Autoimmune Epilepsy

Autoimmune epilepsy is epilepsy with seizures as the main manifestation of a central nervous system autoimmune process, with neural specific antibodies or immune mediated inflammation, and with no or minor features of encephalitis. It differs from acute symptomatic seizures in autoimmune encephalitis, which resolve with treatment. Antibodies include anti-GAD65, LGI1, CASPR2, NMDA receptor, GABA-B receptor, AMPA receptor and others.

Seizures are drug resistant, and clues include a subacute onset, multiple seizure types, faciobrachial dystonic seizures, cognitive and psychiatric change, autonomic features, and other autoimmune disease or cancer.

Pathophysiology. Antibodies to surface antigens alter receptor function and cause hyperexcitability. Intracellular antigen antibodies (GAD65) mark T-cell mediated neuronal injury with poorer response to treatment.

Frequent, drug resistant focal seizures, often temporal (anti-LGI1: faciobrachial dystonic seizures, hyponatraemia, memory loss), with memory impairment, behavioural change, sleep disturbance, dysautonomia, movement disorder and, in anti-GAD65 disease, stiff person features, diabetes and ataxia.

Red flags.

• Faciobrachial dystonic seizures.
• Rapid cognitive decline or psychosis with seizures.
• Status epilepticus without cause.

Serum and CSF neural antibodies (cell based assays), CSF cell count, protein and oligoclonal bands. MRI (medial temporal T2 and FLAIR hyperintensity, or normal). EEG and prolonged video EEG. FDG-PET may show temporal hyper- or hypometabolism. Cancer screening (CT chest, abdomen and pelvis, testicular and pelvic imaging, FDG-PET). Exclude infection and structural causes.

Differential diagnosis.

• Non-immune epilepsy (mesial temporal sclerosis, cortical dysplasia).
• Infectious encephalitis, metabolic and mitochondrial disease.
• Psychiatric disorder and Creutzfeldt-Jakob disease.

Immunotherapy. Offer a time limited course, with treatment evaluated after 2 to 3 months.

• Methylprednisolone 1 g IV daily for 3 to 5 days, then prednisolone taper, or oral prednisolone 1 mg/kg daily.
• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, or plasma exchange.
• Second line: rituximab 1 g IV twice, 2 weeks apart, cyclophosphamide, mycophenolate mofetil 1 g twice daily, or azathioprine 2 to 3 mg/kg daily.

Antiseizure drugs. Sodium channel blockers (carbamazepine, oxcarbazepine, lacosamide) respond best in anti-LGI1 and CASPR2 disease. Levetiracetam, valproate and others as needed. Seizures often respond poorly to antiseizure drugs alone.

Tumour. Treat any underlying cancer.

Cognition and mood. Rehabilitation and psychiatric care.

Monitoring. Seizure frequency, antibody titres, MRI and drug adverse effects.

Referral and escalation. Refer to neurology and epilepsy services with autoimmune expertise.