West Nile Encephalitis Workup

Updated: Mar 03, 2017
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
  • Print

Approach Considerations


West Nile encephalitis (WNE), as with many viral illnesses, may manifest as mild leukopenia or a white blood cell (WBC) count that is borderline or in the low end of the reference range. Leukocytosis suggests another diagnosis.

In patients who present with acute encephalitis, leukocytosis should suggest eastern equine encephalitis (EEE), California encephalitis, or St. Louis encephalitis.


Although relative lymphopenia is not specific for WNE, it is a helpful diagnostic finding if present in a patient with aseptic meningitis, meningoencephalitis, or particularly encephalitis of unknown cause.

Although patients with human immunodeficiency virus (HIV) or Venezuelan equine encephalitis often present with relative lymphopenia, the relative lymphopenia with WNE is profound and prolonged, which should suggest the diagnosis.

ESR/CRP ratio

An ESR/CRP ratio of less than 1 suggests WNE in adults with encephalitis.

Serum transaminases

Mild elevations of serum glutamic-pyruvic transaminase (SGPT) levels are not a feature of most arboviral encephalitides.

In addition to WNE, mild elevations of serum glutamic-oxaloacetic transaminase (SGOT)/SGPT levels in a patient with encephalitis should suggest Epstein-Barr virus, Rocky Mountain spotted fever, ehrlichiosis, HHV-6 infection, or Legionnaires disease.

Serum ferritin levels

Serum ferritin levels are highly elevated in WNE and not in other causes of encephalitis. The magnitude/duration of serum ferritin elevations also has prognostic importance.


This is the most sensitive method of making a presumptive diagnosis of encephalitis. In HSV-1 encephalitis, electroencephalography reveals an abnormal temporal lobe focus as early as the first few days of the disease.

The electroencephalogram in patients with WNE shows diffuse bilateral focal abnormalities, especially global slowing. [16]

Lumbar puncture

CSF reveals mild to moderate pleocytosis with a lymphocytic predominance in WNE. [17, 18] 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.

CSF testing for immunoglobulin M (IgM) antibodies against West Nile virus (WNV) should be performed (in addition to testing of the patient’s serum).

Histologic findings

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


Serologic Testing

West Nile encephalopathy may be cultured from the blood within the first 2 weeks of initial infection, but it is not usually culturable from CSF.

A specific diagnosis can be confirmed via serum testing. Various serologic methods are available, but the enzyme-linked immunoassay (ELISA) is the best test currently available. Plaque reduction neutralization test (PRNT) can be performed through the CDC.

The polymerase chain reaction (PCR) assay is also available at selected centers.

Most centers start by testing serum and CSF for IgM antibody directed against West Nile virus. If the IgM serology is positive, no further diagnostic confirmation is required (ie, PRNT). Paired serologic testing of acute- and convalescent-phase specimens or PCR testing can be obtained in patients with an ELISA result that is unreactive for IgM. A highly elevated acute immunoglobulin G (IgG) titer or a 4-fold or greater rise between acute and convalescent IgM titer is diagnostic of WNE.

The CDC has established criteria for the laboratory diagnosis of West Nile virus infection. [19]


CT Scanning and MRI

Since the differential diagnoses of WNE include HSV-1 meningoencephalitis and encephalitis, a head CT or MRI scan may be helpful in excluding HSV-1 infection after several days.

CT or MRI scans may exhibit changes in a 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 early in the disease process.

Most other causes of aseptic meningitis, meningoencephalitis, or encephalitis, including systemic disorders with an encephalitic component, have nonfocal temporal lobe findings on CT and MRI scans.