Chronic active herpes simplex type 2 encephalitis in an asymptomatic immunocompetent child

Abstract

A unique form of chronic, active, granulomatous herpes simplex type 2 encephalitis is described in an asymptomatic, immunocompetent 8-year-old girl who acquired the virus as a neonate. The extensive, bilateral cerebral parenchymal involvement was discovered incidentally. Diagnosis was confirmed by a combination of serial neuroimaging, brain biopsy, and quantitative polymerase chain reaction targeted to DNA sequences in the glycoprotein G gene, allowing differentiation between herpes simplex virus types 1 and 2. The clinical course over a 5-year period, treatment with intermittent intravenous steroids, and daily valacyclovir, diagnostic imaging, and laboratory studies are reviewed in detail. This form of herpes simplex virus type 2 encephalitis hasn't been described previously and is significant because of its prolonged indolent course, absence of neurological findings or suggestive history, and benign behavior in this child, who is now 14 years old. The authors believe this entity can be unsuspected and underdiagnosed in the general pediatric population, especially in those with a prior maternal history of herpes simplex virus type 2 infection.

Figure 1

Axial computed tomography (CT) (A and B) and magnetic resonance imaging (MRI) scans (C and D) at initial presentation showing extensive right hemispheric white matter abnormalities with bilateral frontal (A) and right temporal (B) calcifications. Postcontrast T1-weighted MR images showing postcontrast enhancement (C and D). Compare Figure 1D with Figure 2A-1.

Figure 2

Selected serial axial fluid attenuation inversion recovery magnetic resonance images (MRIs) showing evolution of herpes simplex virus type 2 encephalitis over a 48-month period. The number of months since initial diagnosis is shown in the lower right-hand corner of each image. The first column of images represent the appearance of the brain at the time of diagnosis. Each row of images A through E depicts the brain at the same anatomical level: (A) superior to the body of the corpus callosum, (B) lateral ventricles at the splenium and genu of the corpus callosum with bifurcation of the fornix, (C) through the thalamic nuclei and genu of the internal capsule, (D) through the basal ganglia and superior cerebellar cistern, and (E) temporal lobes and mesencephalic red nuclei.

Figure 3

(A) Lesion biopsy site showing diffuse, chronic, granulomatous inflammation. Scattered areas of necrosis are present (arrows). Many multinucleated giant cells are seen—representative examples being highlighted with arrowheads. Hematoxylin and eosin stain × 100. Scale bar 100 μm (B) higher-power view of the lesion biopsy site showing chronic granulomatous inflammation and large, multinucleated giant cells (arrows). Hematoxylin and eosin stain × 600. Scale bar 100 μm.

Figure 4

Detection and quantification of herpes simplex virus types 1 and 2 by quantitative polymerase chain reaction. DNA oligo primers are targeted to sequences in the glycoprotein G gene, which are highly specific for each virus and easily differentiates between the two. (A) Linear view of SYBR Green fluorescence PCR amplification of target DNA in the patient’s sample and in herpes simplex virus DNA standards. (B) The standard curve used to calculate the number of herpes simplex type 2 DNA copies in the patient’s sample is derived from a 10-fold serial dilution of a known herpes simplex type 2 DNA concentration provided by Advanced Biotechnologies. (C) The final products after 40 cycles of amplification on the ABI 7500, separated by electrophoresis on a 1% agarose gel.