Smith Zachariah Z, Benison Alexander M, Bercum Florencia M, Dudek F Edward, Barth Daniel S
Department of Psychology and Neuroscience, University of Colorado , Boulder, Colorado.
Department of Neurosurgery, University of Utah School of Medicine , Salt Lake City, Utah.
J Neurophysiol. 2018 May 1;119(5):1818-1835. doi: 10.1152/jn.00721.2017. Epub 2018 Feb 14.
Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received considerable attention, nonconvulsive seizures have not been closely examined, even though they may reflect the earliest signs of epileptogenesis and potentially guide research on antiepileptogenic interventions. The definition of nonconvulsive seizures based on brain electrical activity alone has been controversial. Here we define and quantify electrographic properties of convulsive and nonconvulsive seizures in the context of the acquired epileptogenesis that occurs after pilocarpine-induced status epilepticus (SE). Lithium-pilocarpine was used to induce the prolonged repetitive seizures characteristic of SE; when SE was terminated with paraldehyde, seizures returned during the 2-day period after pilocarpine treatment. A distinct latent period ranging from several days to >2 wk was then measured with continuous, long-term video-EEG. Nonconvulsive seizures dominated the onset of epileptogenesis and consistently preceded the first convulsive seizures but were still present later. Convulsive and nonconvulsive seizures had similar durations. Postictal depression (background suppression of the EEG) lasted for >100 s after both convulsive and nonconvulsive seizures. Principal component analysis was used to quantify the spectral evolution of electrical activity that characterized both types of spontaneous recurrent seizures. These studies demonstrate that spontaneous nonconvulsive seizures have electrographic properties similar to convulsive seizures and confirm that nonconvulsive seizures link the latent period and the onset of convulsive seizures during post-SE epileptogenesis in an animal model. Nonconvulsive seizures may also reflect the earliest signs of epileptogenesis in human acquired epilepsy, when intervention could be most effective. NEW & NOTEWORTHY Nonconvulsive seizures usually represent the first bona fide seizure following a latent period, dominate the early stages of epileptogenesis, and change in severity in a manner consistent with the progressive nature of epileptogenesis. This analysis demonstrates that nonconvulsive and convulsive seizures have different behavioral outcomes but similar electrographic signatures. Alternatively, epileptiform spike-wave discharges fail to recapitulate several key seizure features and represent a category of electrical activity separate from nonconvulsive seizures in this model.
尽管毛果芸香碱诱导癫痫发生过程中出现的惊厥性癫痫发作受到了广泛关注,但非惊厥性癫痫发作却未得到深入研究,即便它们可能反映癫痫发生的最早迹象,并有可能为抗癫痫发生干预措施的研究提供指导。仅基于脑电活动来定义非惊厥性癫痫发作一直存在争议。在此,我们在毛果芸香碱诱导癫痫持续状态(SE)后发生的获得性癫痫发生的背景下,定义并量化惊厥性和非惊厥性癫痫发作的脑电图特性。使用锂 - 毛果芸香碱诱导具有SE特征的长时间重复性癫痫发作;当用副醛终止SE后,癫痫发作在毛果芸香碱治疗后的2天内再次出现。然后通过连续、长期的视频脑电图测量一个从数天到超过2周的明显潜伏期。非惊厥性癫痫发作在癫痫发生的起始阶段占主导,始终先于首次惊厥性癫痫发作出现,但在后期仍会出现。惊厥性和非惊厥性癫痫发作的持续时间相似。惊厥性和非惊厥性癫痫发作后,发作后抑郁(脑电图背景抑制)持续超过100秒。主成分分析用于量化表征两种类型自发性复发性癫痫发作的电活动的频谱演变。这些研究表明,自发性非惊厥性癫痫发作具有与惊厥性癫痫发作相似的脑电图特性,并证实非惊厥性癫痫发作在动物模型中SE后癫痫发生过程中连接了潜伏期和惊厥性癫痫发作的起始。非惊厥性癫痫发作也可能反映人类获得性癫痫中癫痫发生的最早迹象,此时进行干预可能最为有效。新发现与值得注意的点非惊厥性癫痫发作通常代表潜伏期后的首次真正癫痫发作,在癫痫发生的早期阶段占主导,并以与癫痫发生的渐进性相一致的方式在严重程度上发生变化。该分析表明,非惊厥性和惊厥性癫痫发作具有不同的行为结果,但具有相似的脑电图特征。或者,癫痫样棘波放电未能概括几个关键的癫痫发作特征,并且在此模型中代表与非惊厥性癫痫发作不同的一类电活动。