Neurologic Sequelae Present in Children Following HSV-Associated Encephalitis

Among children who develop encephalitis associated with a herpes simplex virus (HSV) infection, approximately half present with some form of neurologic sequelae, according to findings from a systematic review and meta-analysis published in BMC Infectious Diseases.

Encephalitis is defined as “an inflammation of the cerebral parenchyma characterized by clinical manifestations associated with neurological dysfunction.” Signs and symptoms, including altered mental state, neurologic deficits, fever, and headaches, which typically present acutely, should be explored for a possible diagnosis of encephalitis. The etiology of encephalitis can be infectious or noninfectious, with viruses being responsible for the majority of cases when an infectious cause is identified. Of these viruses, HSV is reported most often among preschool children.

Researchers sought to evaluate the general prevalence and types of neurologic sequelae reported among children following a case of HSV-associated acute viral encephalitis. A systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, with the protocol registered in the International Prospective Register for Systemic Reviews (PROSPERO).

They included observational studies of children and adolescents between 2 months and 18 years of age who had experienced an HSV infection, as confirmed by laboratory testing, and for whom the studies described data about neurologic sequelae following a bout of acute viral encephalitis. Review articles, case series, studies with less than 10 patients with HSV infection, and letters to the editor were all excluded from the meta-analysis. All articles published prior to 1980 were excluded as well, because acyclovir therapy had not yet been established as a treatment for HSV infection. A random effects model was utilized for the meta-analysis of general prevalence and types of neurologic sequelae.

To describe the symptoms observed at the onset of encephalitis, the researchers considered any of the following symptoms reported in the primary studies as a change in mental state suggested by encephalitis: disorientation, drowsiness, change of mental state, change in consciousness, and coma. The types of neurologic sequelae described in the studies were classified into 5 major groups: seizures, motor disabilities, visual impairments, mental disabilities, and others (eg, areflexia, hyperreflexia, sensory disturbances, and cranial nerve palsy).

Overall, 2827 articles were selected in the initial search, and 9 studies were included in the systematic review and meta-analysis. According to results of the meta-analysis, the general prevalence of neurologic sequelae reported was 50.7% (95% CI, 39.2-62.2). The most commonly reported sequelae were associated with mental disability, with a prevalence of 42.1% (95% CI, 30.0-55.2). In contrast, the least commonly reported sequelae were associated with visual impairment, with a prevalence of 5.9% (95% CI, 2.2-14.6).

Several limitations of the systematic review and meta-analysis should be noted. All of the studies included in the meta-analysis were retrospective in design, which may lead to information and/or memory bias. Additionally, the report on type of neurologic sequelae varied among the studies. In fact, most of the studies specified the types of sequelae in a descriptive manner; however, 2 of the studies only classified the severity of the neurologic sequelae presented by the patients.

“Although acute viral encephalitis has diagnostic criteria, diagnostic tests, and
well established treatment, we also perceive a considerable number of patients with neurological sequelae that are scarcely explored in the studies, which usually focus on the acute phase of the infection,” the researchers acknowledged.

They concluded that “Quality prospective studies, with representative samples and with standardization of type and time of the outcome are needed to advance in interventions that can influence the evolution of this disease and improve the future prognosis of these children.”