Introduction to Encephalitis in Children

Encephalitis is one of the most challenging illnesses in medicine. There are a myriad of potential infectious agents and few specific tests to uncover the culprit. Compounding this diagnostic challenge is the lack of effective therapy for most forms of encephalitis. As polymerase chain reaction (PCR) technology becomes more widely available, our ability to diagnose the various causes of encephalitis will likely improve.

Definition
Encephalitis is an inflammation or infection of the parenchyma of the brain sometimes accompanied by infection of the surrounding tissues (meningoencephelitis), specifically the pia mater, the arachnoid, and the cerebrospinal fluid (CSF).

Causative Agents
Yearly outbreaks of encephalitis occur in the warm months in the United States and usually are associated with insect vectors, such as mosquito-born arboviruses. Eastern equine, Western equine, St. Louis encephalitis, and La Crosse are the most common arboviruses causing encephalitis. By the summer of 2005, West Nile virus had been identified in every state in the continental United States. Although several states documented only avian infections (Washington state, West Virginia, Vermont, New Hampshire, and Maine), it is only a matter of time before the human population is affected. Sporadic cases of herpes simplex encephalitis (HSV) occur year-round and always should be included in the differential of encephalitis, especially since it is one of the few treatable causes of infectious encephalitis. Rickettsial (Rocky Mountain spotted fever; RMSF) and spirochetal (Lyme disease, syphilis) agents may have encephalitis as part of the disease process.

Incidence
Although the true incidence of encephalitis is unknown, it has been estimated that in the United States there are about 20,000 cases per year for all types of encephalitis.

Mode of Transmission
The seasonal forms of arboviral encephalitis cycle in birds and small mammals and are transmitted to humans and domestic animals by insect vectors, most commonly mosquitoes. Direct person-to-person spread does not occur.

Incubation Period
Incubation period depends on the specific virus and varies from 3 days to 14 days after exposure.

Clinical Manifestations
The classic presentation of encephalitis is that of increasing lethargy, behavioral changes, and neurologic deficits. There is often a preceding “viral” prodrome consisting of headache, fever, and vomiting. The presence of gastrointestinal symptoms may be suggestive of enteroviral infection. Seizures are a common element at presentation.

Careful physical examination may reveal the presence of insect bites (arboviruses, Lyme disease, RMSF), rashes (RMSF, enteroviruses), scratches/bites (cat-scratch disease, possibly rabies), or vesicular lesions (enteroviruses or HSV). Nuchal rigidity is indicative of concomitant meningitis (i.e., meningoencephalitis), but is not always present. Focal neurologic deficits, if present, can suggest the area(s) of inflammation in the brain. Progression to stupor and coma often is rapid, necessitating intubation and ventilatory support.

In encephalitis, the laboratory should be used in an effort to make a specific diagnosis. However, despite careful evaluation, only a small percentage of encephalitis cases have an etiologic agent established .

CSF examination may reveal a modest pleocytosis with normal or elevated opening pressure and protein, and normal or depressed glucose levels. There may be no white or red cells in the spinal fluid because the infection is present in the brain parenchyma, not the meninges. CSF should be sent for HSV PCR, and for enteroviral PCR if the season is appropriate. A specific diagnosis for either etiology allows discontinuation of antibiotics.

Electroencephalography often reveals a focal periodicity against a diffuse, slow-wave background pattern.

Differential Diagnosis
The differential diagnosis of encephalitis includes other infections of the central nervous system as well as noninfectious causes.

• Central nervous system depression may occur in the context of sepsis, particularly severe sepsis in a young child. 
• Brain abscesses, spinal abscesses, and subdural or subarachnoid infection may present with encephalopathy. 
• Postinfectious central nervous system syndromes such as acute cerebellar ataxia, acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome may also mimic encephalitis, particulary if the child has a low-grade fever.
• Noninfectious etiologies to consider in patients with encephalopathic presentation must include ingested toxins or drugs. Some of the more common street drugs (phencyclidine [PCP], lysergic acid diethylamide [LSD], cocaine, and amphetamines) may present with fever and altered mentation in an adolescent and be mistaken for early encephalitis. Collagen vascular disorders, particularly systemic lupus erythematosus, can present with central nervous system signs.