Meningitis & Encephalitis 101
Meningitis and encephalitis (ME) are often some of the most terrifying diseases in medicine mainly because of the high mortality rates if left untreated or if treated incorrectly. Meningitis refers to inflammation of the meninges, or the membranous layers that surround the brain and spinal cord, while encephalitis refers to inflammation of the brain itself.1 Inflammation of the meninges along with the surrounding cerebral tissue is referred to as meningoencephalitis.2 These diseases along with other central nervous system (CNS) infections can have a wide range of symptoms including fever, headache, seizures, and confusion.1 They are also generally characterized by altered consciousness that lasts over 24 hours.3
In developed countries, meningitis affects between 4 to 30 people per 100,000 each year while encephalitis affects between 3 to 7 people per 100,000 each year.4 In the United States, there are approximately 20,000 encephalitis-related hospitalizations per year with an average of 1,400 deaths each year.5 There are over 70,000 meningitis-related hospitalizations in the US each year with a mortality rate as high as 11.4%.4 Overall, these conditions result in over $2 billion in hospitalization and healthcare costs in the US each year.4
The most common causes of meningitis are viral infections, followed by bacterial and, rarely, fungal or parasitic infections. Viral, or aseptic, meningitis is usually mild and often clears on its own. Viruses that can cause this infection include enteroviruses, herpes simplex viruses (HSV 1 & 2), and varicella-zoster virus (VZV).1 Several strains of bacteria can cause acute bacterial meningitis, most commonly Streptococcus pneumoniae (pneumococcal meningitis), Neisseria meningitides (meningococcal meningitis), Haemophilus influenza, Escherichia coli, Listeria monocytogenes, and Mycobacterium tuberculosis.1 Parasitic or fungal meningitis are relatively uncommon. Parasitic Cryptococcus neoformans, cysticercosis (a tapeworm), as well as cerebral malaria are also causes.1
While the majority of all reported cases stem from viral etiologies, up to 60% of cases remain undiagnosed.1,6 The most common causes are HSV 1, HSV 2 , VZV, enterovirus, and arboviruses (such as West Nile virus).1,3 Arbovirus refers to any virus that is transmitted to humans and other vertebrates by an arthropod vector, such as ticks or mosquitoes.1,3
About 30% of herpes simplex encephalitis cases result from primary HSV 1 or 2 infections while the majority of cases are from viral reactivation.1 HSV 1 is typically acquired during childhood, however, HSV 2 is often transmitted through sexual contact. Over 90% of the global population has HSV, with each individual at risk of developing herpes simplex encephalitis.7
VZV is also recognized as one of the leading causes of adult encephalitis. Studies have shown that VZV is the second most common etiology identified, second only to HSV.8 Before the availability of a vaccine, it was estimated that greater than 90% of the population would acquire VZV by the age of 15 and each of these persons would be at risk for developing acute VZV encephalitis.7
ME occurs in all ages, from neonates to adults, and during all seasons.1 The prognosis for people with encephalitis or meningitis varies. In most cases, individuals who experience very mild encephalitis or meningitis can make a full recovery with early diagnosis and prompt treatment. However, in some severe cases, untreated CNS infection can reach mortality rates as high as 70% and for those who survive, only a minority will achieve full recovery for neurological symptoms. It is therefore critical for accurate and timely laboratory testing that can be used for proper diagnosis and treatment of the underlying cause.
Patient management is highly dependent on pathogen identification, with unfavorable outcomes directly correlated to delays of correct treatments and therapies.9 Delayed or incorrect treatments stemming from poor diagnosis can lead to severe neurological disabilities and ultimately death.4,5,9,10References
1. National Institutes of Health. (2019). Meningitis and encephalitis fact sheet. Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Meningitis-and-Encephalitis-Fact-Sheet<
2. Johns Hopkins Medicine. (n.d.). Herpes meningoencephalitis. Retrieved from https://www.hopkinsmedicine.org/health/conditions-and-diseases/herpes-hsv1-and-hsv2/herpes-meningoencephalitis<
3. Venkatesan, A. & Geocadin, R. G.(2014). Diagnosis and management of acute encephalitis: A practical approach. Neurology Clinical Practice. Retrieved from https://cp.neurology.org/content/4/3/206
4. Polage, C. R. & Cohen, S. H. (2016). State-of-the-art microbiologic testing for community-acquired meningitis and encephalitis. Journal of Clinical Microbiology, 54(5), 1197-1202.
5. Leber, A., Everhart, K., Balada-Llasat, J., Cullison, J., Daly, J., Holt, A., . . . Bourzac, K. M. (2016). Multicenter evaluation of BioFire FilmArray meningitis/encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid. Journal of Clinical Microbiology, 54(9), 2251-2261.
6. Bookstaver, P.B., Mohorn, P.L., Shah, A., et al. (2017). Management of viral central nervous system infections: A primer for clinicians. J Cent Nerv Syst Dis. DOI: 9:1179573517703342.
7. Seward, J. & Jumaan, A. (2007). VSV: persistence in the population. In: Arvin, A., Campadelli-Fiume, G., Mocarski, E., et al. (editors). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; Chapter 40. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK47367/
8. Pahud, B. A., Glaser, C.A., Dekker, C.L., Arvin, A.M., & Schmid, D.S. (2011). Varicella zoster disease of the central nervous system: Epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine. J Infect Dis. 203(3), 316–323.
9. Cuomo, L., Trivedi, P., Cardillo, M.R., Gagliardi, F.M., Vecchione, A., Caruso, R., Calogero, A., Frati, L., Faggioni, A., & Ragona, G. (2001). Human herpesvirus 6 infection in neoplastic and normal brain tissue. J Med Virol. 63, 45-51.
10. Gomez, C. A., Pinsky, B. A., Liu, A., & Banaei, N. (2016). Delayed diagnosis of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with FilmArray syndromic polymerase chain reaction panel. Open Forum Infectious Diseases,4(1), 245.