Impaired Cerebral Hemodynamics and Their Association with Autonomic Dysfunction in Epilepsy: A Transcranial Doppler–Based Case–Control Study
Introduction; - Epilepsy is increasingly recognized as a disorder involving widespread neural networks, including the central autonomic network (CAN) and cerebrovascular regulatory circuits. Impairment in dynamic cerebral autoregulation and altered cerebrovascular reactivity may contribute to peri-ictal instability, cognitive decline, and elevated risk of Sudden Unexpected Death in Epilepsy (SUDEP). However, studies examining integrated autonomic and cerebrovascular physiology in epilepsy are limited. Aim: To evaluate cerebral hemodynamic indices—mean cerebral artery velocity (MCAv), breath-holding index (BHI), autoregulatory slope index (ASI), and cerebrovascular resistance (CVR)—in adults with epilepsy and to examine their relationship with autonomic dysfunction using the modified Composite Autonomic Scoring Scale (mCASS). Methods: In this prospective case–control analysis, 180 adults with epilepsy and 180 matched healthy controls underwent standardized autonomic testing and transcranial Doppler (TCD) assessment. TCD parameters included baseline MCAv, BHI (rebreathing CO₂ response), ASI (Valsalva Phase II autoregulation), and CVR (MAP/MCAv during tilt). Autonomic function was scored using mCASS. Statistical analysis employed Mann–Whitney U, Kruskal–Wallis, and Spearman correlation tests. Results: Epilepsy patients demonstrated significantly impaired cerebral hemodynamics compared with controls: lower MCAv (48.2 ± 9.3 vs 55.7 ± 8.6 cm/s, p < 0.001), reduced BHI (0.82 ± 0.21 vs 1.14 ± 0.29, p < 0.001), more negative ASI (–18.3 ± 9.1 vs –9.8 ± 6.7, p < 0.001), and higher CVR (2.12 ± 0.31 vs 1.78 ± 0.22, p < 0.001). Among epilepsy subtypes, temporal lobe epilepsy (TLE) showed the greatest impairment, followed by idiopathic generalized epilepsy (IGE), and then controls (p < 0.001 for all comparisons). Significant correlations were observed between autonomic dysfunction and cerebral hemodynamics. Higher mCASS scores correlated with lower BHI (r = –0.52), more negative ASI (r = 0.49), and elevated CVR (r = 0.54) (all p < 0.001). Conclusion: Epilepsy is associated with substantial disruption of cerebral hemodynamics, particularly reduced cerebrovascular reactivity and impaired autoregulation. These disturbances strongly correlate with the severity of autonomic dysfunction, suggesting shared neuropath physiological mechanisms within CAN–vascular circuits. TCD-based hemodynamic evaluation may provide critical insights into SUDEP risk, epilepsy severity, and neurovascular health in epilepsy patients.