Eilbes Melissa, Gallo Alexander, Osmani Wasif A, Bittencourt-Silva Paloma, Manis Anna D, Hodges Matthew R
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Epilepsia. 2025 Jul;66(7):2578-2591. doi: 10.1111/epi.18360. Epub 2025 Mar 11.
Patients with uncontrolled epilepsy are at high risk for sudden unexpected death in epilepsy (SUDEP), which likely results from a pathological, seizure-induced disruption of vital physiological systems. The objective of this study was to characterize seizure-induced physiological dysfunction leading to death in SS rats and determine the importance of time of day of seizures regarding mortality rates.
Male and female SS rats were surgically implanted with an arterial pressure telemeter and chronically housed in a custom plethysmograph. This setup allowed for continuous measurement of breathing, blood pressure, heart rate, body temperature, and behavior before and during a 10-day seizure protocol. Audiogenic seizure inductions were time-restricted to the early (8-10 a.m.) or late (4-6 p.m.) inactive periods. We assessed acute and chronic physiological functions before, during, and after repeated seizures in both survival and death events.
Time-restricted audiogenic seizures in SS rats induced transient disruptions in breathing, blood pressure, heart rate, and temperature, which eventually normalized in both survival and death events. However, after returning to physiological normalization, death was preceded by subsequent spontaneous physiological decompensation, characterized by altered breathing patterns, hypotension, and hypothermia. Finally, seizure-induced mortality was highest during the early and late inactive periods compared to historical data without time restriction and was greater in females than in males but did not correlate with prior seizure severity or number.
Understanding the causes of SUDEP in patients with epilepsy is limited due to unpredictable and heterogeneous circumstances and incomplete physiological data. This study provides insights into seizure-induced and delayed physiological decompensation leading to SUDEP-like events, demonstrating a need for additional prospective, integrated physiological measures for a more complete picture of SUDEP.
癫痫控制不佳的患者发生癫痫猝死（SUDEP）的风险很高，这可能是由病理性的、癫痫发作引起的重要生理系统紊乱所致。本研究的目的是描述导致SS大鼠死亡的癫痫发作引起的生理功能障碍，并确定癫痫发作时间对死亡率的重要性。
对雄性和雌性SS大鼠进行手术植入动脉压遥测仪，并长期饲养在定制的体积描记器中。这种设置允许在为期10天的癫痫发作方案之前和期间连续测量呼吸、血压、心率、体温和行为。听源性癫痫发作诱导被限制在早期（上午8 - 10点）或晚期（下午4 - 6点）的非活动期。我们评估了存活和死亡事件中反复癫痫发作之前、期间和之后的急性和慢性生理功能。
SS大鼠的限时听源性癫痫发作引起呼吸、血压、心率和体温的短暂紊乱，在存活和死亡事件中最终都恢复正常。然而，在恢复到生理正常状态后，死亡之前会出现随后的自发性生理失代偿，其特征为呼吸模式改变、低血压和体温过低。最后，与无时间限制的历史数据相比，癫痫发作诱导的死亡率在早期和晚期非活动期最高，并且雌性高于雄性，但与先前癫痫发作的严重程度或次数无关。
由于情况不可预测且异质性以及生理数据不完整，对癫痫患者中SUDEP原因的理解有限。本研究为导致类似SUDEP事件的癫痫发作诱导和延迟生理失代偿提供了见解，表明需要额外的前瞻性、综合生理测量以更全面地了解SUDEP。
