Autonomic consequences of brief seizures

短暂癫痫发作的自主神经后果

• 批准号: 6562338
• 负责人: MARK G STEWART
• 金额: $ 17.59万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6562338
• 关键词: autonomic disorder; autonomic nervous system; blood pressure; bradycardia; electrocardiography; electrodes; electroencephalography; electromyography; generalized seizures; heart rate; laboratory rat; neuromuscular function; partial seizure; video recording system

DESCRIPTION (provided by applicant): Focal and generalized seizures can influence autonomic nervous system (ANS) function. Flushing, sweating and piloerection are reported in some patients with simple partial seizures. A broader spectrum of autonomic signs, including changes in heart rate and rhythm (most often bradycardia), blood pressure (most often pressure increases), pupillary size, vasomotor and sudomotor activity, GI motility and secretion, is reported in patients with complex partial seizures. Generalized tonic-clonic seizures can be associated with severe increases in blood pressure and changes in heart rate (e.g. complete nodal block). In spite of an apparent pattern of increasing autonomic dysfunction with increasing seizure intensity, sudden death during a seizure is not limited to cases of status epilepticus or even generalized tonic-clonic seizures. It is possible that some seizures, particularly those that result in sudden death, cause dangerous autonomic over-activity. The extent of seizure-induced alterations in autonomic nervous system function, acutely and chronically, has not been well studied. It is not clear whether autonomic changes are entirely secondary to motor manifestations or if autonomic consequences are independent have motor activity, perhaps even being significant in a non-convulsive seizure. The short term goals of this pilot study are to determine experimentally the feasibilty of measuring peripheral parameters related to ANS function before, during and after seizures of different onset (focal vs. generalized) and duration; and to correlate changes with the types of seizures. We have developed a custom chronic recording system for long-term monitoring of blood pressure (BP), electrocardiogram (ECG), and peripheral nerve activity (sympathetic postganglionic axons) in freely-behaving rats to assess changes mediated by the autonomic nervous system. We will determine the feasibility of adapting our system to monitor autonomic parameters during 5 seizure conditions: a) focal seizures; b) focal seizures with secondary generalization; c) primarily generalized seizures; d) status epilepticus; and e) spontaneous seizures in a chronic seizure model. Specifically, we will compare focal with generalized seizures, and primarily generalized with secondarily generalized seizures. In animals that develop spontaneous seizures, we will compare triggered with spontaneous seizures. We will also correlate the duration of electroencephalographic seizure activity with the intensity of motor convulsions. Focal and secondarily generalized seizures will be studied in perirhinal kindled rats. Primarily generalized seizures will be studied in rats exposed to flurothyl gas. Status epileptics and spontaneous seizures will be studied in rats injected with kainic acid. Lastly, we will define whether any changes in autonomic parameters can predict the occurrence of sudden death in the fraction of animals that die during flurothyl-induced seizures. Defining seizure-induced autonomic changes will permit development of specific therapies to reduce or prevent some of the serious acute consequences of seizures, such as sudden death, and will improve understanding of the long-term consequences of repeated seizures.

描述（由申请人提供）： 局灶性癫痫发作会影响自主神经系统（ANS）功能。据报道，一些简单的部分癫痫发作的患者据报道，潮红，出汗和毛毛。在复杂部分癫痫发作的患者中报道了更广泛的自主迹象，包括心率和节奏的变化（最常见于心动过缓），血压（最常见的压力升高），瞳孔大小，血管舒缩和Sudomotor活性，胃肠道运动和分泌。普遍的强直性持续性癫痫发作可能与血压的严重升高和心率变化有关（例如，完全淋巴结障碍）。尽管随着癫痫发作强度的增加而增加了自主性功能障碍的明显模式，但癫痫发作期间的猝死不仅限于癫痫持续状态甚至广义的隆隆声癫痫发作。有些癫痫发作，尤其是导致猝死的癫痫发作会导致危险的自主神灵过度活动。在急性和慢性上，癫痫发作诱导的自主神经系统功能变化的程度尚未得到很好的研究。尚不清楚自主神经的变化是否完全是运动表现的次要，或者自主神经后果是独立的，甚至可能在非震惊的癫痫发作中具有重要意义。这项试验研究的短期目标是通过实验确定与ANS功能相关的外围参数的痛苦，此前，期间和之后发作（焦点与广义）和持续时间的发作之前，之中和之后；并将变化与癫痫发作的类型相关联。我们已经开发了一种定制的慢性记录系统，用于长期监测血压（BP），心电图（ECG）和周围神经活性（交感神经后轴突），以评估自主神经系统介导的变化。我们将确定适应系统以在5个癫痫发作条件下监测自主参数的可行性：a）局灶性癫痫发作； b）具有次级概括的局灶性癫痫发作； c）主要的癫痫发作； d）癫痫持续状态； E）在慢性癫痫发作模型中自发癫痫发作。具体而言，我们将将焦点与广义癫痫发作进行比较，并主要用次要概括性癫痫发作进行概括。在发生自发癫痫发作的动物中，我们将与自发癫痫发作触发的比较。我们还将将脑电图癫痫发作活性的持续时间与运动抽搐的强度相关联。将在周围点燃大鼠中研究焦点和次要的癫痫发作。将在暴露于雌激素的大鼠中研究主要的癫痫发作。将在注射海藻酸的大鼠中研究状态癫痫和自发癫痫发作。最后，我们将定义自主参数的任何变化是否可以预测在氟噻硫基诱导的癫痫发作期间死亡的动物的猝死发生。定义癫痫发作引起的自主神经变化将允许开发特定的疗法，以减少或防止癫痫发作的某些严重急性后果，例如猝死，并将提高人们对重复癫痫发作的长期后果的理解。