Japanese Encephalitis Workup

Updated: Oct 05, 2018
  • Author: Antonette B Climaco, MD; Chief Editor: Burke A Cunha, MD  more...
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Workup

Approach Considerations

Japanese encephalitis virus (JEV) infection should be suspected in a patient with symptoms and signs of neurologic infection who has recently traveled in an endemic country.

CBC count

A complete blood cell (CBC) count often shows nonspecific modest leukocytosis in the first week of illness. This may be followed by a relative leukopenia. A mild anemia may also be present. In one study, 15% of children with Japanese encephalitis had thrombocytopenia.

Serum sodium levels

Serum sodium levels may be depressed owing to inappropriate antidiuretic hormone secretion.

Liver function tests

A study of Indian children during the Uttar Pradesh Japanese encephalitis outbreak in 2005 noted elevated liver function test results in a large number of patients (all had elevated aspartate aminotransferase [AST] levels; 47.2% had elevated alanine aminotransferase levels). [12]

Serology

IgM antibody can be detected in CSF by 4 days after the onset of symptoms and in the serum by 7 days after symptom onset. See Immunoassays for more details.

Viral isolation

Isolation of Japanese encephalitis virus from clinical specimens or even the identification of positive genetic viral sequences in tissue, blood, or CSF is diagnostic. However, virus isolation is reported to be difficult in humans because of transient and low-level viremia.

For laboratory worker safety, a biosafety level 3 is required for working with Japanese encephalitis virus.

MRI and CT scanning

Magnetic resonance imaging (MRI) and computed tomography (CT) scans often show bilateral thalamic lesions with hemorrhage, with MRI being more sensitive. The basal ganglia, putamen, pons, spinal cord, and cerebellum may also show abnormalities. Hyperintense lesions may be observed in the areas of the thalamus, cerebrum, and cerebellum on T2-weighted MRIs.

Electroencephalography

Electroencephalography (EEG) often reveals diffuse continuous delta slowing, a diffuse delta pattern with spikes, theta waves, and burst suppression.

EEG changes do not correlate with the severity of Japanese encephalitis or its outcome.

Histologic findings

Changes are found in the thalamus, substantia nigra, brain stem, hippocampus, cerebellum, and spinal cord and include focal neuronal degeneration with diffuse and focal microglial proliferation and lymphocytic perivascular cuffing.

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Lumbar Puncture

Lumbar puncture is performed to obtain CSF samples for diagnosis and for ruling out other causes of encephalitis.

The opening pressure is usually normal but may be raised.

CSF protein levels are mildly elevated, often less than 900 mg/dL. CSF glucose levels are often normal.

CSF cell count will show between 10 and several hundred white blood cells with lymphocytic predominance.

Japanese encephalitis virus may be isolated from the blood during the first week of illness. The CSF rarely yields virus, except in severe or fatal cases.

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Immunoassays

The diagnosis of Japanese encephalitis is supported by a capture immunoassay methodology demonstrating IgM antibody in the CSF or the serum. Alternatively, 4-fold increase between the acute-phase and convalescent-phase serum may be used to establish a diagnosis of recent infection.

Japanese encephalitis virus–specific IgM capture-enzyme-linked immunoassay (ELISA) on serum or CSF is the standard diagnostic test for Japanese encephalitis. Sensitivity is nearly 100% when both serum and CSF are tested. False-negative results may occur if the samples are tested too early (eg, within the first week of illness). IgM antibody can be detected in CSF by 4 days after the onset of symptoms and in the serum by 7 days after symptom onset. Of note, IgM may be found in the serum but not in the CSF in vaccinated persons or in those with asymptomatic infections.

Some cross-reactivity may arise from other flaviviruses (eg, dengue and West Nile virus) and from Japanese encephalitis and yellow fever vaccinations. This phenomenon may contribute to misdiagnosis; parallel testing for Japanese encephalitis virus and other flaviviruses (eg, dengue) may be necessary.

IgM dot enzyme immunoassays for CSF and serum are simple, portable tests that compare favorably with capture ELISA for field diagnosis (sensitivity of 98.3% and specificity of 99.2% when compared with capture ELISA as the standard). [23]

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