Acquired neuropathies

Chapter 23 _ part 1
Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP)
• Most common cause of acute generalized weakness
• Annual incidence:1-4/100,000 general population
• Slight male predominance
• Peak age of onset in the 3-4 decade of life
• 60-70% of patient note some form of Acute illness 1-3 wk before
onset of neurologic symptom (C.j 32%-CMV 13%-EBV 10%-
M.pnumonia 5%)
 Clinical features
• most patient initially note Tingling and numbness in distal of lower
limb and shortly there after in the distal upper limb
• Aching, prickly, or burning neuritic pain sensations in the back and
limbs in 50% of patients
• Large fiber modality (vibration ,touch , position)more severely
affected than small fiber modality (pain, temperature)
• progressive weakness usually ensues and is the major complaint of
most patients
• Onset usually begins in lower limbs and ascends
• Mild facial weakness in 50% of patient during course of illness.
• Occasionally a descending presentation with onset in the cranial
nerve and progress to the arm and leg
• External urethral and anal sphincter usually spared .although may be
involved in severe disease.
• Autonomic instability is common in AIDP
• The disease usually progresses over the course of 2-4 wk.
• Progression of symptom and sign for over 8 wk excludes GBS and
suggest the diagnosis of CIDP.
• Respiratory failure in 30%
• Neck flexion ,extension and shoulder abduction correlate well with
diaphragmatic strength and thus important to follow closely.
• Most patients gradually recover satisfactory function over several
months
• The mortality rate about 5%
• Patient die result of RDS ,aspiration Pneumonia ,pulmonary embolism
,arrhythmia and sepsis
• Risk factor for poor prognosis (slower and incomplete recovery):
1. age greater than 50-60years,
2. abrupt onset of profound weakness,
3. need for mechanical ventilation,
4. distal CMAP Ampl less than 10-20% of normal.
 Lab feature
• Elevated CSF protein accompanied by no or only a few mononuclear
cell is the characteristic laboratory findings and evident in over 80% of
patient after 2 wk.
• In patient with CSF pleocytosis of more than 10 Lymphocytes (cell
count >50), AIDP like neuropathies related to lyme disease, recent HIV
infection, sarcoidosis need to be considered.
• Elevated liver function test evident in many patient. In such cases
important to evaluate for viral hepatitis (A,B,C),EBV,CMV
• Antiganglioside Ab particularly anti GM1 correlates well with c.j
infection.
 Motor NCS
• Electrophysiologic hallmark of demyelination:
1. prolonged distal latency
2. Slow NCV
3. Temporal dispersion
4. Conduction block
5. Prolonged F-wave latency
• A hallmark is the asymmetric and multifocal character of the EDX
abnormality
• Always perform F-wave study in both upper and lower limb in patients
suspected of having AIDP because of early predilection for the
proximal nerve segments and spinal roots.
• 5-7day after acute axonal loss, it is impossible to distinguish between
axonal loss and conduction block
• Examination of the phrenic and facial nerve may be interest in AIDP.
• Facial and supraorbital nerve evaluated with direct facial nerve
stimulation and blink reflex.
• There does not appear to be a correlation between the nerve
conduction velocity or distal motor latency and clinical severity of the
neuropathy
• Distal CMAP Ampl less than 10-20% normal are associated with a
poorer prognosis.
• Maximum degree of motor conduction abnormality occur within 3-8
wk.
 S-NCS
• Upper limb SNAP particularly median nerve affected more severely
and earlier than sural SNAPs.
• It can take 4-6wk for SNAP abnormalities to peak.
• The parameter most adversely affected is SNAP Amp.
• With a pure sensory presentation , other Disorders (acute sensory
neuronopathy or ganglionopathy) must be ruled out.
 Needle EMG
• EMG in patients with AIDP is primarily adjunctive to explore the
possibility of other disease entities.
• Earliest finding a reduced number of normal-appearing MUAP firing at
rapid rate.
• Fib and psw may first be seen between wk 2-4,peaking at about 6-
15wk;maximize earlier in proximal muscle than in distal muscle.
• Myokymia can be detected especially in facial muscles.
 Autonomic testing
• Autonomic instability can be assessed by measuring the EKG R-R
interval variation.
• SSR (doesnt have contribute to diagnosis and prognosis)
 Plasma Exchange
• reduced the time necessary to improve one clinical grade, time to
walk unaided, time on a ventilator after 1-6 month.
• 200-250 ml/kg over 10-14 day.
• The removed plasma is replaced with albumin.
 IVIG
• Replaced PE in many centers as the treatment choice for AIDP
because it is more widely available and easer to use than PE.
• Dose of IVIG is 2 gr/kg infused over 2-5 days .
• Treatment should begin preferably within first 7-10day of symptoms .
• Improvement often not immediate .mean time to improvement
ranged from 6-27 day
• Unlike CIDP, corticosteroid do not appear beneficial in the treatment
of AIDP; in fact ,some patient have done worse.
 AIDP in children
• The clinical , lab and EDX findings similar to adult
• 75% have an antecedent infection
• Major presenting complaint is pain
• Most children with AIDP have a satisfactory recovery , even those
with significant reduction in CMAP Amp.
Acute motor-sensory axonal neuropathy
(AMSAN)
• Clinically and at least by initial EDX ,patient with AMSAN are
indistinguishable from AIDP.
• Patient with AMSAN develop rapidly progressive and severe
generalized weakness over only a few day as opposed to a couple of
wk in most patient with AIDP.
• Ophtalmoplegia and difficulty in swallowing may be noted .
• Muscle of facial expression are profoundly weak.
• Most patient require ventilator support.
• Sensation to all modality is reduced.
• Complete areflexia is usually evident.
• Prognosis of AMSAN much poorer than AIDP ;most patient have a
slow or incomplete recovery.
• Some authorities suggest that C.j infection and GM1 Ab are more
commonly associated with axonal form of GBS.
• Histologic evaluation performed early in the course of disorder is the
only way to differentiate axonal GBS from pseudoaxonal GBS.
• Markedly diminish Amp or absent CMAP within 7-10 day of onset.
• SNAP Amp are profoundly reduced or absent.
• Markedly abnormal reduction in recruitment .
• Abundant fib and psw detected in most muscle especially distal limb.
Acute motor axonal neuropathy
(AMAN) (chinese paralytic
syndrome)
• In northern china, AMAN is the most common variant of GBS.
• Serologic evidence of recent C.j infection detected in 67-92 % of patient.
• As in AMSAN , there is an abrupt onset of generalized weakness.the distal
muscle often are affected more severely than proximal limb muscle.
• Sensory sign and symptom are absent.
• DTR may be normal or absent.
• Patient generally make a good recovery within one years ,but residual distal
limb weakness is common.
• Mortality rate is less than 5%
• The absence of prominent CSF pleocytosis help distinguish AMAN
from poliomyelitis , which it can mimic.

