Plow Ela B, Carey James R, Nudo Randolph J, Pascual-Leone Alvaro
Berenson-Allen Center for Noninvasive Brain Stimulation, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Stroke. 2009 May;40(5):1926-31. doi: 10.1161/STROKEAHA.108.540823. Epub 2009 Apr 9.
Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result.
Regarding cortical stimulation, it is important to determine the (1) location of peri-infarct representations by integrating multiple neuroanatomical and physiological techniques; (2) role of other mechanisms of stroke recovery; (3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to ensure no alteration/displacement of current density; and (5) applicability of lessons generated from noninvasive brain stimulation studies in humans. In terms of combining stimulation with rehabilitation, we should understand (1) the principle of homeostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning; and (3) that subject-specific intervention may be necessary.
Future cortical stimulation trials should consider the factors that may have contributed to the peculiar results of the Phase III trial and address those in future study designs.
中风后常常会残留运动功能缺损。目前正在探寻促进功能恢复的更新的有效策略。脑刺激作为引导适应性可塑性的一种手段,颇具吸引力。动物研究以及人体的I期和II期试验表明,康复与同期侵入性皮质刺激相结合具有安全性、可行性和有效性。然而,最近的一项III期试验显示这种联合治疗并无优势。我们对各项试验的结果进行了批判性审查,并讨论了导致这一独特结果的因素。
关于皮质刺激,确定以下几点很重要:(1)通过整合多种神经解剖学和生理学技术来确定梗死灶周围表征的位置;(2)中风恢复的其他机制的作用;(3)梗死灶周围组织和下行通路的存活能力;(4)病变几何形状,以确保电流密度无改变/位移;(5)从人体非侵入性脑刺激研究中获得的经验教训的适用性。就刺激与康复相结合而言,我们应该了解:(1)稳态可塑性的原理;(2)持续皮质活动和学习阶段的影响;(3)可能需要针对个体的干预措施。
未来的皮质刺激试验应考虑可能导致III期试验出现特殊结果的因素,并在未来的研究设计中加以解决。