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
{"title":"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。","authors":"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","doi":"10.1111/epi.18012","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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 <i>Macaca fascicularis</i> monkeys at three temperatures.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Significance</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18012","citationCount":"0","resultStr":"{\"title\":\"Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model—A preliminary study\",\"authors\":\"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\",\"doi\":\"10.1111/epi.18012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). 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Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model—A preliminary study
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.
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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