eMedicine Specialties > Infectious Diseases > CNS Infections

West Nile Encephalitis: Differential Diagnoses & Workup

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Aug 1, 2008

Differential Diagnoses

Encephalopathy, Hypertensive
Epidural Abscess

Other Problems to Be Considered

Encephalopathy due to systemic illnesses

Encephalopathy is a feature of many systemic illnesses that the clinician should consider in patients presenting with encephalitis. Most of these patients have extra-CNS findings that suggest the underlying disease process. Common disorders with CNS manifestations that may mimic West Nile encephalitis (WNE) include subacute bacterial endocarditis, Legionnaires disease, Rocky Mountain spotted fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus type 6 infection, and systemic lupus erythematosus cerebritis.

Other arthropod-borne viral encephalitides

The clinical presentation of WNE is not dissimilar from other causes of arthropod-borne viral encephalitis (eg, Japanese equine encephalitis, St. Louis encephalitis), including mental confusion, stupor, or coma. However, the clinical presentation of arthropod-borne viral encephalitis is characterized by rapid onset and severe headache. Arthropod-borne viral encephalitis has some distinctive features that indicate a prospective clinical diagnosis (see Images 1-2).

The differential diagnoses for aseptic meningitis is extensive but may be reduced to 2 common clinical entities.

Enteroviral aseptic meningitis

The most common cause of aseptic meningitis encountered during the summer months is enteroviral meningitis. Enteroviral aseptic meningitis is most commonly due to coxsackieviruses but may also be due to enterocytopathogenic human orphan virus or nonparalytic strains of poliovirus. Enteroviral meningitis may occur after water exposure in swimming pools, lakes, streams, or oceans as well as after contact with infected individuals.

Acute enteroviral CNS infections usually manifest as aseptic meningitis, uncommonly as meningoencephalitis, or rarely as encephalitis. Nonexudative pharyngitis, maculopapular extremity rash, loose stools, and even diarrhea often accompany enteroviral aseptic meningitis, which provides clues to its presence.

Enteroviral meningitis is not accompanied by paralysis or prolonged and/or profound lymphopenia.

Herpesvirus type 1 encephalitis

Herpes simplex virus encephalitis due to herpesvirus type 1 (HSV-1) is the most common cause of non–arthropod-borne (nonseasonal) encephalitis in the United States. HSV-1 infection usually manifests as encephalitis, uncommonly as meningoencephalitis, or rarely as aseptic meningitis (see Image 3).

Nonsteroidal anti-inflammatory drugs

In patients who present with aseptic meningitis, consider drug-induced aseptic meningitis, most commonly due to nonsteroidal anti-inflammatory drugs (NSAIDs). A patient presenting with aseptic meningitis with no predisposing risk factors may have recently been taking NSAIDs or may be currently taking NSAIDs.

Workup

Laboratory Studies

  • Leukopenia
    • West Nile encephalitis (WNE), as with many viral illnesses, may manifest as mild leukopenia or a WBC count that is borderline or in the low end of the reference range. Leukocytosis suggests a complication or superinfection.
    • In patients who present with acute encephalitis, leukocytosis should suggest eastern equine encephalitis (EEE), California encephalitis, or St. Louis encephalitis.
  • Lymphopenia
    • Although lymphopenia is not specific for WNE, it is a helpful diagnostic finding if present in a patient with aseptic meningitis, meningoencephalitis, or encephalitis of unknown cause.
    • Although patients with HIV or Venezuelan equine encephalitis often present with encephalitis and lymphopenia, lymphopenia with WNE is profound and prolonged, which should suggest the diagnosis.
  • Serum transaminases
    • Mild elevations of serum glutamic-oxaloacetic transaminase (SGOT) levels are not a feature of most encephalitides due to arboviral causes.
    • Mild elevations of the SGOT/serum glutamic-pyruvic transaminase (SGPT) level in a patient with encephalitis should suggest Epstein-Barr virus, Rocky Mountain spotted fever, ehrlichiosis, human herpesvirus type 6 infection, or Legionnaires disease in addition to WNE.
    • Serum amylase/lipase levels are increased in some cases of WNE.
  • Serologic testing
    • WNE may be cultured from the blood within the first 2 weeks of initial infection, but it is not usually culturable from cerebrospinal fluid (CSF).
    • A specific diagnosis can be confirmed via serum testing. Various serologic methods are available, but enzyme immunoassay (EIA) with plaque reduction neutralization test is the best test currently available. Polymerase chain reaction is also available at selected research centers.
    • A highly elevated acute titer or a 4-fold or greater rise between acute and convalescent titer is diagnostic of WNE.

Imaging Studies

  • CT scanning and MRI
    • Since the differential diagnoses of WNE include HSV-1 meningoencephalitis or encephalitis, a head CT scan or MRI is helpful to exclude HSV-1 infection, the only treatable cause of viral encephalitis.
    • CT scan or MRI may exhibit changes in one temporal lobe, which is highly characteristic of HSV-1 encephalitis. Early CT scan and MRI findings are often negative.
    • CT scans are less sensitive and may not reveal abnormalities if obtained very early in the disease process.
    • All other causes of aseptic meningitis, meningoencephalitis, or encephalitis, including systemic disorders with an encephalitic component, yield negative findings (nonfocal temporal lobe findings) on CT scan and MRI.
    • CNS lupus may be suggested by the diffuse uptake over the cerebral cortex, suggesting cerebritis.

Other Tests

  • Electroencephalography
    • This is the most sensitive method of making a presumptive diagnosis of HSV-1 encephalitis. EEG reveals an abnormal temporal lobe focus as early as the first few days of the disease.
    • The EEG in patients with WNE shows diffuse bilateral focal abnormalities in the temporal lobe.

Procedures

  • Lumbar puncture
    • CSF reveals mild-to-moderate pleocytosis with a lymphocytic predominance in WNE. CSF protein levels are variably elevated, and the CSF glucose level is not decreased.
    • The CSF lactic acid level is not elevated, and RBCs, excluding traumatic taps, are not present in WNE. CSF Gram stain and bacterial culture findings are negative.

Histologic Findings

Brain biopsy findings exhibit diffuse encephalitis, which is nonspecific and nondiagnostic for WNE.

More on West Nile Encephalitis

Overview: West Nile Encephalitis
Differential Diagnoses & Workup: West Nile Encephalitis
Treatment & Medication: West Nile Encephalitis
Follow-up: West Nile Encephalitis
Multimedia: West Nile Encephalitis
References
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Further Reading

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Keywords

West Nile encephalitis, WNE, West Nile virus encephalitis, WNVE, West Nile virus, viral encephalitis, western equine encephalitis, WEE, eastern equine encephalitis, EEE, Japanese encephalitis, Venezuelan encephalitis

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Contributor Information and Disclosures

Author

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Wesley W Emmons, MD, FACP, Assistant Professor, Department of Medicine, Thomas Jefferson University; Consulting Staff, Infectious Diseases Section, Department of Internal Medicine, Christiana Care, Newark, DE
Wesley W Emmons, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International AIDS Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance
John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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