Last reviewed: 24 Aug 2023
Last updated: 06 Jun 2023



History and exam

Key diagnostic factors

  • fever
  • rash
  • altered mental state
  • focal neurologic deficit
  • meningismus
  • parotitis
  • lymphadenopathy
  • optic neuritis
  • acute flaccid paralysis
  • movement disorder
More key diagnostic factors

Other diagnostic factors

  • cough
  • gastrointestinal infection
  • seizures
  • biphasic illness
  • autonomic and hypothalamic disturbances
  • myocarditis/pericarditis
  • jaundice
  • arthritis
  • retinitis
  • parkinsonism
Other diagnostic factors

Risk factors

  • age <1 or >65 years
  • immunodeficiency
  • vaccination
  • postinfection
  • blood/body fluid exposure
  • organ transplantation
  • animal or insect bites
  • location
  • season
  • occupation
  • hunting/trekking in woods
  • swimming or diving in warm freshwater or nasal/sinus irrigation
  • spelunking (cave-exploring)
  • death in animals
  • cancer
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC
  • peripheral blood smear
  • serum electrolytes
  • liver function tests
  • blood cultures
  • throat swab
  • nasopharyngeal aspirate
  • sputum culture
  • chest radiography
  • CT brain
  • MRI brain
  • electroencephalogram (EEG)
  • cerebrospinal fluid (CSF) analysis
  • CSF culture
  • CSF serology
  • CSF polymerase chain reaction (PCR)
More 1st investigations to order

Investigations to consider

  • stool enteroviral culture
  • IgG and IgM antibodies (blood)
  • PCR (blood)
  • HIV serology/RNA test
  • CSF biomarkers/prion protein assay
  • paraneoplastic antibodies (blood and CSF)
  • abdominal/pelvic ultrasound
  • whole-body CT
  • whole-body PET scans
  • magnetic resonance spectroscopy
  • next-generation sequencing of CSF
  • brain biopsy
More investigations to consider

Treatment algorithm


immunocompetent host: suspected viral etiology

immunocompromised host: suspected viral etiology


confirmed herpes simplex virus (HSV) encephalitis

confirmed varicella zoster virus (VZV) encephalitis

confirmed cytomegalovirus (CMV) encephalitis

confirmed Epstein-Barr virus (EBV) encephalitis

confirmed herpes B encephalitis

confirmed human herpes 6 encephalitis

confirmed nonherpes virus etiology

nonviral etiology


convalescent phase: all etiologies



Payal B. Patel, MD

Assistant Professor of Neurology

Department of Neurology

University of Washington




PBP has received research funding support from the National Institute of Health and Bayer Pharmaceuticals. PBP has received an honorarium as an author from Medlink Neurology and Continuum Neurology.


Dr Payal B. Patel would like to gratefully acknowledge Dr Leo H. Wang, Dr Louise T. Wang, Dr Catalina C. Ionita, Dr Manjunath Markandaya, Dr David Janicke, Dr Robert Schmidt, and Dr Kimiko Domoto-Reilly, previous contributors to this topic.


LHW, LTW, CCI, MM, DJ, RS, and KDR declare that they have no competing interests.

Peer reviewers

Russel Dale, MBChB, MRCPCH, MSc, PhD

Professor of Paediatric Neurology

The University of Sydney

Consultant Neurologist

The Children's Hospital at Westmead




RD declares that he has no competing interests.

Arun Venkatesan, MD, PhD

Associate Professor, Neurology


Johns Hopkins Encephalitis Center

Johns Hopkins Hospital




AV declares that he has no competing interests.

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