Electroencephalography for prognostication of outcome in adults with severe herpes simplex encephalitis
Authors: Jeantin Lina , Dupuis Claire , Vellieux Geoffroy , Jaquet Pierre , de Montmollin Etienne , Timsit Jean-François , Sonneville Romain ,   the ENCEPHALITICA Study Group, Alves Mikael , Argaud Laurent , Bailly Pierre , Barbier François , Bouadma Lila , Brulé Noelle , Bruneel Fabrice , Chabanne Russell , Conrad Marie , da Silva Daniel , Dailler Frederic , Daubin Delphine , Demeret Sophie , Lerolle Nicolas , Marechal Julien , Mourvillier Bruno , El Kalioubi Ahmed , Sarton Benjamine , Silva Stein , Susset Vincent , Tadié Jean Marc , Timsit Jean-Françoit , Wolff Michel , Lautrette Alexandre , Novy Emmanuel , Guidet Bertrand , Mateos François , Brault Clément , Maestraggi Quentin , Razazi Keyvan , Quenot Jean-Pierre , Joret Aurélie , Levrat Albrice , Massri Alexandre , Robert Alexandre , Contou Damien , Mira Jean-Paul , Stephane Gaudry , Voiriot Guillaume , Berger Asael , Das Vincent , Engrand Nicolas , Murgier Martin , Siami Shidasp , Hraiech Sami , Mariotte Eric , Ragot Claire , Stoclin Annabelle , Trouiller Pierre , Schmidt Mathieu , Sazio Charline 
Published: February 2023

Abstract
Background
Electroencephalography (EEG) is recommended for the practical approach to the diagnosis and prognosis of encephalitis. We aimed to investigate the prognostic value of standard EEG (stdEEG) in adult patients with severe herpes simplex encephalitis.

Methods
We performed a retrospective analysis of consecutive ICU patients with severe herpes simplex encephalitis in 38 French centers between 2006 and 2016. Patients with at least one stdEEG study performed at ICU admission were included. stdEEG findings were reviewed independently by two investigators. The association between stdEEG findings (i.e., background activity, lateralized periodic discharges, seizures/status epilepticus, and reactivity to painful/auditory stimuli) and poor functional outcome, defined by a score on the modified Rankin Scale (mRS) of 3 to 6 (moderate to severe disability or death) at 90 days, were investigated.

Results
We included 214 patients with at least one available stdEEG study. The first stdEEG was performed after a median time of one (interquartile range (IQR) 0 to 2) day from ICU admission. At the time of recording, 138 (64.5%) patients were under invasive mechanical ventilation. Lateralized periodic discharges were recorded in 91 (42.5%) patients, seizures in 21 (9.8%) and status epilepticus in 16 (7.5%). In the whole population, reactivity to auditory/noxious stimuli was tested in 140/214 (65.4%) patients and was absent in 71/140 (33.2%) cases. In mechanically ventilated patients, stdEEG reactivity was tested in 91/138 (65.9%) subjects, and was absent in 53/91 (58.2%) cases. Absence of reactivity was the only independent stdEEG finding associated with poor functional outcome in the whole population (OR 2.80, 95% CI 1.19 to 6.58) and in the subgroup of mechanically ventilated patients (OR 4.99, 95% CI 1.6 to 15.59). Adjusted analyses for common clinical predictors of outcome and sedation at time of stdEEG revealed similar findings in the whole population (OR 2.03, 95% CI 1.18 to 3.49) and in mechanically ventilated patients (OR 2.62, 95% CI 1.25 to 5.50).

Conclusions
Absence of EEG reactivity to auditory/noxious stimuli is an independent marker of poor functional outcome in severe herpes simplex encephalitis.