Obeso J A, Olanow C W, Rodriguez-Oroz M C, Krack P, Kumar R, Lang A E
N Engl J Med. 2001 Sep 27;345(13):956-63. doi: 10.1056/NEJMoa000827.
Increased neuronal activity in the subthalamic nucleus and the pars interna of the globus pallidus is thought to account for motor dysfunction in patients with Parkinson's disease. Although creating lesions in these structures improves motor function in monkeys with induced parkinsonism and patients with Parkinson's disease, such lesions are associated with neurologic deficits, particularly when they are created bilaterally. Deep-brain stimulation simulates the effects of a lesion without destroying brain tissue.
We performed a prospective, double-blind, crossover study in patients with advanced Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus or pars interna of the globus pallidus and who then underwent bilateral high-frequency deep-brain stimulation. We compared scores on the motor portion of the Unified Parkinson's Disease Rating Scale when the stimulation was randomly assigned to be turned on or off. We performed unblinded evaluations of motor function preoperatively and one, three, and six months postoperatively.
Electrodes were implanted bilaterally in 96 patients in the subthalamic-nucleus group and 38 patients in the globus-pallidus group. Three months after the procedures were performed, double-blind, crossover evaluations demonstrated that stimulation of the subthalamic nucleus was associated with a median improvement in the motor score (as compared with no stimulation) of 49 percent, and stimulation of the pars interna of the globus pallidus with a median improvement of 37 percent (P<0.001 for both comparisons). Between the preoperative and six-month visits, the percentage of time during the day that patients had good mobility without involuntary movements increased from 27 percent to 74 percent (P<0.001) with subthalamic stimulation and from 28 percent to 64 percent (P<0.001) with pallidal stimulation. Adverse events included intracranial hemorrhage in seven patients and infection necessitating removal of the leads in two.
Bilateral stimulation of the subthalamic nucleus or pars interna of the globus pallidus is associated with significant improvement in motor function in patients with Parkinson's disease whose condition cannot be further improved with medical therapy.
丘脑底核和苍白球内侧部神经元活动增加被认为是帕金森病患者运动功能障碍的原因。虽然在这些结构中制造损伤可改善帕金森病模型猴和帕金森病患者的运动功能,但此类损伤会伴有神经功能缺损,尤其是双侧损伤时。脑深部电刺激可模拟损伤的效果而不破坏脑组织。
我们对晚期帕金森病患者进行了一项前瞻性、双盲、交叉研究,这些患者的电极被植入丘脑底核或苍白球内侧部,随后接受双侧高频脑深部电刺激。我们比较了刺激随机开启或关闭时统一帕金森病评定量表运动部分的评分。我们在术前以及术后1个月、3个月和6个月对运动功能进行了非盲评估。
丘脑底核组96例患者和苍白球组38例患者接受了双侧电极植入。手术3个月后,双盲交叉评估显示,刺激丘脑底核使运动评分中位数改善49%(与无刺激相比),刺激苍白球内侧部使运动评分中位数改善37%(两项比较P均<0.001)。在术前至术后6个月的访视期间,接受丘脑底核刺激的患者白天无不自主运动且活动良好的时间百分比从27%增至74%(P<0.001),接受苍白球刺激的患者从28%增至64%(P<0.001)。不良事件包括7例颅内出血和2例因感染需要移除电极导线。
双侧刺激丘脑底核或苍白球内侧部可使药物治疗无法进一步改善病情的帕金森病患者的运动功能显著改善。