Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis
Authors: Benjamine Sarton, Pierre Jaquet, Djida Belkacemi, Etienne de Montmollin, Fabrice Bonneville, Charline Sazio, Aurelien Frérou, Marie Conrad, Delphine Daubin, Russell Chabanne, Laurent Argaud, Frédéric Dailler, Noëlle Brulé, Nicolas Lerolle, Quentin Maestraggi, Julien Marechal, Pierre Bailly, Keyvan Razazi, Francois Mateos, Bertrand Guidet, Albrice Levrat, Vincent Susset, Alexandre Lautrette, Jean-Paul Mira, Ahmed El Kalioubie, Alexandre Robert, Alexandre Massri, Jean François Albucher, Jean Marc Olivot, Jean Marie Conil, Lila Boudma, Jean-François Timsit, Romain Sonneville, Stein Silva, Pierre Jaquet, Etienne de Montmollin, Claire Dupuis, Mikael Alves, Laurent Argaud, Pierre Bailly, François Barbier, Lila Bouadma, Noelle Brulé, Fabrice Brunel, Russell Chabanne, Marie Conrad, Daniel Da Silva, Frederic Dailler, Delphine Daubin, Sophie Demeret, Nicolas Lerolle, Julien Marechal, Bruno Mourvillier, Ahmed El Kalioubi, Benjamine Sarton, Stein Silva, Romain Sonneville, Vincent Susset, Jean Marc Tadié, Jean-Françoit Timsit, Michel Wolff, Alexandre Lautrette, Emmanuel Novy, Bertrand Guidet, François Mateos, Clément Brault, Quentin Maestraggi, Keyvan Razazi, Jean-Pierre Quenot, Aurélie Joret, Albrice Levrat, Alexandre Massri, Alexandre Robert, Damien Contou, Jean-Paul Mira, Stephane Gaudry, Guillaume Voiriot, Asael Berger, Vincent Das, Nicolas Engrand, Martin Murgier, Shidasp Siami, Sami Hraiech, Eric Mariotte, Claire Ragot, Annabelle Stoclin, Pierre Trouiller, Mathieu Schmidt, Charline Sazio
Journal: JAMA Network Open (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> All patients underwent a standard brain MRI during the first 30 days after ICU admission. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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 &gt;60 years had left thalamic lesions). <h3>Conclusions and Relevance</h3> 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.