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

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.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy

“…A battery of tests comprising a deep breathing test, the Valsalva maneuver test, the head-up tilt test, and the Q-sweat test was performed to conduct standardized ANS evaluations of the adrenergic, cardiovagal, and sudomotor functions in patients [ 30 , 32 , 33 ]. Cardiovagal function was assessed by testing the heart rate (HR) response to deep breathing at a defined rate and to the Valsalva maneuver [ 30 , 34 ]. Sudomotor function was measured using a quantitative sudomotor axon reflex test (QSART) that applies the Q-sweat test [ 30 , 34 , 35 ].…”

“…Cardiovagal function was assessed by testing the heart rate (HR) response to deep breathing at a defined rate and to the Valsalva maneuver [ 30 , 34 ]. Sudomotor function was measured using a quantitative sudomotor axon reflex test (QSART) that applies the Q-sweat test [ 30 , 34 , 35 ]. HR was recorded using a basic three-lead electrocardiogram (ECG; Ivy Biomedical, model 101; Branford, CT, USA).…”

“…BP and ECG were recorded during normal breathing after the patients had undergone a 15 min rest period in the supine position. The sweat output was measured using a Q-sweat device (WR Medical Electronics Co., Stillwater, MN, USA) [ 30 , 35 ].…”

“…However, it is unclear whether cerebral autoregulation becomes impaired in patients with epilepsy who have autonomic dysfunction. In our recent study, the central autonomic system was suggested to be potentially perturbed in patients with long-term and severe epilepsy, particularly temporal lobe epilepsy, thereby contributing to autonomic dysfunction and impaired cerebral autoregulation [ 30 ]. Therefore, we hypothesize that autonomic dysfunction may contribute to impaired cerebral autoregulation in patients with epilepsy.…”

The role of chronobiology in drug-resistance epilepsy: The potential use of a variability and chronotherapy-based individualized platform for improving the response to anti-seizure drugs

“…Chronic or severe epilepsy and, mainly, TLE may disturb BDNF and IGF-1 signaling in the central ANS, leading to autonomic dysfunction and reduced cerebral autoregulation in subjects with focal epilepsy. During the interictal period, lowered levels of BDNF and IGF-1 are associated with decreased autonomic functions and reduced cerebral autoregulation [77].…”