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Last reviewed: 14 Mar 2025
Last updated: 04 Mar 2025

Summary

Definition

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
  • vector exposure and/or animal bites
  • location
  • vaccination
  • post-infection
  • blood/body fluid exposure
  • organ transplantation
  • 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
  • chest radiography
  • CT brain
  • MRI brain
  • electroencephalogram (EEG)
  • cerebrospinal fluid (CSF) analysis
  • CSF culture
  • CSF serology
  • CSF polymerase chain reaction (PCR)

Investigations to consider

  • stool enteroviral culture
  • sputum culture
  • IgG and IgM antibodies (blood or CSF)
  • 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

Contributors

Authors

Sung G Ji, MD, PhD

Behavioral Neurology Fellow

Department of Neurology

University of Washington

Seattle

WA

Disclosures

SGJ declares that he has no competing interests.

Payal B. Patel, MD

Assistant Professor of Neurology

Department of Neurology

University of Washington

Seattle

WA

Disclosures

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.

Acknowledgements

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.

Disclosures

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

Peer reviewers

Alejandro Rabinstein, MD

Professor of Neurology

Mayo Clinic

Rochester

MN

Disclosures

AR has participated in advisory board meetings for Astra Zeneca, Chiesi, and Shionogi.

Rodrigo Hasbun, MD, MPH, FIDSA

Professor of Medicine

UT Health McGovern Medical School

Houston

TX

Disclosures

RH has received research support and personal fees from Biomeriaux (Biofare Diagnostics).

Russel Dale, MBChB, MRCPCH, MSc, PhD

Professor of Paediatric Neurology

The University of Sydney

Consultant Neurologist

The Children's Hospital at Westmead

Sydney

Australia

Disclosures

RD declares that he has no competing interests.

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