Acquired Acquired neuropathiesneuropathies

chap:23chap:23

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

Shiraz Medical school

GBSGBS

In one report earliest feature:In one report earliest feature:

proximal nerve edema+ degeneration proximal nerve edema+ degeneration

myelin sheath within first week of illnessmyelin sheath within first week of illness In other study prominent perivascularIn other study prominent perivascular

inflammation in spinal inflammation in spinal root ,ganglia ,cranialroot ,ganglia ,cranial

nerve and randomly along peripheral nerve and randomly along peripheral

nervenerve

Acute inflammatory demyelinating Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)polyradiculoneuropathy (AIDP)

Most common cause of acute generalized Most common cause of acute generalized weaknessweakness

Annual incidence:1-4/100000 general Annual incidence:1-4/100000 general populationpopulation

Slight male predominanceSlight male predominance Peak age of onset in the 3-4 decade of lifePeak age of onset in the 3-4 decade of life 60-70% of patient note some form of Acute 60-70% of patient note some form of Acute

illness 1-3 wk before onset of neurologic illness 1-3 wk before onset of neurologic symptom (C.j 32%-CMV 13%-EBV 10%- symptom (C.j 32%-CMV 13%-EBV 10%- M.pnumonia 5%)M.pnumonia 5%)

most patient initially note Tingling and numbness inmost patient initially note Tingling and numbness in distal of lower limb and shortly thereafter in the distal distal of lower limb and shortly thereafter in the distal upper limbupper limb

Large fiber modality (vibration ,touch , position) Large fiber modality (vibration ,touch , position) more severly affected than small fiber modality (painmore severly affected than small fiber modality (pain, temperature), temperature)

A few patient present only with sensory symptom A few patient present only with sensory symptom but EDX sign of motor involvement are typicalbut EDX sign of motor involvement are typical

Major complaint of most patient : progressive Major complaint of most patient : progressive weakness weakness

Mild facial weakness in 50%of patient Mild facial weakness in 50%of patient during during

course of illness.course of illness. Occasionally a descending presentation Occasionally a descending presentation

withwith

onset in the cranial nerve and progress to onset in the cranial nerve and progress to the the

arm and legarm and leg External urethral and anal sphincter usuallyExternal urethral and anal sphincter usually

spared .although may be involved in severespared .although may be involved in severe

disease.disease.

Autonomic instability is common in AIDPAutonomic instability is common in AIDP

Neonatal GBS : in infant of a mother with GBS due to Ab Neonatal GBS : in infant of a mother with GBS due to Ab crossing the placenta.crossing the placenta.

The disease usually progresses over the course of 2-4 wk.The disease usually progresses over the course of 2-4 wk.

Progression of symptom and sign for over 8 wk excludes Progression of symptom and sign for over 8 wk excludes GBS and suggest the diagnosis of CIDP.GBS and suggest the diagnosis of CIDP.

Respiratory failure in 30% Respiratory failure in 30%

Neck flexion ,extension and shoulder abduction correlate Neck flexion ,extension and shoulder abduction correlate well well

with diaphragmatic strenght and thus important to follow with diaphragmatic strenght and thus important to follow closely.closely.

Most patients gradually recover Most patients gradually recover satisfactorysatisfactory

function over several monthsfunction over several months

The mortality rate about 5%The mortality rate about 5%

Patient die result of RDS ,aspiration Patient die result of RDS ,aspiration

Pneumonia ,pulmonary Pneumonia ,pulmonary embolism ,arrhythmia and sepsisembolism ,arrhythmia and sepsis

Risk factor for poor prognosis Risk factor for poor prognosis (slower and incomplete recovery): (slower and incomplete recovery):

1.1. age greater than 50-60years,age greater than 50-60years,

2.2. abrupt onset of profound abrupt onset of profound weakness,weakness,

3.3. need for mechanical ventilation,need for mechanical ventilation,

4.4. distal CMAP Ampl less than 10-distal CMAP Ampl less than 10-20% of normal.20% of normal.

Lab featureLab feature Elevated CSF protein accompanied by no or only a fewElevated CSF protein accompanied by no or only a few mononuclear cell is the characteristic laboratory findings and mononuclear cell is the characteristic laboratory findings and evident in over 80% of patient after 2 wk.evident in over 80% of patient after 2 wk.

In patient with CSF pleocytosis of more than 10 In patient with CSF pleocytosis of more than 10 Lymphocytes (cell count >50), AIDP like neuropathies related Lymphocytes (cell count >50), AIDP like neuropathies related to lyme disease, recent HIV infection, sarcoidosis need to beto lyme disease, recent HIV infection, sarcoidosis need to be considered.considered.

Elevated liver function test evident in many patient. In suchElevated liver function test evident in many patient. In such cases important to evaluate for viral hepatitis (A,B,C),EBV, cases important to evaluate for viral hepatitis (A,B,C),EBV, CMVCMV Antiganglioside Ab particularly anti GM1 correlates wellAntiganglioside Ab particularly anti GM1 correlates well with c.j infection.with c.j infection.

histopathologyhistopathology

The entire peripheral motor and sensory The entire peripheral motor and sensory

nervous system including cranial nerve can benervous system including cranial nerve can be

involved from the most proximal aspect of theinvolved from the most proximal aspect of the

ventral and dorsal root to the terminal region of ventral and dorsal root to the terminal region of

the intramuscular and sensory nerve fibers.the intramuscular and sensory nerve fibers. An initial preference for the nerve root An initial preference for the nerve root

region ,areas where peripheral nerve commonlyregion ,areas where peripheral nerve commonly

entrapped and the motor nerve terminals.entrapped and the motor nerve terminals.

