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CLINICAL AND

ELECTROPHSIOLOGICAL

ASSESMENT OF VARIOUS

CHRONIC ACQUIRED

DEMYLINATING

POLYNEUROPATHYPHENOTYPES

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CADP

CIDP

DADS MMN

MADSAM

Clinical scheme for approaching chronic acquired demylinatingpolyneuropathy.

Without sensory involvement

with sensory involvement

With proximal muscles involvement

Without proximal muscles involvement

Asymmetrical pattern of

weaknessSymmetrical pattern of

weakness

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Distal Acquired Demyelinating Symmetric (DADS ) Neuropathy :

DADS is a distal acquired demyelinating symmetric polyneuropathy

that presents predominantly with sensory symptoms.

Patients withsymmetric, length dependent, distal sensory or distalsensory>motor or sensorimotor neuropathy.

Clinical features:

Features of the disorder include an increased prevalence in men and in

persons over the age of 50 years.

All patients with DADS have slowly progressive course, with only

distal symptoms, and weakness is confined mostly to the distal lower

limbs muscle groups in a symmetric , length-dependent fashion and

an unsteady gait.

Progress over years limited to the ankles and knees, hands do not

become involved until the symptoms are up to the knees.

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Antibodies: Length Dependent Neuropathies

Anti-MAG

DADS-MNeuropathy

Distal Acquired

DemyelinatingSymmetric

Sensory

Neuropathy with

IgM

IgM only

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Electrodiagnostic study findings in DADS patients:

Sensory conduction studies were normal in both upper

and lower limb nerves. Upper limb nerves show normal

motor conduction study parameters.

Lower limbs motor nerve conduction studiesdemonstrate widespread uniform distal slowing with

absence of conduction block.

Absence of multifocality and conduction block supportsthe diagnosis of DADS .

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Needle EMG findings:

Evidence of chronic denervation and reinnervation, increased

MUAP duration, amplitude, and polyphasia. A reduced

recruitment pattern in the distal lower limb muscles.

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Differential Diagnosis lumbosacral polyradiculopathy/ stenosis .

myelopathies .

structural (discs, tumors) .

non-structural (MS, B12 deficiency) .

vascular insufficiency (exercise related calf cramps,achy pain >> numbness, tingling)

orthopedic (stress fracture, plantar fasciitis)

DSP: Youre right! You just cant prove it.

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Multifocal Motor Neuropathy

Is an acquired immune mediated, chronic

demyelinating neuropathy. First described

by Lewis and colleagues in 1982.

In 1988 Pestrenk et al used the term MMN

as a distinct clinical entity with especial

character.

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Clinical Features The clinical diagnosis of MMN is based on the

presence of slowly or stepwise progressive asymmetric

limb weakness in the distribution of at least twodistinct motor nerves and lasting at least two monthswith minimal or no sensory symptoms and absence ofclinical signs of upper motor neuron involvement

- MMN is characterized by slowly progressiveasymmetrical weakness and muscle atrophy, whichmay be accompanied by cramps, fasciculations, andmyokymia.

- Early in the disease course weakness is more

pronounced than atrophy in affected muscles.- This is an important clinical feature distinguishing

MMN from MND, in which atrophy is generallyconsistent with the degree of weakness.

-

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- The disease usually begins and remainsmore prominent in the upper

extremities. The most striking clinicalfeature is the multifocal distribution ofthe weakness, which, in the beginning,may be localized within the territory ofindividual peripheral nerves.

MMN is more common in males (the male-to-femaleratio is about 3:1).

The age at onset of symptoms is usually early in thefifth decade of life, ranging from the second toeight decade of life .

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History: Typically, MMN manifests with aslowly progressive, asymmetric,predominantly distal weakness developingover years. Weakness usually starts in adistribution of a single peripheral nerve withunilateral intrinsic hand weakness, wrist drop

or foot drop. Initial involvement of the distalupper extremities is most common. Typicallydiagnosis is delayed by several years becauseof slow insidious progression and

misdiagnosis of the disorder. However thediagnosis is not difficult if thecondition is kept in mind.

