Acute viral encephalitis in children: Pathogenesis, incidence, and etiology
- Hordur S Hardarson, MD
Hordur S Hardarson, MD
- Landspitali University Hospital
Viral infection of the central nervous system most often leads to meningitis, meningoencephalitis, or encephalitis, in descending order of frequency . Encephalitis implies inflammation of the brain and strictly speaking is a pathological diagnosis. However, in practice, most patients with encephalitis are diagnosed based on clinical manifestations of brain dysfunction and laboratory or imaging evidence of inflammation (ie, white blood cells in the cerebrospinal fluid and/or inflammation on brain imaging).
Encephalitis is an acute, life-threatening emergency, requiring prompt intervention. Although discussed separately, the assessment and management often are performed simultaneously (table 1).
The pathogenesis, epidemiology, and etiology of viral encephalitis in children and adolescents will be discussed here. The clinical manifestations, differential diagnosis, evaluation, treatment, and prevention of viral encephalitis in children and adolescents and viral encephalitis in adults are discussed separately. (See "Acute viral encephalitis in children: Clinical manifestations and diagnosis" and "Acute viral encephalitis in children: Treatment and prevention" and "Viral encephalitis in adults".)
Central nervous system (CNS) infections are described according to the site of infection:
●Encephalitis – Encephalitis is inflammation of the brain parenchyma and is associated with neurologic dysfunction. Characteristic clinical features include altered mental status (decreased level of consciousness, lethargy, personality change, unusual behavior), seizures, and/or focal neurologic signs, often accompanied by fever, headache, nausea, and vomiting . (See "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Clinical features'.)
- Whitley RJ. Viral encephalitis. N Engl J Med 1990; 323:242.
- Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013; 57:1114.
- Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47:303.
- Glaser C, Long SS. Encephalitis. In: Principles and Practice of Pediatric Infectious Diseases, 4th ed, Long SS, Pickering LK, Prober CG (Eds), Elsevier Saunders, Edinburgh 2012. p.297.
- Bronstein DE, Shields WD, Glaser CA. Encephalitis and meningoencephalitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th ed, Cherry JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2014. p.492.
- Guo Y, Audry M, Ciancanelli M, et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med 2011; 208:2083.
- Vora NM, Holman RC, Mehal JM, et al. Burden of encephalitis-associated hospitalizations in the United States, 1998-2010. Neurology 2014; 82:443.
- George BP, Schneider EB, Venkatesan A. Encephalitis hospitalization rates and inpatient mortality in the United States, 2000-2010. PLoS One 2014; 9:e104169.
- Britton PN, Khoury L, Booy R, et al. Encephalitis in Australian children: contemporary trends in hospitalisation. Arch Dis Child 2016; 101:51.
- Koskiniemi M, Korppi M, Mustonen K, et al. Epidemiology of encephalitis in children. A prospective multicentre study. Eur J Pediatr 1997; 156:541.
- Koskiniemi M, Rautonen J, Lehtokoski-Lehtiniemi E, Vaheri A. Epidemiology of encephalitis in children: a 20-year survey. Ann Neurol 1991; 29:492.
- Bagdure D, Custer JW, Rao S, et al. Hospitalized Children With Encephalitis in the United States: A Pediatric Health Information System Database Study. Pediatr Neurol 2016; 61:58.
- Glaser CA, Honarmand S, Anderson LJ, et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 2006; 43:1565.
- Fowler A, Stödberg T, Eriksson M, Wickström R. Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol 2008; 12:484.
- Galanakis E, Tzoufi M, Katragkou A, et al. A prospective multicenter study of childhood encephalitis in Greece. Pediatr Infect Dis J 2009; 28:740.
- Kolski H, Ford-Jones EL, Richardson S, et al. Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995. Clin Infect Dis 1998; 26:398.
- Felsenstein S, Yang S, Eubanks N, et al. Human parechovirus central nervous system infections in southern California children. Pediatr Infect Dis J 2014; 33:e87.
- Pillai SC, Hacohen Y, Tantsis E, et al. Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome. Pediatrics 2015; 135:e974.
- Khetsuriani N, Lamonte-Fowlkes A, Oberst S, et al. Enterovirus surveillance--United States, 1970-2005. MMWR Surveill Summ 2006; 55:1.
- Elbers JM, Bitnun A, Richardson SE, et al. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics 2007; 119:e399.
- Cherry JD. Recognition and management of encephalitis in children. Adv Exp Med Biol 2009; 634:53.
- Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis 2005; 16:17.
- Hjalmarsson A, Blomqvist P, Sköldenberg B. Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality. Clin Infect Dis 2007; 45:875.
- Doja A, Bitnun A, Jones EL, et al. Pediatric Epstein-Barr Virus-Associated Encephalitis: 10-Year Review. J Child Neurol 2006; 21:385.
- McJunkin JE, de los Reyes EC, Irazuzta JE, et al. La Crosse encephalitis in children. N Engl J Med 2001; 344:801.
- Balfour HH Jr, Siem RA, Bauer H, Quie PG. California arbovirus (La Crosse) infections. I. Clinical and laboratory findings in 66 children with meningoencephalitis. Pediatrics 1973; 52:680.
- Hayes EB, O'Leary DR. West Nile virus infection: a pediatric perspective. Pediatrics 2004; 113:1375.
- Solomon T. Flavivirus encephalitis. N Engl J Med 2004; 351:370.
- Lindsey NP, Hayes EB, Staples JE, Fischer M. West Nile virus disease in children, United States, 1999-2007. Pediatrics 2009; 123:e1084.
- Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA 2013; 310:308.
- Lindsey NP, Lehman JA, Staples JE, et al. West nile virus and other arboviral diseases - United States, 2013. MMWR Morb Mortal Wkly Rep 2014; 63:521.
- Fujimoto S, Kobayashi M, Uemura O, et al. PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis. Lancet 1998; 352:873.
- Amin R, Ford-Jones E, Richardson SE, et al. Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review. Pediatr Infect Dis J 2008; 27:390.
- Arnold JC, Singh KK, Milder E, et al. Human metapneumovirus associated with central nervous system infection in children. Pediatr Infect Dis J 2009; 28:1057.
- Park A, Suh SI, Son GR, et al. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study. Neuroradiology 2014; 56:163.