Encephalitis Workup

Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. Accordingly, in addition to standard blood and urine tests, studies may be performed to identify the infectious agent causing the encephalitis. ^[5] It is important, when possible, to distinguish acute arboviral encephalitides from potentially treatable acute viral encephalitides, especially herpes simplex encephalitis (HSE) and varicella-zoster encephalitis, as a high suspicion for these disorders and prompt treatment can reduce the severity of neurological sequelae and can be lifesaving.

A complete blood count (CBC) with differential should be performed, although findings are often within the normal range.

Serum electrolyte levels are usually normal unless dehydration is present; the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs in 25% of patients with St Louis encephalitis.

The serum glucose level should be determined to rule out confusion due to treatable hypoglycemia and to compare with the cerebrospinal fluid (CSF) glucose value. Low serum results are found in nutritionally deprived patients, while diabetic patients may present with elevated glucose levels compatible with complicating hyperosmolar state or diabetic ketoacidosis.

Blood urea nitrogen (BUN) and creatinine levels are helpful to assess hydration status, and liver function tests should be performed to assess for end-organ dysfunction or the need to adjust antimicrobial therapy dosing regimens.

A lumbar puncture (LP) should be performed on all patients suspected of having a viral encephalitis. A platelet count and coagulation profile are indicated in patients who are chronic alcohol users, have liver disease, and those in whom disseminated intravascular coagulation (DIC) is suspected. The patient may require platelets or fresh frozen plasma (FFP) before LP.

A urinary electrolyte test should be performed if SIADH is suspected. Urine or serum toxicology screening may be indicated in selected patients presenting with a toxic delirium or confusional state.

Herpes simplex virus (HSV) cultures of suspicious lesions and a Tzanck smear should be obtained. Viral cultures of CSF, including HSV, should be performed, although the incidence of the latter being positive is rare. Blood cultures for bacterial pathogens should be obtained.

Complement fixation antibodies are useful in identifying arbovirus. Cross-reactivity exists among a subgroup of arboviruses, the flaviviruses (eg, viruses that cause St Louis encephalitis, Japanese virus encephalitis [JE], and West Nile encephalitis [WNE]), and the antibodies found in persons inoculated with yellow fever vaccine.

Heterophile antibody and cold agglutinin testing for Epstein-Barr virus (EBV) may be helpful.

Serologic tests for toxoplasmosis can be helpful in light of an abnormal computed tomography (CT) scan, particularly in the case of single lesions. However, the overlap in titer levels between exposed but currently uninfected and reactivated groups may complicate interpretation.

Performance of a head CT scan with and without contrast agent should be performed in virtually all patients with encephalitis. This should be done prior to LP if there are focal complaints or findings, signs to search for evidence of elevated intracranial pressure (ICP), obstructive hydrocephalus, or mass effect due to focal brain infection. Head CT scanning also helps exclude brain hemorrhage or infarction as a cause of an encephalopathic state. Magnetic resonance imaging (MRI) is more sensitive than CT scanning in demonstrating brain abnormalities earlier in the disease course.

In HSE, MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT commonly shows areas of edema or petechial hemorrhage in the same areas. EEE and tick-borne encephalitis may show similar increased MRI signal intensity in the basal ganglia and thalamus.

In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated.

In HSE, electroencephalography (EEG) often documents characteristic paroxysmal lateral epileptiform discharges (PLEDs), even before neuroradiography changes. Eventually, PLEDs are positive in 80% of cases; however, the presence of PLEDs is not pathognomonic for HSE.

CSF analysis is essential. Typical patterns of findings in the CSF pressure and CSF analysis follow in the Table 1 regarding bacterial versus viral versus fungal (including cryptococcal) meningitis or encephalitis.

Table. Cerebrospinal Fluid Findings by Type of Organism (Open Table in a new window)

The most important diagnostic test in the emergency department (ED) to rule out bacterial meningitis is prompt Gram staining and, if available, polymerase chain reaction (PCR) of the CSF in patients with suspected HSV encephalitis. PCR for HSV DNA is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. Arguably, a series of quantitative PCRs documenting the decline of viral load with acyclovir treatment is strongly supportive of the diagnosis of HSV, and selected patients my avoid need for brain biopsy.

Although most histologic features are nonspecific, brain biopsy is the criterion standard because of its 96% sensitivity and 100% specificity.

The presence of Negri bodies in the hippocampus and cerebellum are pathognomonic of rabies, as are HSV Cowdry type A inclusions with hemorrhagic necrosis in the temporal and orbitofrontal lobes.