Paeds · neurology-neurodisability-and-neuromuscular

Autoimmune encephalitis

Also known as Anti-NMDA receptor encephalitis · Antibody-mediated encephalitis · Post-herpes simplex autoimmune encephalitis · Limbic encephalitis · Cell-surface antibody encephalitis

Fellowship guide to autoimmune encephalitis in children. Covers the Graus 2016 diagnostic tiers of possible, probable, and definite disease with the specific anti-NMDA receptor criteria, the distinction between cell-surface antibody syndromes that respond to immunotherapy and intracellular onconeural syndromes that often do not, the pathophysiology of antibody-mediated NMDA receptor internalisation versus cytotoxic T-cell injury, the staged presentation from prodrome through psychiatric change to seizures, movement disorder, and dysautonomia, the first-line immunotherapy ladder of methylprednisolone, intravenous immunoglobulin, and plasma exchange and the second-line ladder of rituximab and cyclophosphamide at ten to fourteen days, the ovarian teratoma association and the search for and removal of occult tumours, the extreme delta brush EEG pattern and CSF pleocytosis, the Titulaer outcome data on early treatment and second-line therapy, and the prolonged multidisciplinary recovery with cognitive and school reintegration.

high11 referencesUpdated 16 July 202620 min readVerification in progress

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Red flags

A child with rapid onset psychiatric change, seizures, and abnormal movements has autoimmune encephalitis until proven otherwise, not a primary psychiatric diagnosisDo not wait for antibody results to start immunotherapy once infection is reasonably excluded; early treatment is the strongest predictor of good outcomeHypoventilation and autonomic instability in anti-NMDAR encephalitis can kill and mandate intensive care monitoringA post-pubertal girl with anti-NMDAR encephalitis has an ovarian teratoma until imaging proves otherwise, and tumour removal is the most effective single interventionClinical relapse weeks after treated herpes simplex encephalitis is usually post-HSE autoimmune encephalitis, not recurrent infectionIntracellular onconeural antibody syndromes are often poorly responsive to immunotherapy and demand a tumour search and honest prognosis

Life stages

infanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

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Recognises autoimmune encephalitis as a treatable cause of subacute neuropsychiatric decline and states that anti-NMDAR is the commonest subtype in childrenStates the first-line and second-line immunotherapy ladder and the need to start steroids or IVIG early while excluding infectionIdentifies the ovarian teratoma association in anti-NMDAR encephalitis and the need for imaging to find and remove itApplies the Graus 2016 diagnostic criteria distinguishing possible, probable, and definite autoimmune encephalitis and the specific anti-NMDAR criteriaExplains the mechanistic distinction between cell-surface antibodies with receptor internalisation and intracellular onconeural antigens with cytotoxic T-cell injuryJustifies the timing of second-line rituximab or cyclophosphamide at 10 to 14 days for poor first-line response, drawing on Titulaer and the paediatric consensusGraus diagnostic tiers and the six symptom groups of probable anti-NMDAR encephalitisFirst-line methylprednisolone, IVIG, and plasma exchange doses and second-line rituximab and cyclophosphamide doses with maximaThe extreme delta brush EEG pattern, CSF lymphocytic pleocytosis, and the search for an occult tumourRuns the workup and first-line immunotherapy of a child with subacute psychiatric change and abnormal movements while treating seizures and dysautonomiaDecides on and times second-line therapy and tumour removal and coordinates the intensive care and rehabilitation courseCounsels the family on the cause, the prolonged recovery, the relapse risk, and the cognitive and school reintegration planLevel 1: Recognition that subacute neuropsychiatric decline with seizures or movement disorder can be autoimmune and treatableLevel 2: Application of the Graus diagnostic criteria, the antibody workup, and the first-line immunotherapy ladderLevel 3: Coordination of second-line therapy, tumour surveillance, intensive care of dysautonomia, and long-term cognitive rehabilitationAnti-NMDAR encephalitis as the commonest paediatric autoimmune encephalitis and its prodrome, psychiatric, neurological, and dysautonomic phasesThe Graus 2016 diagnostic tiers and the distinction between cell-surface and intracellular antigen syndromesThe first-line and second-line immunotherapy ladder and the Titulaer outcome data on early treatment and second-line therapyStructured assessment and first-line management of a child with subacute psychiatric change, seizures, and movement disorderRecognition of dysautonomia and hypoventilation needing intensive care, and the tumour search in anti-NMDAR diseaseCommunication of the diagnosis, the prolonged recovery, and the relapse surveillance and school reintegration to the familyAutoimmune encephalitis as a treatable mimic of primary psychiatric and infectious encephalitic illness in childrenFirst-line steroids, IVIG, and plasma exchange and second-line rituximab and cyclophosphamide with doses and timingThe ovarian teratoma association, the EEG and CSF findings, and the long-term cognitive and seizure outcomesRecognition of subacute neuropsychiatric decline with seizures and movement disorder as possible autoimmune encephalitisStepwise immunotherapy with first-line then second-line agents and tumour removalMultidisciplinary care of dysautonomia, prolonged recovery, cognitive rehabilitation, and relapse surveillanceCanadian diagnostic approach to autoimmune encephalitis using the Graus criteria and antibody testing in CSF and serumFirst-line and second-line immunotherapy with the paediatric consensus doses and the timing of second-line therapyCoordination of intensive care, rehabilitation, and long-term follow-up including cognitive and psychiatric sequelae

