Transcript Hereditary Neuropathies

HEREDITARY MOTOR AND
SENSORY NEUROPATHIES
Alireza Ashraf, M.D.
Associate Professor of Physical Medicine & Rehabilitation
Shiraz Medical school
CHARCOT-MARIE-TOOTH DISEASE AND
RELATED 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.

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.
Charcot-Marie-Tooth Disease Type I

CMT1 :The most common .

The ratio of CMT1 to CMT2 is approximately 2:1.

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.
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………………….
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.
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."

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.

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.

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.

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.
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.
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.

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.

Patients with CMT1 may be born with

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.
normal or only minimally slowed nerve
conduction velocities.

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.
.
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.
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.

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

The most dramatic finding is a greater than 60% reduction in
nerve conduction velocity compared to expected normal values.
conduction block or temporal dispersion.

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).
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………………..

As noted above, patients with CMT1 do

This contrasts with the presence of
conduction block or temporal dispersion in
patients with acquired forms of
demyelinating neuropathy (e.g., GuillainBarre svndrome and chronic inflammatory
demyelinating neuropathy).
not usually demonstrate conduction block
or temporal dispersion.

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.

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 < 4.0 MS).

The blink reflex can also be markedly abnormal in
that the R1 response may be as long as 26 ms
(normal < 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.
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

Visual evoked potentials also reveal similar slowing of
the optic pathways.
peripherally
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 ЧV 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.

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.

The MUAPs fire at high rates and in reduced numbers
(reduced recruitment).

The MUAPs are typically of long duration, high
amplitude, and polyphasic.

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.
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.

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

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.‘

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……………..
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.
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.
CMT2D

UnIike CMT2A and CMT2B, weakness and atrophy

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.
of the hands are more severe than in the distal
legs.
CMT2 E

Distal sensory loss, hypo- or
areflexia, and pes cavus deformities
were common.

Some patients exhibited
hyperkeratosis of the hands and feet.

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.

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.
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.
HNPP

Tomaculous neuropathy
Pmp-22
 AD
 MEDIAN,ULNAR,RADIAL,PERONEAL&
BRACHIAL PLEXUS
 DTR(diminished)
 HAMMERTOES
 PES CAVUS

EDX
CONDUCTION BLOCK
 TEMPORAL DISPERSION
 Fib &Psw
 Fasciculation
 CRD
 Reduced recruitment
 Polyphasic
 Larg amp &Long duration

CMT 3






Dejerine Sottas
Infancy-early childhood
Congenital hypomyelination neuropathy
Pmp-22 ,EGR-2
Hypotonia-Respiratory distressarthrogryposis-Swallowing difficultiesPeripheral nerve enlargement-AtaxiaHearing loss-Abnormal pupillary reactionPes cavus-Kyphoscoliosis
Elevated CSF.
EDX
NCVs are 5-10 m/s or less.
 Proximal muscles:increased
IA,Psw,Fib
 Distal muscles:Reduced IA,Little in
the way of sustained Fib &Psw
 Near the terminal stage of the
disease,low-amplitude MUAP with
long or short durations may be
documented

CMT 4A
FIRST 2 YEARS OF LIFE
 MILD SENSORY LOSS
 SCOLIOSIS

CMT 4B
FLOPPY AT BIRTH
 DTR:absent
 TOMACULAE

CMT 4C
Delay in walking until 18-24 months
 Deformities in the feet and spine by 5
years of age
 Sensory loss
 DTR:absent
 HYPERTROPHY OF NERVES

CMT 4D
 HEREDITARY
MOTOR AND
SENSORY NEUROPATHY WITH
DEAFNESS-LOM
 (HMSN-L)
CMT 4E
PMP-22,,,,EGR2……………………………
 Same as CMT
3……………………………..

CMT 4F
ATAXIA………………………………………
 KYPHOSCOLIOSIS………………………..
 PES CAVUS…………………………………

LAB
CSF protein is reportedly normal in
CMT4A and CMT 4C
 Elevated in some reported cases of
CMT4B

EDX
NCVs are markedly in CMT4A,4B &4F
 CMT 4A,4B &4F:less than 20 m/s
 CMT 4C :24 m/s
 Fib,Psw,polyphasic &decreased
recruitment

CMT X
Similar to CMT 1
 MEN
 Foot drop,pes cavus,hammertoes
&claw-hand
 DTR:Diminished
 Unlike CMT1,the nerves are not
profoundly hypertrophic

EDX

SAME AS CMT1,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
BUT NCVs IN MEN WITH CMTX
ARE APPROXIMATELY 10 m/s
FASTER THAN THOSE RECORDED
IN Pt WITH CMT1…………..
CMT 2X
Axonal motor-sensory neuropathy
 Deafness
 MR
 First few years of life

HMSN-L
AR
 Demyelinating neuropathy
 First decade: gait difficulties due to
distal leg weakness
 Second decade: hands
 Third decade: hearing loss

EDX
BAVP reveal both peripheral and
central slowing of auditory
conduction…..
 VEP is normal…………

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
LAB
CK is often
elevated………………………
 DM 2…………………………………………
 HLP………………………………………….