• Characteristic NCS feature in AMAN is low Amp or unobtainable

CMAP with normal SNAP.
• When CMAP are obtained, DML and NCV are normal.
• F-wave usually unobtainable but , when present, show normal
latency.
Miller – fisher syndrome
• M/F=2/1 , mean age of onset in the early 40s.
• An antecedent infection in 2/3 of cases.
• Diplopia is the most common initial complaint.
• Areflexia is the most common sign(evident in over 82%)
• Whether the ataxia is secondary to sensory dysfunction or a
cerebellar lesion is controversial. most patient have sensory ataxia.
• Ptosis usually accompanies the ophtalmoparesis, but pupillary
involvement is uncommon.
• Nearly 50% of patient describe paresthesia in face and distal limbs.
• anti GQ1b demonstrate in most patient.
• Most prominent EDX abnormality in MFS is reduced SNAP Amp
• CMAP in the arm and legs are usually normal but ,mild to moderate
reduction in facial CMAP demonstrate in over 50% of patient.
• Blink reflex may be abnormal.
• There is generally no abnormal spontaneous activity in limb or
paraspinal muscles but , fib may be detected in facial muscle.
Chronic inflammatory
demyelinating
polyneuropathy(CIDP)
• An immune-mediated neuropathy characterized by a relapsing or
progressive course.
• Slight male predominance
• Peak age of onset in the 4-6 decade of life
• Sign and symptom of neuropathy must be progressive for at least 2
month, which distinguishes CIDP from GBS or AIDP.
• Four typical clinical course of progression
1. Chronic monophasic(15%)
2. Chronic relapsing(fluctuation of weakness or improvement over week or
months)34%
3. Stepwise progression 34%
4. Steady progression15%