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Target exams

RACP DWERACP DCEMRCPCH TheoryMRCPCH ClinicalABP General Pediatrics

Red flags

Life stages

infanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

Care settings

outpatientwarded-acutepicuretrieval

Clinical exam formats

written-onlyracp-dce-long-caseracp-dce-short-casemrcpch-history-managementmrcpch-communicationrcpsc-structured-oral

Board mappings

Overview & Definition

A child who changes over days to weeks from healthy to confused, agitated, and twitching, with seizures that will not settle and movements that look bizarre, is presenting one of the most treatable and most missed diagnoses in paediatric neurology. Autoimmune encephalitis is an immune attack on the brain in which antibodies or T cells target specific neuronal proteins, producing a subacute syndrome that straddles psychiatry, epilepsy, and movement disorder. The single most important fact for the exam, and for a real child, is that it is treatable and that early treatment changes lives. [1]

The disease was reframed for modern medicine by the description of anti-NMDA receptor encephalitis in 2008 by Dalmau and colleagues, who showed that an antibody against the NMDA glutamate receptor causes a stereotyped, recoverable, and often paraneoplastic encephalitis in young people. [3] That discovery opened the field: dozens of antibody targets are now known, and autoimmune encephalitis is recognised to be as common in children as infectious encephalitis. The Graus 2016 clinical approach gives a bedside framework that lets you treat on suspicion rather than wait weeks for a result. [1]

Three ideas hold this topic together. The diagnosis turns on a tempo, a pattern of brain involvement, and the exclusion of mimics, not on a single test. The treatment is a ladder from first-line steroids, immunoglobulin, and plasma exchange to second-line rituximab and cyclophosphamide, and the timing of that ladder is the chief determinant of outcome. And the antibody target predicts the response, because antibodies against cell-surface proteins like NMDAR are reversible while antibodies against intracellular antigens are T-cell mediated and often permanent. [2]

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References11Show ledger

[1]Graus F, Titulaer MJ, Balu R, et al A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol, 2016.PMID 26906964
[2]Titulaer MJ, McCracken L, Gabilondo I, et al Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol, 2013.PMID 23290630
[3]Dalmau J, Gleichman AJ, Hughes EG, et al Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol, 2008.PMID 18851928
[4]Schmitt SE, Pargeon K, Frechette ES, et al Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology, 2012.PMID 22933737
[5]Abboud H, Probasco JC, Irani S, et al Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry, 2021.PMID 33649022
[6]Abboud H, Probasco JC, Irani S, et al Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management. J Neurol Neurosurg Psychiatry, 2021.PMID 33649021
[7]Nosadini M, Thomas T, Eyre M, et al. International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. Neurol Neuroimmunol Neuroinflamm, 2021.PMID 34301820
[8]Nosadini M, Eyre M, Molteni E, et al. Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA Neurol, 2021.PMID 34542573
[9]Olivé-Cirera G, Fonseca E, Chen LW, et al. Differential diagnosis and comparison of diagnostic algorithms in children and adolescents with autoimmune encephalitis in Spain: a prospective cohort study and retrospective analysis. Lancet Neurol, 2025.PMID 39706634
[10]Guasp M, Rosa-Justicia M, Muñoz-Lopetegi A, et al. Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders. Lancet Neurol, 2022.PMID 36115362
[11]Armangue T, Leypoldt F, Málaga I, et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol, 2014.PMID 24318406

Autoimmune encephalitis

Also known as Anti-NMDA receptor encephalitis · Antibody-mediated encephalitis · Post-herpes simplex autoimmune encephalitis · Limbic encephalitis · Cell-surface antibody encephalitis

high11 referencesUpdated 16 July 202620 min readVerification in progress

Practise this topic

Overview & Definition

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References11Show ledger

[1]Graus F, Titulaer MJ, Balu R, et al A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol, 2016.PMID 26906964
[2]Titulaer MJ, McCracken L, Gabilondo I, et al Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol, 2013.PMID 23290630
[3]Dalmau J, Gleichman AJ, Hughes EG, et al Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol, 2008.PMID 18851928
[4]Schmitt SE, Pargeon K, Frechette ES, et al Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology, 2012.PMID 22933737
[5]Abboud H, Probasco JC, Irani S, et al Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry, 2021.PMID 33649022
[6]Abboud H, Probasco JC, Irani S, et al Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management. J Neurol Neurosurg Psychiatry, 2021.PMID 33649021
[7]Nosadini M, Thomas T, Eyre M, et al. International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. Neurol Neuroimmunol Neuroinflamm, 2021.PMID 34301820
[8]Nosadini M, Eyre M, Molteni E, et al. Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA Neurol, 2021.PMID 34542573
[9]Olivé-Cirera G, Fonseca E, Chen LW, et al. Differential diagnosis and comparison of diagnostic algorithms in children and adolescents with autoimmune encephalitis in Spain: a prospective cohort study and retrospective analysis. Lancet Neurol, 2025.PMID 39706634
[10]Guasp M, Rosa-Justicia M, Muñoz-Lopetegi A, et al. Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders. Lancet Neurol, 2022.PMID 36115362
[11]Armangue T, Leypoldt F, Málaga I, et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol, 2014.PMID 24318406