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Acute and chronic cardiorespiratory consequences of focal intrahippocampal administration of seizure-inducing agents. Implications for SUDEP
Autonomic Neuroscience ( IF 2.7 ) Pub Date : 2021-08-04 , DOI: 10.1016/j.autneu.2021.102864
Thelma A Lovick 1 , John G R Jefferys 2
Affiliation  

The risk factors for SUDEP are undoubtedly heterogenous but the main factor is the frequency of generalized tonic-clonic seizures with apnoea and/or cardiac abnormalities likely precipitating the lethal event. By its very nature modelling SUDEP experimentally is challenging, yet insights into the nature of the lethal event and precipitating factors are vital in order to understand and prevent fatalities. Acute animal models, which induce status epilepticus (SE), can be used to help understand pathophysiological processes during and following seizures, which sometimes lead to death. The most commonly used method to induce seizures and status epilepticus is systemic administration of an ictogenic agent. Microinjection of such agents into restricted regions within the brain induces a more localised epileptic focus and circumvents the risk of direct actions on cardiorespiratory control centres. Both approaches have revealed substantial cardiovascular and respiratory consequences, including death as a result of apnoea, which may be of central origin, obstructive due to laryngospasm or, at least in genetically modified mice, a result of spreading depolarisation to medullary respiratory control centres.

SUDEP is by definition a result of epilepsy, which in turn is diagnosed on the basis of two or more unprovoked seizures. The incidence of tonic-clonic seizures is the main risk factor, raising the possibility that repeated seizures cause cumulative pathological and/or pathophysiological changes that contribute to the risk of SUDEP. Chronic experimental models, which induce repeated seizures that in some cases lead to death, do show progressive development of pathophysiological changes in the myocardium, e.g. prolongation of QT the interval of the ECG or, over longer periods, ventricular hypertrophy. However, the currently available evidence indicates that seizure-related deaths are primarily due to apnoeas, but cardiac factors, particularly cumulative cardiac pathophysiologies due to repeated seizures, are potential contributing factors.



中文翻译:

癫痫诱导剂局灶性海马内给药的急性和慢性心肺后果。对 SUDEP 的影响

SUDEP 的危险因素无疑是异质的,但主要因素是全身强直阵挛发作的频率,伴有呼吸暂停和/或心脏异常可能诱发致命事件。就其本质而言,对 SUDEP 进行实验建模具有挑战性,但深入了解致命事件的性质和诱发因素对于了解和预防死亡事故至关重要。诱发癫痫持续状态 (SE) 的急性动物模型可用于帮助了解癫痫发作期间和之后的病理生理过程,有时会导致死亡。诱发癫痫发作和癫痫持续状态的最常用方法是全身给药。将此类药物显微注射到大脑内的受限区域会引起更局部的癫痫病灶,并避免对心肺控制中心直接采取行动的风险。这两种方法都揭示了严重的心血管和呼吸系统后果,包括呼吸暂停导致的死亡,呼吸暂停可能是中枢性的,由于喉痉挛导致阻塞,或者至少在转基因小鼠中,是将去极化扩散到延髓呼吸控制中心的结果。

根据定义,SUDEP 是癫痫的结果,而癫痫又是根据两次或两次以上无端癫痫发作来诊断的。强直阵挛发作的发生率是主要的危险因素,这增加了反复发作导致累积性病理和/或病理生理变化的可能性,从而增加了 SUDEP 的风险。慢性实验模型会诱发在某些情况下导致死亡的重复癫痫发作,但确实显示出心肌病理生理学变化的逐渐发展,例如 QT 延长、心电图间隔或在更长的时间内,心室肥大。然而,目前可用的证据表明,与癫痫发作相关的死亡主要是由于呼吸暂停,但心脏因素,特别是反复发作引起的累积心脏病理生理学,是潜在的促成因素。

更新日期:2021-08-05
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