Viral encephalitis in the adult: a review

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Jone Bocos Portillo Lara Pardina Vilella David A. Anguizola Tamayo Lucia Vidorreta Ballesteros Aintzine Ruisanchez nieva Juan Carlos Garcia-Monco


Viral encephalitis represents a medical emergency that requires prompt diagnosis and proper management. Patient presentation includes fever, headache, mental status changes, and seizures in different combinations. While herpes simplex virus is the most common cause of sporadic encephalitis worldwide, certain arboviral (arthropod borne) infections remain a health challenge in certain parts of the globe. Zika virus has been recently added to the list of potential offenders. Despite important advances in technology, a substantial percentage of encephalitis cases still remain without a specific diagnosis. Cerebrospinal fluid analysis with viral nucleic acid detection by PCR and neuroimaging are paramount in diagnosing encephalitis and establishing a specific viral etiology. Empiric therapy with acyclovir is required in suspected cases of encephalitis, and maintained for 3 weeks upon confirmation of herpetic etiology.  Without specific therapy, herpes encephalitis conveys high mortality and morbidity rates. General support measures are also critical and have been defined in pertinent guidelines. We will here review the most common encephalitis in adults and their diagnostic and therapeutic modalities.

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BOCOS PORTILLO, Jone et al. Viral encephalitis in the adult: a review. Medical Research Archives, [S.l.], v. 4, n. 5, sep. 2016. ISSN 2375-1924. Available at: <>. Date accessed: 26 sep. 2023.
Encephalitis, Herpes virus, viral encephalitis, arbovirus
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Abend, N. S., D. Bearden, I. Helbig, J. McGuire, S. Narula, J. A. Panzer, A. Topjian and D. J. Dlugos (2014). "Status epilepticus and refractory status epilepticus management." Semin Pediatr Neurol 21(4): 263-274.

Abu Khattab, M., H. Al Soub, M. Al Maslamani, J. Al Khuwaiter and Y. El Deeb (2009). "Herpes simplex virus type 2 (Mollaret's) meningitis: a case report." Int J Infect Dis 13(6): e476-479.

Ambrose, H. E., J. Granerod, J. P. Clewley, N. W. Davies, G. Keir, R. Cunningham, M. Zuckerman, K. J. Mutton, K. N. Ward, S. Ijaz, N. S. Crowcroft and D. W. Brown (2011). "Diagnostic strategy used to establish etiologies of encephalitis in a prospective cohort of patients in England." J Clin Microbiol 49(10): 3576-3583.

Atkinson, B., P. Hearn, B. Afrough, S. Lumley, D. Carter, E. J. Aarons, A. J. Simpson, T. J. Brooks and R. Hewson (2016). "Detection of Zika Virus in Semen." Emerg Infect Dis 22(5): 940.

Barnett, E. M., G. Jacobsen, G. Evans, M. Cassell and S. Perlman (1994). "Herpes simplex encephalitis in the temporal cortex and limbic system after trigeminal nerve inoculation." J Infect Dis 169(4): 782-786.

Bogovic, P. and F. Strle (2015). "Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management." World J Clin Cases 3(5): 430-441.

Booss, J. and A. C. Tselis (2014). "A history of viral infections of the central nervous system: foundations, milestones, and patterns." Handb Clin Neurol 123: 3-44.

Cao-Lormeau, V. M., A. Blake, S. Mons, S. Lastere, C. Roche, J. Vanhomwegen, T. Dub, L. Baudouin, A. Teissier, P. Larre, A. L. Vial, C. Decam, V. Choumet, S. K. Halstead, H. J. Willison, L. Musset, J. C. Manuguerra, P. Despres, E. Fournier, H. P. Mallet, D. Musso, A. Fontanet, J. Neil and F. Ghawche (2016). "Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study." Lancet 387(10027): 1531-1539.

Cardenas, G., J. L. Soto-Hernandez, A. Diaz-Alba, Y. Ugalde, J. Merida-Puga, M. Rosetti and E. Sciutto (2014). "Neurological events related to influenza A (H1N1) pdm09." Influenza Other Respir Viruses 8(3): 339-346.

Carmena Carmena, J., M. Macia Soler, A. Cremades Mira and M. J. Alcaraz Soriano (2004). "[Herpes simplex 1 virus Mollaret meningitis]." Rev Clin Esp 204(8): 418-419.

