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Multicenter Study
. 2025 Sep 2;8(9):e2532478.
doi: 10.1001/jamanetworkopen.2025.32478.

Outcomes of Critically Ill Adult Patients With Acute Encephalitis

Romain Sonneville  1   2 , Camille Couffignal  3 , Bertrand Souweine  4 , Suela Demiri  5 , Nicolas Terzi  6 , Fabrice Bruneel  7 , Armand Mekontso Dessap  8 , Maelle Martin  9 , Clémence Marois  10 , Pierre Bailly  11 , Achille Kouatchet  12 , Guillaume Voiriot  13 , Florian Reizine  14 , Sarah Benghanem  15 , Guillaume Louis  16 , Marie Conrad  9 , Sami Hraiech  17 , Arnaud W Thille  18 , Jean-Christophe Navellou  19 , Damien Contou  20 , Simon Bourcier  21 , Marc Tran  22 , Frederic Dailler  23 , Laurent Argaud  24 , Charles Cerf  25 , Bertrand Guidet  26 , Damien Roux  27 , Lionel Kerhuel  28 , Guillaume Van Der Meersch  29 , Saad Nseir  30 , Adrien Joseph  31 , Daniel Da Silva  32 , Pascal Beuret  33 , Benjamine Sarton  34 , Candice Estellat  35 , Virginie Godard  3 , Jérôme Honnorat  36 , Philippa Catherine Lavallée  37 , Marina Esposito-Farèse  3 , Jean-François Timsit  1   2 ; ENCEPHALITICA Investigator Study Group
Collaborators, Affiliations
Multicenter Study

Outcomes of Critically Ill Adult Patients With Acute Encephalitis

Romain Sonneville et al. JAMA Netw Open. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Sonneville reported receiving grants from Advanz Pharma, AOP Health, and LFB outside the submitted work. Dr. Terzi reported receiving personal fees from Fisher & Paykel outside the submitted work. Dr. Marois reported receiving personal fees from Alexion (advisory board) and Novartis (teaching and congress participation) and grants from Fondation Matmut Paul Bennetot (research) outside the submitted work. Dr. Bailly reported being a medical coordinating investigator for Sedana outside the submitted work. Dr. Voiriot reported receiving grants from bioMérieux and SOS Oxygène and personal fees from SOS Oxygène (support for attending meeting) and Oxyvie (support for attending meeting) outside the submitted work. Dr. Thille reported receiving grants, personal fees, and nonfinancial support from Fisher & Paykel outside the submitted work. Dr. Nseir reported receiving personal fees from Pfizer (lecture), Merck Sharp & Dohme (lecture), bioMérieux (lecture), Medtronic (lecture), Fisher & Peykel (lecture), and Mundi Pharma (advisory board) outside the submitted work. Dr. Timsit reported receiving personal fees from Advanz Pharma (lectures), Mundipharma (lecture), Pfizer (lecture), and Menarini (advisory board) and research grants from Pfizer and Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Factors Associated With an Unfavorable Outcome, Multivariable Analysis
An unfavorable outcome was moderate to severe disability or death, defined by a modified Rankin score of 3 to 6. CSF indicates cerebrospinal fluid; EEG, electroencephalography; GCS, Glasgow Coma Scale; IV, intravenous; OR, odds ratio; SAPS, Simplified Acute Physiology score; SOFA, sequential organ failure assessment.
Figure 2.
Figure 2.. Patient Functional Status on the Modified Rankin Scale Up to 1 Year After Severe Encephalitis
The lines between each bar represent changes in Rankin score between time points. ICU indicates intensive care unit.
Figure 3.
Figure 3.. Patient Location up to 1 Year After Severe Encephalitis
ICU indicates intensive care unit.
See this image and copyright information in PMC

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