Neuromyotonia

Neuromyotonia is a disorder of peripheral nerve hyperexcitability with continuous muscle fibre activity, causing stiffness, myokymia, cramps and delayed relaxation. It may be acquired (autoimmune, paraneoplastic or toxic), hereditary (potassium channel gene variants) or associated with neuropathy and drugs. Isaacs syndrome and Morvan syndrome are forms.

Causes include voltage gated potassium channel complex antibodies (CASPR2, LGI1), thymoma, lung cancer, lymphoma, hereditary neuropathy, radiation, gold, and toxins (mercury, penicillamine).

Pathophysiology. Reduced potassium channel function causes ectopic, repetitive firing of the distal motor axon.

Muscle twitching, cramps, stiffness and slowed relaxation, hyperhidrosis, and worsening with exertion, with persistence during sleep. Features of the cause may be present: thymoma or cancer, neuropathy or encephalopathy.

Electromyography shows neuromyotonic discharges, doublets, triplets and multiplets at high frequency (40 to 300 Hz), which persist during sleep or after nerve block. Test for CASPR2, LGI1 and other antibodies. Check calcium, magnesium, potassium, thyroid function, creatine kinase, and glucose. Screen for thymoma and cancer. Review drugs and toxin exposure.

Differential diagnosis.

• Cramp fasciculation syndrome, stiff person syndrome and myotonic disorders.
• Tetany (hypocalcaemia), hypomagnesaemia, tetanus and benign fasciculation.
• Motor neuron disease and chronic neuropathy.

Treat the cause. Remove thymoma or cancer, stop the offending drug, and correct metabolic abnormalities.

Symptomatic drugs (sodium channel blockers).

• Carbamazepine 100 mg twice daily, increased to 200 to 400 mg twice daily (maximum 1200 mg daily).
• Phenytoin 300 mg daily with levels, lamotrigine, or mexiletine 150 mg twice daily, increased to 200 mg three times daily (avoid with heart block).
• Gabapentin or pregabalin for pain and cramps.
• Acetazolamide for some inherited forms, with monitoring of bicarbonate.

Immunotherapy. For antibody mediated disease: plasma exchange or intravenous immunoglobulin 0.4 g/kg daily for 5 days, with prednisolone and steroid sparing agents.

Monitoring. Sodium and liver tests (carbamazepine), heart rhythm (mexiletine), and symptoms.

Referral and escalation. Refer to neurology.

Special groups. In pregnancy, discuss carbamazepine with neurology and give folic acid 5 mg daily.