Back to the future: encephalitis lethargica as an autoimmune disorder?

Autoimmune encephalitis Encephalitis lethargica History of neurology Pathophysiology

Journal

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

ISSN: 1590-3478

Titre abrégé: Neurol Sci

Pays: Italy

ID NLM: 100959175

Informations de publication

Date de publication:
09 Sep 2023

Historique:

received: 29 07 2023

accepted: 30 08 2023

medline: 9 9 2023

pubmed: 9 9 2023

entrez: 9 9 2023

Statut: aheadofprint

Résumé

More than 100 years after its emergence, the exact pathophysiological mechanisms underlying encephalitis lethargica (EL) are still elusive and awaiting convincing and complete elucidation. This article summarizes arguments proposed over time to support or refute the hypothesis of EL as an autoimmune neuropsychiatric disorder triggered by an infectious process. It also provides a critical evaluation of modern cases labeled as EL and a comprehensive differential diagnosis of autoimmune neurological conditions that could mimic EL. The evidence supporting the autoimmune nature of historical EL is sparse and not entirely convincing. It is possible that autoimmune mechanisms were involved in the pathogenesis of this disease as an idiosyncratic response to a yet unidentified infectious agent in genetically predisposed individuals. Although there has been an increase in the incidence of presumed autoimmune encephalomyelitis since the peak of EL pandemics, most evidence does not support an underlying autoimmune mechanism. There are significant differences between historical and recent EL cases in terms of clinical symptomatology, epidemiology, and neuropathological features, suggesting that they are different entities with only superficial similarity. The term "encephalitis lethargica," still frequently used in the medical literature, should not be used for cases occurring at present in the sporadic form. Historical EL should be kept apart from recent EL, as they differ in important aspects.

Identifiants

DOI: 10.1007/s10072-023-07053-8 PMID: 37688743

pubmed: 37688743

doi: 10.1007/s10072-023-07053-8

pii: 10.1007/s10072-023-07053-8

doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

Informations de copyright

Références

von Economo C (1917) Encephalitis lethargica. Wien Klin Wochenschr 30:581–585

Brigo F, Martini M, Lorusso L, Study Group on the History of Neurology of the Italian Neurological Society (2021) “You are older, although you do not know that”: time, consciousness, and memory in “A kind of Alaska” by Harold Pinter (1930-2008). Eur Neurol 84:486–489

doi: 10.1159/000517325 pubmed: 34284399

Brigo F, Lorusso L, Martini M (2022) L’eredità socio-culturale dell’encefalite letargica e la sua rappresentazione nella cultura popolare e di massa. Conf Cephalal et Neurol 32(1):e2022004

Cruchet R, Moutier F, Calmette A (1917) Quarante cas d’encéphalo-myélite subaiguë. Bulletins et Mémoires de la Société médicale des Hôpitaux série 41:614–616

Vilensky JA (2011) Encephalitis lethargica during and after the epidemic. Oxford University Press

Foley P (2018) Encephalitis lethargica - the mind and brain virus. Springer Nature

doi: 10.1007/978-1-4939-0384-9

Stern F (1928) Die epidemische Encephalitis. Julius Springer, Berlin

doi: 10.1007/978-3-642-90811-8

von Economo C (1929) Die encephalitis lethargica, ihre Nachkrankheiten und ihre Bechandlung. Urban and Swarzenberg, Vienna

Tilney F, Howe HS (1920) Epidemic encephalitis (encephalitis lethargica). Paul B. Hoeber, New York

Kyrieleis W (1931) Die Augenveränderungen bei den entzündlichen Erkrankungen des Zentralnervensystems. In: Schieck F, Bruckner A (eds) Kurzes Handbuch der Ophthalmologie. Sechster Band: Auge und Nervensystem. Julius Springer, Berlin, pp 669–799

Vilensky JA, Foley P, Gilman S (2007) Children and encephalitis lethargica: a historical review. Pediatr Neurol 37(2):79–84

doi: 10.1016/j.pediatrneurol.2007.04.012 pubmed: 17675021

Spatz H (1930) Ergebnis der anatomischen Untersuchung von 70 Fällen von Encephalitis epidemica. Zentralblatt für die gesamte Neurologie und Psychiatrie 56:435–437

van Bogaert L (1958) Encéphalite léthargique type A (Maladie d’Economo). In: Scholz W, Lubarsch O, Henke F, RössIe R (eds) Nervensystem. Zweiter Teil: Erkrankungen des zentralen Nervensystems II; Bandteil A (Handbuch der speziellen pathologischen Anatomie und Histologie), Band 13. Springer, Berlin, Göttingen, Heidelberg, pp 313–361

doi: 10.1007/978-3-642-94735-3_7

Klarfeld (1920) Histopathologie der Encephalitis choreatica. Allgemeine Zeitschrift für Psychiatrie und psychisch-gerichtliche Medizin 76:812–816

