CLINICAL AND ELECTROPHSIOLOGICAL ASSESMENT OF VARIOUS CHRONIC ACQUIRED DEMYLINATING POLYNEUROPATHY PHENOTYPES

Clinical scheme for approaching chronic acquired demylinating polyneuropathy. CADP

CIDP
With proximal muscles involvement

MADSAM
DADS
with sensory involvement

MMN
Without sensory involvement

Without proximal muscles involvement

Symmetrical pattern of weakness

Asymmetrical pattern of weakness

Distal Acquired Demyelinating Symmetric (DADS ) Neuropathy :

DADS is a distal acquired demyelinating symmetric polyneuropathy that presents predominantly with sensory symptoms. Patients with symmetric, length dependent, distal sensory or distal sensory>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.

Antibodies: Length Dependent Neuropathies

DADS-M Neuropathy
Distal Acquired Demyelinating Symmetric Sensory Neuropathy with IgM

Anti-MAG
IgM only

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 studies demonstrate widespread uniform distal slowing with absence of conduction block. Absence of multifocality and conduction block supports the diagnosis of DADS .

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.

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.

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.

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 two distinct motor nerves and lasting at least two months with minimal or no sensory symptoms and absence of clinical signs of upper motor neuron involvement - MMN is characterized by slowly progressive asymmetrical weakness and muscle atrophy, which may be accompanied by cramps, fasciculations, and myokymia. - 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 generally consistent with the degree of weakness. -

- The disease usually begins and remains more prominent in the upper extremities. The most striking clinical feature is the multifocal distribution of the weakness, which, in the beginning, may be localized within the territory of individual peripheral nerves.
MMN is more common in males (the male-to-female ratio is about 3:1). The age at onset of symptoms is usually early in the fifth decade of life, ranging from the second to eight decade of life .

 History: Typically, MMN manifests with a slowly progressive, asymmetric, predominantly distal weakness developing over years. Weakness usually starts in a distribution of a single peripheral nerve with unilateral intrinsic hand weakness, wrist drop or foot drop. Initial involvement of the distal upper extremities is most common. Typically diagnosis is delayed by several years because of slow insidious progression and misdiagnosis of the disorder. However the diagnosis is not difficult if the condition is kept in mind.

Clinical and electrodiagnostic criteria for the diagnosis of MMN include the following: Weakness without objective sensory loss in the distribution of 2 or more nerves is present. Definite conduction block is present in 2 or more motor nerves outside of common entrapment sites. Sensory nerve conduction velocity is normal across the segments with demonstrated motor conduction block. Results are normal for sensory nerve conduction studies on all tested nerves, with a minimum of 3 nerves tested. Upper motor neuron signs, including spasticity, clonus, extensor plantar response, and pseudobulbar palsy are absent.

 Physical examination reveals weakness in a multifocal pattern in the upper and lower limbs, paralleling peripheral nerves as opposed to the spinal segmental root distribution seen in most neuron diseases. Weakness is often more pronounced than the degree 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

Electrodiagnostic Studies
Because of the multifocal nature of the disease extensive standardized bilateral electrophysiological examination should 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.

 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 with demonstrated motor conduction block.

This helps to differentiate MCB in MMN from other entities, which typically show blocks to both motor and sensory conductions.

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.

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:

1-Amyotrophic Lateral Sclerosis (ALS). 2-Chronic Inflammatory Demyelinating Polyradiculoneuropathy. 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

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).

Patients with Multifocal Acquired Demyelinating Sensory and Motor (MADSAM) neuropathy ( LewisSumner syndrome ): MADSAM is a dysimmune multifocal demyelinating sensorimotor neuropathy. It is considered as a clinical asymmetrical variant of chronic immune demyelinating polyneuropathy (CIDP); it is five times less frequent than CIDP

Phenotype-MADSAM Neuropathy
Sensory and Motor Often painful Hands more than ankles Individual Nerves Stepwise Slowing, CB, TD
Prednisone or IVIg (50%)

Phenotype-MADSAM Neuropathy
Key DDx:
Brachial plexopathy Vasculitic mononeuropathy multiplex Compression neuropathies HNPP (genetic testing)

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 complete areflexia.

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 .

summary
Patients with suspected CADP, should not be considered 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.

Classic CIDP:
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.

 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.

 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.

 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 characteristic of CIDP. partial conduction block is located mainly at the intermediate mid forearm segment of median and ulnar nerves.

With

studying evidence of conduction block, the need for less demyelinating elements of NCS is required.

There are 5 criteria for demyelination (prolonged distal motor latencies, slowed conduction velocity, delayed or absent F waves, conduction block and/ abnormal temporal dispersion.

DADS:
slowly progressive course, with only distal symptoms, and the weakness is confined to the distal lower limbs in a symmetric fashion. nerve conduction study : DADS patients presented with prolonged distal motor latencies. Absence of mutifocality and conduction block.

MMN
In MMN, limb weakness without sensory loss is asymmetric in the distribution of individual peripheral nerves 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.

 In MMN, the distribution of demyelination is random in arm nerves and that the distribution of axonal loss is in a length-dependent manner.

It is not uncommon that MMN patients undergo unnecessary release surgeries after being misdiagnosed as carpal tunnel syndrome or ulnar entrapments.

The confusion is resolved by recognizing that the involvement
is multifocal and that the focal demyelinating features are not localized to entrapment sites.

MADSAM
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 sensory involvement. The disability is significantly higher in CIDP and MADSAM than in DADS and MMN patients. MADSAM neuropathy behave electrophysiologically as if there are a multifocal attack on peripheral nerves.