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Background and purpose Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis. Methods A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit ( ICU) of a university hospital over a 20-year period. Patients' characteristics and outcomes were compared between two 10-year periods: (i) 1991-2001 and (ii) 2002-2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (m RS) score of 4-6 (severe disability or death) 90 days after admission. Results A total of 279 patients were studied. Causes of encephalitis were infections ( n = 149, 53%), immune-mediated causes ( n = 41, 15%) and undetermined causes ( n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune-mediated causes. At day 90, 208 (75%) patients had an m RS = 0-3 and 71 (25%) had an m RS = 4-6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio ( OR) 7.09, 95% confidence interval (95% CI) 3.06-17.03], aspiration pneumonia ( OR 4.02, 95% CI 1.47-11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53-0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17-2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01-1.07). Conclusions Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission. [ABSTRACT FROM AUTHOR]