Motor NCSMotor NCS

Electrophysiologic hallmark of Electrophysiologic hallmark of demyelination:demyelination:

1.1. prolonged distal latencyprolonged distal latency

2.2. Slow NCVSlow NCV

3.3. Temporal dispersionTemporal dispersion

4.4. Conduction blockConduction block

5.5. Prolonged F-wave latencyProlonged F-wave latency

A hallmark is the asymmetric and multifocalA hallmark is the asymmetric and multifocal

character of the EDX abnormalitycharacter of the EDX abnormality Always perform F-wave study in both upperAlways perform F-wave study in both upper

and lower limb in patients suspected of havingand lower limb in patients suspected of having

AIDP because of early predilection for theAIDP because of early predilection for the

proximal nerve segments and spinal roots.proximal nerve segments and spinal roots.

In patient with rapid recovery ,particularly after In patient with rapid recovery ,particularly after PE or IVIG the improved clinical status probably PE or IVIG the improved clinical status probably result from coduction block resolution rather result from coduction block resolution rather than remyelination or regeneration of the axons.than remyelination or regeneration of the axons.

Two important caveats about conduction block:Two important caveats about conduction block:1.1. First, 5-7day after acute axonal loss, it is First, 5-7day after acute axonal loss, it is

impossible to distinguish between axonal loss impossible to distinguish between axonal loss and conduction blockand conduction block

2.2. Second,in acute disease small reduction in CMAP Second,in acute disease small reduction in CMAP Ampl may be result from conduction block; however Ampl may be result from conduction block; however

,in,in more chronic disease or later in acute disease more chronic disease or later in acute disease

alterationalterationin conduction velocity may result in in conduction velocity may result in

pseudocoduction pseudocoduction block.block.

Examination of the pherenic and facial Examination of the pherenic and facial nervenerve

may be interest in AIDP.may be interest in AIDP. Facial and supraorbital nerve evaluated Facial and supraorbital nerve evaluated

with with

direct facial nerve stimulation and blink direct facial nerve stimulation and blink reflex.reflex.

Maximum degree of motor conduction Maximum degree of motor conduction

abnormality occure within 3-8 wk.abnormality occure within 3-8 wk.

Early abnormalities of distal CMAP Ampl Early abnormalities of distal CMAP Ampl and latency and F-wave reflect the early and latency and F-wave reflect the early predilection for involvement of the predilection for involvement of the proximal spinal roots and distal motor proximal spinal roots and distal motor nerve terminals in AIDP.nerve terminals in AIDP.

There does not appear to be a There does not appear to be a correlationcorrelation

between the nerve conduction velocity between the nerve conduction velocity oror

distal motor latency and clinical severity distal motor latency and clinical severity ofof

the neuropathy ,the neuropathy ,although distal CMAPalthough distal CMAP

Ampl less than 10-20% normal are Ampl less than 10-20% normal are

associated with a poorer prognosisassociated with a poorer prognosis..

S-NCSS-NCS

Upper limb SNAP particularly median Upper limb SNAP particularly median nervenerve

affected more severly and earlier than sural affected more severly and earlier than sural

SNAPs. SNAPs. Unlike most axonopathies , in which theUnlike most axonopathies , in which the

earliest and most severe abnormalities earliest and most severe abnormalities

involve the distal lower limb nerve (suralinvolve the distal lower limb nerve (sural

SNAP), demyelinating disease are just asSNAP), demyelinating disease are just as

likely to affect the median and ulnar SNAPs.likely to affect the median and ulnar SNAPs.

It can take 4-6wk for SNAP abnormalities It can take 4-6wk for SNAP abnormalities to peak.to peak.

The parameter most adversely affected isThe parameter most adversely affected is SNAP Ampl.SNAP Ampl. Reduced SNAP Ampl can result from Reduced SNAP Ampl can result from secondary axonal secondary axonal

degeneration ,conductiondegeneration ,conduction block or phase cancelation.block or phase cancelation. With a pure sensory presentation , other With a pure sensory presentation , other Disorders (acute sensory neuronopathy or Disorders (acute sensory neuronopathy or ganglionopathy) must be ruled out.ganglionopathy) must be ruled out.

Needle EMGNeedle EMG EMG in patients with AIDP is primarily EMG in patients with AIDP is primarily

adjunctive to explore the possibility of other adjunctive to explore the possibility of other

disease entities.disease entities. Earliest finding a reduced number of normal-Earliest finding a reduced number of normal-

appearing MUAP firing at rapid rate.appearing MUAP firing at rapid rate. Fib and psw may first be seen between wk 2-Fib and psw may first be seen between wk 2-

4,peaking at about 6-15wk;maximize earlier in4,peaking at about 6-15wk;maximize earlier in

proximal muscle than in distal muscle.proximal muscle than in distal muscle. Myokymia can be detected especially in facialMyokymia can be detected especially in facial

muscles. muscles.

Autonomic testingAutonomic testing

Autonomic instability can be Autonomic instability can be assessed by measuring the assessed by measuring the EKG R-R EKG R-R intervalinterval variation. variation.

A alternative method is A alternative method is SSR.SSR.

Plasma ExchangePlasma Exchange

reduced the time necessary to improve onereduced the time necessary to improve one

clinical grade, time to walk unaided, time on clinical grade, time to walk unaided, time on a a

ventilator and percentage of patient ventilator and percentage of patient improvingimproving

after 1-6 month.after 1-6 month. Total amount of exchanged is Total amount of exchanged is

200-250ml/kg 200-250ml/kg

over 10-14 day.over 10-14 day. The removed plasma is replaced with The removed plasma is replaced with

albumin.albumin.

IVIGIVIG

Replaced PE in many centers as the Replaced PE in many centers as the

treatment choice for AIDP because it is more treatment choice for AIDP because it is more

widely available and easer to use than PE.widely available and easer to use than PE. Dose of IVIG is 2 gr/kg infused over 2-5 days.Dose of IVIG is 2 gr/kg infused over 2-5 days. Treatment should begin preferably within first 7-Treatment should begin preferably within first 7-

10 10

day of symptoms.day of symptoms. Improvement often not immediate .mean time to Improvement often not immediate .mean time to

improvement ranged from 6-27 day.improvement ranged from 6-27 day. Unlike CIDP, corticosteroid do not appear Unlike CIDP, corticosteroid do not appear

beneficial in the treatment of AIDP; in fact ,some beneficial in the treatment of AIDP; in fact ,some

patient have done worse. patient have done worse.

