Autoimmune Encephalitis

Autoimmune encephalitis is a group of immune mediated brain inflammatory disorders with antibodies to neuronal surface or intracellular antigens.

• Surface antibodies (treatable): NMDA receptor, LGI1, CASPR2, AMPA, GABA B, GABA A, DPPX, IgLON5, mGluR5.

• Intracellular (paraneoplastic, T cell mediated, poorer response): Hu, Ma2, CV2, amphiphysin, GAD65.

• Incidence of about 1 per 100,000; tumours associated in 20 to 50% depending on antibody.

• Subacute onset (under 3 months) of memory deficits, psychiatric features, seizures, movement disorders.

• Rapidly progressive short term memory loss, confusion, psychosis, agitation, seizures (including faciobrachial dystonic seizures in LGI1), dyskinesias, autonomic instability, hyponatraemia (LGI1), sleep disorder.

• Reduced consciousness or catatonia in severe disease.

• Relapse in 12 to 25%.

• Graus criteria (possible, probable, definite): subacute onset, plus MRI (medial temporal FLAIR hyperintensity), CSF pleocytosis, or EEG abnormality, exclusion of other causes.

• Antibody testing in serum and CSF (CSF is more sensitive for NMDA receptor; serum for LGI1).

• MRI brain, EEG (extreme delta brush in NMDA), CSF cell count, protein, oligoclonal bands, infectious PCR (HSV).

• Tumour screening: CT chest/abdomen/pelvis, pelvic MRI/transvaginal ultrasound (ovarian teratoma), testicular ultrasound, mammography, PET CT.

• Exclude infections, Creutzfeldt-Jakob disease, primary psychiatric illness, metabolic disease.

• First line immunotherapy (start early, even while awaiting antibody results): methylprednisolone 1 g IV daily for 3 to 5 days, plus IVIG 2 g/kg over 5 days or plasma exchange (5 to 7 sessions).

• Tumour removal (teratoma resection) as soon as feasible.

• Second line if no improvement in 2 to 4 weeks: rituximab 375 mg/m2 weekly for 4 doses (or 1 g x 2), cyclophosphamide 750 mg/m2 monthly; tocilizumab, bortezomib for refractory cases.

• Maintenance in relapsing disease: mycophenolate mofetil 1 g twice daily, azathioprine 2 mg/kg for 6 to 12 months.

• Symptomatic: antiseizure drugs (levetiracetam, lacosamide), antipsychotic cautiously (low dose), benzodiazepines, avoid haloperidol in catatonia/NMS-like risk.

• ICU support, neurorehabilitation; recovery takes months.

• Repeat tumour screening for up to 4 years.