Acute viral encephalitis in children: Treatment and prevention
- Hordur S Hardarson, MD
Hordur S Hardarson, MD
- Landspitali University Hospital
- Section Editors
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
- Gary R Fleisher, MD
Gary R Fleisher, MD
- Editor-in-Chief — Adult and Pediatric Emergency Medicine
- Section Editor — Pediatric Signs and Symptoms
- Egan Family Foundation Professor
- Harvard Medical School
- Douglas R Nordli, Jr, MD
Douglas R Nordli, Jr, MD
- Section Editor — Pediatric Neurology
- Chief of Neurology
- Children’s Hospital Los Angeles
- Vice Chair of Neurology
- USC Keck School of Medicine
Viral infection of the central nervous system (CNS) most often leads to meningitis, meningoencephalitis, or encephalitis, in descending order of frequency . Encephalitis is inflammation of the brain parenchyma, manifest by neurologic dysfunction (eg, altered mental status, behavior, or personality; motor or sensory deficits; speech or movement disorders; seizure) and evidence of CNS inflammation (eg, cerebrospinal fluid pleocytosis and/or findings consistent with encephalitis on neuroimaging or electroencephalogram) .
The treatment and prevention of viral encephalitis in children will be discussed here. The pathogenesis, etiology, clinical manifestations, and diagnosis of viral encephalitis in children are discussed separately. (See "Acute viral encephalitis in children: Pathogenesis, incidence, and etiology" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis".)
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'.)
●Meningitis – Meningitis is inflammation of the meninges and is typically manifested by fever, headache, nausea, vomiting, photophobia, and stiff neck. (See "Viral meningitis: Clinical features and diagnosis in children", section on 'Clinical features'.)
- Whitley RJ. Viral encephalitis. N Engl J Med 1990; 323:242.
- 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.
- 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.
- Pandey S, Rathore C, Michael BD. Antiepileptic drugs for the primary and secondary prevention of seizures in viral encephalitis. Cochrane Database Syst Rev 2016; :CD010247.
- Thompson C, Kneen R, Riordan A, et al. Encephalitis in children. Arch Dis Child 2012; 97:150.
- 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.
- Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis 2005; 16:17.
- Whitley RJ, Nahmias AJ, Soong SJ, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 1980; 66:495.
- Whitley RJ, Soong SJ, Dolin R, et al. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med 1977; 297:289.
- Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 1986; 314:144.
- Whitley R, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 1991; 324:444.
- Sköldenberg B, Forsgren M, Alestig K, et al. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 1984; 2:707.
- Kimberlin DW. Acyclovir Dosing in the Neonatal Period and Beyond. J Pediatric Infect Dis Soc 2013; 2:179.
- American Academy of Pediatrics. Non-HIV antiviral drugs. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.919.
- American Academy of Pediatrics. Herpes simplex. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.432.
- Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis 2002; 34:1154.
- American Academy of Pediatrics. Red Book Online News. Shortage of intravenous acyclovir. http://aapredbook.aappublications.org/site/news#76 (Accessed on December 04, 2012).
- Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep 2006; 55:1.
- Hoke CH Jr, Vaughn DW, Nisalak A, et al. Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. J Infect Dis 1992; 165:631.
- Makhoul B, Braun E, Herskovitz M, et al. Hyperimmune gammaglobulin for the treatment of West Nile virus encephalitis. Isr Med Assoc J 2009; 11:151.
- Solomon T, Dung NM, Wills B, et al. Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial. Lancet 2003; 361:821.
- Kawano G, Iwata O, Iwata S, et al. Determinants of outcomes following acute child encephalopathy and encephalitis: pivotal effect of early and delayed cooling. Arch Dis Child 2011; 96:936.
- Martinez-Torres F, Menon S, Pritsch M, et al. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]. BMC Neurol 2008; 8:40.
- Rautonen J, Koskiniemi M, Vaheri A. Prognostic factors in childhood acute encephalitis. Pediatr Infect Dis J 1991; 10:441.
- Fowler A, Stödberg T, Eriksson M, Wickström R. Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol 2008; 12:484.
- Fowler A, Stödberg T, Eriksson M, Wickström R. Long-term outcomes of acute encephalitis in childhood. Pediatrics 2010; 126:e828.
- Michaeli O, Kassis I, Shachor-Meyouhas Y, et al. Long-term motor and cognitive outcome of acute encephalitis. Pediatrics 2014; 133:e546.
- Wang IJ, Lee PI, Huang LM, et al. The correlation between neurological evaluations and neurological outcome in acute encephalitis: a hospital-based study. Eur J Paediatr Neurol 2007; 11:63.
- Pillai SC, Hacohen Y, Tantsis E, et al. Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome. Pediatrics 2015; 135:e974.
- Willoughby RE, Long SS. Encephalitis, meningoencephalitis, acute disseminated encephalomyelitis, and acute necrotizing encephalopathy. In: Principles and Practice of Pediatric Infectious Diseases, 2nd ed, Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone, New York 2008. p.310.
- 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.
- Rismanchi N, Gold JJ, Sattar S, et al. Neurological Outcomes After Presumed Childhood Encephalitis. Pediatr Neurol 2015; 53:200.
- Fowlkes AL, Honarmand S, Glaser C, et al. Enterovirus-associated encephalitis in the California encephalitis project, 1998-2005. J Infect Dis 2008; 198:1685.
- Chang LY, Hsia SH, Wu CT, et al. Outcome of enterovirus 71 infections with or without stage-based management: 1998 to 2002. Pediatr Infect Dis J 2004; 23:327.
- Pérez-Vélez CM, Anderson MS, Robinson CC, et al. Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge. Clin Infect Dis 2007; 45:950.
- Ho M, Chen ER, Hsu KH, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 1999; 341:929.
- Cherry JD. Recognition and management of encephalitis in children. Adv Exp Med Biol 2009; 634:53.
- OVERVIEW OF TREATMENT
- SUPPORTIVE CARE
- Management of complications
- EMPIRIC THERAPY
- Empiric acyclovir
- - Dose
- - Duration
- IV acyclovir not available
- Empiric antibiotics
- - Bacterial meningitis
- - Rickettsial infection
- - Ehrlichiosis
- Other empiric therapy
- SPECIFIC THERAPY
- ADJUNCTIVE THERAPIES
- Neurologic sequelae
- Outcomes of specific viral pathogens
- LONG-TERM FOLLOW-UP
- PREVENTION AND CONTROL
- Primary prevention
- Infection control
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS