Anti NMDA Receptor Encephalitis

Anti NMDA receptor encephalitis is the commonest autoimmune encephalitis, with antibodies to the GluN1 subunit.

• Typically young women (80%), also children and men; ovarian teratoma in 40 to 50% of women aged 18 to 45; less in children and men.

• Triggers: tumour, herpes simplex encephalitis (post infection in 20%).

• Stages: prodrome (headache, fever), psychosis, seizures and decreased responsiveness, dyskinesias and autonomic instability, hypoventilation.

• 80% substantially recover; relapse in 12%; mortality 5 to 10%.

• Psychosis, agitation, paranoia, insomnia, behavioural change, catatonia.

• Memory loss, language disturbance (mutism), seizures, orofacial dyskinesias, choreoathetosis, rigidity.

• Autonomic: tachycardia, bradycardia, hypotension, hyperthermia, central hypoventilation.

• Children: seizures, movement disorders, behavioural regression.

• Anti GluN1 IgG in CSF (essential; serum may be falsely negative).

• EEG: diffuse slowing, extreme delta brush; MRI normal in 2/3, or mild FLAIR changes.

• CSF: lymphocytic pleocytosis, oligoclonal bands.

• Tumour search: pelvic MRI, transvaginal ultrasound, CT, testicular ultrasound; repeat every 6 months for 4 years.

• Exclude HSV encephalitis (PCR), schizophrenia, neuroleptic malignant syndrome, drug intoxication.

• Teratoma removal (laparoscopic oophorectomy or cystectomy) promptly.

• First line: methylprednisolone 1 g IV daily for 5 days, IVIG 2 g/kg over 5 days, or plasma exchange 5 to 7 exchanges.

• Second line within 2 to 4 weeks of no response: rituximab 375 mg/m2 weekly for 4 doses and/or cyclophosphamide 750 mg/m2; tocilizumab 8 mg/kg monthly, bortezomib for refractory cases.

• Supportive: ICU for hypoventilation, careful sedation (benzodiazepines, avoid haloperidol), antiepileptics, autonomic management, thromboprophylaxis, nutrition, nursing for catatonia.

• Long term maintenance (mycophenolate, azathioprine) in relapsing cases or after delayed treatment.

• Rehabilitation: cognitive, psychiatric and physical, recovery takes months to over 2 years.

• Contraception counselling and follow up for relapses.