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Erschienen in: Journal of Neurology 10/2023

03.07.2023 | Original Communication

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort

verfasst von: Giacomo Brisca, Chiara Marini, Silvia Buratti, Marcello Mariani, Domenico Tortora, Giovanni Morana, Daniela Pirlo, Marta Romanengo, Giulia Cannizzaro, Ramona Cordani, Francesca Canzoneri, Maria Grazia Calevo, Lino Nobili, Diego Franciotta, Elio Castagnola, Andrea Moscatelli, Maria Margherita Mancardi

Erschienen in: Journal of Neurology | Ausgabe 10/2023

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Abstract

Background

Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time.
We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008–2021), with the evaluation of all children managed for acute encephalitis.

Methods

We retrospectively reviewed clinical, laboratory, neuroradiological, and EEG data from the acute phase and outcome of all immunocompetent patients diagnosed with acute encephalitis. According to the newly proposed criteria for pediatric autoimmune encephalitis, we divided patients into infectious, definite autoimmune, probable autoimmune, and possible autoimmune, and performed a comparison between the different groups.

Results

48 patients (26 females, mean age 4.4 years), 19 with infections, and 29 with autoimmune encephalitis, were included. Herpes simplex virus 1 encephalitis was the most frequently identified etiology followed by anti-NMDA receptor encephalitis. Movement disorders at onset and a longer hospital stay were observed more frequently in autoimmune compared to infectious encephalitis (p p < 0.001 and p = 0.001, respectively).
Among the autoimmune group, children who started immunomodulatory treatment earlier (within 7 days from onset) had more frequent complete functional recovery (p = 0.002).

