Morvan Syndrome

Morvan syndrome is a rare autoimmune disorder combining peripheral nerve hyperexcitability, autonomic dysfunction, severe insomnia and encephalopathy with hallucinations. It is mainly associated with CASPR2 antibodies (sometimes with LGI1). Over 80% are men, with a median age of about 60 years, and thymoma occurs in 30 to 40% of cases.

Pathophysiology. Antibodies to the voltage gated potassium channel complex cause neuronal hyperexcitability in the peripheral nerve, autonomic system and limbic and thalamic circuits.

Neuromyotonia (myokymia, cramps, stiffness), pain, hyperhidrosis, tachycardia, hypertension, constipation, urinary dysfunction, weight loss, profound insomnia with loss of normal sleep structure, confusion, agitation, hallucinations and memory loss. The condition can be fatal from autonomic and sleep failure.

Red flags.

• Severe insomnia with confusion and autonomic instability.
• Dangerous arrhythmia or weight loss.

Serum and CSF CASPR2 and LGI1 antibodies by cell based assay. Electromyography shows neuromyotonic and myokymic discharges. Polysomnography shows disrupted sleep architecture. MRI is often normal. Screen for thymoma and other tumour with CT chest and FDG-PET, and repeat if negative. Check sodium and thyroid function.

Differential diagnosis.

• Isaacs syndrome (no encephalopathy), limbic encephalitis and delirium tremens.
• Fatal familial insomnia and Creutzfeldt-Jakob disease.
• Thyrotoxicosis and drug withdrawal.

Immunotherapy (first line).

• Methylprednisolone 1 g IV daily for 3 to 5 days, then prednisolone 1 mg/kg daily with slow taper.
• Plasma exchange (5 exchanges) or intravenous immunoglobulin 0.4 g/kg daily for 5 days.
• Rituximab 1 g IV twice, 2 weeks apart, or cyclophosphamide for poor response. Azathioprine or mycophenolate mofetil for maintenance.

Tumour. Resect thymoma, as this improves outcome.

Symptom control. Carbamazepine 100 mg twice daily, increased to 200 to 400 mg twice daily, for hyperexcitability, and clonazepam for sleep and cramps. Treat autonomic features and arrhythmia, and give nutrition support.

Sleep. Short term sedative hypnotics with care, as sleep often recovers with immunotherapy.

Prognosis. Most improve with early therapy, and relapse can occur.

Monitoring. Heart rhythm, blood pressure, weight, cognition, antibody levels where used, and tumour surveillance.

Referral and escalation. Refer urgently to neurology.