Acquired Neuropathies

Guillain-Barré Syndrome (GBS) and Variants

Also “acute inflammatory demyelinating polyneuropathy.” Acute onset of peripheral and cranial nerve dysfunction. Frequently preceded by respiratory or gastrointestinal infection immunization, or surgery.

Incidence: 0.6 to 1.9/100,000 persons/year. Most frequent acquired demyelinating neuropathy.
Symptoms and signs: rapidly progressive (days); symmetric limb weakness, loss of tendon reflexes, facial diplegia, oropharyngeal and respiratory weakness, paresthesias and impaired sensation in hands and feet. About 20% require mechanical ventilation.
Variants: acute motor axonal neuropathy (AMAN): motor axonal degeneration; little or no demyelination or inflammation. Many follow Campylobacter jejuni infection. Miller-Fisher syndrome: triad of gait ataxia, areflexia, ophthalmoparesis; sometimes pupillary abnormalities. Nerve conduction normal. CSF changes as in GBS.
Laboratory data: elevated CSF protein, normal cell count. Nerve conduction slow; often normal at first. AMAN: anti-GM₁ or GD_1a ganglioside antibodies. Miller-Fisher: anti-GQ_1b antibodies.
Pathology: focal segmental demyelination with perivascular and endoneurial infiltrates of lymphocytes and monocytes or macrophages.
Differential diagnosis: acute West Nile viral infection (can present as acute paralytic syndrome), HIV neuropathy, porphyric neuropathy, toxic neuropathy (n-hexane, thallium, arsenic), botulism, tick paralysis.
Course: worsens for days to 3 weeks; then plateaus, followed by gradual improvement to normal or nearly normal function. Autonomic instability (blood pressure instability, arrhythmia) may seriously complicate course.
Treatment: early plasmapheresis or IVIG accelerates recovery, reduces long-term neurologic disability. Intensive care unit observation, mechanical ventilation, aspiration precautions. Mortality 5%.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Clinical features: insidious or acute onset limb weakness, depressed tendon reflexes, impaired sensation. Often follows viral infection.
Laboratory data: CSF protein usually increased. Slow nerve conduction.
Pathology: segmental demyelination, lymphocytic infiltrates in peripheral nerves. Nerves may be enlarged.
Course: chronic progressive or relapsing.
Treatment: glucocorticoids, plasmapheresis, IVIG, immunosuppressive drugs often beneficial.

Multifocal Motor Neuropathy

Weakness, wasting, fasciculation with active or absent tendon reflexes. Can mimic ALS (lower motor neuron syndrome). Often asymmetric. Nerve conduction studies define multifocal motor conduction block. Anti-GM₁, anti-GD_1a antibodies sometimes found. Reversible with IVIG or immunosuppressive drug therapy.

Sensory Neuronopathy and Neuropathy

Numbness, paresthesias, pain; distal, radicular, or whole body; tendon reflexes present or absent; normal strength. EMG: reduced or absent sensory potentials. CSF protein normal or slightly elevated. Variable response to glucocorticoids or immunosuppressive therapy.

Etiology: autoimmune disease, HIV-1 infection, vitamin B₆ deficiency, paraneoplastic neuropathy, amyloidosis, toxic neuropathy.

Idiopathic Autonomic Neuropathy

Acute or subacute onset of postural syncope, diminished tearing, sweating; impaired bladder function; marked intestinal dysmotility; diminished sexual potency in men. May follow viral infection. Self-limited, with partial or complete recovery.

Vasculitic and Cryoglobulinemic Neuropathies

Mononeuritis multiplex or distal symmetric polyneuropathy. Nerve and muscle biopsies: inflammatory cell infiltrates, necrosis of blood vessel walls.

Vasculitis confined to peripheral nerves or associated with systemic disease: periarteritis nodosa, cryoglobulinemia, Churg-Strauss syndrome, Sjögren syndrome, Wegener granulomatosis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis.

May respond to prednisone, cyclophosphamide. Plasmapheresis for cryoglobulinemia.

Neuropathies with Myeloma or Nonmalignant IgG or IgA Monoclonal Gammopathy

Peripheral neuropathy in 50% of patients with osteosclerotic myeloma and immunoglobulin G (IgG) or IgA monoclonal gammopathy. Also with primary amyloidosis, cryoglobulinemia. Demyelination, axonal degeneration both present.

Neuropathies with IgM Monoclonal Antibodies that React with Peripheral Nerve Glycoconjugate Antigens