Expression of human cytomegalovirus components in the braintissues of patients with Rasmussen\u2019s encephalitis

Yao Zhang,Tianfu Li,Changqing Liu,Shuai Chen,Yisong Wang,Jing An,Guoming Luan,Yuguang Guan,Sichang Chen

doi:10.1007/s12250-016-3917-z

Abstract

Rasmussen’s encephalitis (RE) is a rare and severe progressive epileptic syndromewith unknown etiology. Infection by viruses, including human cytomegalovirus (HCMV),has been speculated to be a potential trigger for RE. However, no viral antigenshave been detected in the brains of patients with RE; thus, a possible clinicallinkage between viral infections and RE has not been firmly established. In thisstudy, we evaluated the expression of HCMV pp65 antigen in brain sections from 26patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associationsbetween HCMV infection and clinical parameters. Elevated expression of HCMV pp65protein and DNA was observed in 88.5% (23/26) and 69.2% (18/26) of RE cases,respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity ofHCMV pp65 staining was correlated with a shorter duration of the prodromal stage,younger age of seizure onset, and more severe unilateral cortical atrophy. Elevatedexpression of HCMV pp65 was observed in RE brain tissue and was correlated with theclinical features of RE disease. In summary, our results suggested that HCMVinfection may be involved in the occurrence and progression of RE disease. Thus,further studies are needed to determine whether early treatment with anti-HCMVantibodies could modulate the course of RE.

Highlights

Rasmussen’s encephalitis (RE) is a rare, chronic, progressive neurological syndrome that often occurs inThe etiology and pathogenesis of RE are unclear (Varadkar et al, 2014)
Since various pathological characteristics observed in the brains of patients with RE, such as lymphocyte infiltration, neuron loss, vascular cuffing, and microgliosis (Pardo et al, 2004), are similar to those observed in viral encephalitis, virus infection has been proposed to be an important cause of RE (Rasmussen et al, 1958)
This hypothesis was supported by data from previous studies in which nucleic acids of human cytomegalovirus (HCMV), herpes simplex virus 1(HSV-1), and Epstein-Barr virus (EBV) were detected in the brain tissues of patients with RE by in situ hybridization or polymerase chain reaction (PCR), viral antigen has not been reliably detected (Walter and Renella, 1989; Power et al, 1990; Jay et al, 1995)

Summary

Introduction

Rasmussen’s encephalitis (RE) is a rare, chronic, progressive neurological syndrome that often occurs inThe etiology and pathogenesis of RE are unclear (Varadkar et al, 2014). Since various pathological characteristics observed in the brains of patients with RE, such as lymphocyte infiltration, neuron loss, vascular cuffing, and microgliosis (Pardo et al, 2004), are similar to those observed in viral encephalitis, virus infection has been proposed to be an important cause of RE (Rasmussen et al, 1958) This hypothesis was supported by data from previous studies in which nucleic acids of human cytomegalovirus (HCMV), herpes simplex virus 1(HSV-1), and Epstein-Barr virus (EBV) were detected in the brain tissues of patients with RE by in situ hybridization or polymerase chain reaction (PCR), viral antigen has not been reliably detected (Walter and Renella, 1989; Power et al, 1990; Jay et al, 1995). Additional, more comprehensive investigations are needed to identify the presence of viral antigens and nucleic acids in the brain tissues of patients with RE, and the clinical relevance of these findings needs to be carefully analyzed

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