Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B.

Misa Miyake,Yoshiyuki Takahashi,Jun Natsume,Yoko Sakaguchi,Seiji Kojima,Tetsushi Yoshikawa,Hiroki Miura,Yoshiki Kawamura,Shigetaka Suzuki,Hiroshi Toyama,Masaharu Tanaka,Naoko Ishihara

doi:10.3390/microorganisms9040776

Abstract

The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippocampus was performed. Of the 107 patients that received HSCT at Nagoya University Hospital Between July 2008 and April 2014, 20 were eligible for volumetric analysis. Eight patients had HHV-6B infection, of whom two had encephalopathy at the time of HHV-6B infection. None of the 12 patients without HHV-6B infection had encephalopathy. The median ratio of the right hippocampal volume from before to after transplantation was 0.93 in patients with HHV-6B infection and 1.02 in without HHV-6B infection (p = 0.007). The median ratio of the left hippocampal volume ratio in patients with and without HHV-6B infection was 0.92 and 1.00, respectively (p = 0.003). Among the eight patients with HHV-6B infection, four had a marked reduction in hippocampal volume (volume ratio < 0.90). Only one of these patients had neurological symptoms at the time of HHV-6B infection. The reduction in the hippocampal volume ratio was higher in pediatric HSCT recipients with HHV-6B infection than those without viral infection. Neurological follow-up may be required for pediatric HSCT recipients with HHV-6B infection.

Highlights

Primary human herpesvirus 6B (HHV-6B) infection can cause exanthem subitum [1]. the disease is a benign febrile illness in young children, central nervous system (CNS) complications such as febrile seizures [2,3,4] and encephalitis [5,6,7,8] can sometimes occur
HHV-6B is a major cause of post-transplant acute limbic encephalitis (PALE) [21,22,23,24]
Hippocampal MRI volumetric analysis is used to elucidate the pathophysiology of various types of neurological diseases, such as mesial temporal lobe epilepsy, Alzheimer’s disease, and post-traumatic stress disorder [38,39,40]

Summary

Introduction

Primary human herpesvirus 6B (HHV-6B) infection can cause exanthem subitum [1]. the disease is a benign febrile illness in young children, central nervous system (CNS) complications such as febrile seizures [2,3,4] and encephalitis [5,6,7,8] can sometimes occur. Primary human herpesvirus 6B (HHV-6B) infection can cause exanthem subitum [1]. HHV-6B establishes latency in various body sites, including the CNS [9,10,11]. HHV-6B can reactivate in immunocompromised patients, such as hematopoietic stem cell transplantation (HSCT) recipients [12,13,14,15,16]. Viral reactivation may be associated with a variety of diseases after transplantation [12,15,17,18,19,20]. HHV-6B is a major cause of post-transplant acute limbic encephalitis (PALE) [21,22,23,24]. It has been suggested that HHV-6B is involved in the pathogenesis of temporal lobe epilepsy, a type of refractory adult epilepsy [25,26]

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