Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model—A preliminary study

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY
Epilepsia Pub Date : 2024-05-25 DOI:10.1111/epi.18012
Napoleon Torres, Etienne de Montalivet, Quentin Borntrager, Selimen Benahmed, Antoine Legrain, Eleonora Adesso, Nicolas Aubert, Fabien Sauter-Starace, Thomas Costecalde, Felix Martel, David Ratel, Christophe Gaude, Vincent Auboiroux, Brigitte Piallat, Tetiana Aksenova, Jenny Molet, Stephan Chabardes
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引用次数: 0

Abstract

Objective

Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures.

Methods

A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures.

Results

Hippocampal seizures were observed 40–120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures.

Significance

In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices.

Abstract Image

病灶冷却:在中位颞叶癫痫灵长类动物模型中治疗耐药性癫痫的替代疗法--初步研究。
目的:病灶冷却正在成为治疗耐药性癫痫(DRE)的一种相关疗法。然而,我们还缺乏有关其在控制源自海马等深层区域的癫痫发作方面有效性的数据。我们提出了一种专门针对这些大脑结构的局灶性大脑冷却热电解决方案:方法:我们开发了一种植入式装置原型,包括温度传感器和用于注射青霉素的插管,以便在非人灵长类癫痫模型的冷却尖端附近创建致痫区(EZ)。在海马中反复注射青霉素,以颞叶内侧为目标。从距离 EZ 2 毫米的立体脑电图导线记录信号。一旦癫痫发作次数趋于稳定,就进行病灶冷却,并使用定制的检测算法监测体温和电临床事件。在三种温度下对两只猕猴进行了测试:结果:注射后 40-120 分钟观察到海马癫痫发作,持续时间和频率在 120 分钟左右趋于稳定。与对照组相比,降温至 21°C 的海马癫痫发作次数有所减少(对照组:每 20 分钟发作 4.34 次,标准差 1.704 次;降温至 21°C:每 20 分钟发作 1.38 次,标准差 1.704 次):1.38次,标准差为每20分钟1.004次)。降温至 17°C 的效果更为明显,癫痫发作频率减少了近 80%。病灶降温后,癫痫发作持续时间和发作间期放电次数保持不变。反复注射青霉素数月后,观察到海马硬化,与人类的记录相似。此外,通过检测EZ中与癫痫发作开始相关的0.3°C的温度变化,可以识别癫痫发作:意义:在癫痫治疗中,最终目标是在副作用最小的情况下完全控制癫痫发作。对EZ进行局部降温可以替代手术和现有的神经调控装置。
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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
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