Pediatric Herpes Simplex Virus Encephalitis

Abstract

Knowledge on pediatric herpes simplex virus encephalitis is limited. Here we summarize 6 neonates and 32 children diagnosed by polymerase chain reaction (n = 37) or serological studies (n = 1), respectively. Diagnosis was difficult, as only 15 patients presented neurologic symptoms. Moreover, cerebrospinal fluid glucose, protein, and leukocytes were normal in 6 patients. Subsequently, all but 2 showed neurologic symptoms. Diffusion-weighted neuroimaging was the most sensitive early imaging method. Despite acyclovir treatment, 8 patients experienced early relapses, showing movement abnormalities, impaired vigilance, and seizures. Diffuse white matter changes, found in 3 of 5 relapse patients on neuroimaging, and a negative cerebrospinal fluid herpes simplex virus polymerase chain reaction suggested inflammatory processes. All relapse patients were again treated with acyclovir, and 3 responded to additional corticosteroid treatment. Whereas outcome after relapses was poor, overall outcome was good. No child died; 14 were asymptomatic at discharge, and neuroimaging remained normal in 7 of 30 patients studied.

Childhood encephalitis: relationship between diffusion abnormalities and clinical outcome

“…In contrast to the previous studies revealing an association of poor outcome with imaging abnormalities [2][3][4][5], our results did not support such an association in the majority of patients. This discrepancy may be explained by our use of a comparatively more systematic imaging scoring method covering the entire brain, various and different causative agents in our patients, and a relatively large number of patients in our cohort.…”

“…We did not directly compare the outcome of the LRD (+) group with that of the LRD (−) group, because a potential interaction may exist between diffusion of the lesions and the extent of the lesions, which was represented by the imaging score in our study. The extent of abnormality is generally believed to be related to the outcome of patients in encephalitis [2][3][4][5]. In order to delineate such potential interaction, we used logistic regression analysis to evaluate the association of LRD with the outcome of these two groups of patients.…”

“…Although the mortality of patients with encephalitis has declined over the years, patients who have recovered from encephalitis often live with significant neurological sequelae. The extent of neuroimaging abnormalities has been correlated with patient outcome, revealing that the patients with a worse outcome had abnormal MR findings [2], diffuse lesions [3], deep white matter involvement [4], and brain stem involvement [5].…”

Safety of High-dose Acyclovir in Infants With Suspected and Confirmed Neonatal Herpes Simplex Virus Infections

“…8 A retrospective study of infants and children found that 50% of the 6 neonates and 22% of the 32 non-neonates had seizures at the time of presentation. 20 Another retrospective study of 26 infants with CNS HSV disease found that seizures occurred in 54% of patients; in 35%, the seizures were present at presentation. 21 A clinical trial that enrolled 186 infants with neonatal HSV disease found that seizures were present in 57% of infants with CNS disease and in 22% of infants with disseminated disease; overall 27% of infants had seizures at presentation.…”

Absence of Pleocytosis Alone Is Insufficient To Exclude Encephalitis Caused by Herpes Simplex Virus in Children

“…Regarding pleocytosis, the 2012 International Encephalitis Consortium consensus statement affirms that "CSF may be devoid of cells in immunocompromised patients and early in the course of infection" (4). Furthermore, case series of nonneonatal pediatric HSE estimate that the initial CSF examination may not demonstrate pleocytosis in as many as 4% to 26% of children (not restricted to those Ͻ 2 years old) in whom HSE is subsequently confirmed (2,(5)(6)(7).…”