AIDP in childrenAIDP in children

The clinical , lab and EDX findings The clinical , lab and EDX findings similar to adultsimilar to adult

75%75% have an antecedent infection have an antecedent infection Major presenting complaint Major presenting complaint is is painpain Most children with AIDP have a Most children with AIDP have a

satisfactory recovery , even those satisfactory recovery , even those with significant reduction in CMAP with significant reduction in CMAP Ampl.Ampl.

Acute motor-sensory axonal neuropathy Acute motor-sensory axonal neuropathy (AMSAN)(AMSAN)

Clinically and at least by initial EDXClinically and at least by initial EDX ,patient with AMSAN are indistinguishable,patient with AMSAN are indistinguishable from AIDP.from AIDP. Patient with AMSAN develop rapidly Patient with AMSAN develop rapidly progressive and severe generalizedprogressive and severe generalized weakness weakness over only a few dayover only a few day as opposed as opposed to a couple of wk in most patient with to a couple of wk in most patient with AIDP.AIDP.

Ophtalmoplegia and difficulty in swallowing may Ophtalmoplegia and difficulty in swallowing may bebe

noted.noted. Muscle of facial expression are profoundly weak.Muscle of facial expression are profoundly weak. Most patient require ventilator support.Most patient require ventilator support. Sensation to all modality is reduced.Sensation to all modality is reduced. Complete areflexia is usually evident.Complete areflexia is usually evident. Prognosis of AMSAN much poorer than Prognosis of AMSAN much poorer than

AIDP ;most patient have a slow or incomplete AIDP ;most patient have a slow or incomplete recovery.recovery.

Some authorities suggest that C.j infection andSome authorities suggest that C.j infection and GM1 Ab are more commonly associated with GM1 Ab are more commonly associated with

axonal axonal form of GBS.form of GBS.

Histologic evaluationHistologic evaluation performed performed earlyearly in the in the

course of disorder is the course of disorder is the only wayonly way to differentiate to differentiate

axonal GBS from psudoaxonal GBS.axonal GBS from psudoaxonal GBS. Markedly diminish Ampl or absent CMAP within Markedly diminish Ampl or absent CMAP within

7-7-

10 day of onset.10 day of onset. SNAP Ampl are profoundly reduced or absent.SNAP Ampl are profoundly reduced or absent. Markedly abnormal reduction in recruitment .Markedly abnormal reduction in recruitment . Abundant fib and psw detected in most muscle Abundant fib and psw detected in most muscle

especially distal limb.especially distal limb.

Acute motor axonal neuropathy (AMAN)Acute motor axonal neuropathy (AMAN)

(chinese paralytic syndrome(chinese paralytic syndrome)) In northern china, AMAN is the most common In northern china, AMAN is the most common variant of GBS.variant of GBS.

Serologic evidence of recent C.j infection Serologic evidence of recent C.j infection detected in 67- 92% of patient.detected in 67- 92% of patient.

As in AMSAN , there is an abrupt onset of As in AMSAN , there is an abrupt onset of generalized weakness.the distal muscle often aregeneralized weakness.the distal muscle often are affected more severly than proximal limb muscle.affected more severly than proximal limb muscle.

Sensory sign and symptom are absent.Sensory sign and symptom are absent.

DTR may be normal or absent.DTR may be normal or absent.

Patient generally make a good recovery within one years, Patient generally make a good recovery within one years, but residual distal limb weakness is common.but residual distal limb weakness is common.Mortality rate is less than 5%Mortality rate is less than 5%

The absence of prominent CSF pleocytosisThe absence of prominent CSF pleocytosis help distinguish AMAN from poliomyelitis, help distinguish AMAN from poliomyelitis, which it can mimic.which it can mimic. The fact that many patient with AMAN The fact that many patient with AMAN recover quickly suggests that low Ampl orrecover quickly suggests that low Ampl or unobtainable distal CMAP are due notunobtainable distal CMAP are due not necessarily to axonal degeneration but tonecessarily to axonal degeneration but to distal conduction block .distal conduction block .

Characteristic NCS feature in AMAN Characteristic NCS feature in AMAN is low Ampl or unobtainable CMAP is low Ampl or unobtainable CMAP with normal SNAP.with normal SNAP.

When CMAP are obtained, DML and When CMAP are obtained, DML and NCVare normal.NCVare normal.

F-wave usually unobtainable F-wave usually unobtainable but,when present, show normal but,when present, show normal latency.latency.

Other variant of GBSOther variant of GBS

1.1. Miller – fisher syndromeMiller – fisher syndrome

2.2. Idiopathic cranial polyneuropathyIdiopathic cranial polyneuropathy

3.3. Pharyngeal-cervical-bracial Pharyngeal-cervical-bracial weaknessweakness

4.4. Para paretic weaknessPara paretic weakness

Miller Miller –– fisher syndrome fisher syndrome

M/F=2/1 , mean age of onset in the early 40s.M/F=2/1 , mean age of onset in the early 40s. An antecedent infection in 2/3 of cases.An antecedent infection in 2/3 of cases. Diplopia is the most common initial complaint.Diplopia is the most common initial complaint. Whether the ataxia is secondary to sensory Whether the ataxia is secondary to sensory

dysfunction or a cerebellar lesion is controversial. dysfunction or a cerebellar lesion is controversial. InIn

our experience , most patient have sensory our experience , most patient have sensory ataxia.ataxia.

Ptosis usually accompanies the ophtalmoparesis Ptosis usually accompanies the ophtalmoparesis

,but pupillary involvement is uncommon.,but pupillary involvement is uncommon.

