Numerous viruses may cause viral meningitis. Some of these viruses are widespread, but many are endemic in specific geographic areas. Non-polio human enteroviruses are the most common cause of viral meningitis.[1]Mount HR, Boyle SD. Aseptic and bacterial meningitis: evaluation, treatment, and prevention. Am Fam Physician. 2017 Sep 1;96(5):314-22.
http://www.ncbi.nlm.nih.gov/pubmed/28925647?tool=bestpractice.com
[4]Centers for Disease Control and Prevention. About viral meningitis. Jan 2024 [internet publication].
https://www.cdc.gov/meningitis/about/viral-meningitis.html
[13]Bystritsky RJ, Chow FC. Infectious meningitis and encephalitis. Neurol Clin. 2022 Feb;40(1):77-91.
http://www.ncbi.nlm.nih.gov/pubmed/34798976?tool=bestpractice.com
Herpes viruses cause a spectrum of central nervous system (CNS) disease, including meningitis, myelitis, and encephalitis. Herpes simplex virus (HSV)-1 is the most common cause of viral encephalitis in the Western world, whereas HSV-2 is more commonly associated with viral meningitis.[13]Bystritsky RJ, Chow FC. Infectious meningitis and encephalitis. Neurol Clin. 2022 Feb;40(1):77-91.
http://www.ncbi.nlm.nih.gov/pubmed/34798976?tool=bestpractice.com
Varicella zoster virus is a relatively common cause of viral meningitis, which may occur during primary infection or with shingles but may occur without any rash.[13]Bystritsky RJ, Chow FC. Infectious meningitis and encephalitis. Neurol Clin. 2022 Feb;40(1):77-91.
http://www.ncbi.nlm.nih.gov/pubmed/34798976?tool=bestpractice.com
[14]McGill F, Griffiths MJ, Bonnett LJ, et al. Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study. Lancet Infect Dis. 2018 Sep;18(9):992-1003.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30245-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30153934?tool=bestpractice.com
Meningitis is a common manifestation of mumps, occurring in up to 10% of cases, although mumps is now uncommon in vaccinated populations.[15]Jimenez-Caballero PE, Servia M, Mondejar-Marin B, et al. Mumps meningitis: a case mix in a neurology department [in Spanish]. Rev Neurol. 2005 Apr 1-15;40(7):420-2.
http://www.ncbi.nlm.nih.gov/pubmed/15849676?tool=bestpractice.com
Arboviruses cause neurologic infection in many parts of the world.[16]Kohil A, Jemmieh S, Smatti MK, et al. Viral meningitis: an overview. Arch Virol. 2021 Feb;166(2):335-45.
https://www.doi.org/10.1007/s00705-020-04891-1
http://www.ncbi.nlm.nih.gov/pubmed/33392820?tool=bestpractice.com
West Nile virus emerged in the US in 1999 and around 1 in 150 people infected develop neuroinvasive disease, such as meningitis or encephalitis.[12]Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med. 2001 Jun 14;344(24):1807-14.
https://www.nejm.org/doi/10.1056/NEJM200106143442401
http://www.ncbi.nlm.nih.gov/pubmed/11407341?tool=bestpractice.com
[17]Centers for Disease Control and Prevention. About West Nile virus. May 2024 [internet publication].
https://www.cdc.gov/west-nile-virus/about/index.html
Less common arboviruses in North America include Eastern and Western equine encephalitis viruses, La Crosse virus, and St. Louis encephalitis virus.[18]McJunkin JE, de los Reyes EC, Irazuzta JE. La Crosse encephalitis in children. N Engl J Med. 2001 Mar 15;344(11):801-7.
https://www.nejm.org/doi/10.1056/NEJM200103153441103
http://www.ncbi.nlm.nih.gov/pubmed/11248155?tool=bestpractice.com
[19]Chadwick DR. Viral meningitis. Br Med Bull. 2006 Feb 10;75-76:1-14.
https://academic.oup.com/bmb/article/75-76/1/1/333333
http://www.ncbi.nlm.nih.gov/pubmed/16474042?tool=bestpractice.com
Viral meningitis may occur in 10% of symptomatic HIV seroconversion illnesses.[19]Chadwick DR. Viral meningitis. Br Med Bull. 2006 Feb 10;75-76:1-14.
https://academic.oup.com/bmb/article/75-76/1/1/333333
http://www.ncbi.nlm.nih.gov/pubmed/16474042?tool=bestpractice.com
Viral meningitis is a rare manifestation of influenza. In up to 50% of cases, no etiological agent is identified.[13]Bystritsky RJ, Chow FC. Infectious meningitis and encephalitis. Neurol Clin. 2022 Feb;40(1):77-91.
http://www.ncbi.nlm.nih.gov/pubmed/34798976?tool=bestpractice.com
Enteroviruses are spread by the fecal-oral route.[3]McGill F, Heyderman RS, Michael BD, et al. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect. 2016 Apr;72(4):405-38.
https://www.journalofinfection.com/article/S0163-4453(16)00024-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26845731?tool=bestpractice.com
The nonpolio enteroviruses and arboviruses initially replicate outside the CNS in tissues such as muscle, liver, and the respiratory or gastrointestinal tracts, and then reach the CNS by hematogenous spread. Viral penetration of the blood-brain barrier occurs by infection of either endothelial cells, migrating leukocytes, the choroid plexus epithelium, or lymphoid tissue.[16]Kohil A, Jemmieh S, Smatti MK, et al. Viral meningitis: an overview. Arch Virol. 2021 Feb;166(2):335-45.
https://www.doi.org/10.1007/s00705-020-04891-1
http://www.ncbi.nlm.nih.gov/pubmed/33392820?tool=bestpractice.com
It is unclear whether HSV infects the CNS as a result of hematogenous spread or by retrograde spread along peripheral nerves.[20]Bergstrom T, Vahlne A, Alestig K, et al. Primary and recurrent herpes simplex virus type 2-induced meningitis. J Infect Dis. 1990 Aug;162(2):322-30.
http://www.ncbi.nlm.nih.gov/pubmed/2165105?tool=bestpractice.com
Once within the CNS, viruses spread through the subarachnoid space leading to meningitis, and may go on to infect neurons and glial cells leading to encephalitis or myelitis. The cellular immune response to viral infection of the CNS leads to the accumulation of lymphocytes within the cerebrospinal fluid (CSF) and the release of inflammatory cytokines such as interleukin (IL)-6 and TNF. The inflammatory response increases the permeability of the blood-brain barrier and this allows diffusion of circulating immunoglobulins into the CSF. The importance of the cell-mediated response in controlling infection is illustrated by the increased incidence and severity of infection with varicella zoster virus and cytomegalovirus (CMV) in patients with impaired T-cell responses.