Autoimmune Encephalitis
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Direct answer
Subacute onset is the first clue to autoimmune encephalitis: working-memory deficits, psychiatric change or depressed consciousness evolving over under three months, in a patient whose MRI may show medial temporal T2 hyperintensity, EEG may show focal slowing, and CSF may show mild pleocytosis — the Graus criteria assemble these into possible, and antibody or cancer evidence upgrades to probable or definite. Anti-NMDA-receptor encephalitis is the archetype: prodromal fever, then psychosis and catatonia, then seizures, orofacial dyskinesia, autonomic storms and hypoventilation needing intensive care, with ovarian teratoma as the adult trigger and CSF antibody more sensitive than serum. LGI1 encephalitis affects older men with faciobrachial dystonic seizures, hyponatraemia and rapid memory decline and is rarely paraneoplastic. Treatment is a fixed ladder — methylprednisolone, immunoglobulin and plasma exchange as first line, rituximab and cyclophosphamide as second — and delay to second-line therapy is the strongest modifiable predictor of poor outcome.
What you must remember
- Graus 2016 possible-AE criteria: subacute (<3 months) working-memory deficit, seizures, psychiatric symptoms or level-of-consciousness change, plus at least one of new focal CNS signs, CSF pleocytosis, EEG focal slowing or MRI medial temporal hyperintensity — with reasonable exclusion of alternatives.
- Anti-NMDAR clinical choreography: prodrome (fever, viral-like illness), psychiatric stage (psychosis, insomnia, catatonia — often first admission to psychiatry), neurologic stage (seizures, dyskinesia especially orofacial and limb choreoathetosis, dysautonomia, central hypoventilation), prolonged recovery over months.
- Anti-NMDAR workup: CSF and serum antibody (CSF is the more sensitive), pelvic ultrasound or CT for teratoma in women, EEG extreme delta brush in a subset, MRI normal in many.
- LGI1: faciobrachial dystonic seizures — brief, frequent, ipsilateral arm-face dystonic posturing — often precede cognitive decline by months and respond to immunotherapy, not antiepileptics; hyponatraemia is a bonus clue; thymoma rare.
- Other surface targets in one breath: GABA-B receptor — status epilepticus with small cell lung cancer; GABA-A receptor — refractory multifocal seizures with florid MRI; AMPAR — psychosis and memory loss with thymoma or carcinoma; Caspr2 — Morvan syndrome with neuromyotonia and insomnia; DPPX — diarrhoea and stiffness.
- First-line therapy: intravenous methylprednisolone 1 g daily for 3-5 days plus intravenous immunoglobulin 2 g/kg or plasma exchange; second line: rituximab with or without cyclophosphamide; anti-IL6 and interleukin-directed agents for refractory NMDAR.
- Hashimoto's encephalopathy (SREAT): encephalopathy with high anti-thyroid peroxidase antibodies, steroid-responsive, is diagnosed by response, not antibody titre alone.
A trajectory worth memorising
A 19-year-old hostel student is taken to the emergency department after a week of insomnia, talking to walls and refusing food; two days later she has a generalised seizure. Routine investigations, including electrolytes and infective screen, are unremarkable; the psychiatric admission collapses when orofacial grimacing, rigidity, tachycardia and hypoventilation appear. The sequence of management is the exam: continuous EEG (diffuse slowing, later extreme delta brush), CSF (mild lymphocytic pleocytosis, normal glucose, oligoclonal bands may be present), MRI (medial temporal signal in some, normal in many), and CSF anti-NMDA-receptor antibody positive; pelvic imaging finds an ovarian teratoma. Tumour resection plus methylprednisolone and immunoglobulin begin the first week; because she remains in intensive care with dysautonomia at four weeks, rituximab and cyclophosphamide are added — escalation on schedule rather than as a last resort. She recovers over four to six months, and relapse risk falls with sustained second-line therapy. Every delay in that paragraph is a marker of worse outcome, which is why the Graus criteria exist: to license early empirical immunotherapy while antibodies are still in the pipeline.
How the exam frames it
Expect three question shapes: criteria application (which feature upgrades possible to probable), antibody-syndrome matching (faciobrachial dystonic seizures to LGI1, diarrhoea and stiffness to DPPX, status epilepticus to GABA-B), and management sequencing (what to add when first-line fails at two to four weeks — rituximab, not more antipsychotics). The psychiatric-admission trap is the favourite: a first-episode psychosis with fever, dyskinesia or autonomic instability deserves CSF and EEG before it deserves a diagnosis of schizophrenia. For Indian practice, teratoma screening and ICU-level plasma exchange are available at most medical college hospitals, while rituximab biosimilars have made second-line therapy affordable; the true bottleneck is diagnostic delay, usually from attributing the first week to primary psychiatric illness.
Frequently asked questions
What are the Graus criteria for possible autoimmune encephalitis?
Subacute onset under three months of memory deficit, psychiatric symptoms, seizures or reduced consciousness, with at least one supportive feature among focal CNS signs, CSF pleocytosis, EEG slowing or medial temporal MRI changes, after excluding alternatives.
Which antibody causes faciobrachial dystonic seizures?
LGI1, typically in older men, frequently with hyponatraemia and preceding antibody-negative cognitive decline.
Which sample is more sensitive for anti-NMDA-receptor antibody?
Cerebrospinal fluid — serum can be negative when CSF is positive, so paired testing is standard.
What constitutes first-line therapy for autoimmune encephalitis?
Intravenous methylprednisolone with intravenous immunoglobulin or plasma exchange, started promptly, plus tumour search and removal where an antibody predicts one.
When is second-line therapy indicated?
Persistence or worsening despite first-line treatment at two to four weeks — rituximab with or without cyclophosphamide, since delayed escalation predicts worse outcomes.