• Relapsing form has an earlier age of onset ,usually in twenties

• Relapses have associated with pregnancy
• Most patient present with relapsing or progressive symmetric
proximal and distal weakness of the arms and legs.
• Early in the course of illness ,only distal weakness may be observed.
however . If weakness remain distal , other diagnoses need to
considered : hereditary demyelinating neuropathy ,Para protein
related neuropathy , distal acquired demyelinating neuropathy.
• Although most patient (80%)have both motor and sensory
involvement , a few patient may have pure motor (10%) or pure
sensory(5-10%)sign and symptom.
• Sensory abnormality in 68-84%of patient ,primarily affecting large
fiber modality(vibration ,touch)
• Sensory ataxia, positive Romberg sign ,wide base gait may be found.
• Chronic sensory demyelinating neuropathy: only sensory sign and
symptom
• Most patient with a demyelinating neuropathy who have mainly
sensory sign and symptom with normal or only mild distal weakness
have an IgM monoclonal gammopathy .
• Whenever a pure sensory neuropathy is present ,consideration should
be given to other diseases well, such as sjogren syndrome or
paraneoplastic neuronopathy, both associated with sensory
ganglionitis.
• Most patient have areflexia or hyporeflexia
• Some patient develop dropped head syndrome secondary to neck
extensor weakness
• Cranial nerve involvement occasionally occurs but is usually mild and not
the presenting feature
• Autonomic dysfunction (incontinency , impotency) less common.
• Respiratory insufficiency reported in 8-15 % of patient.
• 3-5% of patient have evidence of CNS demyelination clinically .
• Patient may developed a myelopathy due to compression of spinal cord
by hypertrophied nerve roots.
• CIDP like neuropathy :
1. HIV infection
2. Hepatitis
3. Inflammatory bowel disease
4. DM
5. SLE
6. Monoclonal gamopathy of uncertain significance (MGUS)
7. Lymphoma
8. Bone marrow and solid organ transplantation
9. Paraneoplastic complication of pancreas and colon carcinoma, SCLC , melanoma,
cholangiocarcinoma
10. Toxic induced neuropathy (procainamide, cyclosporine and tacrolimus)
 LAB feature
• An elevated CSF protein is found in 80-95% of patient.
• Cell count is usually normal.
• WBC CSF should be <10/mm3
• Elevated CSF cell count should lead to consideration of HIV infection,
lyme, leukemic infiltration of nerve root
• Oligoclonal band demonstrated in the CSF in 65%
 M-NCV
• CMAP parameter is the most useful diagnostic test
• The best studied motor parameter is NCV
• Increased CMAP Amp , Increased NCV ,decreased conduction block,
seen in association with improvement in strength
 S-NCV
• >80% low Amp or unobtainable SNAP.
• A characteristic finding is abnormal median or ulnar SNAP when the
sural SNAP are normal.
• A similar discrepancy between the upper and lower limb SNAP seen in
sensory ganglinopathy , but the EDX abnormality in such cases are
axonal , not demyelinating.
 EMG
• Widespread fib and PSW are commonly detected in intrinsic foot and
hand muscle and more proximal muscle.
• The degree of fib and PSW is high during an exacerbation with a
reduction during clinical remission.
 Treatment
• Treatment of choice depend on other medical problem(avoid IVIG in
renal deficiency) and accessibility.
• Corticosteroid
• prednisone 1/5mg/kg per day for 2-4wk or intermittent high-dose IV
• Functional muscle recovery is first noted in the proximal limb muscle
• Ca(1000-1500 mg/day) , Vit D (400-800 U/day)
• BMD every 6 months
• PE: unfortunately response to PE is transient, usually lasting only a
few wk

