Absence of CSF Pleocytosis Prevalent in Encephalitis and Can Delay Empiric Treatment
Clinical question: Is there a difference in clinical factors and outcomes among patients with new-onset encephalitis based on whether their initial cerebrospinal fluid (CSF) studies demonstrate the presence or absence of pleocytosis, and do these differing CSF findings affect the administration of empiric therapy?
Background: Optimal management of patients with encephalitis includes prompt recognition, accurate diagnosis, and timely intervention. Clinical diagnostic criteria have been established for this purpose: they often rely on initial CSF studies, including the presence of pleocytosis (≥5 WBC/µL), as a key indicator of central nervous system inflammation. However, the absence of pleocytosis has been noted in cases of encephalitis (especially those of autoimmune and idiopathic etiologies). This study aimed to compare the clinical factors and outcomes in cases of encephalitis based on this difference, as well as determine if it significantly affected the timely administration of empiric therapy.
Study design: Retrospective study
Setting: Hospital systems in Houston and Baltimore
Synopsis: A total of 597 adult patients with all-cause encephalitis-related ICD-9 discharge codes were included, of whom 151 (25.3%) had no pleocytosis on CSF analysis. Of this subgroup, they were equally likely to have an infectious versus autoimmune etiology (31.1% versus 25.6%, P >.05). Within the infectious subgroup, 40% of cases were due to HSV-1; 23.7% of these exhibited no pleocytosis. Patients without pleocytosis were less likely to receive empiric acyclovir than those with pleocytosis (47.7% versus 71.1%, P <.001). The presence of pleocytosis was associated with neurologic dysfunction at presentation but was not correlated with worse outcomes or mortality.
A substantial proportion of cases examined in this study remained idiopathic, likely leading to underdiagnosis which may affect these results. This was also an observational study that is at risk of confounding. Nevertheless, these findings suggest that the absence of pleocytosis cannot reliably discriminate between infectious and autoimmune etiologies of encephalitis. They also imply that empiric therapy should not necessarily be delayed if clinical suspicion remains high.
Bottom line: The absence of CSF pleocytosis in encephalitis is prevalent in infectious, autoimmune, and idiopathic cases of encephalitis, and can lead to delayed initiation of empiric therapy.
Citation: Habis R, et al. Absence of cerebrospinal fluid pleocytosis in encephalitis. Clin Infect Dis. 2024:ciae391. doi: 10.1093/cid/ciae391.
Dr. Wynkoop is an academic hospitalist in the section of hospital medicine at UPMC Presbyterian Hospital, and an assistant professor of medicine at the University of Pittsburgh School of Medicine, both in Pittsburgh.