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）： 局灶性和全身性癫痫发作可影响自主神经系统（ANS）功能。在一些单纯部分性癫痫发作的患者中报告了潮红、出汗和竖毛。复杂部分性癫痫发作患者报告了更广泛的自主神经体征，包括心率和节律（最常见的是心动过缓）、血压（最常见的是血压升高）、瞳孔大小、血管扩张和催汗活动、GI运动和分泌的变化。全身强直阵挛性癫痫发作可能与血压严重升高和心率变化（例如完全性淋巴结阻滞）有关。尽管随着癫痫发作强度的增加，自主神经功能障碍明显增加，但癫痫发作期间的猝死并不限于癫痫持续状态或甚至全身强直阵挛性癫痫发作的病例。有些癫痫发作，特别是那些导致猝死的癫痫发作，可能会导致危险的自主神经过度活动。急性和慢性癫痫引起的自主神经系统功能改变的程度还没有得到很好的研究。目前尚不清楚自主神经的变化是否完全继发于运动表现，或者自主神经的后果是否独立于运动活动，甚至可能在非惊厥性癫痫发作中很重要。本初步研究的短期目标是通过实验确定在不同发作（局灶性与全身性）和持续时间的癫痫发作之前、期间和之后测量与ANS功能相关的外周参数的可行性;并将变化与癫痫发作的类型相关联。我们开发了一种自定义的慢性记录系统，用于长期监测自由行为大鼠的血压（BP）、心电图（ECG）和外周神经活动（交感神经节后轴突），以评估自主神经系统介导的变化。我们将确定在5种癫痫发作条件下调整我们的系统以监测自主参数的可行性：a）局灶性癫痫发作; B）局灶性癫痫发作伴继发性全身性癫痫发作; c）主要全身性癫痫发作; d）癫痫持续状态;以及e）慢性癫痫发作模型中的自发性癫痫发作。具体来说，我们将比较局灶性与全身性发作，以及主要全身性与次要全身性发作。在发生自发性癫痫发作的动物中，我们将比较触发性癫痫发作和自发性癫痫发作。我们还将脑电图发作活动的持续时间与运动性惊厥的强度相关联。将在嗅周点燃大鼠中研究局灶性和继发性全身性癫痫发作。将在暴露于氟乙烷气体的大鼠中研究原发性全身性癫痫发作。将在注射红藻氨酸的大鼠中研究癫痫持续状态和自发性癫痫发作。最后，我们将确定是否在自主参数的任何变化可以预测猝死的发生在氟乙烯诱导的癫痫发作期间死亡的动物的分数。定义癫痫引起的自主神经变化将允许开发特定的治疗方法，以减少或预防癫痫发作的一些严重急性后果，如猝死，并将提高对反复发作的长期后果的理解。