The clinical profiles and outcomes of patients with herpesviruses in cerebrospinal fluid: 2019 - 2022
DOI:
https://doi.org/10.7196/SAMJ.2026.v116i5.3441Keywords:
Herpesvirus, Cerebrospinal fluid, CSF, Human Immunodeficiency Virus, HIV, CSF viral panelAbstract
Background. Herpesviruses are ubiquitous and commonly cause neurological syndromes. A paucity of data exists describing the clinical profiles and outcomes of these viruses in cerebrospinal fluid (CSF).
Objectives. To describe the clinical profile and outcomes of patients with a positive CSF viral panel testing for six herpesviruses (herpes simplex virus 1 and 2 (HSV1; HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV6)).
Methods. A retrospective descriptive study included all hospitalised patients aged 13 years and older in whom a herpesvirus was detected by a herpesvirus panel performed on CSF. A folder review was performed to acquire demographic, clinical and laboratory information.
Results. We identified 204 CSF herpesviruses in 184 patients. Most were people living with HIV (n=137/184, 74.5%). EBV was the most frequently identified herpesvirus (n=152/204, 74.5%). The herpesvirus was considered the cause of the clinical neurological syndrome in 20 patients (20/184, 10.9%), of whom most had VZV (7/20, 35%). Patients with VZV presented with encephalopathy (4/11, 36.4%), meningoencephalitis (3/11, 27.3%) and stroke (3/11, 27.3%). Encephalopathy, seizures and lower-limb weakness (n=5/19, 26.3%) were more common in patients with CMV. Those with HSV1 presented with seizures (n=2/5, 40%) and those with HSV2 with encephalopathy (n=3/6, 50%) and meningoencephalitis (n=2/6, 33.3%). EBV was the most common herpesvirus in patients with tuberculosis (TB) (45/49, 91.8%). Antiviral therapy was prescribed in 19/184 (10.3%) patients. The in-hospital mortality rate of all patients was 21.7%.
Conclusion. EBV was the most common herpesvirus detected on CSF. Most patients with TB and HIV had EBV detected in their CSF, which may represent reactivation in these patients. This study highlighted the undertreatment of CMV and overtreatment of EBV. Greater awareness regarding the clinical indications for antiviral therapy in this setting is needed.
References
1. Kleinschmidt-DeMasters BK, Gilden DH. The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol 2001;11(4):440-451. https://doi.org/10.1111/j.1750-3639.2001.tb00413.x
2. Ishimaru S, Kawamura Y, Miura H, et al. Detection of human herpesviruses in cerebrospinal fluids collected from patients suspected of neuroinfectious diseases. J NeuroVirol 2021;28(1):92-98.
https://doi.org/10.1007/s13365-021-01040-5
3. Stahl JP, Mailles A. Herpes simplex virus encephalitis update. Curr Opin Infect Dis 2019;32(3):239- 243. https://doi.org/10.1097/QCO.0000000000000554
4. Kupila L, Vuorinen T, Vainionpaa R, et al. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology 200;66(1):75-80. https://doi.org/10.1212/01.wnl.0000191407.81333.00
5. Miller AC, Koeneman SH, Arakkal AT, et al. Incidence, duration, and risk factors associated with missed opportunities to diagnose herpes simplex encephalitis: A population-based longitudinal
study. Open Forum Infect Dis 2021;8(9):ofab400. https://doi.org/10.1093/ofid/ofab400.
6. HandleyG,PankowS,JenniferDienBard,etal.Distinguishingcytomegalovirusmeningoencephalitis from other viral central nervous system infections. J Clin Virol 202;142:104936. https://doi.
org/10.1016/j.jcv.2021.104936
7. Matthews E, Beckham JD, Piquet AL, et al. Herpesvirus-associated encephalitis: An update. Curr Trop Med Rep 2022;9(3):92-100. https://doi.org/10.1007/s40475-022-00255-8
8. Corcoran C, Rebe K, van der Plas H, et al. The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons. J Clin Virol 2008;42(4):433-436. https://doi.org/10.1016/j.jcv.2008.03.017
9. Soldan SS, Lieberman PM. Epstein–Barr virus and multiple sclerosis. Nature Rev Microbiol 2022;21:1- 14.https://doi.org/10.1038/s41579-022-00770-5
10. Dos Reis HL, Cavalcante FS, dos Santos KR, et al. Herpes zoster as a sign of AIDS and nonadherence to antiretroviral therapy: a case report. Clinics (Sao Paulo) 2011;66(12):2179-2181. https://doi. org/10.1590/S1807-59322011001200028
11. Marais G, Naidoo M, McMullen K, et al. Varicella‐zoster virus reactivation is frequently detected in HIV‐infected individuals presenting with stroke. J Med Virol 2022;94(6):2675-2683. https://doi. org/10.1002/jmv.27651.
12. Siddiqi OK, Ghebremichael M, Dang X, et al. Molecular diagnosis of central nervous system opportunistic infections in HIV-infected Zambian adults. Clin Infect Dis 2014;58(12):1771-1777. https://doi.org/10.1093/cid/ciu191.
