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Western Equine Encephalitis: Differential Diagnoses & Workup
Updated: Oct 31, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Infective endocarditis
Mumps
Rabies virus
Stroke
Metabolic encephalopathy
Reye syndrome
Epstein-Barr virus (EBV)
Workup
Laboratory Studies
- Because of the large number of potential organisms that can be responsible for the signs and symptoms of this disease, diagnosis is often delayed and difficult. Laboratory confirmation is also difficult because it requires either specific serologic findings or isolation of the virus in brain tissue or cerebrospinal fluid (CSF). However, isolation from either the blood or CSF is often difficult because of the low viremia associated with western equine encephalitis (WEE).
- The current guidelines of the Centers for Disease Control and Prevention (CDC) for diagnosis of an arbovirus require an acute febrile illness with encephalitis during a time when transmission of the virus is likely and 1 more of the following criteria:
- A greater than 4-fold increase in the viral antibody titer between acute and convalescent sera (often 10 wk apart)
- Viral isolation from the CSF, blood, or tissue
- Immunoglobulin M (IgM) positive to the organism in the CSF
- Presumptive positive diagnoses can be made based on the remaining biochemical assays (eg, hemagglutinin inhibition, immunofluorescence, neutralization, complement fixation).
- Blood cultures are unlikely to help in these situations but may be performed if suspicion of bacterial meningitis is high.
- The use of biochemical assays is most valuable for diagnosis. Obtain sera at 2- to 3-day intervals to assess for a potential outcome upon early suspicion. The potential drawbacks include an inability to rapidly receive the results of these tests. Potential assays for isolation include the following:
- Enzyme-linked immunosorbent assay (ELISA) is used to detect IgM primarily during convalescent stages or prolonged courses and is virus-specific.
- ELISA may also reveal antiarboviral immunoglobulin G (IgG) and yields results similar to those of the neutralization assay. The current use of this assay is primarily as an adjunct to the IgM ELISA.4
- Serum hemagglutinin inhibition titer of at least 1:320 is used most commonly and allows differentiation among EEE, WEE, and VEE.
- A complement fixation titer of at least 1:128 is found primarily in convalescing patients.
- An immunofluorescence titer of at least 1:256 is uncommon.
- A neutralization assay titer of at least 1:160 is common.
- Clinicians may document the presence of WEE in a specimen by inoculating mice or embryonated eggs (Vero cell plaque assay).
- A leukocytosis with a left shift often is present but is less than that observed in EEE. Otherwise, no prominent laboratory anomalies are unique to WEE.
- CSF findings (from lumbar puncture)
- Increased protein and protein concentration in CSF: This is often present (approximately 90-110 mg/dL) and occurs with a high prevalence.
- Elevated CSF RBC count
- Elevated CSF WBC count: Initial WBC count is 50-500/µL, with a median of 350/µL and a predominance of lymphocytes.
- No hypoglycorrhachia
- Occasional viral isolation
- Occasional IgM positivity, which can provide a presumptive diagnosis
- A final alternative study, which should provide rapid diagnosis in the future, is polymerase chain reaction (PCR) analysis of the various organisms known to cause encephalitis. PCR analysis has been performed in WEE since 1996, but initial uses were primarily to differentiate between various cross-species of the virus. Recent studies, however, are more promising for PCR because they indicate that it is much more accurate than the 10% likelihood of serological diagnostics yielding positive results. Other advantages of PCR include the ability to target antiviral therapy, to reduce the need for brain biopsy, and to increase the speed of diagnosis (ie, the panel can often be run in 72 h). The current limitation of PCR is that it will likely require a state or national effort, which may not be available for WEE. The currently used assay is the TaqMan reverse transcriptase PCR assay.
Imaging Studies
Encephalitis can be identified early with neuroimaging studies (eg, CT scanning, MRI), which are routinely performed in patients with CNS symptoms.
Recent advances in imaging studies have shown that previous neuroradiographic manifestations of WEE were not precisely defined. Early studies revealed a predilection for the thalamic nuclei and the basal ganglia; however, these changes are also common in infections with Japanese encephalitis, measles, mumps, echovirus 25, Creutzfeldt-Jakob (CJ) disease, cyanide poisoning, and carbon monoxide poisoning and therefore are not entirely sensitive. Both CT scanning and MRI may play an important part in the early identification of WEE. Of note, in patients who recovered, most radiographic changes resolved.
- CT scanning
- This is an excellent modality for either monitoring the evolution of lesions or determining primary areas of disease.
- The most common finding is a lesion of the basal ganglia. Lesions vary in size and may exhibit secondary mass effect with edema.
- A CT scan may reveal areas of punctate hemorrhage, focal edema with mass effect, poorly marginated lesions, or interventricular hemorrhage.
- In elderly patients, the findings could mimic early infarction or nonspecific common findings.
- Occasionally, meningeal enhancement may also be observed and may indicate a subarachnoid hemorrhage or meningitis.
- MRI
- MRI is often sensitive to early changes secondary to EEE, but no studies have been completed with WEE. In EEE, MRI was more sensitive and revealed more abnormalities with increased detail compared to CT scan, and these findings probably would be the same in studies of WEE.
- The lesions are best observed with T2-weighted images and appear as areas of increased signal intensity.
- The most commonly affected areas of the CNS include the basal ganglia (ie, unilateral or asymmetric with occasional internal capsule involvement) and thalamic nuclei. Other areas include the brain stem (often the midbrain), periventricular white matter, and cortex (most often temporally).
Other Tests
- Throat swab: Occasionally, the virus can be recovered by this method.
- EEG: EEG often reveals generalized slowing and disorganization of the background. This is often followed by epileptiform activity that varies from isolated discharges to gross seizure activity.
- Lumbar puncture: If suspicion is high, lumbar puncture is absolutely indicated as soon as possible. Assess the CSF for elevated opening pressures and send CSF for a CBC count with differential; Gram stain; glucose and protein levels; acid-fast bacillus; India ink stain; Venereal Disease Research Laboratory (VDRL) test; herpes PCR; and bacterial, viral, and fungal culture.
- Brain biopsies: Biopsies are not frequently performed anymore, and these procedures are often a last resort.
Histologic Findings
CNS histopathology
The perikaryon and dendrites are primarily affected and demonstrate evidence of cytoplasmic swelling, eosinophilia, and nuclear pyknosis. Occasionally, mature viral particles are present in extracellular spaces. The brain is grossly edematous, and evidence of inflammation both parenchymally and perivascularly is present. Perivascular inflammation, vasculitis, thrombi, neurolysis (cell membrane rupture), neuronophagia, and demyelination may be observed. The areas primarily affected grossly are the thalamic nuclei and basal ganglia. Infants who die of WEE or neonates infected in utero often have massive neuroparenchymal destruction. Of those who survive, most have a normal brain grossly, but some cysts may be present.
More on Western Equine Encephalitis |
| Overview: Western Equine Encephalitis |
 Differential Diagnoses & Workup: Western Equine Encephalitis |
| Treatment & Medication: Western Equine Encephalitis |
| Follow-up: Western Equine Encephalitis |
| References |
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Further Reading
Keywords
western equine encephalitis, WEE, inflammation of the brain parenchyma, meninges, herpes simplex virus, arbovirus, Culex tarsalis, C tarsalis, Aedes species, eastern equine encephalitis, EEE, Venezuelan equine encephalitis, VEE, Sindbis virus, neurotropic alphavirus, diffuse CNS involvement, meningitis, meningoencephalitis, St. Louis encephalitis, Aedes albifasciatus, A albifasciatus, encephalitides
