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Outcomes of Critically Ill Adult Patients With Acute Encephalitis

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ImportanceFunctional outcomes and long-term recovery after severe encephalitis are not well characterized.ObjectiveTo determine the incidence of functional disability or death at 3 months and to describe recovery trajectories through 1 year after encephalitis.Design, Setting, and ParticipantsThis prospective multicenter cohort study was conducted across 31 French centers from October 2017 to April 2021 and included adults with probable or confirmed encephalitis and clear cerebrospinal fluid findings requiring care in the intensive care unit. Data analysis was performed between May 2023 and June 2025.ExposureCauses of encephalitis were categorized into 4 different groups: infectious, autoimmune, other causes, and unknown origin.Main Outcomes and MeasuresThe primary end point was an unfavorable outcome at 3 months, defined by a modified Rankin scale score of 3 to 6, indicating moderate to severe disability or death.ResultsAmong the 310 patients included (median [IQR] age, 60 [43-70] years; 177 male [57.1%]), 123 (39.7%) were diagnosed with infectious encephalitis, 42 (13.5%) with autoimmune encephalitis, 37 (11.9%) with other encephalitis causes, and 108 (34.8%) with encephalitis of unknown origin. Overall, 161 patients (51.9%; 95% CI, 46.2%-57.6%) had an unfavorable outcome at 3 months, including 84 deaths (27.1%). Independent factors associated with unfavorable outcome included age (odds ratio [OR] per 5-year increment, 1.28, 95% CI, 1.16 to 1.41) and immunocompromised status (OR, 3.12; 95% CI, 1.57 to 6.40), while intravenous acyclovir on the day of ICU admission was associated with a favorable outcome (OR, 0.38; 95% CI, 0.20 to 0.72). The proportion of patients achieving functional independence remained stable from 3 months to 1 year (difference in proportions, 1.1%; 95% CI, −6.9% to 9.2%). Analyses based on encephalitis cause groups revealed that patients with autoimmune encephalitis showed significant improvement through 1 year (difference in proportions, 8.9%; 95% CI, 1.2% to 16.6%), whereas no significant changes were seen in patients with infectious causes (difference in proportions, 1.2%; 95% CI, −6.9% to 9.2%), other causes (difference in proportions, 1.2%; 95% CI: −6.8% to 9.2%), or unknown origin (difference in proportions, −1.9%; 95% CI: −10.0% to 6.2%).Conclusions and RelevanceIn this cohort study of adults with severe encephalitis requiring intensive care, one-half of patients had an unfavorable outcome at 3 months. Functional recovery at 1 year varied by cause of encephalitis, with patients with autoimmune encephalitis experiencing more favorable outcomes than those with other causes, suggesting a possible role for targeted long-term support in certain cases.
American Medical Association (AMA)
Romain Sonneville Camille Couffignal Bertrand Souweine Suela Demiri Nicolas Terzi Fabrice Bruneel Armand Mekontso Dessap Maelle Martin Clémence Marois Pierre Bailly Achille Kouatchet Guillaume Voiriot Florian Reizine Sarah Benghanem Guillaume Louis Marie Conrad Sami Hraiech Arnaud W. Thille Jean-Christophe Navellou Damien Contou Simon Bourcier Marc Tran Frederic Dailler Laurent Argaud Charles Cerf Bertrand Guidet Damien Roux Lionel Kerhuel Guillaume Van Der Meersch Saad Nseir Adrien Joseph Daniel Da Silva Pascal Beuret Benjamine Sarton Candice Estellat Virginie Godard Jérôme Honnorat Philippa Catherine Lavallée Marina Esposito-Farèse Jean-François Timsit Moustafa ABDEL-NABEY Melanie ADDA Hamou Zakaria AIT Virginie ANZANO Romain ARRESTIER Pierre ASFAR Claire BACHELIER François BAGATE Elodie BARON Thomas BAUDRY François BELONCLE Morgan BENAIS Ines BENDIB Brice BENELLI Sarah BENGHANEM Helene BERINGUER Enora BERTI Astrid BERTIER Morage BERTRIX Sebastien BESSET Alexandra BEURTON Naike BIGE Clarisse BLAYAU Florence BOISSIER Pierre-Edouard BOLLAERT Marjolaine BOREL Lila BOUADMA Athenais BOUCLY Simon BOURCIER Radhia BOUZGARROU Cedric BRUEL Côme BUREAU Cyril CADOZ Laure CALVET Emmanuel CANET Albert CAO Alain CARIOU Romain CARRILLON Pedro CAVALEIRO Julien CHARPENTIER Delphine CHATELLIER Vibol CHHOR Jean-Daniel CHICHE Sebastien CLERC Benjamin COIFFARD Remi COUDROY Pierre COUHAULT Elisabeth COUPEZ Guilhem COURTE Aurélie CRAVOISY-POPOVIC Thibault CREUTIN Laura CROSBY Silva Daniel DA Florence DAVIET Montmollin Etienne DE Maxens DECAVELE Thecle DEGROOTE Robin DELERIS Sophie DEMERET Suela DEMIRI Julien DEMISELLE Martin DRES Louis-Marie DUMONT Julien DUPEYRAT Pierre DUPLAND Claire DUPUIS Kalioubie Ahmed EL Morgane FAURE Laura FEDERICI Alexis FERRE Jean-Marie FOREL Guillaume FRANCHINEAU Jean-Pierre