• PE used usually in combination with prednisone, in patient with

severe generalized weakness

• PE used alone in:

 Patient in whom we wish to avoid long term prednisone(poorly controlled DM or HIV
infection)
 Whom IVIG is contraindicated (renal insufficiency)
• IVIG: for many authorities , IVIG has become the treatment of choice
in CIDP.
• A IgA level should be assayed before administering IVIG . patient who
are IgA deficiency due to IgE anti IgA antibody or a congenital
deficiency may develop anaphylactic reaction to IVIG.
• Azathioprine
• Cyclophosphamide
• Cyclosporine: decreased relapse rate in patient with the relapsing
form of CIDP and improved strength and function in those with the
chronic progressive form
• Interferon
 prognosis
• More than 90% improve with treatment
• At least 50% relapse within the next 4 years
• Patients treated early are more likely to respond
• Poor long term prognosis:
• progressive course
• CNS involvement
• axonal loss
 CIDP in children
• Commonly present with difficulty in ambulating
• Response to standard form of therapy
• CIDP may be confused with a hereditary neuropathy (CMT)
 Family history
 EDX :CMT associated with symmetric and diffuse involvement of peripheral
neuropathy.
 Thus temporal dispersion and conduction block are not seen
 there is usually uniform slowing of conduction velocity as well as symmetric
involvement of proximal and distal segment.
 In contrast , the multifocal nature of CIDP result in nonuniform slowing of conduction
velocity, temporal dispersion and conduction block.
 Para protein – related
neuropathies (monoclonal
gammopathy) and CIDP
• IgG is the most common paraprotein in the general population

• IgM is the most common monoclonal protein in patient with

peripheral neuropathy
• IgM neuropathy:
• IgM-MGUS neuropathy are typically demyelinating but can be axonal.
• The IgM neuropathy seem to be less responsive to immonotheraphy than IgG
and IgA neuropathy.
• At least 50% of IgM group have antibody against myelin – associated
glycoprotein(MAG)
• Sensory ataxia and tremor were common.
• IgM neuropathy experience more disability related to sensory loss. weakness
was only a minor feature.
• In IgM neuropathy ,NCV more slowing and prolongation of distal latency
compared with IgG and IgA.
• Patient with MGUS-CIDP:
• had a more indolent course
• more frequent sensory disturbance with ataxia
• less severe weakness than patient with idiopathic CIDP
• Idiopathic CIDP had a significant improvemen trate(88%) than MGUS
CIDP(50%)
 Distal acquired demyelinating
symmetric neuropathy (DADS)
• Mild symmetric distal weakness and sensory loss
• Monoclonal protein detected in 75% cases(IgM) and most anti MAG
positive
• No significant EDX difference between IgM-DADS and idiopathic DADS
• Demyelinating features excluding CB
• Patient with IgM-DADS neuropathy demonstrated a poor response to
immunotherapy , whereas patient with idiopathic DADS and CIDP
usually improved with therapy.
 Multifocal motor neuropathy
(MMN) (multifocal demyelinating
neuropathy with conduction block)
• An immune mediate demyelinating neuropathy characterized
clinically by asymmetric weakness and atrophy, typically in the
distribution of individual peripheral nerve.
• MMN is commonly misdiagnosed as ALS ;
• however muscle involvement is in the distribution of individual peripheral
nerves, not spinal roots
• Bulbar muscle involvement is uncommon
• Incidence of MMN much less than ALS(1/50)
• M/F=3/1
• Age at onset of symptom usually early in fifth decade of life.
• Typically, diagnosis is delayed by several years because of the slow ,insidious
progression and misdiagnosis of the disorder.
• Patient develop focal muscle weakness accompanied by cramps and
fasciculation, usually beginning in the distal Upper limbs.
• Patient generally present with intrinsic hand weakness ,wrist drop or foot drop
• Sensory exam should be normal.
• DTR variable in unaffected limb, whereas depress or absent in weak muscle
• In contrast to CIDP and MADSAM, CSF protein is usually normal in
patients with MMN.
• Twenty to 80% of MMN have detectable IgM antibody direct against
gangliosides ,mainly GM1
• A high titers the antibodies appear to be rather specific for MMN ,but
the sensitivity of the testis too low.
• The most sensitive and specific test is the NCS.
 EDX
• There is often evidence of conduction block in multiple upper and
lower limb nerves.
• conduction block is not located at the expected common nerve
entrapment sites, but in the mid-forearm or leg, upper arm, across
brachial plexus, or nerve root region.
• conduction block may be present not only in multiple different nerves
but also at several location along the course of the same nerve.
• A reduction in distal CMAP AMPL can be seen in chronic lesions due
to secondary axonal loss.
• Although motor conduction block has been considered the EDX
hallmark of MMN, other features of demyelination:(prolonged distal
latency, temporal dispersion ,slow conduction velocity and prolonged
or absent F-waves) are typically present on motor NCS.
• Diagnosis does not require conduction block if other features of
demyelination are present.
• SNAP parameters is normal.
 Needle EMG
• Unaffected muscles should demonstrate no abnormalities.
• In weak muscle: reduced recruitment , fib and PSW, fasciculation
potential and rarely myokymic discharge.
• These abnormalities improve after treatment.
 Treatment
• In contrast to CIDP and MADSAM neuropathy ,few patients(<3%)With
MMN improve with high doses of corticosteroids or PE.
• Intravenous cyclophosphamide was the first immunosuppressive agent
demonstrated to be effective in MMN ,over 70% of reported patients
improved clinically after treatment.
• IVIG is now the treatment of choice in MMN

