Multifocal Motor Neuropathy

Multifocal motor neuropathy is a rare, immune mediated, chronic, asymmetric, purely motor neuropathy that causes slowly progressive weakness without sensory loss, with conduction block on nerve conduction studies. It is treatable with immunoglobulin.

The prevalence is about 0.6 to 2 in every 100,000 people, with an incidence of about 0.3 in every 100,000 each year. Men are affected about 2 to 3 times more than women, and onset is usually between 20 and 50 years.

Immunology. IgM antibodies against GM1 ganglioside are found in 30 to 80% of cases.

Course. Slowly progressive asymmetric weakness, mostly of the arms, with wasting later and accumulating axonal loss if untreated. Most patients respond to immunoglobulin, but responses wane over years.

Pathophysiology.

Anti-GM1 antibodies bind nodes of Ranvier on motor axons and, with complement activation, impair nerve conduction, producing conduction block.

Chronic block leads to axonal degeneration and muscle wasting.

• Asymmetric distal weakness of the hand, wrist and foot (for example wrist drop or finger extension), following individual nerve territories.
• Muscle cramps, fasciculations and myokymia; wasting develops later.
• Reflexes reduced in weak limbs but may be normal or brisk.
• No sensory loss or only minor; no bulbar or upper motor neuron signs.

Red flags.

• Upper motor neuron signs, bulbar weakness or respiratory involvement (motor neurone disease).
• Sensory loss or a rapid course (chronic inflammatory demyelinating polyneuropathy, vasculitis).
• Weakness worsening after corticosteroids or plasma exchange.

• Nerve conduction studies showing motor conduction block outside usual entrapment sites, in at least two nerves, with normal sensory conduction.
• Anti-GM1 IgM antibodies (supportive but not essential); normal or mildly raised cerebrospinal fluid protein.
• Ultrasound or MRI of nerves showing enlargement; MRI of the brachial plexus and spine to exclude other causes.
• Electromyography showing chronic denervation; creatine kinase and serum protein electrophoresis.
• Exclude HIV, diabetes, lymphoma, paraproteinaemia and lead exposure.

Differential diagnosis. Motor neurone disease, chronic inflammatory demyelinating polyneuropathy (Lewis-Sumner variant), hereditary neuropathy with liability to pressure palsies, cervical radiculopathy, spinal muscular atrophy, inclusion body myositis and compressive neuropathy.

• Intravenous immunoglobulin, first line: 2 g/kg in total given over 2 to 5 days for induction. Maintenance 1 g/kg every 2 to 4 weeks, or 2 g/kg every 4 to 8 weeks, adjusted to response. Maximum 2 g/kg in any 4 week period. Infusion rate is set by the product label, starting slowly. Monitor renal function, blood pressure, hypersensitivity, haemolysis, aseptic meningitis, thrombosis and fluid overload; check IgA before the first dose. Avoid in IgA deficiency with anti-IgA antibodies and in severe heart failure; use caution in renal impairment, diabetes and older adults; slow the infusion in those with thrombosis risk. Review need by reducing dose or extending the interval every 6 to 12 months.
• Subcutaneous immunoglobulin as an alternative for maintenance, at a weekly dose equal to the intravenous dose divided by the interval in weeks, adjusted to response, under specialist supervision.
• Corticosteroids and plasma exchange are not effective and may worsen weakness; avoid them.
• Second line immunosuppression (cyclophosphamide or rituximab) for patients who fail immunoglobulin, by specialist centres, with careful consideration of risk.
• Physiotherapy, occupational therapy, splints and hand function aids.
• Cramp management with stretching.

Monitoring. Assess strength and function monthly at first, then every 3 months; repeat nerve conduction studies yearly; monitor renal function and IgG levels where relevant.

Referral and escalation. Neuromuscular specialist for diagnosis and immunoglobulin; haematology or immunology for second line therapy.

Special groups. Pregnancy: immunoglobulin is generally acceptable with specialist advice. Older adults: higher thrombotic and renal risk.