Diagnostic Yield of Next-Generation Sequencing in CSF or Brain Biopsy for Severe Encephalitis Requiring Intensive Care.

Objectives: The aim of this study was to evaluate the contribution of metagenomic next-generation sequencing (mNGS) in critically ill patients with encephalitis of unknown etiology. Methods: This retrospective study (2016-2023) was conducted in a tertiary care referral neuro-ICU at La Pitié-Salpêtrière Hospital (Paris, France). The inclusion criteria were encephalitis with unknown etiology and mNGS performed on CSF, brain biopsy, and/or autopsy. We assessed the yield of mNGS and whether specific treatments were initiated. Neurologic outcome at 1 year was assessed using the Glasgow Outcome Scale-Extended (GOSE-1: death; GOSE-8: upper good recovery). Results: A total of 49 patients were included, of whom 44.9% were immunosuppressed. At 1 year, 38.8% had a GOSE score 4-8 and 47.7% died. mNGS was performed on the CSF of 40 of 49 patients (81.6%) and on brain biopsy of 19 of 49 patients (38.8%), including 12 patients who underwent both CSF and biopsy testing. Among the 40 mNGS analyses performed on the CSF, 7 (17.5%) yielded positive results but only 1 (2.5%) was likely causative. Conversely, 7 of 19 mNGS analyses (36.8%) on biopsies were positive and causative. Regarding the yield of mNGS in the entire cohort, 15 of 49 patients (30.6%) had a positive result but only 7 of 49 (14.3%) were causative (dengue virus, measles virus, rubella virus, Nocardia spp, HHV6, astrovirus, and orthobunyavirus), all from brain biopsies of immunocompromised patients. Conversely, 8 of 49 mNGS analyses (16.3%) were noncausative (polyomavirus, HHV8, HHV7, EBV, 2 pegiviruses, and 2 rhinoviruses). Specific treatments were initiated in 4 of 7 patients (57%). Among the 34 patients with a negative mNGS result, 5 (14.7%) were diagnosed with infectious encephalitis using conventional methods. Conclusion: In critically ill patients with encephalitis of unknown etiology, mNGS performed on brain biopsy could reduce diagnostic uncertainty.