Anti-AMPA Receptor Encephalitis

Anti-AMPA receptor encephalitis is a rare autoimmune limbic encephalitis with antibodies to the GluA1 or GluA2 subunits of the AMPA receptor. It affects middle aged women mostly (median age about 60), and about 60 to 70% have an underlying tumour (lung, breast, thymus).

Pathophysiology. Antibodies cause reversible internalisation of AMPA receptors, with loss of synaptic function. Relapses are frequent.

Subacute amnesia, confusion, psychosis, behaviour change, seizures, and sometimes cerebellar signs. Presentation can mimic psychiatric disease. Relapse occurs in about a third.

Red flags.

• Subacute confusion and seizures in a middle aged or older woman with cancer.
• Relapse after initial improvement.

Serum and CSF antibodies against AMPA receptor by cell based assay. MRI shows medial temporal T2 or FLAIR hyperintensity (in about 50%) or may be normal. CSF shows mild pleocytosis and oligoclonal bands. EEG shows temporal slowing or epileptiform activity. Search for tumour: CT chest, abdomen and pelvis, mammography and FDG-PET, repeated if negative.

Differential diagnosis.

• Herpes simplex virus encephalitis, other limbic encephalitis (LGI1, GABA-B receptor, paraneoplastic).
• Primary psychiatric illness, Hashimoto encephalopathy and Creutzfeldt-Jakob disease.

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 (5 sessions).
• Second line: rituximab 1 g IV twice, 2 weeks apart, or cyclophosphamide 750 mg/m2 IV monthly.
• Maintenance in relapsing disease: mycophenolate mofetil 1 g twice daily or azathioprine 2 to 3 mg/kg daily.

Tumour. Resect and treat the tumour, since this reduces relapses.

Seizures. Levetiracetam 500 to 1500 mg twice daily (adjust to eGFR), and avoid sodium channel blockers if hyponatraemia.

Supportive care. Antipsychotics only if essential (low dose), cognitive rehabilitation and psychological support.

Monitoring. Cognition, MRI, relapse and tumour surveillance for 4 years.

Referral and escalation. Refer urgently to neurology and oncology.