eMedicine Specialties > Neurology > Neurological Infections

Viral Encephalitis: Differential Diagnoses & Workup

Author: Francisco de Assis Aquino Gondim, MD, MSc, PhD, Professor Adjunto II, Departments of Physiology and Pharmacology, Neurology Residency Program Director, Faculdade de Medicina, Universidade Federal do Ceará, Brazil
Coauthor(s): Gisele Ramos de Oliveira, MD, Staff Physician, Department of Neurology, Saint Louis University School of Medicine; Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Contributor Information and Disclosures

Updated: Jan 11, 2007

Differential Diagnoses

Other Problems to Be Considered

Complex partial status epilepticus
Myoclonus
Partial seizures with secondary generalization
Seizure, partial (focal)
Benign epilepsy syndromes

Workup

Laboratory Studies

• Usually, general laboratory studies are not helpful except to identify a viral infectious process (eg, lymphocytic predominance in the CBC count rather than polymorphonuclear cells indicative of bacterial infection). During epidemics, viral encephalitis is diagnosed readily on clinical grounds. However, sporadic cases of viral encephalitis are often difficult to distinguish from other febrile illnesses (eg, a child with gastroenteritis, dehydration, and convulsions) or from intoxications.
• In most instances, the currently available specific laboratory tests only help provide a retrospective diagnosis. Serologic tests depend on the occurrence of a rise in antibody titer. However, the early detection of specific immunoglobulin M (IgM) antibody may assist early diagnosis.
• Anti-West Nile virus IgM is detectable in the cerebrospinal fluid (CSF) and serum 10 days after infection onset. A polymerase chain reaction (PCR)–based test for rapid detection of West Nile virus has recently been developed in California. A diagnosis of Japanese B encephalitis can be confirmed serologically with demonstration of IgM in the CSF (sensitivity and specificity >95%). The PCR test may detect the virus within 2 days, but the test's reliability is uncertain. Enzyme-linked immunosorbent assays (ELISA) for detection of IgM and immunoglobulin G (IgG) of dengue fever are available for serum and CSF.

Imaging Studies

• CT scan
  • In HSV encephalitis, CT scan may show low-density lesions in the temporal lobes, which may not be present until 3-4 days after onset.
  • Edema and hemorrhages may be found, and, after 1 week, contrast enhancement may be observed.
  • CT findings are usually not helpful in differentiating the different viral encephalitides. However, given the low cost and ready availability in most institutions, CT scan can be used to evaluate acute disease progression and to follow up on complications.
  • CT scan can readily reveal important complications, such as hemorrhage, hydrocephalus, and herniation, and can help guide neurosurgical interventions.
• MRI
  • MRI is more sensitive than CT scan in identifying viral encephalitides.
  • In herpesvirus encephalitis, MRI typically shows temporal lobe lesions, which may be hemorrhagic and unilateral or bilateral. Inferomedial temporal lobe and cingulate gyrus are the areas most commonly detected by MRI. In children and infants, a more widespread pattern may be observed.
  • MRI may help in differentiating Japanese B encephalitis from Nipah virus encephalitis. Japanese B encephalitis is characterized by gray matter involvement. Nipah virus encephalitis is associated with multiple, small, white matter lesions.
  • The rhombencephalitis caused by enterovirus 71 can be visualized by T2-weighted MRI, which shows hyperintense signals in the brainstem.
  • A peculiar MRI pattern on diffusion-weighted imaging and magnetic resonance spectroscopy has been described in an acute and rapid form of subacute sclerosing panencephalitis.
• Relying on MRI findings to make the diagnosis of encephalitis or to distinguish among the different viral etiologies is usually not advisable.

Other Tests

• Electroencephalography
  • In herpesvirus encephalitis, electroencephalography (EEG) shows abnormalities in four fifths of biopsy-proven cases. Focal temporal changes, diffuse slowing, and periodic complexes and periodic lateralizing epileptiform discharges (PLEDs) are commonly described. Frontal slowing and occasional frontal spikes have been described in encephalitis associated with influenza virus.
  • Japanese B encephalitis is commonly associated with 3 EEG patterns: diffuse continuous delta activity, diffuse delta activity with spikes, and alpha coma pattern. In one study, EEG pattern did not correlate with the Glasgow coma scale score and outcome.
  • In St. Louis encephalitis, EEG is characterized by diffuse delta activity, and spike and waves are not prominent in the acute stage.

Procedures

• Spinal tap should be performed immediately once a space-occupying lesion is ruled out.
  • CSF examination is critical to establish the diagnosis and reveals, acutely, a typical viral profile: mildly elevated protein (60-80 mg/dL), normal glucose, and a moderate pleocytosis, up to 1000 leukocytes/µL. Mononuclear cells usually predominate, although early in fulminant encephalitis, polymorphonuclear leukocytes predominate, glucose and chloride concentrations in the CSF are normal, and protein is increased. Viral cultures are rarely helpful for acute management. Findings from CSF cultures for enteroviruses, mumps, and certain arboviruses may be positive.
  • Herpesvirus encephalitis may be associated with increased red blood cells and xanthochromia in the CSF. The fluid should be sent for HSV-1 and HSV-2 PCR to detect HSV DNA. PCR is highly specific and remains positive for as long as 5 days after initiation of treatment. Intrathecal antibodies can also be quantified.

Histologic Findings

• In acute viral encephalitis, capillary and endothelial inflammation of cortical vessels is a pathologic hallmark occurring in the gray matter or at the junction of the gray matter and white matter. Lymphocytic infiltration of the gray matter and neuronophagia may also occur. Astrocytosis and gliosis become prominent with disease progression.
• Some histopathologic features, such as Cowdry type A inclusion bodies in HSV and Negri bodies in rabies, are unique to viral infections. Arboviruses cause little histopathologic change outside the nervous system, with the possible exception of renal involvement in St. Louis encephalitis.
• Gross examination reveals varying degrees of meningitis, cerebral edema, congestion, and hemorrhage in the brain.
• Microscopic examination confirms a leptomeningitis with round-cell infiltration, small hemorrhages with perivascular cuffing, and nodules of leukocytes or microglial cells. Demyelination may follow the destruction of oligodendroglias and involvement of ependymal cells may lead to hydranencephaly. Neuronal damage is seen as chromatolysis and neuronophagia. Areas of necrosis may be extensive, especially in eastern equine encephalitis, Japanese B encephalitis, and the Far East form of tick-borne encephalitis.
• In patients who survive the initial illness, varying degrees of repair are observed, which may include calcification. The pattern of distribution of lesions in the brain is rarely sufficiently specific to enable identification of the infecting virus. However, the lesions in eastern equine encephalitis are concentrated in the cortex. In western equine encephalitis, lesions are concentrated in the basal nuclei. In St. Louis encephalitis, lesions are concentrated in substantia nigra, thalamus, pons, cerebellum, cortex, bulb, and anterior horn cells.
• Herpesvirus encephalitis in infants is usually part of a widespread infection that produces focal necrotic lesions with typical intranuclear inclusions in many organs. In adults and in some children, lesions are confined to the brain. Necrotic foci may be macroscopically evident as softening. Hemorrhage and Cowdry type A inclusions bodies are found readily in the margins of areas of necrosis.
• Herpesvirus has tropism for the temporal cortex and pons, but the lesions may be widespread. Rabies virus tends to exhibit a tropism for the temporal lobes, affecting the Ammon horns. Autopsy studies in individuals with West Nile virus have shown particular brainstem involvement, especially the medulla, with endoneural mononuclear inflammation of cranial nerve roots.

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