Autoimmune encephalitis (AE) is a CNS disease in differential diagnosis with common neuropsychiatric conditions such as epilepsy, schizophrenia, and dementia.  Differently from these conditions, AE can improve dramatically with immunotherapy. This has led to an overenthusiastic approach from clinicians, that can lead to inappropriate diagnosis. Flanagan et al. decided to approach the delicate topic of misdiagnosis by retrospectively analyzing 107 patients initially considered as AE, but that were later differently classified.  More than half of the patients had either neurodegenerative or psychiatric/functional conditions. Main driver of the misdiagnosis in half of the patients was the overinterpretation of positive serum antibodies. Remarkably, 72% of patients did not fulfill Graus criteria for AE. An unnecessary immunotherapy course was administered to 84 patients, and 20% developed adverse events.
This important study provides a useful representation of a common scenario in routine clinical practice. The misdiagnosis of AE can be common, especially if current AE criteria are not fulfilled, and a proper evaluation of the whole spectrum of differential diagnosis, and careful consideration of the relevance of autoantibody findings are crucial to avoid unnecessary and potentially harmful immunotherapy.
- Misdiagnosis of AE can be common, but most misdiagnosed patients don’t fulfill AE criteria
- Most frequent reasons for misdiagnosis are overinterpretation of serum autoantibody positivity
- Immunotherapy is often given to patient’s misdiagnosed with AE, leading to potentially avoidable side effects
- Careful consideration of differential diagnosis is crucial to improve patient’s management
- Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016 Apr;15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20. PMID: 26906964; PMCID: PMC5066574.
- Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, Blackburn KM, Turaga S, Binks S, Zitser J, Gelfand JM, Day GS, Dunham SR, Rodenbeck SJ, Clardy SL, Solomon AJ, Pittock SJ, McKeon A, Dubey D, Zekeridou A, Toledano M, Turner LE, Vernino S, Irani SR. Autoimmune Encephalitis Misdiagnosis in Adults. JAMA Neurol. 2023 Jan 1;80(1):30-39. doi: 10.1001/jamaneurol.2022.4251. PMID: 36441519; PMCID: PMC9706400.
Stefano Masciocchi, IRCCS Mondino Foundation
Publish on behalf of the Scientific Panel on Neuroimmunology