Comparing molecular quantification of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) with quantitative structural and functional disease severity in patients with HSV encephalitis (HSVE): Implications for improved therapeutic approaches.

BACKGROUND: Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies.

OBJECTIVES: To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity.

STUDY DESIGN: HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes.

RESULTS: Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75-1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5-1.6), p = 0.72; OR = 1.0(CI 0.5-1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5-3.3), p = 0.57; OR = 2.3(CI 0.7-8), p = 0.2].

CONCLUSIONS: Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.