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Clinical and electrodiagnostic criteriafor the diagnosis of MMN include thefollowing: Weakness without objective sensory loss in thedistribution of 2 or more nerves is present.

Definite conduction block is present in 2 or more motornerves outside of common entrapment sites.

Sensory nerve conduction velocity is normal across thesegments with demonstrated motor conduction block.

Results are normal for sensory nerve conductionstudies on all tested nerves, with a minimum of 3

nerves tested. Upper motor neuron signs, including spasticity, clonus,

extensor plantar response, and pseudobulbar palsy areabsent.

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Physical examination reveals weakness in a

multifocal pattern in the upper and lower

limbs, paralleling peripheral nerves as opposedto the spinal segmental root distribution seen in

most neuron diseases.

Weakness is often more pronounced than thedegree of atrophy early in the course of the

illness; however, decreased muscle bulk can

result in time from secondary axonal

degeneration. Deep tendon reflexes are highly

variable in that unaffected region can be

normal, whereas weak and atrophic muscles are

usually associated with depressed reflexes

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Electrodiagnostic StudiesBecause of the multifocal nature of the disease extensive

standardized bilateral electrophysiological examinationshould be done.

- Conduction block in motor nerves is considered the

electrodiagnostic hallmark of MMN.

- In MMN motor conduction block occurs most frequently in

the ulnar and median nerves.

- Conduction block may be seen at any level of the peripheral

nerve including the root, plexus and compression points.

- Outside the sites of MCB nerve conductions are normal or

nearly normal.

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Sensory nerve conduction study findings:

The sensory nerves demonstrate normal sensory nerve

action potential parameters. Of importance, there are no sensory conduction

abnormalities even across the same segments withdemonstrated motor conduction block.

This helps to differentiate MCB in MMNfrom other entities, which typically showblocks to both motor and sensoryconductions.

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The motor abnormalities within a given patient are

more likely to be non-homogenous. The conduction

abnormalities are usually multifocal, involving any

segment of the peripheral nerves at a random

fashion with significant variation between different

nerves.

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Needle EMG findings in MMN:

The unaffected muscles demonstrate no abnormalities,

while muscles with clinical weakness but preserved bulk

shows few fibrillation and positive sharp wave.

In chronically atrophied muscles, needle EMG

examination shows positive sharp waves, fasciculation,

long duration polyphasic motor unit potentials with

increased amplitude of the sampled units and reduced

recruitment pattern.

Differential diagnosis of MMN:

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Differential diagnosis of MMN:

1-Amyotrophic Lateral Sclerosis (ALS).

2-Chronic Inflammatory DemyelinatingPolyradiculoneuropathy.

3-Lewis-Sumner syndrome (MADSAM).

4-Mononeuritis multiplex.

neurologic emergency

multiple mononeuropathies

acute/subacute onset

asymmetrical

not length dependent pattern

vasculitides (PAN, Churg-Strauss, Sjogrens syndrome)

consider diabetes, multiple entrapments

i h i l d

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5- Neurogenic thoracic outlet syndrome.

6-Hereditary motor sensory neuropathy type

2.

7-Hereditary neuropathy with liability to

pressure palsies (HNPP).

8-Lead neuropathy.9-Porphyric neuropathy.

10-Spinal muscular atrophy (adult onset).

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Patients with Multifocal Acquired Demyelinating

Sensory and Motor (MADSAM) neuropathy ( Lewis-

Sumner syndrome):

MADSAM is a dysimmune multifocal demyelinating

sensorimotor neuropathy. It is considered as a clinical

asymmetrical variant of chronic immune demyelinatingpolyneuropathy (CIDP); it is five times less frequent

than CIDP

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Phenotype-MADSAM Neuropathy

Sensory and Motor Often painful

Hands more than

ankles

Individual Nerves

Stepwise

Slowing, CB, TD

Prednisone or IVIg(50%)

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Phenotype-MADSAM Neuropathy

Key DDx:

Brachial plexopathy

Vasculitic mononeuropathy

multiplex

Compression neuropathies

HNPP (genetic testing)

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The initial symptoms are started in the distal

part of the upper limbs.Pain and paresthesia are present in asymmetric

fashion.