Nearly 50% of patient describe paresthesia in Nearly 50% of patient describe paresthesia in faceface

and distal limbs.and distal limbs. Areflexia is evident in over 82% Areflexia is evident in over 82% anti GQ1b demonstrate in most patient.anti GQ1b demonstrate in most patient. Most prominent EDX abnormality in MFS isMost prominent EDX abnormality in MFS isreduced SNAP Amplreduced SNAP Ampl.. CMAP in the arm and legs are usually normal CMAP in the arm and legs are usually normal

but,but, mild to moderate reduction in facial CMAP mild to moderate reduction in facial CMAP demonstrate in over 50% of patient.demonstrate in over 50% of patient. Blink reflex may be abnormal.Blink reflex may be abnormal. There is generally no abnormal spontaneous There is generally no abnormal spontaneous activity in limb or paraspinal muscles but , fib may activity in limb or paraspinal muscles but , fib may

bebe detected in facial muscle.detected in facial muscle.

Chronic inflammatory demyelinatingChronic inflammatory demyelinating polyneuropathy(CIDP)polyneuropathy(CIDP)

An immune-mediated neuropathy An immune-mediated neuropathy

characterized by a relapsing or progressive characterized by a relapsing or progressive

course.course. Relapsing form=recurrent polyneuritisRelapsing form=recurrent polyneuritis Progressive form=progressive hypertrophicProgressive form=progressive hypertrophic

neuritis or chronic GBSneuritis or chronic GBS Sign and symptom of neuropathy must be Sign and symptom of neuropathy must be

progressive for at least 2 month, which progressive for at least 2 month, which

distinguishes CIDP from GBS or AIDP.distinguishes CIDP from GBS or AIDP.

Four typical clinical course of progressionFour typical clinical course of progression1.1. Chronic monophasic(15%)Chronic monophasic(15%)2.2. Chronic relapsing(fluctuation of weakness Chronic relapsing(fluctuation of weakness

or improvement over week or or improvement over week or months)34%months)34%

3.3. Stepwise progression 34%Stepwise progression 34%4.4. Steady progression15%Steady progression15% Pattern of disease progression in CIDP Pattern of disease progression in CIDP

analogous to MS.analogous to MS. CIDP most commonly present in adult with CIDP most commonly present in adult with

a peak incidence at about 40-60 years; a peak incidence at about 40-60 years; slightly increased prevalence in men.slightly increased prevalence in men.

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

Relapses have associated with pregnancyRelapses have associated with pregnancy

Most patient present with relapsing orMost patient present with relapsing or

progressive symmetric proximal and distal progressive symmetric proximal and distal

weakness of the arms and legs.weakness of the arms and legs. Early in the course of illness ,only distalEarly in the course of illness ,only distal

weakness may be observed. however . Ifweakness may be observed. however . If

weakness remain distal , other diagnoses weakness remain distal , other diagnoses

need to considered : hereditary need to considered : hereditary demyelinating demyelinating

neuropathy ,Para protein related neuropathy,neuropathy ,Para protein related neuropathy,

distal acquired demyelinating neuropathy.distal acquired demyelinating neuropathy.

Although most patient (80%)have both Although most patient (80%)have both

motor and sensory involvement , a few motor and sensory involvement , a few patientpatient

may have pure motor (10%) or pure may have pure motor (10%) or pure

sensory(5-10%)sign and symptom.sensory(5-10%)sign and symptom. Sensory abnormality in 68-84%of patient , Sensory abnormality in 68-84%of patient ,

primarily affecting large fiber modalityprimarily affecting large fiber modality

(vibration ,touch)(vibration ,touch) Sensory ataxia, positive Romberg Sensory ataxia, positive Romberg

sign ,widesign ,wide

base gait may be found.base gait may be found.

Chronic sensory demyelinating neuropathy: only sensory Chronic sensory demyelinating neuropathy: only sensory sign and symptom. however EDX reveal motor nervesign and symptom. however EDX reveal motor nerve abnormality.abnormality.

Most patient with a demyelinating neuropathy who have Most patient with a demyelinating neuropathy who have mainly sensory sign and symptom with normal or only mild mainly sensory sign and symptom with normal or only mild distal weakness have an distal weakness have an IgM monoclonal gammopathyIgM monoclonal gammopathy . .

Whenever a pure sensory neuropathy is present ,Whenever a pure sensory neuropathy is present , consideration should be given to other diseases well, such asconsideration should be given to other diseases well, such as sjogren syndrome or paraneoplastic neuronopathy, both sjogren syndrome or paraneoplastic neuronopathy, both associated with sensory ganglionitis.associated with sensory ganglionitis.

Most patient have areflexia or hyporeflexia.Most patient have areflexia or hyporeflexia.

Some patient develop dropped head syndrom secondarySome patient develop dropped head syndrom secondary to neck extensor weakness.to neck extensor weakness.

Autonomic dysfunction (incontinency , impotency) less Autonomic dysfunction (incontinency , impotency) less common.common.

Respiratory insufficiency reported in 8-15 % of patient.Respiratory insufficiency reported in 8-15 % of patient.

3-5% of patient have evidence of CNS demyelination 3-5% of patient have evidence of CNS demyelination clinically .clinically .

Patient may developed a myelopathy due to compression of Patient may developed a myelopathy due to compression of spinalspinal

cord by hypertrophied nerve roots.cord by hypertrophied nerve roots.

