Changes in cerebrospinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures.

Naoyuki Tanuma,Rie Miyata,Akihisa Okumura,Masaya Kubota,Keisuke Nakajima,Masaharu Hayashi,Shin-Ichiro Hamano

doi:10.1155/2014/564091

Abstract

To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n = 16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n = 10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.

Highlights

Viral infection-associated acute encephalopathy/encephalitis is a serious complication with neurological sequelae
We measured the levels of oxidative stress markers (8-hydroxy-2󸀠-deoxyguanosine: 8-OHdG and hexanoyl-lysine adduct: hexanoyllysine adduct (HEL)), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV6-associated encephalopathy and complex febrile seizure (FS) associated with human herpesvirus-6 (HHV-6) infection
All patients with complex FS associated with HHV-6 infection were without neurological sequelae

Summary

Introduction

Viral infection-associated acute encephalopathy/encephalitis is a serious complication with neurological sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a new subtype characterized by a prolonged febrile seizure (FS) on day 1, which usually lasts longer than 30 min, as the initial neurological symptom [1, 2]. Recent studies demonstrated three potential major pathomechanisms of viral associated encephalopathy: metabolic error, cytokine storm, and excitotoxicity [4]. Mediators of Inflammation oxidative stress was confirmed to play a role in adultonset neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis [6, 7]. We measured the levels of oxidative stress markers (8-hydroxy-2󸀠-deoxyguanosine: 8-OHdG and hexanoyl-lysine adduct: HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV6-associated encephalopathy and complex FS associated with HHV-6 infection

Patients and Methods

Results

Discussion