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……………

HNA






AD,Axonal
Pain,weakness &sensory loss
Childhood
Parsonage-Turner Sx
Multifocal sensory
neuropathy(Wartenberg’s migrant
neuropathy)
Hypotelorism,Epicanthal fold,Cleft
palate,Syndactylly,Micrognathia & Facial
asymmetry
EDX
Distal latencies and conduction
velocities of the CMAP and SNAPs
are relatively preserved
 Fib,Psw,Decreased recruitment&
Polyphasic……………………………..

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
LAB
CSF normal
 Increased IgA

EDX
Normal or only mildly reduced CMAPs
and SNAPs amplitudes
 Near nerve recordings:reduced amp
of A delta and C-fibers
 Abnormal QST
 SSR:absent

HSAN 2









Infancy
AR
Severe loss of sensation to all
modalities(particularly touch pressure/vibration)
Whitlow
Lancinating pains:neg
Romberg
Impaired sweating,bladder dysfunction
&impotence
Postural hypotension:neg
Scoliosis
PATHOLOGY
 Virtual
absence of large
myelinated fibers
 Mild loss of small myelinated and
unmyelinated fibers
EDX
Absent SNAP
 Normal or only mildly reduced CMAPs
amp
 Abnormal QST(particularly vibration)
 EMG:Reduced recruitment,long
duration
polyphasic,Fib&Psw

HSAN 3





Riley-day Sx;Familial 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







Seizures
Intelligence is normal
Impairment in
position,vibration,pain,taste & corneal
reflexes
Tonic pupils
Postural hypotension
MMT: nl but DTR:absent
Short stature & scoliosis
PATHOLOGY
 Marked
reduction of small
myelinated and unmyelinated
fibers and to a lesser extent
large myelinated fibers
EDX
Decreased SNAP amp,mild slowing
of CMAP velocities
 Abnormal QST
 Normal SSR

HSAN 4
AR
 ANHYDROSIS
 SELF MUTILATION
 POSTURAL HYPOTENSIN
 PAIN & TEMPERATURE
 VIBRATORY :LESS AFFECTED

EDX
There can be slight reductions in
CMAPs & SNAPs amplitudes and
conduction velocities,but not as
severe as that seen in HSAN2 or
HSAN3……………
 SSR:unobtainable

HSAN 5

Fail to recognize or react to PAINFUL
stimuli despite having normal
sensitivity to other sensory
modalities…..
EDX
NCS,EMG,SSR,QST&SEP:normal
 WITHDRAWAL TO PAIN:abnormal

FAP
AXONAL
 Transthyretin,apolipoprotein A1 &gelsolin
 Small myelinated & unmyelinated fibers
 SNAP:Diminished in amp &normal or
mildly prolonged in latency
 CMAP:Motor are less severely affected
 CTS
 Fib & Psw,PPP,Long duration &Large Amp
 QST:Cold & heat …..No vibration

PORTUGUESE







Numbness,Pain,Temperature &
Lancinating pains in feet
CTS:neg
Impotence,constipation,persistent
diarrhea
Cranial neuropathy
Liver,kidney,heart &cornea
Arrhytmia
Die:50 years
INDIANA/SWISS
Nephropathy & cardiomyopathy:neg
 Impotence
 CTS
 Mild sensorimotor polyneuropathy
 Survival:Long

VAN ALLEN
Numbness and painfull dysesthesias
 Muscle weakness and atrophy
 Diarrhea,Constipation &
Gastroparesis
 Hypertension & renal failure

FINNISH
Mild generalized sensorimotor
polyneuropathy
 Corneal dystrophy
 Cranial neuropathy

LIPID METABOLISM
DISORDERS







METACHROMATIC LEUKODYSTROPHY
KRABBE’S DISEASE
FABRY’S DISEASE
ADRENOLEUKODYSTROPHY
REFSUM’S DISEASE
TANGIER DISEASE
CEREBROTENDINOUS XANTHOMATOSIS
MLD
LATE INFANTILE(1-4)
 JUVENILE(3-21)
 ADULT ONSET(after 21)
 AR

 Late
infantile: Difficulty
ambulating,muscle cramps,limb
pain,weakness,hypotonia,hyporeflexi
a.slurred
speech,seizure,quadriparetic,spastic
&blind

Adult –onset: Progressive
psychosis,dementia,spasticity,visual
impairment,urinary
incontinence,cerebellar dysfunction
& extrapyramidal signs…….
LAB
Csf protein: elevated
 Arylsulfatase
A(PROSAPOSIN):decreased

