A recent article published in The American Journal of Case Reports on January 14, 2024, presents a significant case that could pave the way for a paradigm shift in the treatment of severe Herpes Simplex Virus-1 (HSV-1) encephalitis. A 21-year-old man exhibiting immediate improvement from a clinically and radiographically severe case of HSV-1 encephalitis following treatment with intravenous immunoglobulin (IVIG) and glucocorticoids in addition to standard acyclovir therapy suggests that immunomodulatory therapy could play a crucial role in treating this life-threatening disease.


Herpes Simplex Encephalitis (HSE) is a serious and often devastating infection of the central nervous system, primarily caused by Herpes Simplex Virus-1 (HSV-1). Upon infection, a patient typically presents with headache, fever, and a range of neurological deficits. Treatment traditionally includes the antiviral drug acyclovir, which suppresses viral replication but does little to address the immune-mediated brain damage that ensues from the inflammatory response to the virus. In this groundbreaking report, the potential efficacy of adjunctive therapy combining IVIG and glucocorticoids with acyclovir is explored with compelling results.

Case Report

The patient, a young male, was hospitalized with a four-day history of nausea, headache, and fever, and was subsequently diagnosed with HSV-1 encephalitis through PCR of cerebrospinal fluid (CSF). In light of his severe symptoms, the medical team decided to commence an innovative treatment consisting of IVIG (0.5 g/kg daily for 3 days), dexamethasone, and prolonged acyclovir therapy due to persistently positive HSV-1 CSF PCR results.

Contrary to typical prognoses for severe cases, the young man responded remarkably well to this combined treatment. Although he later developed N-methyl-D-aspartate (NMDA) receptor antibodies at six weeks post-treatment, his long-term outcome significantly exceeded expectations typically associated with HSV encephalitis.


This report challenges the existing treatment guidelines for severe HSV encephalitis, as the recovery observed in this case points to the efficacy of immunomodulatory therapies, which are not currently recommended in standard protocols. The report cited studies indicating that HSV-related brain damage is primarily immune-driven rather than directly caused by the viral infection itself.

The Implications for Future Treatment

The notable improvement seen in this patient suggests that aggressive immunomodulatory therapy may be crucial in managing severe HSV encephalitis cases, especially when initiated early in the course of disease.

The Importance of Larger Trials

Given the positive outcome in this case, there is a compelling argument for conducting larger, controlled trials to evaluate the use of IVIG and glucocorticoids alongside acyclovir in the treatment of HSV encephalitis. Such research could lead to a revision of treatment guidelines and potentially improve outcomes for patients afflicted by this severe neurological condition.

DOI and References

DOI: 10.12659/AJCR.941864
1. Sakoulas, G., Roth, J.J., & Van der Kuy, H. (2024). Adjunctive Intravenous Immunoglobulin and Glucocorticoid Therapy in Severe Herpes Simplex Encephalitis with Excellent Outcome Begs for Larger Trials Evaluating Immunomodulatory Therapy. Am J Case Rep, 25, e941864.
2. Hanley DF, Johnson RT, Whitley RJ. (1987). Yes, brain biopsy should be a prerequisite for herpes simplex encephalitis treatment. Arch Neurol, 44, 1289–90.
3. Waggoner-Fountain LA, Grossman LB. (2022). Acyclovir. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
4. Barton LL, Friedman AD. (2023). Complications Associated with Herpes Simplex Encephalitis in Children and Long-term Outcomes: A Systematic Review. J Child Neurol, 38(3), 171-178.
5. Prüss H, Finke C, Höltje M, et al. (2012). N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol, 72(6), 902–11.
6. Wagner JN, Leibetseder A, Troescher A, et al. (2022). Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: A systematic literature review. J Neurol, 269, 712–24.


The case reported in The American Journal of Case Reports asserts the necessity of revisiting the treatment guidelines for HSV encephalitis, focusing on immunomodulatory therapy as an adjunct to antiviral medication. The report signifies a crucial first step toward changing the approach to HSV encephalitis therapy.


1. Herpes Simplex Encephalitis Treatment
2. Adjunctive Therapy HSV Encephalitis
3. Immunomodulatory Therapy HSV
4. IVIG and Glucocorticoids HSV
5. Acyclovir and Immunoglobulin Therapy

Author Contributions

Contributions to the scientific and medical community by George Sakoulas, Jon Roth, and Hugo Van der Kuy have been foundational in exploring innovative treatments for HSV encephalitis, leading up to this latest publication. Their collaborative effort highlights the urgent need for larger, controlled clinical trials to assess the benefits of immunomodulatory therapy in the context of HSV-related neurological diseases.