13. Nagel MA, Gilden D. The relationship between herpes zoster and stroke. Curr Neurol Neurosci Rep 2015;15(4). https://doi.org/10.1007/s11910-015-0534-4
14. Kennedy PGE. The spectrum of neurological manifestations of varicella-zoster virus reactivation. Viruses 2023;15(8):1663. https://doi.org/10.3390/v15081663
15. Amlie-Lefond C, Gilden D. Varicella zoster virus: A common cause of stroke in children and adults. J Stroke and Cerebrovascul Dis 2016;25(7):1561-1569. https://doi.org/10.1016/j. jstrokecerebrovasdis.2016.03.052
16. Webb G, Leong MYM, Bishop E, et al. Diagnostic dilemmas: A review of reported cases of human herpesvirus 6 encephalitis in immunocompetent adults. Open Forum Infect Dis 2024;11(9). https:// doi.org/10.1093/ofid/ofae501
17. Berzero G, Campanini G, Vegezzi E, et al. Human herpesvirus 6 encephalitis in immunocompetent and immunocompromised hosts. Neurol Neuroimmun Neuroinflamm 2021;8(2):e942. https://doi. org/10.1212/NXI.0000000000000942
18. Cinque P, Bossolasco S, Lundkvist Å. Molecular analysis of cerebrospinal fluid in viral diseases of the central nervous system. J Clin Virol 2003;26(1):1-28. https://doi.org/10.1016/s1386-6532(02)00173-7 19. Tygerberg Academic Hospital. Orthopaedic Surgery - Tygerberg Hospital & Stellenbosch University.
http://www.sunorthopaedics.com/tygerberg-hospital.html (accessed 18 March 2025).
20. Shin SY, Kwon KC, Park JW, et al. Evaluation of the Seeplex® Meningitis ACE detection kit for the detection of 12 common bacterial and viral pathogens of acute meningitis. Ann Lab Med
2012;32(1):44-49. https://doi.org/10.3343/alm.2012.32.1.44
21. Musukuma-Chifulo K, Ghebremichael M, Chilyabanyama ON, et al. Characterizing Epstein-Barr
virus infection of the central nervous system in Zambian adults living with HIV. J NeuroVirol
2023;29(6):706-712. https://doi.org/10.1007/s13365-023-01178-4
22. Lee GH, Kim J, Kim HW, et al. Clinical significance of Epstein-Barr virus in the cerebrospinal fluid
of immunocompetent patients. Clin Neurol Neurosurg 2021;202:106507. https://doi.org/10.1016/j.
clineuro.2021.106507
23. Kerr JR. Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors. J Clin Pathol 2019;72(10):651-658. https://doi.org/10.1136/jclinpath-2019-205822
24. Patil A, Goldust M, Wollina U. Herpes zoster: A review of clinical manifestations and management. Viruses 2022;14(2):192. https://doi.org/10.3390/v14020192
25. Centers for Disease Control (CDC). Shingles vaccine recommendations. Shingles (herpes zoster). 2024. https://www.cdc.gov/shingles/hcp/vaccine-considerations/index.html (accessed 18 March 2025) 26. Chretien F, Bélec L, Hilto DA, et al. Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome. Neuropathol Appl Neurobiol 1996;22(5):394-404. https://doi.
org/10.1111/j.1365-2990.1996.tb00909.x
27. Benjamin LA, Kelly M, Cohen D, et al. Detection of herpes viruses in the cerebrospinal fluid of adults with suspected viral meningitis in Malawi. Infection 2012;41(1):27-31. https://doi.org/10.1007/ s15010-012-0292-z
28. Bradshaw MJ, Venkatesan A. Herpes simplex virus-1 encephalitis in adults: Pathophysiology, diagnosis, and management. Neurotherapeutics 2016;13(3):493-508. https://doi.org/10.1007/s13311-016-0433-7 29. Looker KJ, Elmes JAR, Gottlieb SL, et al. Effect of HSV-2 infection on subsequent HIV acquisition: an
updated systematic review and meta-analysis. Lancet Infect Dis 2017;17(12):1303-1316.
30. Berger JR, Houff S. Neurological complications of herpes simplex virus type 2 infection. Arch Neurol
2008;65(5):596-600. https://doi.org/10.1001/archneur.65.5.596
31. Green DA, Pereira M, Miko B, et al. Clinical significance of human herpesvirus 6 positivity on
the filmarray meningitis/encephalitis panel. Clin Infect Dis 2018;67(7):1125-1128. https://doi.
org/10.1093/cid/ciy288.
32. Human Sciences Research Council (HSRC). New HIV survey highlights progress and ongoing disparities in South Africa’s HIV epidemic. Pretoria: HSRC, 2023. https://hsrc.ac.za/press-releases/ phsb/new-hiv-survey-highlights-progress-and-ongoing-disparities-in-south-africas-hiv-epidemic/ (accessed 7 December 2024).
33. Griffiths PD. Herpesviruses and AIDS. J Antimicrob Chemother 1996;37 Suppl B:87-95. https://doi. org/10.1093/jac/37.suppl_b.87
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