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Abstract Details

Herpes Simplex Encephalitis: A Systematic Review of Clinical Outcomes and Treatment Duration
Infectious Disease
P7 - Poster Session 7 (8:00 AM-9:00 AM)
3-002
To systematically review the literature on intravenous acyclovir (ACV) treatment for herpes simplex encephalitis (HSE) and summarize clinical outcomes.
HSE is the leading cause of sporadic fatal encephalitis worldwide and carries high morbidity despite the availability of intravenous ACV. While ACV has dramatically reduced mortality compared to the pre-antiviral era, neurological sequelae remain common, and the optimal duration of therapy is uncertain.

We conducted a systematic search in PubMed, ISI Web of Science, and Google Scholar up to August 19, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify studies reporting outcomes of patients with confirmed HSE treated with intravenous ACV. Eligible designs included randomized controlled trials, cohorts, and case series with reported treatment durations. Outcomes of interest were mortality, functional disability, neurological deficits, seizure and epilepsy. Risk of bias was assessed using design-specific criteria.
Seven studies (n=351 patients) from 2007–2024 met inclusion criteria, spanning neonatal to adult populations across six countries. HSV-1 encephalitis was confirmed by CSF PCR. Patient demographics varied, with mean ages from 0.02 to 46.9 years and 66% male. Treatment approaches were heterogeneous, with acyclovir dosing ranging from 30–60 mg/kg/day, variable treatment durations, and sporadic corticosteroid use across studies. Clinical outcomes were highly variable: seizures occurred in 0–71% of patients, epilepsy was reported mainly in a pediatric ICU cohort, and focal neurological deficits ranged from 18–100%. Functional recovery was mixed, with favorable outcomes (mRS 0–2) in 52–64% of patients. Mortality was generally low, ranging from 0–16% across cohorts.
Current evidence does not clearly demonstrate superiority of 14-day versus 21-day IV ACV regimens for HSE, with substantial neurological morbidity persisting across both strategies. Robust prospective multi-center studies and randomized trials using standardized outcome measures are urgently needed to optimize treatment duration and improve long-term outcomes.
Authors/Disclosures
Gerome B. Vallejos, MD
PRESENTER 		Mr. Vallejos has nothing to disclose.
Anlys Olivera, MD, PhD (NYU Langone Medical Center) Dr. Olivera has nothing to disclose.
Luisa F. Alviz Rodriguez, research assisstant Miss Alviz Rodriguez has nothing to disclose.
Carla Kim Carla Kim has nothing to disclose.
Christopher Bunting, MBBS Dr. Bunting has nothing to disclose.
Sanaullah Mudassir, MD, MBBS (Indira Gandhi Institute of Medical Science) Dr. Mudassir has nothing to disclose.
Rachelle Dugue, MD, PhD Dr. Dugue has nothing to disclose.
John Probasco, MD, FAAN (The Johns Hopkins Hospital) Dr. Probasco has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Clinician. The institution of Dr. Probasco has received research support from Roche/Genentech.
Ava M. Easton, PhD (The Encephalitis Society) Dr. Easton has received personal compensation for serving as an employee of Encephalitis Society. Dr. Easton has received publishing royalties from a publication relating to health care.
Benedict Michael, MD Prof. Michael has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Moore Barlow. The institution of Prof. Michael has received research support from MRC.
Tom Solomon, MD (The University of Liverpool) The institution of Dr. Solomon has received research support from National Institute for Health and Care Research (NIHR).
Jacob Bodilsen Jacob Bodilsen has nothing to disclose.
Rodrigo Hasbun Rodrigo Hasbun has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biomeriaux. The institution of Rodrigo Hasbun has received research support from Biomeriaux.
Arun Venkatesan, MD, PhD (Johns Hopkins Hospital) Dr. Venkatesan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. The institution of Dr. Venkatesan has received research support from NIH. The institution of Dr. Venkatesan has received research support from U.S. DOD.
Kiran Thakur, MD, FAAN (Columbia University College of Physicians and Surgeons) Dr. Thakur has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Delve Bio.