CIDP like neuropathy : CIDP like neuropathy : 1.1. HIV infectionHIV infection2.2. HepatitisHepatitis3.3. Inflammatory bowel diseaseInflammatory bowel disease4.4. DMDM5.5. SLESLE6.6. Monoclonal gamopathy of uncertain significance Monoclonal gamopathy of uncertain significance

(MGUS)(MGUS)7.7. LymphomaLymphoma8.8. Bone marrow and solid organ transplantationBone marrow and solid organ transplantation9.9. Paraneuoplastic complication of pancreas and Paraneuoplastic complication of pancreas and

colon carcinoma, SCC lung , melanoma, colon carcinoma, SCC lung , melanoma, cholangiocarsinomacholangiocarsinoma

10.10. Toxic induced neuropathy (procainamide, Toxic induced neuropathy (procainamide, cyclosporine and tacrolimus) cyclosporine and tacrolimus)

LAB featureLAB feature An elevated CSF protein is found in 80-95% of patient.An elevated CSF protein is found in 80-95% of patient.

Cell count is usually normalCell count is usually normal.. WBC CSF should be <10/mm3WBC CSF should be <10/mm3

Elevated CSF cell count should lead to consideration of Elevated CSF cell count should lead to consideration of HIV infection, lyme, leukemic infiltration of nerve rootHIV infection, lyme, leukemic infiltration of nerve root

Oligoclonal band demonstrated in the CSF in 65%Oligoclonal band demonstrated in the CSF in 65%

MRI with gad may reveal hypertrophy and MRI with gad may reveal hypertrophy and enhancement of the nerve root and peripheral nerve.enhancement of the nerve root and peripheral nerve.

M-NCVM-NCV CMAP parameter most useful diagnostic CMAP parameter most useful diagnostic test in demyelinating process.test in demyelinating process.

a 50% drop in Ampl or negative peak areaa 50% drop in Ampl or negative peak area for define conduction block.for define conduction block.

Increased CMAP Ampl , Increased NCV,Increased CMAP Ampl , Increased NCV, decreased conduction block, seen in decreased conduction block, seen in association with improvement in strength. association with improvement in strength.

Clinical improvement primarily result of Clinical improvement primarily result of resolving conduction block.resolving conduction block.

S-NCVS-NCV

>80% low Ampl or unobtainable SNAP.>80% low Ampl or unobtainable SNAP. A characteristic finding is abnormal A characteristic finding is abnormal

medianmedian

or ulnar SNAP when the sural SNAP are or ulnar SNAP when the sural SNAP are

normal.normal. A similar discrepancy between the upper A similar discrepancy between the upper

and lower limb SNAP seen in sensory and lower limb SNAP seen in sensory

ganglinopathy , but the EDX abnormality in ganglinopathy , but the EDX abnormality in

such cases are axonal , not demyelinating.such cases are axonal , not demyelinating.

EMGEMG

Widespread fib and PSW are Widespread fib and PSW are commonlycommonly

detected in intrinsic foot and hand detected in intrinsic foot and hand musclemuscle

and more proximal muscle.and more proximal muscle.

The degree of fib and PSW is high The degree of fib and PSW is high duringduring

an exacerbation with a reduction during an exacerbation with a reduction during

clinical remission.clinical remission.

treatmenttreatment Treatment of choice depend on other medical Treatment of choice depend on other medical problem(avoid IVIG in renal defficiency) and problem(avoid IVIG in renal defficiency) and

accessibility.accessibility.

Corticosteroid: prednisone 1/5mg/kg per day for Corticosteroid: prednisone 1/5mg/kg per day for 2-2-

4wk,then switch to alternate-day.4wk,then switch to alternate-day.

Functional muscle recovery is first noted in the Functional muscle recovery is first noted in the proximal limb muscleproximal limb muscle. .

PE: unfortunately response to PE is transient, usually PE: unfortunately response to PE is transient, usually lasting only a few wk.lasting only a few wk.

PE used usually in combination with prednisone, in patientPE used usually in combination with prednisone, in patient with severe generalized weakness.with severe generalized weakness.

PE used alone in patient in whom we wish to avoid longPE used alone in patient in whom we wish to avoid long term prednisone(poorly controled DM or HIV infection) or in term prednisone(poorly controled DM or HIV infection) or in whom IVIG is contraindicated (renal insufficiency).whom IVIG is contraindicated (renal insufficiency).

Used a trial course of PE in patient who do not fulfill all of Used a trial course of PE in patient who do not fulfill all of criteria for CIDP or those that have an underlying condition criteria for CIDP or those that have an underlying condition making the diagnosis difficult(DM and superimposed CIDP-making the diagnosis difficult(DM and superimposed CIDP-like neuropathy).like neuropathy).

IVIG: for many authorities , IVIG has IVIG: for many authorities , IVIG has becomebecome

the treatment of choice in CIDP. the treatment of choice in CIDP.

A IgA level should be assayed before A IgA level should be assayed before

administering IVIG.patient who are IgAadministering IVIG.patient who are IgA

deficiency due to IgE anti IgA antibody or a deficiency due to IgE anti IgA antibody or a

congenital deficiency may develop congenital deficiency may develop anaphylacticanaphylactic

reaction to IVIG.reaction to IVIG.

AzathioprineAzathioprine CyclophosphamideCyclophosphamide Cyclosporine: decreased relapse rate Cyclosporine: decreased relapse rate

in patient with the relapsing form of in patient with the relapsing form of CIDP and improved strength and CIDP and improved strength and function in those with the chronic function in those with the chronic progressive form.progressive form.

InterferonInterferon

prognosisprognosis

Require symmetric,proximal and distal arm and legRequire symmetric,proximal and distal arm and leg weakness to diagnose CIDP.weakness to diagnose CIDP.

Patient with mainly sensory symptom, mild distal Patient with mainly sensory symptom, mild distal weakness weakness

or asymmetric motor involvement much less responsive or asymmetric motor involvement much less responsive to to

specific form of therapyspecific form of therapy

Poor long term prognosis: progressive course, CNS Poor long term prognosis: progressive course, CNS involvement and particularly axonal lossinvolvement and particularly axonal loss. .

