Challenges in the Diagnosis and Management of Neonatal Herpes Simplex Virus Encephalitis

Abstract

Research during the past 30 years has transformed our approach to the diagnosis and management of neonatal herpes simplex virus (HSV) encephalitis.1 Nevertheless, early diagnosis of HSV encephalitis and its long-term management continue to challenge practitioners, primarily because of the paucity of clinical symptoms and laboratory abnormalities associated with early disease.1–5 Fonseca-Aten et al,6 in this issue of Pediatrics , report on an infant who developed symptomatic HSV encephalitis during administration of daily oral acyclovir (ACV) given to “suppress” HSV disease. Elements of this case spotlight issues peculiar to HSV that may assist pediatric practitioners in the timely diagnosis and effective management of neonatal HSV encephalitis.1,5,7–10 Neonatal HSV infections are often categorized into 1 of 3 syndromes: skin-eye-mouth, disseminated, and central nervous system (CNS). However, these disease patterns are not discreet, with encephalitis often due to the extension of skin-eye-mouth or disseminated disease. HSV encephalitis affects the brain cortex or, less commonly, the brainstem.1 HSV replication in the cortex of infants can be clinically unapparent,1–5 because cortical function is not required for most activities of infants. HSV CNS infection can be difficult to diagnose by examination of cerebral spinal fluid (CSF), because the meninges may not be significantly inflamed. This is particularly true in the early phases of the illness, during which treatment can have the most impact on reducing long-term neurologic morbidity.1,5,7 Also problematic is that reactivation of HSV in the CNS, which is lytic to the brain parenchyma, may be asymptomatic in infants, with neurologic impairment becoming apparent by 6 to 12 months of age.1,11 The infant reported by Fonseca-Aten et al6 was first diagnosed with encephalitis after seizures at 3 months of … Address correspondence to Lisa M. Frenkel, MD, Departments of Pediatrics and Laboratory Medicine, University of Washington and Children’s Hospital, 307 Westlake Ave N, Suite 300, Room 330, Seattle, WA 98109. E-mail: lfrenkel{at}u.washington.edu