Glycine Receptor Antibody Disease

Glycine receptor antibody disease is an autoimmune disorder of the alpha1 subunit of the glycine receptor, causing progressive encephalomyelitis with rigidity and myoclonus, stiff person syndrome and, less often, other presentations. It occurs in adults (median age about 50) and, rarely, in children.

Tumour (thymoma, lymphoma, lung cancer) is found in a minority (about 10%).

Pathophysiology. Antibodies block the glycine receptor and cause loss of inhibitory control of brainstem and spinal motor neurons, with muscle stiffness, spasms and startle.

Stiffness and painful spasms of the trunk and limbs, exaggerated startle, brainstem signs (diplopia, nystagmus, dysphagia), myoclonus, ataxia, cognitive change and autonomic features (sweating, bladder dysfunction). Respiratory failure can occur. Hyperekplexia is described in children.

Red flags.

• Laryngospasm, respiratory compromise or severe dysautonomia.
• Rapid progression over weeks.

Serum glycine receptor antibodies by cell based assay (CSF may increase sensitivity). Electromyography shows continuous motor unit activity. CSF may show mild pleocytosis or oligoclonal bands. MRI is often normal. Check anti-GAD65, amphiphysin and other antibodies, and search for thymoma and cancer (CT chest, FDG-PET).

Differential diagnosis.

• Stiff person syndrome (anti-GAD65), neuromyotonia, tetanus and strychnine poisoning.
• Progressive encephalomyelitis with rigidity and myoclonus of other cause, and DPPX antibody encephalitis.
• Hereditary hyperekplexia and dystonia.

Symptomatic. Diazepam 2 to 5 mg orally, three times daily, increased gradually, or clonazepam 0.5 mg twice daily, increased to 2 to 4 mg daily. Baclofen 5 mg three times daily, increased to 30 to 80 mg daily in divided doses (do not stop suddenly). Avoid abrupt benzodiazepine withdrawal. Add gabapentin or levetiracetam for spasms and myoclonus.

Immunotherapy.

• Methylprednisolone 1 g IV daily for 3 to 5 days, then prednisolone taper.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange.
• Rituximab 1 g IV twice, 2 weeks apart, or azathioprine, mycophenolate or cyclophosphamide for relapsing disease.

Tumour. Resect thymoma and treat cancer.

Respiratory care. Monitor for laryngospasm and respiratory failure, with early intensive care involvement.

Monitoring. Spasms, function and relapse, with tumour surveillance.

Referral and escalation. Refer to neurology.