CIDP in childrenCIDP in children

Commonly present with difficulty in ambulatingCommonly present with difficulty in ambulating

Response to standard form of therapyResponse to standard form of therapy

CIDP may be confused with a hereditary neuropathy (CMT)CIDP may be confused with a hereditary neuropathy (CMT)

Family historyFamily history

EDX :CMT associated with symmetric and diffuse EDX :CMT associated with symmetric and diffuse involvement of peripheral neuropathy.involvement of peripheral neuropathy.

Thus temporal dispersion and conduction block are not seen. Thus temporal dispersion and conduction block are not seen. there isthere is

usually uniform slowing of conduction velocity as well as usually uniform slowing of conduction velocity as well as symmetric symmetric

involvement of proximal and distal segment.involvement of proximal and distal segment.

In contrast , the multifocal nature of CIDP result in nonuniform In contrast , the multifocal nature of CIDP result in nonuniform slowing ofslowing of

conduction velocity, temporal dispersion and conduction block.conduction velocity, temporal dispersion and conduction block.

Para protein Para protein –– related neuropathies related neuropathies (monoclonal gammopathy) and CIDP(monoclonal gammopathy) and CIDP

Although IgG is the most common paraprotein in the general Although IgG is the most common paraprotein in the general population ,IgM is by far the most common monoclonal protein population ,IgM is by far the most common monoclonal protein in patient with peripheral neuropathy.in patient with peripheral neuropathy.

IgM-MGUS neuropathy are typically demyelinating but can be IgM-MGUS neuropathy are typically demyelinating but can be axonal.axonal.

Demyelinating and axonal neuropathy seem to occure similar Demyelinating and axonal neuropathy seem to occure similar frequency in IgG and IgA-MGUSfrequency in IgG and IgA-MGUS

The IgM neuropathy seem to be less responsive to The IgM neuropathy seem to be less responsive to immonotheraphy than IgG and IgA neuropathy.immonotheraphy than IgG and IgA neuropathy.

At least 50% of IgM group have antibody against myelin – At least 50% of IgM group have antibody against myelin – associated associated

glycoprotein.glycoprotein.

Most patient present with a late onset distal and Most patient present with a late onset distal and

symmetric sensorimotor neuropathy.symmetric sensorimotor neuropathy.

Sensory ataxia and tremor were common.Sensory ataxia and tremor were common.

IgM neuropathy experience more disability relatedIgM neuropathy experience more disability related

to sensory loss. weakness was only a minor feature.to sensory loss. weakness was only a minor feature.

In IgM neurapathy ,NCV more slowing and In IgM neurapathy ,NCV more slowing and

prolongation of distal latency compared with IgG andprolongation of distal latency compared with IgG and

IgA.IgA.

Patient with MGUS-CIDP had a more indolent Patient with MGUS-CIDP had a more indolent course , more frequent sensory disturbance with course , more frequent sensory disturbance with ataxia and less severe weakness than patient ataxia and less severe weakness than patient

with with idiopathic CIDP. idiopathic CIDP.

no difference in various motor parameters.no difference in various motor parameters.

MGUS group had more severe sensory MGUS group had more severe sensory conduction abnormality.conduction abnormality.

Ig-M subgroup: smaller TLI. Ig-M subgroup: smaller TLI.

Idiopathic CIDP had a significant improvement Idiopathic CIDP had a significant improvement rate(88%) than MGUS CIDP(50%)rate(88%) than MGUS CIDP(50%)

Distal acquired demyelinating symmetric Distal acquired demyelinating symmetric neuropathy (DADS)neuropathy (DADS)

Monoclonal protein detected in 75% casesMonoclonal protein detected in 75% cases (IgM)](IgM)]

No significant EDX difference between IgM-DADS,No significant EDX difference between IgM-DADS, idiopathic DADS or CIDP.idiopathic DADS or CIDP.

Patient with IgM-DADS neuropathy demonstrated aPatient with IgM-DADS neuropathy demonstrated a poor response to immunotherapy , whereas patient poor response to immunotherapy , whereas patient with idiopathic DADS and CIDP usually improved withwith idiopathic DADS and CIDP usually improved with therapy.therapy.

Multifocal motor neuropathy (MMN) (multifocal Multifocal motor neuropathy (MMN) (multifocal demyelinating neuropathy with conduction block)demyelinating neuropathy with conduction block)

An immune mediate demyelinating An immune mediate demyelinating

neuropathy characterized clinically by neuropathy characterized clinically by

asymmetric weakness and atrophy, typically inasymmetric weakness and atrophy, typically in

the distribution of individual peripheral nerve.the distribution of individual peripheral nerve.

MMN is commonly misdiagnosed as ALS;MMN is commonly misdiagnosed as ALS;

however muscle involvement is in the however muscle involvement is in the

distribution of individual peripheral nerves, notdistribution of individual peripheral nerves, not

spinal roots.spinal roots.

Incidence of MMN much less than ALS(1/50)Incidence of MMN much less than ALS(1/50)

M/F=3/1M/F=3/1

Age at onset of symptom usually early in fifth decade Age at onset of symptom usually early in fifth decade of life.of life.

Typically, diagnosis is delayed by several years Typically, diagnosis is delayed by several years because of the slow ,insidious progression and because of the slow ,insidious progression and misdiagnosis of the disorder.misdiagnosis of the disorder.

Patient develop focal muscle weakness accompanied Patient develop focal muscle weakness accompanied by by

cramps and fasciculation, usually beginning in the distal cramps and fasciculation, usually beginning in the distal

Upper limbsUpper limbs..

Patient generally present with intrinsic hand Patient generally present with intrinsic hand

weakness ,wrist drop or foot drop.weakness ,wrist drop or foot drop.

Mild sensory symptom have been describedMild sensory symptom have been described

,but if there is objective sensory loss, one ,but if there is objective sensory loss, one should consider MADSAM neuropathy.should consider MADSAM neuropathy.

