latencies..

115
TREATMENT

• Chenodeoxycholic acid

116
HEREDITARY ATAXIAS

• FRIEDREICHS ATAXIA
• VITAMIN E DEFICIENCY
• ABETALIPOPROTEINEMIA
• ATAXIA-TELANGIECTASIA
• SPINOCEREBELLAR ATAXIAS
• MARINESCO-SJOGREN SYNDROME

117
FRIEDREICH

• AR
• Gait ataxia
• Clumsiness
• Tripping
• Scoliosis
• Tremor
• Cardiac symptoms

118

• Dysarthria
• Deafness
• Optic atrophy
• Pes cavus
• Finger to nose ataxia
• Dysdiadochokinesis
• Distal weakness
• Heel-shin ataxia
• Reduction in vibration,position pain
• DTR
• Extensor plantar response
• Dementia
• Wheelchair 16
• Death 37

119
LAB

• MRI Cervical spinal cord may reveal atrophy
• ECG low voltage QRS deep Q waves

120
EDX

• SNAP absent or profound reduction
• Blink reflex normal
• H-reflex absent
• SEP Reduced
• VEP Reduced
• BAEP Reduced
• Magnetic stimulation studies Slowing of central
  conduction motor pathways
• CMAP Less affected than SNAP

121
EMG

• Normal
• Fib Psw

122
Vit E DEFFICIENCY

• AR
• Ataxia,disdiadochokinesis,dysarthria,
  clumsiness,romberg,reduced vibration
  proprioception,pes cavus scoliosis
• Plantar responses extensor
• DTR reduced
• Reduced pain touch temperature,ptosis,ophthalm
  oplegia and retinal pigmentationNegative

123
LAB

• Normal LDL,HDL,TG,VLDL Vit A,D,K
• Reduced Vit E

124
EDX EMG

• Reduced or absent SNAPs
• SEP reduced(central)
• Neurogenic type MUAP parameters
• A rare patient myopathic MUAP parameters

125
TREATMENT

• Vit E 400 mg twice a day and is increased up to
  100 mg/kg/day
• Injection of Vit E 100mg/week

126
ABETALIPOPROTEINEMIA

• Bassen disease
• Ataxia,,,,,steatorrhea,,,,,,retinitis
  pigmentosa,,,,,,loss of sensation in distal of
  upper and lower limbs
• Low weight and stature,reduced DTR,flexor plantar
  responses,reduced in vibration and
  proprioception,disdiadochokinesis,romberg,ophthalm
  oplegia,reduced touch and pain
• Pes cavus,hammer toes,tremor

127
LAB

• Acanthocyte
• Reduced LDL,VLDL,HDL,TG,Vit A,D,K

128
EDX

• SNAP absent or profound reduction
• Blink reflex normal
• H-reflex absent
• SEP Reduced
• VEP Reduced
• BAEP normal
• Magnetic stimulation studies Slowing of central
  conduction motor pathways
• CMAP Less affected than SNAP

129
TREATMENT

• REPLACEMENT OF FAT SOLUBLE VITAMINS