Zhang De Xing, Bertram Edward H
Department of Neurology, University of Virginia, Charlottesville, Virginia, U.S.A.
Epilepsia. 2015 Mar;56(3):479-88. doi: 10.1111/epi.12916. Epub 2015 Jan 29.
The optimal sites and stimulation protocols for brain stimulation in epilepsy have not been found. Clinical trials, which have shown modest benefit in seizure reduction, have involved patients with poorly localized intractable focal epilepsy and stimulation sites without clear relations to specific underlying seizure circuits. The medial dorsal thalamic nucleus is a key node in limbic seizure circuits, and we wished to know what stimulation parameters might control seizures in a kindling model of limbic epilepsy.
In urethane-anesthetized rats, we induced limbic seizures by stimulation of the piriform cortex or CA3 of the hippocampus while recording in the entorhinal cortex or CA1 of the contralateral hippocampus to determine the effect of specific stimulation parameters on seizure duration.
Stimulation consistently suppressed seizure duration from baseline by over 80% (p < 0.001), frequently completely preventing the seizures. Position of the thalamic electrode, stimulus intensity and frequency had a significant influence, with higher stimulus intensities (40 V vs. 20 V) and frequencies (20 Hz vs. 7 Hz) significantly suppressing seizures. The most effective position was the lateral dorsal area of the medial dorsal nucleus (MD), which corresponded to the region of axon entry. Stimulation in the MD center was not effective. An anterior-posterior relationship of the stimulating electrode pair was effective, whereas a medial lateral orientation was not. Successful stimulation suppressed the evoked responses in the entorhinal cortex or CA1.
Position and orientation of the stimulating electrode has to be precise, which suggests that the placement of the electrodes must be tailored to the individual's own seizure circuit. The data also indicate that successful deep brain stimulation induces a fundamental change in system physiology, which could be a marker to guide the development of stimulation parameters for each patient.
尚未找到癫痫脑刺激的最佳部位和刺激方案。临床试验虽显示在减少癫痫发作方面有一定益处，但涉及的是局灶性癫痫定位不佳的患者以及与特定潜在癫痫发作回路无明确关联的刺激部位。内侧背侧丘脑核是边缘系统癫痫发作回路中的关键节点，我们想了解在边缘性癫痫点燃模型中哪些刺激参数可能控制癫痫发作。
在氨基甲酸乙酯麻醉的大鼠中，通过刺激梨状皮质或海马体的CA3诱发边缘性癫痫发作，同时在对侧海马体的内嗅皮质或CA1进行记录，以确定特定刺激参数对癫痫发作持续时间的影响。
刺激始终使癫痫发作持续时间从基线水平抑制超过80%（p < 0.001），经常能完全阻止癫痫发作。丘脑电极的位置、刺激强度和频率有显著影响，较高的刺激强度（40 V对20 V）和频率（20 Hz对7 Hz）能显著抑制癫痫发作。最有效的位置是内侧背侧核（MD）的外侧背侧区域，该区域对应轴突进入区域。在MD中心进行刺激无效。刺激电极对的前后关系有效，而内外侧方向无效。成功的刺激抑制了内嗅皮质或CA1中的诱发反应。
刺激电极的位置和方向必须精确，这表明电极的放置必须根据个体自身的癫痫发作回路进行调整。数据还表明，成功的深部脑刺激会引起系统生理学的根本变化，这可能是指导为每个患者制定刺激参数的一个标志。