Conclusions

Herpes virus and anti-NMDAR encephalitis are the most frequent etiologies within our cohort. Clinical onset and course are extremely variable. Since early immunomodulatory treatment was associated with a better functional outcome, our data confirm that a timely diagnostic classification in definite, probable, or possible autoimmune encephalitis can help the clinician in a successful therapeutic approach.
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Literatur
1.
Zurück zum Zitat Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA; International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013 Oct;57(8):1114–28. https://doi.org/10.1093/cid/cit458. Epub 2013 Jul 15. PMID: 23861361; PMCID: PMC3783060. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA; International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013 Oct;57(8):1114–28. https://​doi.​org/​10.​1093/​cid/​cit458. Epub 2013 Jul 15. PMID: 23861361; PMCID: PMC3783060.
4.
Zurück zum Zitat 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. https://doi.org/10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20. PMID: 26906964; PMCID: PMC5066574. 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. https://​doi.​org/​10.​1016/​S1474-4422(15)00401-9. Epub 2016 Feb 20. PMID: 26906964; PMCID: PMC5066574.
5.
Zurück zum Zitat Cellucci T, Van Mater H, Graus F, Muscal E, Gallentine W, Klein-Gitelman MS, Benseler SM, Frankovich J, Gorman MP, Van Haren K, Dalmau J, Dale RC. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 17;7(2):e663. https://doi.org/10.1212/NXI.0000000000000663. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2020 Apr 15;7(4): PMID: 31953309; PMCID: PMC7051207. Cellucci T, Van Mater H, Graus F, Muscal E, Gallentine W, Klein-Gitelman MS, Benseler SM, Frankovich J, Gorman MP, Van Haren K, Dalmau J, Dale RC. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol Neuroimmunol Neuroinflamm. 2020 Jan 17;7(2):e663. https://​doi.​org/​10.​1212/​NXI.​0000000000000663​. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2020 Apr 15;7(4): PMID: 31953309; PMCID: PMC7051207.
8.
Zurück zum Zitat Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, De Sousa C, Devile C, Fallon P, Gupta R, Hedderly T, Hughes E, Kerr T, Lascelles K, Lin JP, Philip S, Pohl K, Prabahkar P, Smith M, Williams R, Clarke A, Hemingway C, Wassmer E, Vincent A, Lim MJ. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry. 2013 Jul;84(7):748–55. https://doi.org/10.1136/jnnp-2012-303807. Epub 2012 Nov 22. PMID: 23175854; PMCID: PMC3686256. Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, De Sousa C, Devile C, Fallon P, Gupta R, Hedderly T, Hughes E, Kerr T, Lascelles K, Lin JP, Philip S, Pohl K, Prabahkar P, Smith M, Williams R, Clarke A, Hemingway C, Wassmer E, Vincent A, Lim MJ. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry. 2013 Jul;84(7):748–55. https://​doi.​org/​10.​1136/​jnnp-2012-303807. Epub 2012 Nov 22. PMID: 23175854; PMCID: PMC3686256.
12.
Zurück zum Zitat Tembo J, Kabwe M, Chilukutu L, Chilufya M, Mwaanza N, Chabala C, Zumla A, Bates M (2015) Prevalence and risk factors for betaherpesvirus DNAemia in children >3 weeks and <2 years of age admitted to a large referral hospital in sub-Saharan Africa. Clin Infect Dis 60(3):423–431. https://doi.org/10.1093/cid/ciu853. (Epub 2014 Oct 28 PMID: 25352585)CrossRefPubMed Tembo J, Kabwe M, Chilukutu L, Chilufya M, Mwaanza N, Chabala C, Zumla A, Bates M (2015) Prevalence and risk factors for betaherpesvirus DNAemia in children >3 weeks and <2 years of age admitted to a large referral hospital in sub-Saharan Africa. Clin Infect Dis 60(3):423–431. https://​doi.​org/​10.​1093/​cid/​ciu853. (Epub 2014 Oct 28 PMID: 25352585)CrossRefPubMed
13.
Zurück zum Zitat Ongrádi J, Ablashi DV, Yoshikawa T, Stercz B, Ogata M. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals. J Neurovirol. 2017 Feb;23(1):1–19. https://doi.org/10.1007/s13365-016-0473-0. Epub 2016 Aug 18. PMID: 27538995; PMCID: PMC5329081. Ongrádi J, Ablashi DV, Yoshikawa T, Stercz B, Ogata M. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals. J Neurovirol. 2017 Feb;23(1):1–19. https://​doi.​org/​10.​1007/​s13365-016-0473-0. Epub 2016 Aug 18. PMID: 27538995; PMCID: PMC5329081.
17.
18.
Zurück zum Zitat Hansen N, Ernst L, Rüber T, Widman G, Becker AJ, Elger CE, Helmstaedter C (2018) Pre- and long-term postoperative courses of hippocampus-associated memory impairment in epilepsy patients with antibody-associated limbic encephalitis and selective amygdalohippocampectomy. Epilepsy Behav 79:93–99. https://doi.org/10.1016/j.yebeh.2017.10.033. (Epub 2017 Dec 16 PMID: 29253681)CrossRefPubMed Hansen N, Ernst L, Rüber T, Widman G, Becker AJ, Elger CE, Helmstaedter C (2018) Pre- and long-term postoperative courses of hippocampus-associated memory impairment in epilepsy patients with antibody-associated limbic encephalitis and selective amygdalohippocampectomy. Epilepsy Behav 79:93–99. https://​doi.​org/​10.​1016/​j.​yebeh.​2017.​10.​033. (Epub 2017 Dec 16 PMID: 29253681)CrossRefPubMed
20.
