Ákos Szabó C, De La Garza Melissa, Shade Robert, Papanastassiou Alexander M, Nathanielsz Peter
Department of Neurology, UT Health San Antonio, San Antonio, TX, United States.
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States.
Epilepsy Behav. 2021 Jul;120:107973. doi: 10.1016/j.yebeh.2021.107973. Epub 2021 May 4.
To evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment.
The baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified.
Twenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy.
This case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.
评估皮质反应性神经刺激(CRN)对一只患有癫痫和遗传性全身性癫痫(GGE)的雄性狒狒的疗效,以及治疗引起的癫痫发作模式及其昼夜节律的改变。
在狒狒双侧前额顶叶植入两条横跨中央沟内侧的硬膜下电极条。在为期三个月的基线期内,每天下载脑电图(ECoG)数据,然后在为期五个月的治疗期内每2 - 3天下载一次。还对反映发作期或发作间期癫痫放电的长时程发作进行了量化。
基线期记录到23次全身性强直 - 阵挛发作(GTCS)和2次非惊厥性癫痫持续状态(NCSE)发作(中位数为每月8次发作),而治疗期间记录到26次GTCS发作(中位数为每月5次)。同样,长时程发作的每日指数从基线期的0.46降至治疗后的0.29。RNS治疗还改变了发作期ECoG模式和GTCS的昼夜分布。
本病例研究为GGE狒狒模型中的RNS治疗提供了概念验证。皮质反应性神经刺激(CRN)使GTCS发作次数中位数减少了38%。识别出了不同的发作期模式,这些模式在治疗期间发生了变化;其GTCS的昼夜模式也随着治疗逐渐从夜间转移到白天。未来针对丘脑核或结合皮质和皮质下部位的研究,可能会进一步改善GTCS以及其他全身性发作类型的检测和控制。更广泛地说,本研究展示了在狒狒中评估癫痫发作检测以及长期慢性治疗干预的机会。