Carteaux, G., M. Maquart, A. Bedet, D. Contou, P. Brugieres, S. Fourati, L. Cleret de Langavant, T. de Broucker, C. Brun-Buisson, I. Leparc-Goffart and A. Mekontso Dessap (2016). "Zika Virus Associated with Meningoencephalitis." N Engl J Med 374(16): 1595-1596.

Cohen, E. J. (2013). "Prevention of herpes zoster: we need to do better." JAMA Ophthalmol 131(3): 396-398.

Cohen, J. I. (2013). "Clinical practice: Herpes zoster." N Engl J Med 369(3): 255-263.

Cusi, M. G., G. G. Savellini and G. Zanelli (2010). "Toscana virus epidemiology: from Italy to beyond." Open Virol J 4: 22-28.

Davies, N. W., L. J. Brown, J. Gonde, D. Irish, R. O. Robinson, A. V. Swan, J. Banatvala, R. S. Howard, M. K. Sharief and P. Muir (2005). "Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections." J Neurol Neurosurg Psychiatry 76(1): 82-87.

De Filette, M., S. Ulbert, M. Diamond and N. N. Sanders (2012). "Recent progress in West Nile virus diagnosis and vaccination." Vet Res 43: 16.

DeBiasi, R. L., B. K. Kleinschmidt-DeMasters, A. Weinberg and K. L. Tyler (2002). "Use of PCR for the diagnosis of herpesvirus infections of the central nervous system." J Clin Virol 25 Suppl 1: S5-11.

ECDC (2014). Annual epidemiological report. Emerging and vector-borne diseases. .

ECDC (2014). "Rapid Risk assessment on enterovirus."
Engelberg, R., D. Carrell, E. Krantz, L. Corey and A. Wald (2003). "Natural history of genital herpes simplex virus type 1 infection." Sex Transm Dis 30(2): 174-177.

Ferreira, M. L. B. (2016). American Academy of Neurology.
Ganesan, K., A. Diwan, S. K. Shankar, S. B. Desai, G. S. Sainani and S. M. Katrak (2008). "Chikungunya encephalomyeloradiculitis: report of 2 cases with neuroimaging and 1 case with autopsy findings." AJNR Am J Neuroradiol 29(9): 1636-1637.

Garcia E, Y. S., Nishino K, Millot V, Perea W, Briand S (2016). "Zika virus infection: global update on epidemiology and potentially associated clinical manifestations." Wkly Epidemiol Rec 91(7): 73-81.

Garcia-Monco, J. C. (2010). "[Acute encephalitis]." Neurologia 25 Suppl 1: 11-17.

Gilden, D., R. J. Cohrs, R. Mahalingam and M. A. Nagel (2009). "Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment." Lancet Neurol 8(8): 731-740.

Goldberg, T. L., T. K. Anderson and G. L. Hamer (2010). "West Nile virus may have hitched a ride across the Western United States on Culex tarsalis mosquitoes." Mol Ecol 19(8): 1518-1519.

Granerod, J., R. Cunningham, M. Zuckerman, K. Mutton, N. W. Davies, A. L. Walsh, K. N. Ward, D. A. Hilton, H. E. Ambrose, J. P. Clewley, D. Morgan, M. P. Lunn, T. Solomon, D. W. Brown and N. S. Crowcroft (2010). "Causality in acute encephalitis: defining aetiologies." Epidemiol Infect 138(6): 783-800.

Gubler, D. J. (2007). "The continuing spread of West Nile virus in the western hemisphere." Clin Infect Dis 45(8): 1039-1046.

Hacohen, Y., K. Deiva, P. Pettingill, P. Waters, A. Siddiqui, P. Chretien, E. Menson, J. P. Lin, M. Tardieu, A. Vincent and M. J. Lim (2014). "N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse." Mov Disord 29(1): 90-96.

Hart, R. P., J. A. Kwentus, R. B. Frazier and T. L. Hormel (1986). "Natural history of Kluver-Bucy syndrome after treated herpes encephalitis." South Med J 79(11): 1376-1378.
Hasbun, R., J. Abrahams, J. Jekel and V. J. Quagliarello (2001). "Computed tomography of the head before lumbar puncture in adults with suspected meningitis." N Engl J Med 345(24): 1727-1733.

