West Nile Virus (WNV) Infection and Encephalitis (WNE) Differential Diagnoses

Updated: Apr 05, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Diagnostic Considerations

The most important infection to exclude in the differential diagnoses of West Nile encephalitis (WNE) is herpes simplex virus type 1 (HSV-1) encephalitis, because it is the only viral encephalitis that can be treated pharmacologically, and early appropriate intervention will benefit the patient. HSV-1 encephalitis is suggested by temporal lobe abnormalities on electroencephalography (EEG) and later on CT scanning and MRI.

Early in the course of HSV-1 encephalitis, cerebrospinal fluid (CSF) may show a polymorphonuclear predominance but most frequently features a high red blood cell (RBC) count. CSF glucose levels may be increased in HSV-1 encephalitis. CSF studies in patients with WNE generally do not show this finding.

HSV-1 encephalitis 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. Differential diagnoses of meningoencephalitis, including the HSV-1 type, are listed in the chart below.

Differential diagnoses of meningoencephalitis. Differential diagnoses of meningoencephalitis.

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 WNE include subacute bacterial endocarditis, Legionnaires disease, Rocky Mountain spotted fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus type 6 (HHV-6) infection, and systemic lupus erythematosus cerebritis. Other noninfectious causes of encephalopathy to consider initially may include uremia, hyperammonemia, intoxication or ingestion, or other metabolic derangement.

Other arthropod-borne viral encephalitides

The clinical presentation of WNE is not unlike other causes of arthropod-borne viral encephalitis (eg, Japanese encephalitis, equine 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 presumptive clinical diagnosis (as seen in the charts below).

Common encephalitis associations. Common encephalitis associations.
Clinical features of arboviral encephalitis. Clinical features of arboviral encephalitis.

Enteroviral aseptic meningitis

The most common cause of aseptic meningitis encountered during the summer months, particularly in late August or early September, 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.

Excluding enterovirus 71, enteroviral meningitis is not accompanied by paralysis or prolonged and/or profound relative lymphopenia. Enterovirus D68 may also be associated with the above symptoms with a transverse myelitis syndrome and may present similarly to acute flaccid paralysis.

Differential Diagnoses