Melone Marie Anne, Sainju Rup K, Dragon Deidre N, Winnike Harold B, Vilella Laura, Ochoa-Urrea Manuela, Li Xiaojin, Lhatoo Samden D, Wendt Linder H, Ten Eyck Patrick, Richerson George B, Gehlbach Brian K
Department of Pulmonary, Thoracic Oncology and Respiratory Intensive Care, Rouen University Hospital, Rouen, France; Normandie Univ, UNIROUEN, UR3830 GRHVN, Institute for Research and Innovation in Biomedicine, Rouen, France.
Department of Neurology, University of Iowa, Iowa City, IA, United States.
Seizure. 2025 Jun 17;131:95-104. doi: 10.1016/j.seizure.2025.06.007.
Autonomic function is modulated by the respiratory network. We therefore hypothesized that in persons with epilepsy (PWE), generalized convulsive seizures (GCS) would induce greater heart rate variability (HRV) and parasympathetic activation in patients with low interictal central CO chemosensitivity (measured with the hypercapnic ventilatory response, HCVR). We further hypothesized that postictal HRV would be associated with severity of postictal hypercapnia and hypoxemia.
We performed a retrospective analysis of PWE admitted to an epilepsy monitoring unit for video-EEG study and experienced GCS. Time synchronized video-EEG, ECG, respiratory effort, and airflow were continuously measured along with transcutaneous CO and O saturation. Interictal HCVR was measured using a modified hyperoxic rebreathing technique. Postictal respiration was analyzed and included the magnitude and duration of CO rise and O desaturation. HRV measures were derived from 5-minute artifact-free ECG recordings from interictal and postictal periods. Relationships between HRV and respiratory variables were analyzed using Spearman's correlation and multivariate models.
Twenty-six patients had both a GCS and an interictal HCVR. Mean age was 36.6 (±11.8) years and mean duration of epilepsy 16.2 (±12.0) years. Interictal HCVR slope varied from -0.13 to 5.2 (median 2.1) L/min/mm Hg and was not related to postictal RMSSD or the change in RMSSD (interictal wake - postictal) induced by GCS (p > 0.11). In contrast, duration of postictal hypercapnia and oxygen desaturation were both significantly correlated with overall postictal HRV (SDNN) and with multiple HRV measures of parasympathetic tone (RMSSD, HF power, Cardiac Vagal Index). In multivariate analyses, duration of postictal oxygen desaturation was positively associated with increased postictal RMSSD (mean ratio 1.09, 95 % CI 1.04-1.14, p < 0.01).
Postictal ventilation and oxygenation are tightly coupled to multiple measures of heart rate variability, consistent with respiratory modulation of the autonomic nervous system. Patients with more severe postictal respiratory depression exhibit greater parasympathetic activity after GCS even while the frequent occurrence of postictal tachycardia suggests a concomitant increase in sympathetic activity. These results have implications for the interpretation of postictal bradycardia and respiratory dysfunction and their relationships to sudden unexpected death in epilepsy.
自主神经功能受呼吸网络调节。因此，我们推测在癫痫患者（PWE）中，全面性惊厥发作（GCS）会在发作间期中枢CO化学敏感性较低（通过高碳酸通气反应，HCVR测量）的患者中诱发更大的心率变异性（HRV）和副交感神经激活。我们进一步推测发作后HRV将与发作后高碳酸血症和低氧血症的严重程度相关。
我们对入住癫痫监测单元进行视频脑电图研究并经历GCS的PWE进行了回顾性分析。同步记录视频脑电图、心电图、呼吸努力和气流，同时测量经皮CO和氧饱和度。发作间期HCVR采用改良的高氧再呼吸技术测量。分析发作后的呼吸情况，包括CO升高和氧饱和度下降的幅度和持续时间。HRV测量值来自发作间期和发作后的5分钟无伪迹心电图记录。使用Spearman相关性分析和多变量模型分析HRV与呼吸变量之间的关系。
26例患者既有GCS又有发作间期HCVR。平均年龄为36.6（±11.8）岁，癫痫平均病程为16.2（±12.0）年。发作间期HCVR斜率在-0.13至5.2（中位数2.1）L/min/mm Hg之间，与发作后RMSSD或GCS诱发的RMSSD变化（发作间期清醒 - 发作后）无关（p>0.11）。相比之下，发作后高碳酸血症和氧饱和度下降的持续时间均与发作后总体HRV（SDNN）以及副交感神经张力的多种HRV测量值（RMSSD、高频功率、心脏迷走神经指数）显著相关。在多变量分析中，发作后氧饱和度下降的持续时间与发作后RMSSD增加呈正相关（平均比值1.09，95%CI 1.04 - 1.14，p<0.01）。
发作后的通气和氧合与心率变异性的多种测量紧密相关，这与自主神经系统的呼吸调节一致。发作后呼吸抑制更严重的患者在GCS后表现出更大的副交感神经活动，尽管发作后心动过速的频繁发生表明交感神经活动也随之增加。这些结果对解释发作后心动过缓和呼吸功能障碍及其与癫痫猝死的关系具有重要意义。
