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We aimed to study the association of body temperature and other admission factors with outcomes of herpes simplex encephalitis (HSE) adult patients requiring ICU admission. We conducted a retrospective multicenter study on patients diagnosed with HSE in 47 ICUs in France, between 2007 and 2017. Fever was defined as a body temperature higher or equal to 38.3 °C. Multivariate logistic regression analysis was used to identify factors associated with poor outcome at 90 days, defined by a score of 3–6 (indicating moderate-to-severe disability or death) on the modified Rankin scale. Overall, 259 patients with a score on the Glasgow coma scale of 9 (6–12) and a body temperature of 38.7 (38.1–39.2) °C at admission were studied. At 90 days, 185 (71%) patients had a poor outcome, including 44 (17%) deaths. After adjusting for age, fever (OR = 2.21; 95% CI 1.18–4.16), mechanical ventilation (OR = 2.21; 95% CI 1.21–4.03), and MRI brain lesions > 3 lobes (OR = 3.04; 95% CI 1.35–6.81) were independently associated with poor outcome. By contrast, a direct ICU admission, as compared to initial admission to the hospital wards (i.e., indirect ICU admission), was protective (OR = 0.52; 95% CI 0.28–0.95). Sensitivity analyses performed after adjustment for functional status before admission and reason for ICU admission yielded similar results. In HSE adult patients requiring ICU admission, several admission factors are associated with an increased risk of poor functional outcome. The identification of potentially modifiable factors, namely, elevated admission body temperature and indirect ICU admission, provides an opportunity for testing further intervention strategies.

Key Points Question Are early brain changes seen on magnetic resonance imaging (MRI) associated with functional outcomes among adult patients with severe herpes simplex encephalitis (HSE)? Findings In adult patients with HSE, extensive brain changes seen on MRI during the first month after intensive care unit admission were independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients. Meanings These findings suggest that, among adult patients with severe HSE, early MRI data were associated with neurological outcomes, both in terms of brain lesion extension and critical focal MRI signal changes., This cohort study investigates the association between early collected magnetic resonance imaging (MRI) data and functional outcomes 90 days after intensive care unit admission among adults with severe herpes simplex encephalitis., Importance Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures MRI acquisitions were analyzed by radiologists blinded to patients’ outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

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