CSF Pleocytosis in Encephalitis: A Multicenter Retrospective Study
Ralph Habis1, Anna Kolchinski1, Paris Bean2, Ashley Heck2, John Probasco1, Rodrigo Hasbun2, Arun Venkatesan1
1Johns Hopkins Encephalitis Center, Department of Neurology, Johns Hopkins University School of Medicine, Maryland, USA, 2Department of Medicine, Section of Infectious Disease, McGovern Medical School, UTHealth Science Center, Houston, TX, USA
Objective:
The aim of this study is to compare the predictors, etiologies, and prognosis of patients with new-onset encephalitis who have normal levels of white blood cells in their initial cerebrospinal fluid (CSF) profile (<5 cells/µL), mild pleocytosis (5-50 cells/µL), and robust pleocytosis (>50 cells/µL).
Background:

Early diagnosis of encephalitis involves identifying inflammatory signs in the central nervous system. However, the absence of CSF pleocytosis in encephalitis has been increasingly described. Understanding the predictors and outcomes associated with different CSF profiles can aid in the timely diagnosis and management of encephalitis.

Design/Methods:

This retrospective study compares CSF profiles in 626 adult patients diagnosed with encephalitis, including those with all-cause encephalitis, infectious (IE), and autoimmune (AIE) subtypes.

Results:
Among 626 patients with encephalitis, 166 (26.5%) had normocellular CSF, 211 (33.7%) had mild, and 249 (39.8%) had robust pleocytosis. Out of 262 patients with IE, 88.5% of those with bacterial infections had robust pleocytosis, while those with viral and fungal infections had consistent distribution across the three levels of pleocytosis. IE patients with robust pleocytosis were more likely to receive acyclovir in <24hrs (normocellular 77.5%, vs. mild 89.5 p=0.18, and robust 91% p=0.024).  Among 112 AIE patients, only 15 had robust pleocytosis, and 12 of those had anti-NMDAR encephalitis (p<0.001). None of the anti-LGI1/CASPR2 patients had robust pleocytosis, and 88.2% had normocellular CSF. No significant association was found between delays in initiation of appropriate immunotherapy and level of pleocytosis in patients with AIE. Finally, the level of pleocytosis was not associated with worse outcomes in either AIE or IE patients.
Conclusions:

Pleocytosis is a criterion for encephalitis diagnosis, but 116 (26.5%) of our patients had normocellular CSF, among which 47 (28.3%) had IE. Thus, acyclovir initiation shouldn't be delayed in absence of pleocytosis. Robust pleocytosis could suggest the possibility of Anti-NMDAR encephalitis. 

10.1212/WNL.0000000000206027