Autonomic consequences of brief 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。据报道，一些单纯性部分性癫痫患者会出现潮红、出汗和勃起。据报道，复杂部分性癫痫患者的自主神经体征范围更广，包括心率和节律(最常见的是心动过缓)、血压(最常见的是血压增加)、瞳孔大小、血管运动和胃肠运动活动、胃肠道运动和分泌物的变化。全身性强直-阵挛发作可与血压严重升高和心率改变(如完全性结节传导阻滞)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局限于癫痫持续状态，甚至是全身性强直-阵挛发作。一些癫痫发作，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。癫痫发作引起的自主神经系统功能改变的程度，无论是急性的还是慢性的，都没有得到很好的研究。目前尚不清楚自主神经的改变是否完全次要于运动表现，或者自主神经的结果是否独立于运动活动，甚至在非惊厥性发作中可能是显著的。这项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)和持续时间不同的发作前、发作中和发作后测量与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。我们开发了一种定制的慢性记录系统，用于长期监测自由行为大鼠的血压(BP)、心电图(ECG)和周围神经活动(交感神经节后轴突)，以评估自主神经系统介导的变化。我们将确定我们的系统在5种发作情况下监测自主神经参数的可行性：a)局灶性发作；b)局灶性发作伴二次泛化；c)主要是全身性发作；d)癫痫持续状态；e)慢性发作模型中的自发性发作。具体地说，我们将比较局灶性癫痫与全身性癫痫，主要是全身性癫痫与继发性全身性癫痫。在发生自发性癫痫发作的动物中，我们将比较触发和自发癫痫发作。我们还将把脑电发作活动的持续时间与运动性惊厥的强度联系起来。局灶性和继发性全身性癫痫发作将在周围点燃的大鼠中进行研究。主要的全身性癫痫发作将在暴露于氟乙基气体的大鼠中进行研究。注射红藻氨酸的大鼠将研究癫痫持续状态和自发性癫痫发作。最后，我们将确定自主神经参数的任何变化是否可以预测在氟乙基诱发癫痫发作期间死亡的动物中猝死的发生。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，并将提高对反复癫痫发作的长期后果的理解。

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.