P/E reveals weakness in a multifocal pattern in the upper P/E reveals weakness in a multifocal pattern in the upper andand

lower limbs, paralleling a peripheral nerve as opposed to the lower limbs, paralleling a peripheral nerve as opposed to the spinal segmental/root distribution seen in motor neuron spinal segmental/root distribution seen in motor neuron

disease.disease.

A helpful feature is the A helpful feature is the lack of atrophy in weak muscle grouplack of atrophy in weak muscle groupearly in the course of illnessearly in the course of illness; however decreased muscle bulk ; however decreased muscle bulk can result in time from secondary axonal degeneration. can result in time from secondary axonal degeneration.

Sensory exam should be normal.Sensory exam should be normal.

MSR variable in unaffected limb, whereas depress or absent MSR variable in unaffected limb, whereas depress or absent in weak muscle.in weak muscle.

The observation of fasciculation, weakness The observation of fasciculation, weakness and and

essentially preserved sensation is certainly essentially preserved sensation is certainly

suspicious for an anterior horn cell disorder.suspicious for an anterior horn cell disorder.

however ,the multifocal peripheral nerve however ,the multifocal peripheral nerve

involvement ,as opposed to spinal root level of involvement ,as opposed to spinal root level of

dysfunction, combined with sparing of muscle dysfunction, combined with sparing of muscle bulkbulk

point to diagnosis of MMNpoint to diagnosis of MMN..

In contrast to CIDP and MADSAM,CSF protein is In contrast to CIDP and MADSAM,CSF protein is usually normal in patients with MMN.usually normal in patients with MMN.

Twenty to 80% of MMN have detectable IgMTwenty to 80% of MMN have detectable IgM

antibody direct against gangliosides ,mainly antibody direct against gangliosides ,mainly GM1but also GM2.GM1but also GM2.

A high titers the antibodies appear to be rather A high titers the antibodies appear to be rather specific for MMN ,but the sensitivity of the testspecific for MMN ,but the sensitivity of the test

is too low.is too low.

The most sensitive and specific test is the NCS.The most sensitive and specific test is the NCS.

EDXEDX

There is often evidence of conduction block in multiple There is often evidence of conduction block in multiple upper and lower limb nerves.upper and lower limb nerves.

conduction block is not located at the expected conduction block is not located at the expected common nerve entrapment sites, but in the mid-common nerve entrapment sites, but in the mid-forearm or leg, upper arm, across brachial plexus, or forearm or leg, upper arm, across brachial plexus, or nerve root region.nerve root region.

conduction block may be present not only in multipleconduction block may be present not only in multipledifferent nerves but also at several location along the different nerves but also at several location along the

course course of the same nerve.of the same nerve.

A reduction in distal CMAP AMPL can be seen in A reduction in distal CMAP AMPL can be seen in chronic chronic

lesions due to secondary axonal loss.lesions due to secondary axonal loss.

Although motor conduction block has been Although motor conduction block has been considered the EDX hallmark of MMN, other considered the EDX hallmark of MMN, other features of demyelination: features of demyelination:

(prolonged distal latency, temporal (prolonged distal latency, temporal dispersion ,slow dispersion ,slow

conduction velocity and prolonged or absent F-conduction velocity and prolonged or absent F-waves) are typically present on motor NCS.waves) are typically present on motor NCS.

Diagnosis does not require conduction block if Diagnosis does not require conduction block if other features of demyelination are present.other features of demyelination are present.

SNAP parameters is normal.SNAP parameters is normal.

Needle EMGNeedle EMG

Unaffected muscles should demonstrateUnaffected muscles should demonstrate

no abnormalities.no abnormalities.

In weak muscle: reduced recruitment , fib In weak muscle: reduced recruitment , fib

and PSW, fasciculation potential and rarelyand PSW, fasciculation potential and rarely

myokymic discharge.myokymic discharge.

These abnormalities improve after These abnormalities improve after treatment.treatment.

TreatmentTreatment

In contrast to CIDP and MADSAM neuropathy ,few In contrast to CIDP and MADSAM neuropathy ,few patients(<3%)With MMN improve with high doses of patients(<3%)With MMN improve with high doses of corticosteroids or PE.corticosteroids or PE.

Intravenous cyclophosphamide was the first Intravenous cyclophosphamide was the first immunosuppressive agent demonstrated to be immunosuppressive agent demonstrated to be effective in MMN ,over 70% of reported patients effective in MMN ,over 70% of reported patients improved clinically after treatment.improved clinically after treatment.

IVIG is now the treatment of choice in MMN.IVIG is now the treatment of choice in MMN.

Not all patients with MMN respond to IVIG. some Not all patients with MMN respond to IVIG. some seriesseries

have noted that later age of onset and patient who have noted that later age of onset and patient who have have

significant muscle atrophy do not respond as well to significant muscle atrophy do not respond as well to treatment. treatment.

Multifocal acquired demyelinating sensory and motor Multifocal acquired demyelinating sensory and motor

neuropathy (MADSAMneuropathy (MADSAM))

The sign and symptom of MADSAM neuropathy are essentially The sign and symptom of MADSAM neuropathy are essentially those of mononeuropathy multiplex.those of mononeuropathy multiplex.

M/F=2/1M/F=2/1

Mean age of onset in the early 50s.Mean age of onset in the early 50s.

Onset is usually insidious and slowly progressive with initial Onset is usually insidious and slowly progressive with initial involvement usually in the upper limb.involvement usually in the upper limb.

Motor and sensory involvement to peripheral nerve Motor and sensory involvement to peripheral nerve distribution ratherdistribution rather

than generalized stocking and glove pattern.than generalized stocking and glove pattern.

MSR is decreased or absent in a multifocal , asymmetric MSR is decreased or absent in a multifocal , asymmetric distribution.distribution.

CSF protein elevated in 60-80% of patient.CSF protein elevated in 60-80% of patient.

