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Encephalitis — Clinical Guidelines

Overview

Encephalitis refers to inflammation of the brain, often caused by viral infections, leading to severe neurological symptoms including fever, altered mental status, and seizures. 1 2 12 13 17

Diagnosis

Clinical Presentation: Fever, headache, altered mental status, seizures, focal neurological deficits. 1 12 13

Laboratory Tests: Cerebrospinal fluid (CSF) analysis for cell count, protein levels, and viral PCR (e.g., HSV, EBV, JEV). 1 14 16

Imaging: MRI or CT scans to identify characteristic lesions or inflammation. 1 14 24

Serology and Viral Detection: Serological tests and viral antigen detection in CSF or brain tissue. 1 14 24

Electroencephalogram (EEG): Often shows abnormal patterns in encephalitis cases. 9

Management

Antiviral Therapy: Acyclovir for herpes simplex encephalitis; specific antivirals for other viral etiologies as indicated (e.g., ribavirin for flaviviruses). 16 27

Supportive Care: Intensive care support including mechanical ventilation, seizure management, and fluid/electrolyte balance. 9 27

Immunoglobulin Therapy: Considered in severe cases or when specific antivirals are unavailable. 29

Barbiturate Therapy: High-dose barbiturates in severe cases to reduce intracranial pressure. 27

Monitoring: Continuous monitoring of neurological status, ICP, and metabolic parameters. 9

Special Populations

Pediatrics: Increased vigilance for atypical presentations; Japanese encephalitis is a significant concern in endemic regions. 17

Elderly: Higher risk of severe complications and poorer outcomes; tailored supportive care is crucial. 9

Comorbidities: Patients with underlying immunodeficiencies may require more aggressive management and monitoring. 14

Key Recommendations

Initiate Empiric Antiviral Therapy Early in suspected herpes simplex encephalitis despite delayed confirmatory testing. (Evidence: Moderate 16)

Conduct Comprehensive CSF Analysis including PCR for common viral etiologies to guide specific treatment. (Evidence: Moderate 1 14)

Consider Continuous EEG Monitoring in patients with suspected encephalitis to detect early signs of status epilepticus. (Evidence: Moderate 9)

Vaccinate Against Japanese Encephalitis for travelers to endemic regions, especially those staying for extended periods. (Evidence: Expert opinion 20 21)

Monitor for Allergic Reactions post-Japanese encephalitis vaccination, particularly in mass immunization campaigns. (Evidence: Moderate 4 10 11)

