Development of spontaneous recurrent seizures after kainate-induced status epilepticus.
Development of spontaneous recurrent seizures after kainate-induced status epilepticus.
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DOI：
10.1523/jneurosci.0980-08.2009
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发表时间：
2009-02-18
期刊：
影响因子：
--
通讯作者：
Dudek FE
中科院分区：
文献类型：
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作者：
Williams PA;White AM;Clark S;Ferraro DJ;Swiercz W;Staley KJ;Dudek FE
获得性癫痫（即，在对大脑的侮辱之后）通常被认为是一种进行性障碍，并且这种假设进展的性质仍然存在争议。抗癫痫药物治疗必然会混淆人类获得性癫痫患者进行性变化的分析。在这里，我们描述了测试以下假设的实验：获得性癫痫的发展开始于癫痫发作频率增加的连续过程（即，与自发性癫痫发作的概率成比例），最终达到稳定。使用几乎连续的表面皮层和双侧海马记录与无线电遥测和半自动癫痫发作检测，电记录癫痫发作（包括惊厥和非惊厥）的频率进行了定量分析约100天后，红藻氨酸诱导的癫痫持续状态的成年大鼠。自发性复发性癫痫发作的频率不是时间的阶跃函数（如“潜伏期”所暗示的）;相反，癫痫发作频率随时间呈S形函数增加。癫痫发作间隔的分布是非随机的，表明癫痫发作簇（即，短的发作间隔）掩盖了进展的早期阶段，并可能导致发作频率增加。这些数据表明：（1）潜伏期是许多长的发作间期中的第一个，并且不能很好地衡量癫痫发生的时间范围;（2）癫痫发生是一个连续的过程，远远超出了第一次自发性复发性发作;（3）不均匀的发作聚集有助于癫痫发作发生的变异性;和（4）旨在抑制获得性癫痫的抗癫痫治疗的窗口可能延伸到第一次临床发作之后。
Acquired epilepsy (i.e., after an insult to the brain) is often considered to be a progressive disorder, and the nature of this hypothetical progression remains controversial. Antiepileptic drug treatment necessarily confounds analyses of progressive changes in human patients with acquired epilepsy. Here we describe experiments testing the hypothesis that development of acquired epilepsy begins as a continuous process of increased seizure frequency (i.e., proportional to probability of a spontaneous seizure) that ultimately plateaus. Using nearly continuous surface cortical and bilateral hippocampal recordings with radiotelemetry and semi-automated seizure detection, the frequency of electrographically recorded seizures (both convulsive and non-convulsive) was analyzed quantitatively for about 100 days after kainate-induced status epilepticus in adult rats. The frequency of spontaneous recurrent seizures was not a step-function of time (as implied by the “latent period”); rather, seizure frequency increased as a sigmoid function of time. The distribution of inter-seizure intervals was non-random, suggesting that seizure clusters (i.e., short inter-seizure intervals) obscured the early stages of progression, and may have contributed to the increase in seizure frequency. These data suggest that (1) the latent period is the first of many long inter-seizure intervals and a poor measure of the timeframe of epileptogenesis; (2) epileptogenesis is a continuous process that extends much beyond the first spontaneous recurrent seizure; (3) uneven seizure clustering contributes to the variability in occurrence of epileptic seizures; and (4) the window for anti-epileptogenic therapies aimed at suppressing acquired epilepsy probably extends well past the first clinical seizure.