Anti-GABA-A Receptor Encephalitis

Anti-GABA-A receptor encephalitis is a rare autoimmune encephalitis with antibodies to the alpha1, beta3 or gamma2 subunits of the GABA-A receptor. It affects all ages (children and adults), often with refractory seizures and status epilepticus, and has a lower rate of tumour (about 25%, thymoma) than other forms.

Pathophysiology. Antibodies reduce synaptic GABA-A receptor density, resulting in cortical hyperexcitability. The effect is reversible.

Rapid onset of refractory seizures (often multifocal status epilepticus, and epilepsia partialis continua), encephalopathy, cognitive impairment, behavioural change, psychosis, movement disorders and sleep disturbance. Other autoimmune disease or other antibodies may be present.

Red flags.

• New refractory status epilepticus without cause.
• Encephalopathy with multifocal cortical lesions on MRI.

Serum and CSF GABA-A receptor antibodies by cell based assay (CSF more specific). MRI shows multifocal, asymmetric cortical and subcortical T2 or FLAIR hyperintensities. EEG shows epileptiform discharges and slowing. CSF shows mild pleocytosis and raised protein in about half. Screen for thymoma with CT chest, and for other tumour.

Differential diagnosis.

• Herpes simplex virus and other infective encephalitis.
• Anti-NMDA receptor, anti-GABA-B receptor and other autoimmune encephalitis.
• Mitochondrial disease (MELAS), CNS vasculitis and Creutzfeldt-Jakob disease.

Status epilepticus. Lorazepam 4 mg IV, then levetiracetam 60 mg/kg IV (maximum 4500 mg) or valproate 40 mg/kg IV, with anaesthetic agents (midazolam, propofol) and intensive care for refractory status.

Immunotherapy. Start early.

• 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 cyclophosphamide, for poor response.

Tumour. Remove thymoma when found.

Supportive care. Rehabilitation, neuropsychology and prolonged antiseizure therapy until seizure free, with a slow taper.

Prognosis. Most respond to immunotherapy, though recovery takes months.

Monitoring. Seizures, cognition, MRI at 3 to 6 months, and tumour surveillance.

Referral and escalation. Refer urgently to neurology and intensive care.

Special groups. In children, doses of immunotherapy are weight based (immunoglobulin 0.4 g/kg daily, methylprednisolone 20 to 30 mg/kg, maximum 1 g).