Most patients present with decreased or absent

deep tendon reflexes in a multifocal

distribution, although some have completeareflexia.

El t di ti t d fi di i MADSAM ti t

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Electrodiagnostic study findings in MADSAM patients:

Patients with MADSAM neuropathy show all features of

segmental demyelination .

The more multifocal the disease, the easier it is to

distinguish from other CADP phenotype.

The segment of maximal involvement varies from one

patient to another. This explains the diversity of

clinical findings .

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Patients with suspected CADP, should not beconsidered in isolation, but rather should be considered

in conjunction with clinical, electrophysiological and

CSF studies. The CADP disorders appear to be heterogeneous in

terms of clinical presentation.

Identification of proximal weakness in any

sensorimotor neuropathy should herald an additional

element of anticipation from the clinician, as frequently

these neuropathies are treatable.

summary

Classic CIDP:

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CIDP may occur at all ages (in all decades). The clinical signs involve muscle weakness and

sensory disturbances.

The distribution of the clinical signs is (approximately)

symmetrical. There is symmetric proximal and distal weakness,

sensory deficit in both upper and lower extremities.

The degree of severity of CIDP and the way in which it

affects patients varying enormously from one to another.

There is no typical CIDP.

Classic CIDP:

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Sensory complaint tend to be less

conspicuous than motor.

Predominant dysfunction of the large,myelinated sensory fibers presented as impairment

in proprioception and in the sensation of vibration.

The onset of proximal before distal weakness

and being greater than distal.

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It is recommended to investigate for diabetes in all

CIDP patients and to investigate for CIDP in any diabetic

patients with recent motor deterioration.

CIDP occurring in diabetics is recognized as an

important differential diagnosis, since CIDP is treatable.

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Nerve conduction studies in patients with

acquired inflammatory demyelinating

neuropathy, shows multifocal slowing of nerve

conduction at a random fashion, however the

proximal segment is affected more than other

segments. conduction block, is an important

electrodiagnostic character istic of CI DP.

partial conduction block is located mainly at theintermediate mid forearm segment of median and

ulnar nerves.

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With studying evidence of conduction block, the

need for less demyelinating elements of NCS is

required.

There are5 criteria for demyelination

(prolonged distal motor latencies, slowed

conduction velocity, delayed or absent F waves,

conduction block and/ abnormal temporal

dispersion.

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DADS:slowly progressive course, with only distal

symptoms, and the weakness is confined to thedistal lower limbs in a symmetric fashion.

nerve conduction study :DADS patients presented with prolonged distal

motor latencies. Absence of mutifocality and

conduction block.

MMN

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In MMN, limb weakness without sensory loss is

asymmetric in the distribution of individual peripheralnerves and the weakness typically begins in the distal

upper extremities.

The course of the disease is slowly progressive, stepwise

progressive, or undulating over many months or years.

Muscle weakness, muscle atrophy and fasciculations

are the main clinical signs. Muscle weakness may be

present in non-atrophic muscles.Signs of the disease are initially asymmetric and may

remain asymmetric in some patients.Tendon reflexes in affected limbs are decreased or absent.

MMN

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In MMN, the distribution of demyelination is random

in arm nerves and that the distribution of axonal loss isin a length-dependent manner.

It is not uncommon that MMNpatients undergo unnecessary releasesurgeries after being misdiagnosed ascarpal tunnel syndrome or ulnarentrapments.The confusion is resolved by recognizing that the involvement

is multifocal and that the focal demyelinating features are not

localized to entrapment sites.

MADSAM

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MADSAM need to be differentiated from CIDP and

MMN.MADSAM neuropathy more closely resembles CIDP

and probably represents an asymmetric variant.

In MMN and MADSAM the major distinguishing

features are the clinical and electrophysiological sensoryinvolvement.

The disability is significantly higher in CIDP and

MADSAM than in DADS and MMN patients.

MADSAM neuropathy behave electrophysiologicallyas if there are a multifocal attack on peripheral nerves.

MADSAM