Velasco A L, Velasco M, Velasco F, Menes D, Gordon F, Rocha L, Briones M, Márquez I
Unidad de Investigación Médica en Neurofisiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), México, D.F., Mexico.
Arch Med Res. 2000 May-Jun;31(3):316-28. doi: 10.1016/s0188-4409(00)00064-3.
Recent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere. This work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques.SAHCS during 3-4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5-6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3-4 months with no apparent additional undesirable effects on short memory. Also, inhibition of the stimulated hippocampus seems to be one of the possible mechanisms underlying the beneficial antiepileptic effects of SAHCS and CHCS. This was revealed by increased threshold and decreased duration of the afterdischarges induced by hippocampal stimulation, flattening of the hippocampal-evoked response recovery cycles, SPECT hypoperfusion of the hippocampal region, and increased hippocampal benzodiazepine receptor binding. Future studies increasing the number and time of follow-up of patients under hippocampal stimulation are necessary before considering CHCS a reliable procedure for controlling intractable temporal lobe seizures.
最近的动物实验表明，在点燃刺激后对杏仁核或海马体施加电刺激，会对这种癫痫实验模型产生显著且持久的抑制作用。这是一份关于通过慢性海马体电刺激（CHCS）开发一种手术神经调节程序的初步报告，该程序用于控制不适合进行前颞叶切除术的患者的顽固性颞叶癫痫，即患有双侧颞叶病灶或单侧病灶扩散至优势半球周围脑区的患者。这项工作分为两个主要的连续阶段。在第一阶段，我们证明亚急性海马体刺激（SAHCS）可阻断顽固性颞叶癫痫的发生，且对受刺激组织无额外损伤；在第二阶段，我们试图证明CHCS可能产生持续、持久的抗癫痫状态，且对语言和记忆无额外不良影响。此外，利用这种独特且符合伦理规范的情况，我们试图通过多种电生理、单光子计算机断层扫描（SPECT）灌注和放射自显影技术，确定SAHCS和CHCS的抗癫痫作用是否源于对海马体组织刺激的抑制。在前颞叶切除术之前3至4周进行SAHCS，刺激位于靠近杏仁核的前海马足或靠近内嗅皮质的海马旁回的关键区域，5至6天后可消除临床发作，并显著减少病灶处发作间期棘波的数量。对受刺激组织的显微镜分析显示，受刺激的海马体组织与未受刺激的海马体组织之间无明显组织病理学差异。此外，CHCS持续阻断颞叶癫痫的发生达3至4个月，对短期记忆无明显额外不良影响。而且，对受刺激海马体的抑制似乎是SAHCS和CHCS有益抗癫痫作用的潜在机制之一。这通过海马体刺激诱发的后放电阈值升高和持续时间缩短、海马体诱发反应恢复周期变平、海马体区域SPECT灌注不足以及海马体苯二氮䓬受体结合增加得以揭示。在将CHCS视为控制顽固性颞叶癫痫的可靠程序之前，如果要考虑CHCS，有必要增加对接受海马体刺激患者的随访数量和时间进行进一步研究。
