Yang Xiao-Feng, Duffy David W, Morley Robert E, Rothman Steven M
Department of Neurology, Washington University, St. Louis, Missouri, USA.
Epilepsia. 2002 Mar;43(3):240-5. doi: 10.1046/j.1528-1157.2002.33301.x.
The therapy for focal neocortical epilepsy remains suboptimal. We have, therefore, worked to develop techniques to cool small regions of the neocortical surface for seizure mapping and, ultimately, for long-term suppression of focal seizures.
We induced focal neocortical seizures in halothane-anesthetized rats by the microinjection of 4-aminopyridine (4-AP) into the motor cortex. The dura over the injection site was cooled with a Peltier device, and the temperature at the interface between dura and Peltier was measured with a thermocouple. In some experiments, seizures were automatically detected by a computer program that activated the Peltier device.
Monopolar EEG indicated that our seizures were focal and suppressed when cooling was applied directly over the injection site. The threshold temperature required to observe any reduction in seizure duration was 24 degrees C. The temperature gradient across the cooled neocortex was sharp, with the temperature increasing to 31 degrees C at 4 mm below the Peltier, which was cooled to 20 degrees C. Automatic seizure detection reduced the total seizure duration from 43.4 +/- 33.6 s to 5.6 +/- 5.3 s.
Cooling terminates neocortical seizures when applied very close to the epileptogenic focus. The threshold for seizure termination (24 degrees C) may be lower than the threshold for termination of normal cortical activity, suggesting that this technique will not dissociate the anticonvulsant effect of cooling from the disruption of normal behavior. However, when coupled with automatic seizure detection, focal cooling remains an attractive option for development as a treatment for focal epilepsy.
局灶性新皮质癫痫的治疗效果仍不尽人意。因此，我们致力于开发技术，用于冷却新皮质表面的小区域，以进行癫痫发作定位，并最终长期抑制局灶性癫痫发作。
我们通过向氟烷麻醉的大鼠运动皮层微量注射4-氨基吡啶（4-AP）来诱发局灶性新皮质癫痫发作。用珀耳帖装置冷却注射部位上方的硬脑膜，并用热电偶测量硬脑膜与珀耳帖之间界面处的温度。在一些实验中，癫痫发作由激活珀耳帖装置的计算机程序自动检测。
单极脑电图显示，当在注射部位直接进行冷却时，我们诱发的癫痫发作是局灶性的且受到抑制。观察到癫痫发作持续时间有任何缩短所需的阈值温度为24℃。冷却的新皮质上的温度梯度很陡，在冷却至20℃的珀耳帖下方4毫米处温度升至31℃。自动癫痫发作检测将癫痫发作总持续时间从43.4±33.6秒缩短至5.6±5.3秒。
当非常靠近致痫灶应用冷却时，可终止新皮质癫痫发作。癫痫发作终止的阈值（24℃）可能低于正常皮质活动终止的阈值，这表明该技术不会使冷却的抗惊厥作用与正常行为的破坏相分离。然而，当与自动癫痫发作检测相结合时，局灶性冷却作为局灶性癫痫的一种治疗方法，仍是一个有吸引力的开发选择。
