Viral Encephalitis Clinical Presentation

Viral encephalitis is usually marked by acute onset of a febrile illness. Patients with viral encephalitis generally experience signs and symptoms of leptomeningeal irritation (eg, headache, fever, neck stiffness).

Patients with viral encephalitis also develop focal neurological signs; seizures^[20] ; and alteration of consciousness, starting with lethargy and progressing to confusion, stupor, and coma. Behavioral and speech disturbances are common. Abnormal movements can be seen but are rare. Involvement of the hypothalamic/pituitary axis can lead to hyperthermia or poikilothermia.

Symptoms associated with specific viral infections

Specific clues taken from the patient’s history depend on the viral etiology. Clinical findings reflect disease progression according to viral tropism for different central nervous system (CNS) cell types.

Atypical presentations include a reversible frontal lobe and limbic syndrome without disturbances of consciousness or motor function. These presentations have been described in children with influenza virus infection.^{[21, 22]}

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) encephalitis have subacute forms, presenting with a psychiatric syndrome and an anterior opercular syndrome, known as benign recurrent meningitis. HSV-1 encephalitis may produce a brainstem encephalitis, and HSV-2 encephalitis may also produce a myelitis.

West Nile encephalitis (WNE) is usually asymptomatic in areas of endemic disease. In symptomatic individuals, an influenzalike illness occurs after incubation of 3-15 days; CNS involvement occurs in less than 15% of cases. Severe neurologic infection is more common when the virus is introduced in an area of nonendemic disease.^{[23, 24]}

In 1999, during the New York City outbreak of West Nile virus infection, 62 patients developed encephalitis, and 7 died (a case fatality rate of 12%, with all deaths occurring in older patients). Axonal neuropathy, demyelinating polyneuropathy similar to that seen in Guillain-Barré syndrome, encephalitis with and without muscle weakness, and aseptic meningitis were described. Delayed weakness or recurrent clinical weakness after West Nile virus infection has been described.^[25]

Japanese encephalitis (JE) typically affects children and young adults. Older adults are affected in epidemics. The clinical presentation includes a nonspecific prodrome and frequent seizures.^[20]

Dengue fever^[26] classically presents with a severe influenzalike illness or dengue hemorrhagic fever. Less commonly, dengue fever can lead to encephalitis or encephalopathy, transverse myelitis, and mononeuropathy or polyneuropathy similar to that in Guillain-Barré syndrome. The hemorrhagic form may also cause hepatic failure leading to a Reye syndrome–like illness.

Enteroviral encephalitis is usually associated with a good prognosis. However, enterovirus 71 has a high mortality and can present with herpangina or enteroviral hand, foot, and mouth disease. Complications include myocarditis and acute flaccid paralysis. Enterovirus 71 can cause a chronic meningoencephalitis in patients who are immunocompromised.

Mumps encephalitis typically starts 3-10 days after parotitis and usually resolves without sequelae, except for occasional hydrocephalus due to ependymal cell involvement. Measles does not usually cause acute encephalitis.

Rabies virus usually incubates for 20-60 days but is capable of incubating for years. Infection does not occur in all humans bitten by an infected animal but is uniformly fatal when clinical disease develops. After a prodrome of fever, headache, malaise, seizures, and behavioral abnormalities, hydrophobia and aerophobia supervene. Coma and death occur in 1 to several weeks. Once symptoms start, treatment is ineffective.

In southern Vietnam, a viral encephalitis that was caused by avian influenza A (H5N1) and did not involve the respiratory tract was diagnosed in 2 siblings: a 4-year-old boy, who presented with severe diarrhea, seizures, coma, and death, and his sister.^[27] The boy’s cerebrospinal fluid (CSF) revealed only high protein levels, but H5N1 was isolated from CSF, fecal, throat, and serum specimens.

Findings from physical examination are not usually diagnostic. Focal neurologic deficits (eg, opisthotonos, pareses, tremors, ataxia, hypotonia, diplopia), accentuated reflexes, and extensor plantar responses may be observed. Abnormal movements and, rarely, tremor may be seen. Increased intracranial pressure (ICP) can also lead to papilledema and cranial nerve VI palsy.

Findings associated with specific viral infections

A minority of patients with arbovirus infections develop acute encephalitis (or encephalomyelitis), meningitis, or a combination of both. Focal signs are only occasionally prominent in arboviral encephalitis. Patients may also have evidence of spinal cord involvement.

JE can cause marked extrapyramidal manifestations, such as dull masklike face with wide staring eyes, tremor, choreoathetosis, head nodding, and rigidity. Flaccid paralysis, especially involving the lower extremities, has been described as being due to damage to the anterior horn cells.

Parkinsonism can be a sequela of JE, and von Economo encephalitis (encephalitis lethargica) is considered to be a sequela of influenza encephalitis.

Enterovirus 71 can cause rhombencephalitis with myoclonus, tremor, ataxia, cranial nerve involvement, neurogenic pulmonary edema, and coma.

Nipah virus, in addition to the classical encephalitis presentation, produces cerebellar and brainstem signs, as well as segmental myoclonus, significant hypertension, and tachycardia. Encephalitis delayed 4 months after exposure to the virus has been described, suggesting similarities to the subacute sclerosing panencephalitis (SSPE) phenotype.

Secondary bacterial infections of the respiratory and urinary tracts are major complications of encephalitis. Complications depend on the severity of the encephalitis and generally decline in importance as the acute illness passes.

With recovery from acute viral encephalitis, evidence of neuronal injury and death becomes apparent as residual neurologic defects, impairment of intelligence, and psychiatric disturbances. The severity of these sequelae varies according to the causative virus.^{[28, 29, 21, 30]}

Sequelae occur in 30-40% of patients aged 5-40 years and include extrapyramidal features (especially dystonia and occasionally parkinsonism), weakness, and seizure disorders. Sequelae are reported in only 3-10% of cases of JE in Japan. Yet 25-30% of young adult males serving in the armed forces of the United States during World War II had sequelae (including neuroses) 6 months after infection. In addition, 10 of 25 individuals who had JE in Guam in 1948 had neurological or intellectual defects 10 years later.

Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) may be frequent in St Louis encephalitis. Dehydration, respiratory complications, nosocomial infections, and decubitus ulcers may also occur.