Autoimmune encephalitis : Part 1 (Epidemiology, Pathophysiology and Clinical spectrum)



  • Juliane Hiesgen University of Pretoria
  • Prof. Schutte University of Pretoria



autoimmune encephalitis


Since the identification of anti-N-methyl-D-aspartate (NMDA) receptor antibodies about 15 years ago, many patients with rapidly progressing psychiatric symptoms, abnormal movements, seizures or unexplained coma, have been diagnosed with autoimmune encephalitis (AE). The symptom onset is often unspecific and might mimic psychiatric disease, but the later course is frequently characterized by severe disease, often requiring intensive care. Clinical and immunological criteria are helpful in identifying the patients, but no biomarkers exist to guide the clinician in therapy or predict outcome. While persons of all ages can be affected by AE, some types of AE affect more children and young adults and are more prevalent in women. This review will focus on encephalitides associated with neuronal cell-surface or synaptic antibodies, which can result in characteristic syndromes, and are often recognizable on clinical grounds. AE subtypes associated with antibodies against extracellular epitopes can occur with or without tumours. Because the antibodies bind and alter the function of the antigen, the effects are often reversible if immunotherapy is initiated, and the prognosis is favourable in most instances. The first part of this series will introduce the topic, provide an overview of current neuronal surface antibodies and how they present, describe the most common subtype, anti-NMDA receptor encephalitis, and discuss the difficulties in recognizing patients with underlying AE amongst patients with new onset psychiatric disorders.


Abboud H, Probasco JC, Irani S, et al. Autoimmune encephalitis: Proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatr 2021;92:757- 768. 0.1 136/jnnp- 2021- 326096

Dalmau J, Graus F. Antibody-Mediated encephalitis. N Engl J Med 2018;378:840-851. http://doi. org/10.1056/NEJMra1708712

Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018;83(1):166-177.

Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: A multicentre, population-based prospective study. Lancet Inf Dis 2010;10(12):835-844. http://doi/10.1016/s1473-3099(10)70222-x

Roos I, Bhigjee AI. Autoimmune encephalitis: A missed diagnostic and therapeutic opportunity. Afr J Neurol Sci 2017:36(2):67-79.

Peterson K, Rosenblum MK, Kotanides H, et al. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992;42(10):1931-1937. http:// doi/10.1212/wnl.42.10.1931

Dalmau J, Furneaux HM, Gralla RJ, et al. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer – a quantitative western blot analysis. Ann Neurol 1990;27(5):544-552. http://doi/10.1002/ana.410270515

Shams’ili S, Grefkens J, de Leeuw B, et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: Analysis of 50 patients. Brain 2003;126(6):1409-1418. http://doi/10.1093/ brain/awg133

Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003;16:349(16):1543-1554. http://doi/10.1056/NEJMra023009

Dalmau J, Armangué T, Planagumà J, et al. An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: Mechanisms and models. Lancet Neurol 2019;18(11):1045-1057. http:// doi/10.1016/S1474-4422(19)30244-3

Howard CM, Kass JS, Bandi VDP, et al. Challenges in providing critical care for patients with anti- N-methyl-D-aspartate receptor encephalitis. Chest 2014;145(5):1143-1147. http://doi/10.1378/ chest.13-1490

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;12(2):157-165. http://doi/10.1016/S1474-4422(12)70310-1

Wang RJ, Chen BD, Qi D. Anti-N-methyl-D-aspartate receptor encephalitis concomitant with multifocal subcortical white matter lesions on magnetic resonance imaging: A case report and review of the literature. BMC Neurol. 2015;8;15:107. http://doi/10.1186/s12883-015-0366-5.

Kovac S, Alferink J, Ahmetspahic D, et al. Update anti-N-methyl-D-aspartat-rezeptor-enzephalitis [Update on anti-N-methyl-D-aspartate receptor encephalitis]. Nervenarzt 2018;89(1):99-112. http:// doi/10.1007/s00115-017-0405-0

Schmitt SE, Pargeon K, Frechette ES, et al. Extreme delta brush: A unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012;11;79(11):1094-1100. http://doi/10.1212/ WNL.0b013e3182698cd8

Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10(1):63-74. http://doi/10.1016/ S1474-4422(10)70253-2

Armangue T, Spatola M, Vlagea A, et al. Spanish Herpes Simplex Encephalitis Study Group. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: A prospective observational study and retrospective analysis. Lancet Neurol 2018;17(9):760-772. http:// doi/10.1016/S1474-4422(18)30244-8

