Immune-Mediated Neuropathies

Naresh Mullaguri MDNeurology Resident Physician

University of Missouri

GUILLAIN-BARRE´ SYNDROME• First described by Landry in

1859.• Guillain, Barre´, and Strohl

revisited the syndrome more than 50 years later.

• Acute inflammatory demyelinating polyradiculoneuropathy (AIDP).

• GBS =/= AIDP (as some pt’s have axonal loss without demyelination).

• Two-thirds of patients with GBS have antecedent illness (respiratory or gastrointestinal infection) during the preceding month.

• Cytomegalovirus• Campylobacter jejuni• Mass vaccination have not been associated

with a measurable increase in GBS risk.

Clinical features

• Neuropathic symptoms of GBS typically develop rapidly over several days or a few weeks.

• The nadir is reached within the first 2 weeks in about 50% of patients and within 4 weeks in about 90%.

• Tingling and numbness in the distal limbs weakness• Symptoms usually start in the feet and spread

proximally : ‘‘ascending’’ symmetrical paralysis.• Pain (low back pain or as a prickly, burning, or aching

pain of the limbs) is common in GBS and may overshadow the presence of weakness.

Neurologic examination• Acute period : symmetrical

weakness (arms, legs, and sometimes facial muscles) and areflexia (70%).

• Mild sensory loss• Oculomotor paralysis• Autonomic instability• Acute worsening is very

rapid, with perceptible deterioration within only a few hours

Variations of GBS

‘‘descending’’ pattern

Simultaneous weakness in both the arms and the legs

Pharyngeal-cervical-brachial variant

Miller Fisher syndrome (ophthalmoplegia, ataxia, and areflexia)

Multiple cranial neuropathies

Paraplegia or paraparesis

Laboratory Features

Nonspecific:• Albuminocytologic dissociation : nonspecific

and is seen in infectious, neoplastic, vascular, and inflammatory disorders of the brain and spinal cord

• Mild pleocytosis• Gadolinium enhancement of the spinal roots

EMG in GBS

• Early : small-amplitude compound muscle action potentials (CMAPs), prolonged distal motor latencies, and delayed or absent F waves.

• 2nd week : moderate or severe slowing of motor nerve conduction velocities, conduction block, and temporal dispersion

• Needle EMG examination of weak muscles should show reduced recruitment and high firing rate ofmotor units, although fibrillation potentials and positive sharp waves take 2 to 4 weeks to appear

Differential Diagnosis of Guillain-Barre´ Syndrome

A number of diseases, notably myelopathies,neuromuscular junction disorders,and some acute neuropathies, domimic GBS

Management• Hospital admission and close monitoring (continuous pulse oximetry,

respiratory monitoring should include frequent bedside spirometry and measurements of inspiratory and expiratory pressures).

• Plasmapheresis and IV immunoglobulin (IVIg) appear to be equally efficacious in GBS when given within the first 1 to 2 weeks of the disease

• Corticosteroids are not effective• Selection of one over the other depends on the availability and the

relative contraindications• Renal disease or serious vascular risk factors, IVIg is often preferred• About 2% to 6% of patients with Guillain-Barre´ syndrome have a

subsequent relapse.

CHRONIC INFLAMMATORYDEMYELINATING

POLYNEUROPATHIES• The clinical classification

is based on the clinical features, laboratory findings, and associated systemic diseases

• CIDP may also appear in the setting of several systemic diseases.

Classic (Idiopathic) ChronicInflammatory Demyelinating

Polyneuropathy

• Insidious clinical course: Weakness and sensory loss develop over many weeks or several months.

• Any age group but less prevalent in Pediatric population.

• No antecedent illness

Clinical features

• Progressive limb weakness is a nearly universal presenting symptom.

• Patients may have increasing difficulty rising from a chair, going upstairs, opening jars, or lifting objects.

• Numbness and tingling in the hands and feet accompany the weakness.

• Pain is infrequent.

Neurological examination

• Symmetric proximal and distal weakness affecting both arms and legs.

• Facial or extraocular weakness is uncommon.• Bulbar and respiratory weakness are also rare.• Reduced or absent DTR’s• Distal sensory loss is common on examination

EMG in CIDP• Demyelination is demonstrated

on nerve conduction study by the presence of conduction block or temporal dispersion in the CMAPs.

• Motor nerve conduction velocity below 80% of the lower limit of normal

• * Provided if these focal abnormalities are present outside commonnerve entrapment sites

• Amplitude of the CMAPs may also be abnormally low, indicating concomitant axonal loss.

• Axonal loss accumulates as the disease progresses. This complicates the interpretation of nerve conduction velocity, as axonal loss alone can lead to some conduction slowing.

• F waves may be delayed or unrecordable.• Demyelination in CIDP is patchy or multifocal,

with different nerve segments affected to different degrees but in hereditary forms (CMT) the pattern is uniform and conduction block is uncommon

Other Dx tests

• CSF in patients with CIDP shows a moderately elevated protein level without pleocytosis – nonspecific (diabetic neuropathy and infectiousor carcinomatous infiltration of spinal roots)

• Nerve biopsy only when the typical clinical or electrophysiologic features are absent.

• Recurring segmental demyelination and remyelination accompanied by thinly myelinated fibers or a loss of myelinated fibers.

Treatment of CIDP

Chronic Inflammatory Demyelinating Polyneuropathies: Classification By

Weakness and Sensory Loss Patterns

Multifocal Motor Neuropathy

• MMN presents with subacute onset of asymmetric weakness.

• Weakness starts focally as a mononeuropathy, usually in the distal upper limbs ---> spread to contralateral hand, and both legs

• Fasciculations and cramps +/-, muscle bulk maintained until late in the disease.

• DTR – diminished/normal/brisk• Involvement of the cranial nerves, bulbar muscles,

phrenic nerves, and respiratory muscles - rare

• The CSF protein is normal in multifocal motor neuropathy.

• Approximately half of patients with MMN have elevated serum antibodies directed against gangliosides, especially GM1

• EMG: patchy focal demyelination in motor nerves with conduction block and normal sensory nerve conduction study

• Multifocal motor neuropathy primarily responds only to IV immunoglobulin.

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