Anti-GABA-B Receptor Encephalitis

Anti-GABA-B receptor encephalitis is an autoimmune limbic encephalitis with antibodies to the B1 subunit of the GABA-B receptor, with early severe seizures. About 50% (up to 60%) are paraneoplastic, mostly small cell lung cancer, and it is more common in men over 60 years.

Pathophysiology. Antibodies block receptor function, reducing inhibitory signalling and causing hyperexcitability. The effect is reversible with treatment.

Rapid onset (days to weeks) of seizures (often presenting symptom, may be status epilepticus), memory loss, confusion, psychiatric features, ataxia, opsoclonus and sleep disturbance. Some have anti-Kelch-like protein 11, anti-SOX1 or other co-antibodies.

Red flags.

• Refractory seizures with encephalopathy in a smoker.
• Status epilepticus.

Serum and CSF GABA-B receptor IgG by cell based assay. MRI shows medial temporal T2 or FLAIR hyperintensity (in about 70%) or may be normal. EEG shows temporal epileptiform activity. CSF shows mild pleocytosis and oligoclonal bands. Search for small cell lung cancer: CT chest, then FDG-PET if negative, and repeat at 3 to 6 months. Check thyroid antibodies and co-antibodies (SOX1, KLHL11).

Differential diagnosis.

• Herpes simplex virus encephalitis and other viral encephalitis.
• Anti-LGI1, anti-NMDA receptor and other autoimmune encephalitides.
• Non-convulsive status epilepticus and Creutzfeldt-Jakob disease.

Seizures. Treat status epilepticus: lorazepam 4 mg IV (0.1 mg/kg), then levetiracetam 60 mg/kg IV (maximum 4500 mg) or valproate 40 mg/kg IV. Seizures often respond poorly to antiseizure drugs alone and improve with immunotherapy.

Immunotherapy. Start early.

• Methylprednisolone 1 g IV daily for 3 to 5 days.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange.
• Second line: rituximab 1 g IV twice, 2 weeks apart, or cyclophosphamide 750 mg/m2 IV monthly.

Tumour. Treat small cell lung cancer with chemotherapy and radiotherapy, with oncology.

Supportive care. Sedation and ventilation in refractory status epilepticus, rehabilitation and neuropsychiatric support.

Prognosis. Good response to treatment in about 70 to 80%, but prognosis depends on tumour.

Monitoring. Seizure frequency, cognition, MRI and cancer surveillance.

Referral and escalation. Refer urgently to neurology, with intensive care for refractory seizures, and oncology.