De Bruijn MAAM, Bruijstens AL, Bastiaansen AEM, et al. Pediatric autoimmune encephalitis: Recognition and diagnosis. Neurol Neuroimmunol Neuroinflamm 2020;11;7(3):e682. http:// doi/10.1212/NXI.0000000000000682

Cellucci T, Van Mater H, Graus F, et al. Clinical approach to the diagnosis of autoimmune encephalitis in the paediatric patient. Neurol Neuroimmunol Neuroinflamm 2020;7(2):e663. http://doi/10.1212/ NXI.0000000000000663

Florance NR, Davis RL, Lam C, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009;66(1):11-18. http://doi/ 10.1002/ana.21756

Van Coevorden-Hameete MH, de Bruijn MAAM, de Graaff E, et al. The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies. Brain 2019;142(6):1631-1643. http://doi/10.1093/brain/awz094

Zhu F, Shan W, Lv R, et al. Clinical characteristics of anti-GABA-B receptor encephalitis. Front Neurol 2020;21(11):403. http://doi/10.3389/fneur.2020.00403

Kim TJ, Lee ST, Shin JW, et al. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol 2014;15;270(1-2):45-50. http://doi/ 10.1016/j. jneuroim.2014.02.011

Lin J, Li C, Li A. Encephalitis with antibodies against the GABAB receptor: High mortality and risk factors. Front Neurol 2019;26(10):1030. http://doi/10.3389/fneur.2019.01030

Rodriguez A, Klein CJ, Sechi E, et al. LGI1 antibody encephalitis: Acute treatment comparisons and outcome. J Neurol Neurosurg Psychiatr 2022;93(3):309-315. http://doi/10.1136/jnnp-2021-327302

Aurangzeb S, Symmonds M, Knight RK, et al. LGI1-antibody encephalitis is characterised by

frequent, multifocal clinical and subclinical seizures. Seizure 2017;50:14-17. http://doi/ 10.1016/j.


Wang M, Cao X, Liu Q, et al. Clinical features of limbic encephalitis with LGI1 antibody. Neuropsychiatr Dis Treat 2017;16(13):1589-1596. http://doi/10.2147/NDT.S136723

Van Sonderen A, Ariño H, Petit-Pedrol M, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016;87(5):521-528. http://doi/10.1212/WNL0000000000002917

Kayser MS, Titulaer MJ, Gresa-Arribas N. Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis. JAMA Neurol 2013;70(9):1133-1139. http://doi/10.1001/jamaneurol.2013.3216

Endres D, Maier V, Leypoldt F, et al. Autoantibody-associated psychiatric syndromes: A systematic literature review resulting in 145 cases. Psychol Med 2020;52(6):1-12. http://doi/10.1017/ S0033291720002895

Sarkis RA, Coffey MJ, Cooper JJ, et al. Anti-N-methyl-D-aspartate receptor encephalitis: A review of psychiatric phenotypes and management considerations: A report of the American Neuropsychiatric Association Committee on Research. J Neuropsychiatr Clin Neurosci 2019;31(2):137-142. http:// doi/10.1176/appi.neuropsych.18010005

Endres D, Lüngen E, Hasan A, et al. Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: A case series of 91 patients from Germany. Mol Psychiatr 2022;27(3):1479-1489. http://doi/10.1038/s41380-021-01396-4

Najjar S, Steiner J, Najjar A, et al. A clinical approach to new-onset psychosis associated with immune dysregulation: The concept of autoimmune psychosis. J Neuroinflam 2018;13;15(1):40. http:// doi/10.1186/s12974-018-1067-y

Pollak TA, Lennox BR, Müller S, et al. Autoimmune psychosis: An international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatr 2020;7(1):93-108. http://doi/10.1016/S2215-0366(19)30290-1

Steiner J, Prüss H, Köhler S, et al. Autoimmune encephalitis with psychosis: Warning signs, step-by- step diagnostics and treatment. World J Biol Psychiatr 2020;21(4):241-254. http://doi/10.1080/15622 975.2018.1555376

Herken J, Prüss H. Red flags: Clinical signs for identifying autoimmune encephalitis in psychiatric patients. Front Psychiatr 2017;16;8:25. http://doi/10.3389/fpsyt.2017.00025

Emsley R, Flisher AJ, G Grobler et al. The South African Society of Psychiatrists (SASOP) treatment guidelines for psychiatric disorders. S Afr J Psychiatr 2013;19(3):a942. http:/// sajpsychiatry.v19i3.942






How to Cite

Hiesgen J, Schutte C. Autoimmune encephalitis : Part 1 (Epidemiology, Pathophysiology and Clinical spectrum) : -. S Afr Med J [Internet]. 2023 Mar. 2 [cited 2024 May 19];113(3):116-21. Available from:

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