As mentioned above, the cause of many cases of encephalitis remains unknown despite extensive testing. Thus, history and physical exam play a vital role in making the diagnosis of viral encephalitis. Important elements of history include immune status, exposure to insects or animals, travel history, vaccination history, geography, and time of year. The most common sign and symptoms are fever, headache, seizures, and altered mental status. Neuropsychiatric features such as behavioral changes, hallucinations, and/or cognitive decline are often seen. Patients may also have other symptoms or exam findings that are more specific to a given virus. For example, rash and skin vesicles are seen with herpes zoster encephalitis, whereas lymphadenopathy and splenomegaly are usually associated with EBV. HSV encephalitis involves the temporal and frontal lobes, so it is often characterized by psychiatric features, memory deficits, and aphasia. On the other hand, motor symptoms such as choreoathetosis and parkinsonian movements are seen with some arboviruses because they predominately affect the basal ganglia.

Specific features

JE may lead to extrapyramidal symptoms-which mimic Parkinson disease

Enterovirus 71 may cause tremor, myoclonus, ataxia, pulmonary edema, and cranial nerve palsies.

Nipah virus has been shown to produce brainstem and cerebellar signs, hypertension and segmental myoclonus.

Microcephaly is typical of Zika virus infection.

Neuroimaging and lumbar puncture (LP) are essential initial diagnostic studies for evaluating patients with viral encephalitis. Computed tomography (CT) or magnetic resonance imaging (MRI) help exclude increased intracranial pressure and the risk of uncal herniation prior to performing an LP.

CT may show low-density lesions in the temporal lobes when HSV is involved. These lesions usually appear 3-5 day after the infection.

MRI is also the most sensitive imaging modality for showing findings consistent with HSV encephalitis, such as temporal and frontal lobe involvement. Cerebrospinal fluid (CSF) should be analyzed for opening pressure, cell counts, glucose, and protein. CSF evaluation should also include polymerase chain reaction (PCR) testing for HSV-1, HSV-2, and enteroviruses. Additional testing, such as serology for arboviruses and HIV testing, may also be done based on history and clinical presentation. Brain biopsy and body fluid specimen cultures and PCR may also be helpful in establishing the etiology in some cases.[2][10][11]

The CSF will show:

• Normal glucose
• Moderately elevated proteins
• Moderate lymphocytosis

About 10% of patients will have normal CSF studies.

EEG may show abnormalities in patients with seizures. JE is often associated with 3 EEG patterns that include 1) diffuse delta activity with spikes 2) diffuse continuous delta activity and 3) alpha comma activity.

The treatment of viral encephalitis is primarily supportive as there is no specific medical therapy for most central nervous system viral infections. A very important exception to this is HSV encephalitis. When started early, acyclovir has been shown to significantly decrease mortality and morbidity and limit the severity of long-term behavioral and cognitive impairment of HSV encephalitis. Therefore, empirically, it is recommended that physicians start all patients with suspected encephalitis on acyclovir. The recommended dose is 10 mg/kg intravenously (IV) every 8 hours for 14 to 21 days. Although not as effective as it is with HSV, nucleoside analogs are used for other herpesviruses as well. Acyclovir 10 to 15 mg/kg IV every 8 hours for 10 to 14 days, with possible adjunctive corticosteroids in immunocompetent patients, is recommended for varicella-zoster virus. The recommended treatment for CMV encephalitis is a combination of ganciclovir 5 mg/kg IV every 12 hours and foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 21 days.

Another important component of the management of patients with viral encephalitis is serial intracranial pressure (ICP) monitoring. Elevated ICP is associated with poor prognosis. Although there is limited data on their efficacy in viral encephalitis, steroids and mannitol can be given to relieve increased ICP.[12][13][14]

Seizures may need to be managed with valproic acid or phenytoin. For status epilepticus, one may require benzodiazepines. For behavior alterations, one may need to use antipsychotics for a short time.

A broad differential diagnosis, both infectious and noninfectious, should be considered for encephalitis. These alternatives include malignancy, autoimmune or paraneoplastic diseases (e.g., anti-NMDA receptor encephalitis), brain abscess, tuberculosis or drug-induced delirium, neurosyphilis, or bacterial, fungal, protozoal, or helminthic encephalitis.

Most patients with viral encephalitis recover without sequelae. Those who remain symptomatic have difficulties in concentration, behavioral and speech disorders, and/or memory loss. In rare cases, patients may remain in a vegetative state.

Some children may develop seizures and changes in behavior following infection with WEE. Following EEE, children may develop seizures, severe mental retardation and various forms of paralysis. Zike virus infection in pregnancy may be associated with microcephaly. The most common long term complication after viral encephalitis is seizures that may occur in 10-20% of patients over several decades. These seizures often are resistant to medical therapy. Unilateral mesial temporal lobe seizures have good outcomes following neurosurgery.

• Impairment in intelligence
• Mood and behavior changes
• Residual neurological deficits
• Extrapyramidal symptoms (JE)
• Hyponatremia (esp St. Louis encephalitis)
• Encephalopathy
• Mononeuropathy
• Flaccid paralysis
• SIADH (St louis encephalitis)

Patients with viral encephalitis should be admitted to the hospital for supportive care and IV antiviral therapy. They may require intensive care for frequent neurologic exams and/or respiratory support. Early initiation of medical therapy is essential for HSV, the most common cause of viral encephalitis, so all patients with suspected encephalitis should be started empirically on acyclovir as soon as possible.

Viral encephalitis is a serious disorder, and the morbidity and mortality depend on the type of virus and the severity of the infection. Viral encephalitis may primarily involve the brain but has repercussions in many other organs; hence an interprofessional approach in management is key. It has been estimated that a single bout of viral encephalitis can cost upwards of $2 million to the healthcare system. For patients who are untreated, mortality rates can be high. Mortality after herpes encephalitis can range more than 50%, and after western equine encephalitis, children may develop marked behavior changes and seizures. The eastern equine encephalitis can also have crippling effects on children including paralysis, seizures and mental retardation. The recent Zika virus epidemic has resulted in microcephaly in newborn infants. However, mortality is low with the La Crosse and the Venezuelan equine virus. Recent data reveal that the tick-borne encephalitis from the Orient is far more dangerous than the central European tick-borne encephalitis. Patients who acquire the Asian tick-borne encephalitis often have residual seizures for a long time.[15][16][17]

The key to viral encephalitis is prevention. Surveillance of mosquitoes must be done to assess the risk of infectivity. The primary care provider, infectious disease nurse, and pharmacist should educate travelers on how to prevent mosquito bites.

Travelers should wear protective garments to prevent mosquito bite and sleep under a mosquito net. One should also avoid outdoor activities where the risk of tick-borne infections is high. The public has to remove containers of stagnant water from the home surroundings, and insecticide spraying may help. Vaccines are available against the EEE, WEE and VEE. However, their effectiveness is not 100%.[18][19][15]

Given the fact that complications may arise following encephalitis, establishing an interprofessional team to monitor and treat the patient is necessary. In addition to the clinical team, the other members should be therapists, rehab specialists and speech therapists