• do not respond as well to treatment:

• later age of onset
• patient who have significant muscle atrophy.
 Multifocal acquired
demyelinating sensory and motor
neuropathy (MADSAM)
• Lewis summer syndrome
• The sign and symptom of MADSAM neuropathy are essentially those
of mononeuropathy multiplex.
• M/F=2/1
• Mean age of onset in the early 50s.
• Onset is usually insidious and slowly progressive with initial
involvement usually in the upper limb.
• Motor and sensory involvement to peripheral nerve distribution
rather than generalized stocking and glove pattern
• CSF protein elevated in 60-80% of patient.
• Anti GM1 Ab (-)
• As with CIDP and MMN ,NCS demonstrate conduction block, temporal
dispersion, prolonged distal latency and F-wave and slow NCV in one or
more motor nerves.
• SNAP are absent or small AMP
• In contrast to MMN but similar to CIDP , most patient with MADSAM
improvement with steroid
• Most patient improve with IVIG.
Idiopathic sensory neuronopathy /
ganglionopathy
• Believed to be caused by an autoimmune attack directed against the
dorsal root ganglia.

• DDX of sensory neuronopathy includes:

1. paraneoplastic syndrome, which is typically associated with anti-HU antibody
2. Sjogrens syndrome
3. Medication or toxins
4. Infection agents
• A slight female predominance , mean age of onset is 49 Years
• Numbness can begin in face , trunk or limbs.
• Symptoms begin asymmetrically and in the upper limb in nearly one-
half of patients.
• Because of the prominent large fiber sensory loss, patient describe
clumsiness of the hands and gait instability.
• Marked reduction in vibration and position sense.
• The deficit more impaired in upper limb than lower limbs, unlike
length-dependent axonal neuropathy.
• Pain and temperature are less affected.
• Manual muscle testing usually normal
• Sensory ataxia resulting from the loss of proprioception
• Positive Romberg sign
• Idiopathic sensory neuronopathy is a diagnosis of exclusion
• MRI reveal gadolinium enhancement of the posterior spinal roots,
increased signal abnormality on T2 image in the posterior columns.
• Most prominent EDX abnormality is absent or low AMPL SNAP.
• Sensory distal latency and NCV normal or mildly abnormal.
• DML and MNCV and F-waves usually normal.
• H-reflex and Blink reflex typically absent.
• Normal jaw reflex
• Needle EMG is usually normal.
 Treatment
• PE,IVIG and corticosteroid
• A few patient may improved spontaneously
• There is no indication to treat a patient with a stable deficit
Thanks for your attention