A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis
Authors: Le Maréchal Marion , Mailles Alexandra , Seigneurin Arnaud , Tattevin Pierre , Stahl Jean-Paul , Épaulard Olivier ,   Scientific Committee and Investigators Group, Abgrall Sophie , Argaud Laurent , Argemi Xavier , Asseray Nathalie , Baille Guillaume , Baldolli Aurélie , Baudry Thomas , Biberon Julien , Biron Charlotte , Blanchet-Fourcade Geneviève , Blot Mathieu , Bonnan Michael , Bonnetain Anne , Botelho-Nevers Elisabeth , Bourdain Frédéric , Boutoille David , Brasme Hélène , Bruel Cédric , Bruneel Fabrice , Buzele Rodolphe , Canouï Etienne , Casenave Philippe , Castan Bernard , Cazanave Charles , Cazorla Céline , Challan-Belval Thibault , Chavanet Pascal , Chirouze Catherine , Courjon Johan , Da Silva Daniel , De Broucker Thomas , De La Blanchardière Arnaud , De Montmollin Etienne , Degroote Thècle , Delaroche Marine , Denes Eric , Deschanvres Colin , Diard-Detoeuf Capucine , Dinh Aurélien , Epaulard Olivier , Fillatre Pierre , Forestier Emmanuel , Fraisse Thibaut , Froidure Marie , Gaborit Benjamin , Gagneux-Brunon Amandine , Gaillard Nicolas , Galbois Arnaud , Godement Mathieu , Goehringer François , Goubin Pascale , Gravier Simon , Greigert Valentin , Gueit Isabelle , Guimard Thomas , Henry Carole , Hentzien Maxime , Herbrecht Jean-Etienne , Jaquet Pierre , Jomier Fanny , Khatchatourian Lydie , Kernéis Solen , Krause Jessica , Le Bras Morgane , Le Cam Manuela , Le Maréchal Marion , Le Moal Gwenael , Le Turnier Paul , Lecomte Raphaël , Lecompte Anne-Sophie , Lefaucheur Romain , Lejeune Stéphanie , Lescure Xavier , Lesieur Olivier , Lesprit Philippe , Louis Guillaume , Lucas Christelle , Mahieu Rafael , Makinson Alain , Marc Guillaune , Jacques Maria Alexandre Thibault , Marin Nathalie , Martin Aurélie , Martin-Blondel Guillaume , Martinot Martin , Mas Alexandre , Mateu Philippe , Matt Morgan , Maulin Laurence , Mechaï Frédéric , Mira Jean-Paul , Mutez Eugénie , Orain Jérémie , Pachart Anne , Pansu Nathalie , Patrat-Delon Solene , Pavese Patricia , Pellerin Hélène , Pelonde-Erimée Véronique , Pierre Isabelle , Piet Emilie , Ponscarme Diane , Psimaras Dimitri , Puges Mathilde , Raffi François , Reveillon-Istin Mathilde , Rheims Sylvain , Richard-Mornas Aurélie , Riché Agnès , Roubeau Vincent , Ruch Yvon , Runge Isabelle , Savini Hélène , Sonneville Romain , Stahl Jean-Paul , Tattevin Pierre , Tchroboczek Tomasz , Tiercelet Kelly , Touati Saber , Turmel Jean-Marie , Tyvaert Isabelle , Vareil Marc-Olivier , Vidal-Roux Magalie , Vitrat Virginie , Wille Heidi , Zuber Mathieu , Almoyna-Martinez Laurent , Bouchaud Olivier , de Broucker Thomas , Bruneel Fabrice , Castan Bernard , Denes Eric , Epaulard Olivier , Herrmann Jean-Louis , Honnorat Jérome , Mailles Alexandra , Morand Patrice , Raffi François , Roblot France , Stahl Jean-Paul , Sonneville Romain , Tattevin Pierre 
Published: May 2020

Abstract

Background
New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV).

Methods
The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen.

Results
As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis.

Conclusions
No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.