References

1 Jungbäck N, Vollmuth Y, Mögele T, Grochowski P, Schlegel J, Schaller T et al.. Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review. The Lancet. Infectious diseases 2025. link00675-3) 2 Finsterer J. Letter to the Editor. Diagnosis of immune encephalitis requires a workup for specific antibodies and the exclusion of SARS-CoV-2 infection. Psychiatria polska 2025. link 3 Ramalingam PS, Aranganathan M, Hussain MS, Elangovan S, Chellasamy G, Balakrishnan P et al.. Unveiling reverse vaccinology and immunoinformatics toward Saint Louis encephalitis virus: a ray of hope for vaccine development. Frontiers in immunology 2025. link 4 Zhang C, Liu Y, Luo X, Han L, Shen J. Real-world safety profile of live attenuated Japanese encephalitis vaccine before and after the vaccine administration law. PloS one 2025. link 5 Liu F, Ran Q, Zhang H, Li Z, Chen J. Safety profile of Japanese encephalitis vaccines: a comprehensive analysis of vaccine adverse event reports from 1993 to 2025. Frontiers in public health 2025. link 6 Hills SL, Soeung SC, Sarath S, Morn C, Dara C, Fischer M et al.. An evaluation of adverse events following an immunization campaign with the live, attenuated SA14-14-2 Japanese encephalitis vaccine in Cambodia. PloS one 2022. link 7 Varoglu AO, Aksoy A. Herpes simplex encephalitis and pseudotumour cerebri due to ısotretinoin. JPMA. The Journal of the Pakistan Medical Association 2018. link 8 Matata C. Learn about this neurological emergency before it's too late. Nursing standard (Royal College of Nursing (Great Britain) : 1987) 2017. link 9 Sonneville R, Mariotte E, Neuville M, Minaud S, Magalhaes E, Ruckly S et al.. Early-onset status epilepticus in patients with acute encephalitis. Medicine 2016. link 10 Liu Y, Lin H, Zhu Q, Wu C, Zhao Z, Zheng H. Safety of Japanese encephalitis live attenuated vaccination in post-marketing surveillance in Guangdong, China, 2005-2012. Vaccine 2014. link 11 Wang Y, Dong D, Cheng G, Zuo S, Liu D, Du X. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China. Vaccine 2014. link 12 Kakkar M, Rogawski ET, Abbas SS, Chaturvedi S, Dhole TN, Hossain SS et al.. Acute encephalitis syndrome surveillance, Kushinagar district, Uttar Pradesh, India, 2011-2012. Emerging infectious diseases 2013. link 13 Bandyopadhyay B, Bhattacharyya I, Adhikary S, Mondal S, Konar J, Dawar N et al.. Incidence of Japanese encephalitis among acute encephalitis syndrome cases in West Bengal, India. BioMed research international 2013. link 14 Biebl A, Webersinke C, Traxler B, Povysil B, Furthner D, Schmitt K et al.. Fatal Epstein-Barr virus encephalitis in a 12-year-old child: an underappreciated neurological complication?. Nature clinical practice. Neurology 2009. link 15 García-Ribes A, Martínez-González MJ, Prats-Viñas JM. Suspected herpes encephalitis and opercular syndrome in childhood. Pediatric neurology 2007. link 16 Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis. Annals of emergency medicine 2006. link 17 Kabilan L, Vrati S, Ramesh S, Srinivasan S, Appaiahgari MB, Arunachalam N et al.. Japanese encephalitis virus (JEV) is an important cause of encephalitis among children in Cuddalore district, Tamil Nadu, India. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2004. link 18 Konishi E, Shoda M, Kondo T. Prevalence of antibody to Japanese encephalitis virus nonstructural 1 protein among racehorses in Japan: indication of natural infection and need for continuous vaccination. Vaccine 2004. link 19 Plesner AM. Allergic reactions to Japanese encephalitis vaccine. Immunology and allergy clinics of North America 2003. link00102-4) 20 Scrimgeour D. Japanese encephalitis. Australian family physician 2001. link 21 Bucens M, O'Connor L. Japanese encephalitis and the traveller. Australian family physician 1990. link 22 Johnson J, Lucey PA. Encephalitis lethargica, a contemporary cause of catatonic stupor. A report of two cases. The British journal of psychiatry : the journal of mental science 1987. link 23 Ward CD. Encephalitis lethargica and the development of neuropsychiatry. The Psychiatric clinics of North America 1986. link 24 Iwasaki Y, Zhao JX, Yamamoto T, Konno H. Immunohistochemical demonstration of viral antigens in Japanese encephalitis. Acta neuropathologica 1986. link 25 Watson DF, Stern BJ, Levin ML, Dutta D. Isolated cerebral phycomycosis presenting as focal encephalitis. Archives of neurology 1985. link 26 Steiner I, Polacheck I, Melamed E. Dementia and myoclonus in a case of cryptococcal encephalitis. Archives of neurology 1984. link 27 Andréasson S, Larsson LE, Bergström T, Alestig K. Severe acute encephalitis--improved outcome after barbiturate treatment?. Scandinavian journal of infectious diseases 1984. link 28 Hori A, Minwegen J. Intrauterine purulent encephalitis with early stage of hydranencephaly. Case report. Acta neuropathologica 1984. link 29 Pavri KM, Ramamoorthy CL, Dhorje S. Immunoglobulin E in patients with Japanese encephalitis. Infection and immunity 1980. link

Encephalitis