As with CIDP and MMN ,NCS demonstrate As with CIDP and MMN ,NCS demonstrate conduction block, temporal dispersion, prolonged conduction block, temporal dispersion, prolonged distal latency and F-wave and slow NCV in one or distal latency and F-wave and slow NCV in one or more motor nerves.more motor nerves.

SNAP are absent or small AMPL.SNAP are absent or small AMPL.

Fib ,PSW and polyphasic ,long duration MUAP.Fib ,PSW and polyphasic ,long duration MUAP.

In contrast to MMN but similar to CIDP , most In contrast to MMN but similar to CIDP , most patient with MADSAM improvement with steroid.patient with MADSAM improvement with steroid.

Most patient improve with IVIG.Most patient improve with IVIG.

Idiopathic sensory neuronopathy / Idiopathic sensory neuronopathy / ganglionopathyganglionopathy

Believed to be caused by an autoimmuneBelieved to be caused by an autoimmune attack directed against the dorsal root ganglia.attack directed against the dorsal root ganglia.

DDX of sensory neuronopathy includes:DDX of sensory neuronopathy includes:

1.1. paraneoplastic syndrome, which is typically paraneoplastic syndrome, which is typically associated with anti-HU antibodyassociated with anti-HU antibody

2.2. Sjogrens syndromeSjogrens syndrome3.3. Medication or toxinsMedication or toxins4.4. Infection agentsInfection agents

A slight female predominance,mean age of onset is 49 YearsA slight female predominance,mean age of onset is 49 Years

The neuronopathy can present acutely with an abrupt onset The neuronopathy can present acutely with an abrupt onset over a few hours or developed more insidiouslyover a few hours or developed more insidiously

Numbness Numbness can begin in face , trunk or limbs.can begin in face , trunk or limbs.

Symptoms begin Symptoms begin asymmetricallyasymmetrically and in and in the upper limbthe upper limb in in nearly one-half of patients.nearly one-half of patients.

Usually the sensory symptoms are generalized, but they can Usually the sensory symptoms are generalized, but they can remain asymmetric.remain asymmetric.

Because of the prominent large fiber sensory loss, patient Because of the prominent large fiber sensory loss, patient describe clumsiness of the hands and gait instability.describe clumsiness of the hands and gait instability.

Marked reduction in vibration and position sense.Marked reduction in vibration and position sense.

The deficit more impaired in upper limb than The deficit more impaired in upper limb than lower limbs, unlike length-dependent axonal lower limbs, unlike length-dependent axonal neuropathy.neuropathy.

Pain and temperature are less affected.Pain and temperature are less affected.

Manual muscle testing usually normal.Manual muscle testing usually normal.

Patient often complain of weakness.Patient often complain of weakness.

Sensory ataxia resulting from the loss of Sensory ataxia resulting from the loss of proprioceptionproprioception

Positive Romberg signPositive Romberg sign

MSR are decreased or absent.MSR are decreased or absent.

Idiopathic sensory neuronopathy is a Idiopathic sensory neuronopathy is a diagnosis of exclusiondiagnosis of exclusion

MRI reveal gadolinium enhancement of MRI reveal gadolinium enhancement of the the

posterior spinal roots, increased signal posterior spinal roots, increased signal abnormality on T2 image in the posterior abnormality on T2 image in the posterior columns.columns.

Most prominent EDX abnormality is absent or low Most prominent EDX abnormality is absent or low AMPL SNAP.AMPL SNAP.

Sensory distal latency and NCV normal or mildly Sensory distal latency and NCV normal or mildly abnormal.abnormal.

DML and MNCV and F-waves usually normal.DML and MNCV and F-waves usually normal.

H-reflex and Blink reflex typically absent.H-reflex and Blink reflex typically absent.

An abnormal Blink reflex favors a nonparaneuoplastic An abnormal Blink reflex favors a nonparaneuoplastic etiology for sensory neuronopathy but does not etiology for sensory neuronopathy but does not exclude an underlying malignancy.exclude an underlying malignancy.

Needle EMG is usually normal.Needle EMG is usually normal.

treatmenttreatment

PE,IVIG and corticosteroidPE,IVIG and corticosteroid

A few patient may improved A few patient may improved spontaneously.spontaneously.

There is no indication to treat a patientThere is no indication to treat a patient

with a stable deficitwith a stable deficit

Idiopathic autonomic neuropathyIdiopathic autonomic neuropathy

The most common symptom was orthostatic dizziness orThe most common symptom was orthostatic dizziness orlightheadedness(80%)lightheadedness(80%)

GI involvement is the second most common symptom(70%)GI involvement is the second most common symptom(70%)(neusea, vomiting diarrhea , constipation and ileus)(neusea, vomiting diarrhea , constipation and ileus)

Thermoregulatory impairment with heat intolerance and Thermoregulatory impairment with heat intolerance and sweating was present in most patient.sweating was present in most patient.

Blurred vision, dry eye and mouth, urinary retention and Blurred vision, dry eye and mouth, urinary retention and incontinenceincontinence

and impotence are often present.and impotence are often present.

Muscle strength was normal.Muscle strength was normal.

QSART (quantitative sudomotor axon reflex test) score areQSART (quantitative sudomotor axon reflex test) score are abnormal in 85% of patient.abnormal in 85% of patient.

Abnormal thermoregulatory sweat test in 12-97%Abnormal thermoregulatory sweat test in 12-97%

Motor NCS are normal.Motor NCS are normal.

SNCS have normal in most patient. a few SNCS have normal in most patient. a few patient patient

demonstrate reduced SNAP AMPL or slight demonstrate reduced SNAP AMPL or slight prolonged latencyprolonged latency

SSR response may be absent.SSR response may be absent.

PE,IVIG and prednisone tried with variablePE,IVIG and prednisone tried with variablesuccess.success.

Most important aspect of management isMost important aspect of management is supportive therapy for orthostatic hypotension,supportive therapy for orthostatic hypotension, bowel and bladder symptoms. bowel and bladder symptoms.