Last reviewed: 20 Dec 2021
Last updated: 05 Nov 2021



History and exam

Key diagnostic factors

  • presence of risk factors
  • fever
  • rash
  • altered mental state
  • focal neurological deficit
  • meningismus
  • parotitis
  • lymphadenopathy
  • optic neuritis
  • acute flaccid paralysis
  • movement disorder

Other diagnostic factors

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

Risk factors

  • age <1 or >65 years
  • immunodeficiency
  • vaccination
  • post-infection
  • 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

Diagnostic investigations

1st investigations to order

  • FBC
  • 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)

Investigations to consider

  • urine culture
  • 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

Treatment algorithm



Payal B. Patel, MD

Clinical Instructor

Department of Neurology

Yale University

New Haven




PBP declares that she has no competing interests.


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.

Use of this content is subject to our disclaimer