Krack P, Pollak P, Limousin P, Benazzouz A, Deuschl G, Benabid A L
Department of Clinical and Biological Neurosciences, Joseph Fourier University, Grenoble, France.
Brain. 1999 Jun;122 ( Pt 6):1133-46. doi: 10.1093/brain/122.6.1133.
The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on levodopa-induced dyskinaesias was investigated in eight patients with fluctuating Parkinson's disease complicated by functionally disabling off-period dystonia. All of the patients also had severe diphasic and peak-dose chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of levodopa-induced dyskinaesias. Off-period fixed dystonia was reduced by 90% and off-period pain by 66%. After acute levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of levodopa. This allowed the levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute levodopa challenge, concerning both parkinsonism and dyskinaesias, and suppresses off-period dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of levodopa on parkinsonism and improves all kinds of levodopa-induced dyskinaesias to varying degrees. Off-period dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of parkinsonism, the levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period dystonia, mobile diphasic dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons.
在8例伴有功能致残性关期肌张力障碍的帕金森病病情波动患者中，研究了慢性双侧高频刺激丘脑底核（STN）对左旋多巴诱发运动障碍的影响。所有患者还患有严重的双相和剂峰期舞蹈症，因此有可能研究高频刺激对不同类型左旋多巴诱发运动障碍的影响。关期固定性肌张力障碍减少了90%，关期疼痛减少了66%。急性左旋多巴激发后，STN高频刺激使双相性运动性肌张力障碍减少50%，剂峰期舞蹈样运动障碍减少30%。双侧STN高频刺激对统一帕金森病评定量表运动评分的影响与左旋多巴术前效果程度相同。这使得左旋多巴剂量可减少47%。减少药物治疗与持续STN高频刺激相结合，使开期双相和剂峰期运动障碍的持续时间减少52%，强度减少68%。STN急性高频刺激在帕金森病和运动障碍方面模拟急性左旋多巴激发，并抑制关期肌张力障碍。增加电压可诱发重复性肌张力障碍性运动障碍，类似于双相性左旋多巴诱发运动障碍。电压进一步增加会导致从双相型肌张力障碍转变为剂峰型舞蹈性肌张力障碍。STN慢性高频刺激也模拟了左旋多巴对帕金森病的益处，并不同程度地改善各种左旋多巴诱发运动障碍。与STN神经元活动亢进相关的关期肌张力障碍直接受刺激影响并立即消失。STN慢性高频刺激对双相和剂峰期运动障碍的影响更为复杂，直接与STN的功能抑制有关，间接与通过STN的持续功能抑制替代脉冲性多巴胺能刺激有关。STN慢性高频刺激可随着对帕金森病有益作用的增加而非常逐渐地增加刺激参数，同时降低诱发刺激诱导性运动障碍的阈值。随着帕金森病的改善，左旋多巴剂量可逐渐减少。由于双相性肌张力障碍性运动障碍比剂峰期运动障碍改善程度更大，可能涉及直接和间接机制。与几乎没有帕金森病证据且因此STN神经元活动低相关的剂峰期舞蹈样运动障碍大多间接得到改善。固定性关期肌张力障碍、运动性双相肌张力障碍和剂峰期舞蹈性肌张力障碍似乎代表一个连续的临床谱，反映了STN神经元潜在活动模式的连续谱。