EDX
SNAPs:mildly to moderately
prolonged latencies,markedly
reduced in amplitude.
 CMAPs: mildly to moderately
prolonged latencies,mildly to
moderately reduced in amplitude.
 Conduction block & dispersion:neg

TREATMENT

BONE MARROW
TRANSPLANTATION
KRABBE’S
Early infantile
 Late infantile or juvenile
 Adult
 AR


Early infantile:
First 6 months
Hypersensitivity,recurrent
vomiting,seizure,MR,spasticity,deaf,
blind….
death:2 years
LAB
B-Galactosidase activity:decreased
 CSF Protein:50% increased

EDX
SNAPs:mildly to moderately
prolonged latencies,markedly
reduced in amplitude.
 CMAPs: mildly to moderately
prolonged latencies,mildly to
moderately reduced in amplitude.
 Conduction block & dispersion:neg

TREATMENT

BONE MARROW
TRANSPLANTATION
FABRY’S DISEASE







Angiokeratoma corporis diffusum
X-linked
Burning & stabbing pain
Angiokeratoma:umbilicus,scrotum,inguinal
&perineum
Angiectasias:oral mucosa,conjunctiva&
nailbed
Atherosclerosis:HTN,RF,CVD,Stroke
Death:Fifth decade
LAB
A-Galactosidase activity:decreased
 Accumulation of CERAMIDE

EDX & EMG
NORMAL
ALD/AMN
X-linked
 Young male
 Progressive dementia,Seizure,
Spasticity,
Blindness & hearing loss
90 % adrenal insufficiency

LAB
VLCFA : increased
 C22(docosanoic-erusic) : decreased

EDX
ALD:Normal
 AMN:associated with a superimposed
sensorimotor polyneuropathy
 SEP:abnormal
 VEP:normal
 Conduction block :neg

EMG
Increased IA, Psw, Fib
&Fasciculation : neg
 Alternation in voluntary MUAP
characteristics
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TREATMENT

Diets low in VLCFAs and
supplemented with
LORENZO’ oil (erucic and olecic
acids)

BONE MARROW TRANSPLANTATION
REFSUM’S DISEASE
AR
 Phytanic acid
1-Peripheral neuropathy
2-Elevated CSF protein
3-Cerebellar dysfunction
4-Retinitis pigmentosa
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Cardiac
Hearing loss
Anosmia
Ichthyosis
Bilateral drop foot
Paresthesia & pain
Vibration &position
DTR:Reduced
Hypertrophic nerve
LAB
Phytanic acid :elevated
 CSF protein : elevated

EDX&EMG
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………..

TREATMENT
Fishoils, dairy products, ruminant
fats &plasma exchange :elimination
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

LAB
 Serum
HDL :reduced
 Serum triacylglycerol : elevated
EDX & EMG
1-MILD
 2-NORMAL
 3-SEVERE,motor NCVs are reduced
by about 50% in upper and 20-30%
in lower limbs…………Increased
IA,Fib,Psw,PPP,Large Amp & Long
duration

CHOLESTANOLOSIS
Progressive dementia
 Spasticity
 Ataxia
 Mild sensory neuropathy
 Cataracts
 Xanthomas on tendons and skin .
 Premature atherosclerosis


Serum Cholestanol :increased
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……..

TREATMENT
 Chenodeoxycholic
acid
HEREDITARY ATAXIAS
FRIEDREICH’S ATAXIA
 VITAMIN E DEFICIENCY
 ABETALIPOPROTEINEMIA
 ATAXIA-TELANGIECTASIA
 SPINOCEREBELLAR ATAXIAS
 MARINESCO-SJOGREN SYNDROME

FRIEDREICH
AR
 Gait ataxia
 Clumsiness
 Tripping
 Scoliosis
 Tremor
 Cardiac symptoms
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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
LAB
MRI :Cervical spinal cord may reveal
atrophy
 ECG :low voltage QRS & deep Q
waves
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EDX
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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
EMG
Normal
 Fib & Psw

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,ophthalmoplegia
and retinal pigmentation:Negative

LAB
Normal LDL,HDL,TG,VLDL & Vit A,D,K
 Reduced Vit E

EDX & EMG
Reduced or absent SNAPs
 SEP: reduced(central)
 Neurogenic type MUAP parameters
 A rare patient myopathic MUAP
parameters

TREATMENT
Vit E 400 mg twice a day and is
increased up to 100 mg/kg/day
 Injection of Vit E 100mg/week

ABETALIPOPROTEINEMIA
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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,romber
g,ophthalmoplegia,reduced touch and pain
Pes cavus,hammer toes,tremor
LAB
Acanthocyte
 Reduced LDL,VLDL,HDL,TG,Vit
A,D,K

EDX
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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
TREATMENT

REPLACEMENT OF FAT
SOLUBLE VITAMINS