Repeat Lumbar Puncture in Adults with Encephalitis: Patient Characteristics, CSF Dynamics, and Diagnostic Yield

Abstract Background During evaluation for encephalitis, lumbar puncture (LP) plays a critical role in establishing a diagnosis. Repeat LP may be needed when the diagnosis remains in doubt, the specific etiology of encephalitis has not yet been identified, or to aid management decisions. However, findings on repeat LP have not been well characterized, potentially confounding interpretation. Here, we examine the clinical characteristics of patients with encephalitis who underwent repeat LP, the evolution of CSF parameters, and the indications for repeat LP during acute hospitalization. Methods This retrospective study analyzes LP and clinical data from 627 adults with all causes of encephalitis admitted between 2002 and 2022 across two hospital systems in Maryland and Texas. Results Of the 627 patients, 184 (29.3%) underwent repeat LP, with a median interval of 6 days between procedures, and more commonly among those with more severe presentations. Patients were more likely to undergo repeat LP in autoimmune than in infectious encephalitis (42/113 [37.2%] vs. 62/275 [22.5%], p=0.003). In infectious cases, CSF WBC counts decreased when repeat LP occurred ≥7 days after initial LP (p=0.016), whereas no decrease occurred in autoimmune cases. Repeat LP yielded a new diagnosis in 16/184 (8.6%). Among patients without initial pleocytosis, 51.4% developed pleocytosis on repeat LP, associated with worse outcomes. Diagnostic uncertainty was the most common indication. Conclusion Repeat lumbar punctures are performed in one-third of encephalitis hospitalizations and are more common in patients with autoimmune etiologies, severe disease, or diagnostic uncertainty. CSF dynamics differ between infectious and autoimmune etiologies.