Serum Levels of Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 Are Associated With Autonomic Dysfunction and Impaired Cerebral Autoregulation in Patients With Epilepsy.

Shu-Fang Chen,Meng-Han Tsai,Teng-Yeow Tan,Yao-Chung Chuang,Wan-Chen Tsai,Hung-Yi Chuang,Shuo-Bin Jou,Chi-Ren Huang,Chiung-Chih Chang,Nai-Ching Chen

doi:10.3389/fneur.2018.00969

Abstract

Background: Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) may regulate the autonomic nervous system (ANS) in epilepsy. The present study investigated the role of IGF-1 and BDNF in the regulation of autonomic functions and cerebral autoregulation in patients with epilepsy.Methods: A total of 57 patients with focal epilepsy and 35 healthy controls were evaluated and their sudomotor, cardiovagal, and adrenergic functions were assessed using a battery of ANS function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial doppler during the breath-holding test and the Valsalva maneuver. Interictal serum levels of BDNF and IGF-1 were measured with enzyme-linked immunosorbent assay kits.Results: During interictal period, reduced serum levels of BDNF and IGF-1, impaired autonomic functions, and decreased cerebral autoregulation were noted in patients with epilepsy compared with healthy controls. Reduced serum levels of BDNF correlated with age, adrenergic and sudomotor function, overall autonomic dysfunction, and the autoregulation index calculated in Phase II of the Valsalva maneuver, and showed associations with focal to bilateral tonic-clonic seizures. Reduced serum levels of IGF-1 were found to correlate with age and cardiovagal function, a parameter of cerebral autoregulation (the breath-hold index). Patients with a longer history of epilepsy, higher seizure frequency, and temporal lobe epilepsy had lower serum levels of IGF-1.Conclusions: Long-term epilepsy and severe epilepsy, particularly temporal lobe epilepsy, may perturb BDNF and IGF-1 signaling in the central autonomic system, contributing to the autonomic dysfunction and impaired cerebral autoregulation observed in patients with focal epilepsy.

Highlights

The interaction between epileptic seizures and the autonomic nervous system (ANS) is very complex [1]
With respect to gender and age, there were no significant differences between patients and control subjects
Our results indicate a possible role for Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) in regulation ANS functions and cerebral autoregulation in patients with epilepsy

Summary

Introduction

The interaction between epileptic seizures and the autonomic nervous system (ANS) is very complex [1]. Epileptic seizures, which involve the propagation of abnormal neuronal electrical activities, may interact with the ANS through central autonomic centers and contribute to the regulation of autonomic activity [1, 2]. Epilepsy can present with autonomic dysfunction during seizures [3]. Manifestations of autonomic changes in cardiovascular [2, 4, 8] and respiratory [9] function, and the dysfunction of sympathetic-mediated cerebral autoregulation [10] have been suggested as possible mechanisms underlying SUDEP. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) may regulate the autonomic nervous system (ANS) in epilepsy. The present study investigated the role of IGF-1 and BDNF in the regulation of autonomic functions and cerebral autoregulation in patients with epilepsy

Methods

Results

Conclusion