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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2018.00969

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 Chen1, Shuo-Bin Jou2,  Nai Ching Chen1, Hung-Yi Chuang3, Chi-Ren Huang1,  Meng-Han Tsai1, Teng-Yeow Tan1, Wan-Chen Tsai1, Chiung-Chih Chang1 and  Yao-Chung Chuang1*
  • 1Kaohsiung Chang Gung Memorial Hospital, Taiwan
  • 2Mackay Medical College, Taiwan
  • 3Department of Public Health, Kaohsiung Medical University Hospital, Taiwan

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.

Keywords: Epilepsy, autonomic nervous system dysfunction, cerebral autoregulation, Brain-Derived Neurotrophic Factor, Insulin-like growth factor 1

Received: 03 Aug 2018; Accepted: 29 Oct 2018.

Edited by:

Julie Y. Chan, Kaohsiung Chang Gung Memorial Hospital, Taiwan

Reviewed by:

Farida Sohrabji, Texas A&M Health Science Center, United States
Vincenzo Provitera, IRCCS Istituti Clinici Scientifici Maugeri (ICS Maugeri), Italy  

Copyright: © 2018 Chen, Jou, Chen, Chuang, Huang, Tsai, Tan, Tsai, Chang and Chuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yao-Chung Chuang, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833, Taiwan,