Outcomes of Critically Ill Adult Patients With Acute Encephalitis
Romain Sonneville, Camille Couffignal, Bertrand Souweine, Suela Demiri, Nicolas Terzi, Fabrice Bruneel, Armand Mekontso Dessap, Maëlle 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, Frédéric Dailler, Laurent Argaud, Charles Cerf, Bertrand Guidet, Damien Roux, Lionel Kerhuel, Guillaume Van Der Meersch, Saad Nseir, Adrien Joseph, Daniel Silva, Pascal Beuret, Benjamine Sarton, Candice Estellat, Virginie Godard, Jérôme Honnorat, Philippa C. Lavallée, Marina Esposito‐Farèse, Jean‐François Timsit, ENCEPHALITICA Investigator Study Group, Moustafa Abdel-Nabey, Mélanie Adda, Hamou Zakaria AIT, Virginie ANZANO, Romain Arrestier, Pierre Asfar, Claire Bachelier, François Bagate, Ėlodie Baron, Thomas Baudry, François Beloncle, Morgan Benaïs, Inès Bendib, Brice Benelli, Sarah Benghanem, Hélène Beringuer, Enora BERTI, Astrid BERTIER, Morage BERTRIX, Sébastien Besset, Alexandra Beurton, Naïke Bigé, Clarisse Blayau, Florence Boissier, Pierre‐Édouard Bollaert, M.L. Borel, Lila Bouadma, Athénaïs Boucly, Simon Bourcier, Radhia Bouzgarrou, Cédric 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, Sébastien Clerc, Benjamin Coiffard, Rémi Coudroy, Pierre Couhault, Elisabeth Coupez, Guilhem Courte, Aurélie Cravoisy-Popovic, Thibault Creutin, Laura CROSBY, Dimal A. Shah, Florence Daviet, Marcos Felipe Silva de Sá, Maxens Decavèle, Thècle Degroote, Robin Déléris, Sophie Demeret
Abstract
Importance: Functional outcomes and long-term recovery after severe encephalitis are not well characterized. Objective: To determine the incidence of functional disability or death at 3 months and to describe recovery trajectories through 1 year after encephalitis. Design, Setting, and Participants: This 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. Exposure: Causes of encephalitis were categorized into 4 different groups: infectious, autoimmune, other causes, and unknown origin. Main Outcomes and Measures: The 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. Results: Among 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 Relevance: In 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.