Scholz W (1922) Über herdförmige, protoplasmatische Gliawucherung von syncytialem Charakter. Mit einem Ausblick auf ihre Bedeutung für den Verlauf des pathologisch-anatomischen Prozesses bei der Encephalitis epidemica. Zeitschrift für die gesamte Neurologie und Psychiatrie 79:114–179

doi: 10.1007/BF02878449

Lutters B, Foley P, Koehler PJ (2018) The centennial lesson of encephalitis lethargica. Neurology 90(12):563–567

doi: 10.1212/WNL.0000000000005176 pubmed: 29555881

Blackburn KM, Wang C (2020) Post-infectious neurological disorders. Ther Adv Neurol Disord 13:1756286420952901

doi: 10.1177/1756286420952901 pubmed: 32944082 pmcid: 7466892

Dop D, Marcu IR, Padureanu R, Niculescu CE, Padureanu V (2021) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (Review). Exp Ther Med 21(1):94

doi: 10.3892/etm.2020.9526 pubmed: 33363605

Dale RC, Church AJ, Surtees RA, Lees AJ, Adcock JE, Harding B, Neville BG, Giovannoni G (2004) Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Brain 127(Pt 1):21–33

doi: 10.1093/brain/awh008 pubmed: 14570817

Church AJ, Cardoso F, Dale RC, Lees AJ, Thompson EJ, Giovannoni G (2002) Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology 59(2):227–231

doi: 10.1212/WNL.59.2.227 pubmed: 12136062

Vincent A (2004) Encephalitis lethargica: part of a spectrum of post-streptococcal autoimmune diseases? Brain 127(Pt 1):2–3

doi: 10.1093/brain/awh063 pubmed: 14679031

Singer HS, Hong JJ, Yoon DY, Williams PN (2005) Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology 65(11):1701–1707

doi: 10.1212/01.wnl.0000183223.69946.f1 pubmed: 16207842

Rosenow EC (1922) Experimental studies on the etiology of encephalitis. JAMA 79:443–448

doi: 10.1001/jama.1922.02640060025008

Rosenow EC (1924) Streptococci in relation to etiology of epidemic encephalitis. Experimental results in eighty-one cases. J Infect Dis 34:329–389

doi: 10.1093/infdis/34.4.329

Claassen DO, Boes CJ (2009) Rosenow’s rabbits and postencephalitic parkinsonism. Neurology 73(15):1240–1241

doi: 10.1212/WNL.0b013e3181bc01bc pubmed: 19822874

Dale RC, Merheb V, Pillai S, Wang D, Cantrill L, Murphy TK, Ben-Pazi H, Varadkar S, Aumann TD, Horne MK, Church AJ, Fath T, Brilot F (2012) Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain 135(Pt 11):3453–3468

doi: 10.1093/brain/aws256 pubmed: 23065479

Dale RC, Irani SR, Brilot F, Pillai S, Webster R, Gill D, Lang B, Vincent A (2009) N-methyl-D-aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica. Ann Neurol 66(5):704–709

doi: 10.1002/ana.21807 pubmed: 19938173

Armangue T, Olivé-Cirera G, Martínez-Hernandez E, Rodes M, Peris-Sempere V, Guasp M, Ruiz R, Palou E, González A, Marcos MÁ, Erro ME (2023) Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies. Brain:awad238. https://doi.org/10.1093/brain/awad238

Vogrig A, Muñiz-Castrillo S, Desestret V, Joubert B, Honnorat J (2020) Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord 13:1756286420932797

doi: 10.1177/1756286420932797 pubmed: 32636932 pmcid: 7318829

Howard RS, Lees AJ (1987) Encephalitis lethargica. A report of four recent cases. Brain 110(Pt 1):19–33

doi: 10.1093/brain/110.1.19 pubmed: 3801849

Damato V, Balint B, Kienzler AK, Irani SR (2018) The clinical features, underlying immunology, and treatment of autoantibody-mediated movement disorders. Mov Disord 33(9):1376–1389

doi: 10.1002/mds.27446 pubmed: 30218501 pmcid: 6221172

Muñoz-Lopetegi A, Graus F, Dalmau J, Santamaria J (2020) Sleep disorders in autoimmune encephalitis. Lancet Neurol 19(12):1010–1022

doi: 10.1016/S1474-4422(20)30341-0 pubmed: 33212053

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404

doi: 10.1016/S1474-4422(15)00401-9 pubmed: 26906964 pmcid: 5066574

Di Vito A, Donato A, Bria J, Donato F, Donato G (2023) Encephalitis lethargica. What is still wrong? Int J Immunopathol Pharmacol 37:3946320231154997

pubmed: 36716496