Heymann, D. L., A. Hodgson, A. A. Sall, D. O. Freedman, J. E. Staples, F. Althabe, K. Baruah, G. Mahmud, N. Kandun, P. F. Vasconcelos, S. Bino and K. U. Menon (2016). "Zika virus and microcephaly: why is this situation a PHEIC?" Lancet 387(10020): 719-721.

Higgs, S. and D. Vanlandingham (2015). "Chikungunya virus and its mosquito vectors." Vector Borne Zoonotic Dis 15(4): 231-240.

Hjalmarsson, A., P. Blomqvist and B. Skoldenberg (2007). "Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality." Clin Infect Dis 45(7): 875-880.

Janes, V. A., R. Minnaar, G. Koen, H. van Eijk, K. Dijkman-de Haan, D. Pajkrt, K. C. Wolthers and K. S. Benschop (2014). "Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: a comprehensive review." Euro Surveill 19(46).

Kassavetis, P., J. M. Joseph, R. Francois, M. D. Perloff and A. L. Berkowitz (2016). "Zika virus-associated Guillain-Barre syndrome variant in Haiti." Neurology 87(3): 336-337.
Kennedy, P. G. (2005). "Viral encephalitis." J Neurol 252(3): 268-272.

Kimberlin, D. W., R. J. Whitley, W. Wan, D. A. Powell, G. Storch, A. Ahmed, A. Palmer, P. J. Sanchez, R. F. Jacobs, J. S. Bradley, J. L. Robinson, M. Shelton, P. H. Dennehy, C. Leach, M. Rathore, N. Abughali, P. Wright, L. M. Frenkel, R. C. Brady, R. Van Dyke, L. B. Weiner, J. Guzman-Cottrill, C. A. McCarthy, J. Griffin, P. Jester, M. Parker, F. D. Lakeman, H. Kuo, C. H. Lee, G. A. Cloud, A. National Institute of and G. Infectious Diseases Collaborative Antiviral Study (2011). "Oral acyclovir suppression and neurodevelopment after neonatal herpes." N Engl J Med 365(14): 1284-1292.

Kramer, A. H. and T. P. Bleck (2008). "Neurocritical care of patients with central nervous system infections." Curr Treat Options Neurol 10(3): 201-211.

Kupila, L., T. Vuorinen, R. Vainionpaa, V. Hukkanen, R. J. Marttila and P. Kotilainen (2006). "Etiology of aseptic meningitis and encephalitis in an adult population." Neurology 66(1): 75-80.

Li, J., J. A. Loeb, M. E. Shy, A. K. Shah, A. C. Tselis, W. J. Kupski and R. A. Lewis (2003). "Asymmetric flaccid paralysis: a neuromuscular presentation of West Nile virus infection." Ann Neurol 53(6): 703-710.

Libbey, J. E. and R. S. Fujinami (2014). "Adaptive immune response to viral infections in the central nervous system." Handb Clin Neurol 123: 225-247.

Messacar, K., T. L. Schreiner, J. A. Maloney, A. Wallace, J. Ludke, M. S. Oberste, W. A. Nix, C. C. Robinson, M. P. Glode, M. J. Abzug and S. R. Dominguez (2015). "A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA." Lancet 385(9978): 1662-1671.

Mlakar, J., M. Korva, N. Tul, M. Popovic, M. Poljsak-Prijatelj, J. Mraz, M. Kolenc, K. Resman Rus, T. Vesnaver Vipotnik, V. Fabjan Vodusek, A. Vizjak, J. Pizem, M. Petrovec and T. Avsic Zupanc (2016). "Zika Virus Associated with Microcephaly." N Engl J Med 374(10): 951-958.

Musso, D., C. Roche, E. Robin, T. Nhan, A. Teissier and V. M. Cao-Lormeau (2015). "Potential sexual transmission of Zika virus." Emerg Infect Dis 21(2): 359-361.

Nagel, M. A. and D. Gilden (2013). "The challenging patient with varicella-zoster virus disease." Neurol Clin Pract 3(2): 109-117.

Organization, W. H. (2016). "Laboratory testing for Zika virus infection." Interim guidance.

