Brain Biopsy in Cases of Neonatal Herpes Simplex Encephalitis

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Abstract
Neonatal herpes simplex encephalitis (HSE) can represent a difficult diagnostic problem when it occurs without concomitant mucocutaneus lesions and usually requires brain biopsy for diagnosis. Asymptomatic for the initial 2 to 4 weeks of life, the three infants we describe with localized HSE came to medical attention only because they developed persistent seizures and other nonspecific symptoms. Lumbar spinal fluid obtained from these children at clinical presentation showed an encephalitic pattern. Radionuclide brain scans revealed focal uptake of isotope in a variety of cortical areas, and electroencephalograms (EEGs) demonstrated repetitive, high amplitude, polyphasic sharp waves arising from analogous regions. Computed tomography (CT) showed nonspecific ill-defined areas of low density or contrast enhancement that did not correlate well with radionuclide, EEG, or clinical findings in two neonates. No infant had predominant temporal lobe involvement. Because these data suggested a multifocal, encephalitic process, all three infants underwent brain biopsy. A widespread infiltration of leukocytes and macrophages was observed in each specimen, and abundant intranuclear inclusions were present. Electron microscopy revealed abundant herpesvirus particles, and herpes simplex virus (HSV) was subsequently isolated from each sample. From our observations and our review of the literature, we propose the following criteria as indications for brain biopsy: Brain biopsy is warranted to rule out HSE when a neonate presents with seizures, cerebrospinal fluid mononuclear pleocytosis with a negative gram stain, and focal, cortical disease on EEG and radionuclide scan. Additionally, a history of maternal genital HSV infection is helpful but may be absent, the child may have an asymptomatic interval after birth, the CT data can be nonspecific, and, in contrast to adults and older children, neonates with HSV typically lack temporal lobe involvement. Early diagnosis combined with prompt institution of appropriate antiviral therapy could reduce the mortality and morbidity from this destructive illness.

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