Zurück zum Zitat Gaddamanugu S, Shafaat O, Sotoudeh H, Sarrami AH, Rezaei A, Saadatpour Z, Singhal A. Clinical applications of diffusion-weighted sequence in brain imaging: beyond stroke. Neuroradiology. 2022 Jan;64(1):15–30. https://doi.org/10.1007/s00234-021-02819-3. Epub 2021 Oct 1. PMID: 34596716; PMCID: PMC8484843. Gaddamanugu S, Shafaat O, Sotoudeh H, Sarrami AH, Rezaei A, Saadatpour Z, Singhal A. Clinical applications of diffusion-weighted sequence in brain imaging: beyond stroke. Neuroradiology. 2022 Jan;64(1):15–30. https://​doi.​org/​10.​1007/​s00234-021-02819-3. Epub 2021 Oct 1. PMID: 34596716; PMCID: PMC8484843.
21.
Zurück zum Zitat Li R, Jin S, Wang Y, Li JF, Xiao HF, Wang YL, Ma L. Brain Perfusion Alterations on 3D Pseudocontinuous Arterial Spin-Labeling MR Imaging in Patients with Autoimmune Encephalitis: A Case Series and Literature Review. AJNR Am J Neuroradiol. 2022 May;43(5):701–706. https://doi.org/10.3174/ajnr.A7478. Epub 2022 Apr 7. PMID: 35393361; PMCID: PMC9089268. Li R, Jin S, Wang Y, Li JF, Xiao HF, Wang YL, Ma L. Brain Perfusion Alterations on 3D Pseudocontinuous Arterial Spin-Labeling MR Imaging in Patients with Autoimmune Encephalitis: A Case Series and Literature Review. AJNR Am J Neuroradiol. 2022 May;43(5):701–706. https://​doi.​org/​10.​3174/​ajnr.​A7478. Epub 2022 Apr 7. PMID: 35393361; PMCID: PMC9089268.
25.
Zurück zum Zitat Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157–65. https://doi.org/10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3. PMID: 23290630; PMCID: PMC3563251. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157–65. https://​doi.​org/​10.​1016/​S1474-4422(12)70310-1. Epub 2013 Jan 3. PMID: 23290630; PMCID: PMC3563251.
26.
Zurück zum Zitat Byrne S, Walsh C, Hacohen Y, Muscal E, Jankovic J, Stocco A, Dale RC, Vincent A, Lim M, King M. Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome. Neurol Neuroimmunol Neuroinflamm. 2015 Jul 23;2(4):e130. https://doi.org/10.1212/NXI.0000000000000130. PMID: 26236759; PMCID: PMC4516400. Byrne S, Walsh C, Hacohen Y, Muscal E, Jankovic J, Stocco A, Dale RC, Vincent A, Lim M, King M. Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome. Neurol Neuroimmunol Neuroinflamm. 2015 Jul 23;2(4):e130. https://​doi.​org/​10.​1212/​NXI.​0000000000000130​. PMID: 26236759; PMCID: PMC4516400.
27.
Zurück zum Zitat Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ; Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47(3):303–27. https://doi.org/10.1086/589747. PMID: 18582201. Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ; Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47(3):303–27. https://​doi.​org/​10.​1086/​589747. PMID: 18582201.
31.
Zurück zum Zitat Khandaker G, Jung J, Britton PN, King C, Yin JK, Jones CA. Long-term outcomes of infective encephalitis in children: a systematic review and meta-analysis. Dev Med Child Neurol. 2016 Nov;58(11):1108–1115. https://doi.org/10.1111/dmcn.13197. Epub 2016 Jul 16. Erratum in: Dev Med Child Neurol. 2017 Jan;59(1):107. PMID: 27422743. Khandaker G, Jung J, Britton PN, King C, Yin JK, Jones CA. Long-term outcomes of infective encephalitis in children: a systematic review and meta-analysis. Dev Med Child Neurol. 2016 Nov;58(11):1108–1115. https://​doi.​org/​10.​1111/​dmcn.​13197. Epub 2016 Jul 16. Erratum in: Dev Med Child Neurol. 2017 Jan;59(1):107. PMID: 27422743.
32.
Zurück zum Zitat Flet-Berliac L, Tchitchek N, Lépine A, Florea A, Maurey H, Chrétien P, Hacein-Bey-Abina S, Villega F, Cheuret E, Rogemond V, Picard G, Honnorat J, Deiva K. Long-term outcome of paediatric anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol. 2022 Oct 5. https://doi.org/10.1111/dmcn.15429. Epub ahead of print. PMID: 36196688. Flet-Berliac L, Tchitchek N, Lépine A, Florea A, Maurey H, Chrétien P, Hacein-Bey-Abina S, Villega F, Cheuret E, Rogemond V, Picard G, Honnorat J, Deiva K. Long-term outcome of paediatric anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol. 2022 Oct 5. https://​doi.​org/​10.​1111/​dmcn.​15429. Epub ahead of print. PMID: 36196688.
33.
Zurück zum Zitat Salzberg SL, Breitwieser FP, Kumar A, Hao H, Burger P, Rodriguez FJ, Lim M, Quiñones-Hinojosa A, Gallia GL, Tornheim JA, Melia MT, Sears CL, Pardo CA. Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system. Neurol Neuroimmunol Neuroinflamm. 2016 Jun 13;3(4):e251. https://doi.org/10.1212/NXI.0000000000000251. PMID: 27340685; PMCID: PMC4907805. Salzberg SL, Breitwieser FP, Kumar A, Hao H, Burger P, Rodriguez FJ, Lim M, Quiñones-Hinojosa A, Gallia GL, Tornheim JA, Melia MT, Sears CL, Pardo CA. Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system. Neurol Neuroimmunol Neuroinflamm. 2016 Jun 13;3(4):e251. https://​doi.​org/​10.​1212/​NXI.​0000000000000251​. PMID: 27340685; PMCID: PMC4907805.
Metadaten
Titel
Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort
verfasst von
Giacomo Brisca
Chiara Marini
Silvia Buratti
Marcello Mariani
Domenico Tortora
Giovanni Morana
Daniela Pirlo
Marta Romanengo
Giulia Cannizzaro
Ramona Cordani
Francesca Canzoneri
Maria Grazia Calevo
Lino Nobili
Diego Franciotta
Elio Castagnola
Andrea Moscatelli
Maria Margherita Mancardi
Publikationsdatum
03.07.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 10/2023
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-023-11847-3

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