Pepose, J. S., L. H. Hilborne, P. A. Cancilla and R. Y. Foos (1984). "Concurrent herpes simplex and cytomegalovirus retinitis and encephalitis in the acquired immune deficiency syndrome (AIDS)." Ophthalmology 91(12): 1669-1677.

Pruss, H., M. Holtje, N. Maier, A. Gomez, R. Buchert, L. Harms, G. Ahnert-Hilger, D. Schmitz, C. Terborg, U. Kopp, C. Klingbeil, C. Probst, S. Kohler, J. M. Schwab, W. Stoecker, J. Dalmau and K. P. Wandinger (2012). "IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment." Neurology 78(22): 1743-1753.

Raschilas, F., M. Wolff, F. Delatour, C. Chaffaut, T. De Broucker, S. Chevret, P. Lebon, P. Canton and F. Rozenberg (2002). "Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study." Clin Infect Dis 35(3): 254-260.

Rasmussen, S. A., D. J. Jamieson, M. A. Honein and L. R. Petersen (2016). "Zika Virus and Birth Defects--Reviewing the Evidence for Causality." N Engl J Med 374(20): 1981-1987.

Schmidt, A., R. Buhler, K. Muhlemann, C. W. Hess and M. G. Tauber (2011). "Long-term outcome of acute encephalitis of unknown aetiology in adults." Clin Microbiol Infect 17(4): 621-626.

Skoldenberg, B., E. Aurelius, A. Hjalmarsson, F. Sabri, M. Forsgren, B. Andersson, A. Linde, O. Strannegard, M. Studahl, L. Hagberg and L. Rosengren (2006). "Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults." J Neurol 253(2): 163-170.

Sonneville, R., I. Klein, T. de Broucker and M. Wolff (2009). "Post-infectious encephalitis in adults: diagnosis and management." J Infect 58(5): 321-328.

Soong, S. J., N. E. Watson, G. R. Caddell, C. A. Alford, Jr. and R. J. Whitley (1991). "Use of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis: a statistical model and its clinical implications. NIAID Collaborative Antiviral Study Group." J Infect Dis 163(1): 17-22.

Steiner, I., H. Budka, A. Chaudhuri, M. Koskiniemi, K. Sainio, O. Salonen and P. G. Kennedy (2010). "Viral meningoencephalitis: a review of diagnostic methods and guidelines for management." Eur J Neurol 17(8): 999-e957.

Steiner, I., P. G. Kennedy and A. R. Pachner (2007). "The neurotropic herpes viruses: herpes simplex and varicella-zoster." Lancet Neurol 6(11): 1015-1028.

Tunkel, A. R., C. A. Glaser, K. C. Bloch, J. J. Sejvar, C. M. Marra, K. L. Roos, B. J. Hartman, S. L. Kaplan, W. M. Scheld, R. J. Whitley and A. Infectious Diseases Society of (2008). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America." Clin Infect Dis 47(3): 303-327.

Tyler, K. L. (2004). "Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's." Herpes 11 Suppl 2: 57A-64A.

Valencia, I., D. K. Miles, J. Melvin, D. Khurana, S. Kothare, H. Hardison and A. Legido (2004). "Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature." Neuropediatrics 35(6): 371-376.

VanLandingham, K. E., H. B. Marsteller, G. W. Ross and F. G. Hayden (1988). "Relapse of herpes simplex encephalitis after conventional acyclovir therapy." JAMA 259(7): 1051-1053.

Venkatesan, A. and R. G. Geocadin (2014). "Diagnosis and management of acute encephalitis: A practical approach." Neurol Clin Pract 4(3): 206-215.

Whitley, R. J. and D. W. Kimberlin (2005). "Herpes simplex encephalitis: children and adolescents." Semin Pediatr Infect Dis 16(1): 17-23.

Workowski, K. A. (2015). "Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines." Clin Infect Dis 61 Suppl 8: S759-762.

Yan, H. J. (2002). "Herpes simplex encephalitis: the role of surgical decompression." Surg Neurol 57(1): 20-24.

Zhang, S. Y., L. Abel and J. L. Casanova (2013). "Mendelian predisposition to herpes simplex encephalitis." Handb Clin Neurol 112: 1091-1097.