Autoimmune encephalitis: Viva

Branch 1: Making the diagnosis

A strong candidate recognises this as a probable case of anti-NMDA receptor encephalitis and applies the Graus 2016 criteria. The diagnosis turns on the tempo and the pattern rather than on a single test. She has a rapid onset over days of psychiatric symptoms together with at least four of the six major symptom groups of probable anti-NMDAR disease: abnormal behaviour, speech dysfunction, seizures, movement disorder, decreased consciousness, and autonomic dysfunction or hypoventilation. She has an inflammatory CSF with lymphocytic pleocytosis and oligoclonal bands, and her mimics, particularly infectious encephalitis, are being excluded. A normal MRI is fully compatible with the diagnosis. The candidate sends a paired CSF and serum neural antibody panel, with CSF as the more sensitive sample, but does not wait for the result to treat. [1]

Branch 2: Mechanism and prognosis

If the examiner presses on why the prognosis in anti-NMDAR disease is usually better than in an anti-Hu syndrome, the candidate explains that the antibody target sits in different compartments. In anti-NMDAR disease the IgG binds the GluN1 subunit on the cell surface and triggers receptor internalisation and degradation, producing a functional and reversible reduction in NMDA signalling without neuronal death, which is why immunotherapy works. In an intracellular antigen syndrome such as anti-Hu the antibody cannot reach the target, so injury is mediated by cytotoxic CD8 T cells that kill neurons, which is often irreversible and explains the poorer response. [3]

Branch 3: The immunotherapy ladder and its timing

When asked how the candidate runs the ladder, the answer is to secure the airway and breathing first, treat seizures, send the workup, and start first-line immunotherapy with intravenous methylprednisolone 20 to 30 mg per kg per day, maximum 1 g, for three to five days, combined with intravenous immunoglobulin 2 g per kg over two to five days, as soon as infection is reasonably excluded. If the response is poor at 10 to 14 days, the candidate starts second-line therapy with rituximab 375 mg per m2 weekly for four weeks, or cyclophosphamide 750 mg per m2 monthly. The timing matters because Titulaer showed that early immunotherapy and early second-line therapy within the first four weeks are independent predictors of good outcome. [2][7]

Branch 4: The tumour

If a pelvic MRI shows an ovarian teratoma, the candidate arranges urgent removal, because tumour removal is the single most effective intervention in paraneoplastic anti-NMDAR disease and can transform the course. The gynaecology and surgical teams are involved early, and the tumour removal runs in parallel with the second-line immunotherapy. [2]

Branch 5: The post-herpes trap

The examiner then offers a 5-year-old boy who recovers from confirmed herpes simplex encephalitis and returns three weeks later with new choreoathetosis and seizures, with a negative repeat HSV PCR. The strong candidate recognises post-herpes autoimmune encephalitis. Around twenty percent of patients develop a secondary autoimmune encephalitis after herpes simplex virus encephalitis, usually directed against NMDAR, because viral damage exposes neuronal antigens and provokes a self-sustaining immune response. The correct response is first-line immunotherapy, not prolonged or escalated antiviral therapy, because the mechanism is autoimmune rather than recurrent infection. [11]

Branch 6: Prognosis and the family

Asked what to tell the family, the candidate quotes that most children recover well, with good outcome in around seventy-five percent within the first twenty-four months and relapse in around twelve to fifteen percent, and is honest that recovery is long, that cognitive, psychiatric, seizure, and movement disorder sequelae can outlast the acute illness by months, and that formal neuropsychological assessment and a structured school reintegration plan are part of treatment. The candidate gives the family a relapse safety-net and arranges paediatric neurology follow-up. [2]

The examiner rewards a candidate who treats on suspicion, who knows the first-line and second-line ladder with doses and timing, who removes the tumour, who recognises the post-herpes trigger, and who quotes the outcome data honestly. [2]