FRAT Santiago FREITA-RAMOS Rostane GACI Arnaud GACOUIN Aude GARIN Charlotte GARRET Ariane GAVAUD Segolene GENDREAU Etienne GHRENASSIA Sebastien GIBOT Armelle GILARD Tiphaine GIRARD Florent GOBERT Kevin GRAPIN Christophe GUERVILLY Marion HALLARD Geoffroy HARIRI Otto HARTMAN Anne-Fleur HAUDEBOURG Luc HAUDEBOURG Jeremy HEBRAUD Jérôme HONNORAT Pierre JAQUET Paul JAUBERT Florent JOLY Matthieu JOZWIAK Hélène JULIEN Francis KINDA Pascale LABEDADE Pascale LABROCA Guillaume LACAVE Driss LAGHLAM Pauline LAMOUCHE-WILQUIN Jean-Baptiste LASCARROU Virginie LAURENT Guillaume LAURICHESSE Guennec Loïc LE Marec Julien LE Marie LECRONIER Lucie LEFEVRE Camille LEGOUY Stephane LEGRIEL Jérémie LEMARIE Marie LEMERLE Jean-Mathias LITEAUDON Julien LOPINTO Charles-Edouard LUYT Adel MAAMAR Assadi MAKSUD Damien MARIE Eric MARIOTTE Remy MARNAI Olivier MARTIN Paul MASI Rafael MATHIEU Eric MAURY Julien MAYAUX Sandie MAZERAND Alain MERCAT Sybille MERCERON Arnaud-Félix MIAILHE Gael MICHAUD Hélène MIGUERES Jean-Paul MIRA Grégoire MONSEAU Elise MORAWIEC Jean MORIN Satar MORTAZA Lionel NACE Safaa NEMLAGHI Mathilde NEUVILLE Bao-Long NGUYEN Lee NGUYEN Pierre-Yves OLIVIER Gregoire OTTAVY Laurent PAPAZIAN Edwidge PEJU Frederic PENE François PERIER François PHILIPPART Marc PIERROT Olivier POULY Gwenael PRAT Simona PRESENTE Isabelle PRIOUR Thomas RAMBAUD Keyvan RAZAZI Jean REIGNIER Anne RENAULT Thomas RITZENTHALER Alexandre ROBERT Benjamin ROHAUT Guillaume SAVARY Faiza SAYAGH Carole SCHWEBEL Amélie SEGUIN Stein SILVA Fabrice SINNAH Vincent SOUDAY Françoise THOUY Jean-Marie TONNELIER Aurelia TOUSSAINT Marc TRAN Samuel TUFFET Fabrice UHEL Thomas URBINA Anne VEINSTEIN Charles VERNEY Antoine VIEILLARD-BARON Clara VIGNERON Helene VINOUR Sara VIROLLE Lev VOLKOV Constance VUILLARD Nicolas WEISS Paul Henri WICKY Lara ZAFRANI Olivier ZAMBON Noemie ZUCMAN
Title: Outcomes of Critically Ill Adult Patients With Acute Encephalitis
Description:
ImportanceFunctional outcomes and long-term recovery after severe encephalitis are not well characterized.
ObjectiveTo determine the incidence of functional disability or death at 3 months and to describe recovery trajectories through 1 year after encephalitis.
Design, Setting, and ParticipantsThis prospective multicenter cohort study was conducted across 31 French centers from October 2017 to April 2021 and included adults with probable or confirmed encephalitis and clear cerebrospinal fluid findings requiring care in the intensive care unit.
Data analysis was performed between May 2023 and June 2025.
ExposureCauses of encephalitis were categorized into 4 different groups: infectious, autoimmune, other causes, and unknown origin.
Main Outcomes and MeasuresThe primary end point was an unfavorable outcome at 3 months, defined by a modified Rankin scale score of 3 to 6, indicating moderate to severe disability or death.
ResultsAmong the 310 patients included (median [IQR] age, 60 [43-70] years; 177 male [57.
1%]), 123 (39.
7%) were diagnosed with infectious encephalitis, 42 (13.
5%) with autoimmune encephalitis, 37 (11.
9%) with other encephalitis causes, and 108 (34.
8%) with encephalitis of unknown origin.
Overall, 161 patients (51.
9%; 95% CI, 46.
2%-57.
6%) had an unfavorable outcome at 3 months, including 84 deaths (27.
1%).
Independent factors associated with unfavorable outcome included age (odds ratio [OR] per 5-year increment, 1.
28, 95% CI, 1.
16 to 1.
41) and immunocompromised status (OR, 3.
12; 95% CI, 1.
57 to 6.
40), while intravenous acyclovir on the day of ICU admission was associated with a favorable outcome (OR, 0.
38; 95% CI, 0.
20 to 0.
72).
The proportion of patients achieving functional independence remained stable from 3 months to 1 year (difference in proportions, 1.
1%; 95% CI, −6.
9% to 9.
2%).
Analyses based on encephalitis cause groups revealed that patients with autoimmune encephalitis showed significant improvement through 1 year (difference in proportions, 8.
9%; 95% CI, 1.
2% to 16.
6%), whereas no significant changes were seen in patients with infectious causes (difference in proportions, 1.
2%; 95% CI, −6.
9% to 9.
2%), other causes (difference in proportions, 1.
2%; 95% CI: −6.
8% to 9.
2%), or unknown origin (difference in proportions, −1.
9%; 95% CI: −10.
0% to 6.
2%).
Conclusions and RelevanceIn this cohort study of adults with severe encephalitis requiring intensive care, one-half of patients had an unfavorable outcome at 3 months.
Functional recovery at 1 year varied by cause of encephalitis, with patients with autoimmune encephalitis experiencing more favorable outcomes than those with other causes, suggesting a possible role for targeted long-term support in certain cases.

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