Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms
Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms
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DOI：
10.1093/brain/awr122
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发表时间：
2011-07-01
期刊：
影响因子：
14.5
通讯作者：
Rothwell, John C.
中科院分区：
文献类型：
--
作者：
Ruge, Diane;Cif, Laura;Rothwell, John C.
长期结果表明，慢性脑深部电刺激治疗肌张力障碍的益处可维持多年。尽管如此，治疗的神经生理学长期后果及其与临床效果的关系尚不清楚。先前的研究表明，经颅磁刺激测量异常长时程增强样可塑性（配对联想刺激）和GABA a能抑制（短间隔皮质内抑制），这是在肌张力障碍中观察到的，在脑深部刺激几个月后恢复正常。在本研究中，我们对10名DYT 1基因阳性患者进行了至少4.5年的长期脑深部电刺激治疗后的同质组进行了相同的测量。在“进行”脑深部电刺激时和停止脑深部电刺激2天后进行记录。结果表明：（i）平均而言，在中断脑深部刺激之前，配对的联合刺激反应几乎不存在，并且与正常相比，短间隔皮质内抑制减少。这种模式不同于健康志愿者的模式，也不同于脑深部刺激-初始肌张力障碍中所见的可塑性增强和抑制减少的典型模式。这与未经治疗的帕金森病相似，可能与迄今为止无法解释的临床现象有关，例如有时在接受脑深部电刺激治疗的患者中观察到的帕金森症状。(ii)总体而言，当脑深部电刺激关闭2天时，平均生理或临床状态没有变化，表明脑深部电刺激在运动系统中产生了长期的神经重组。(iii)然而，患者之间存在相当大的差异。当脑深部电刺激“开启”时具有较高可塑性水平的患者，当脑深部电刺激停止时具有最佳的临床益处保留，反之亦然。这可能表明，当深部脑刺激关闭时，需要更好的可塑性来长期保持正常运动。(iv)具有最高可塑性的患者是那些接受了最少电流消耗的刺激的患者。这表明，有可能对个体患者的深部脑刺激进行“塑形”，以最大限度地提高对临床状态有影响的有益神经生理模式。这些结果对于理解肌张力障碍患者脑深部电刺激的长期后果和管理具有重要意义。
Long-term results show that benefits from chronic deep brain stimulation in dystonia are maintained for many years. Despite this, the neurophysiological long-term consequences of treatment and their relationship to clinical effects are not well understood. Previous studies have shown that transcranial magnetic stimulation measures of abnormal long-term potentiation-like plasticity (paired associative stimulation) and GABAa-ergic inhibition (short-interval intracortical inhibition), which are seen in dystonia, normalize after several months of deep brain stimulation. In the present study, we examine the same measures in a homogenous group of 10 DYT1 gene-positive patients after long-term deep brain stimulation treatment for at least 4.5 years. Recordings were made 'on' deep brain stimulation and after stopping deep brain stimulation for 2 days. The results show that: (i) on average, prior to discontinuing deep brain stimulation, the paired associative stimulation response was almost absent and short-interval intracortical inhibition was reduced compared with normal. This pattern differs from that in both healthy volunteers and from the typical pattern of enhanced plasticity and reduced inhibition seen in deep brain stimulation-naive dystonia. It is similar to that seen in untreated Parkinson's disease and may relate to thus far unexplained clinical phenomena like parkinsonian symptoms that have sometimes been observed in patients treated with deep brain stimulation. (ii) Overall, there was no change in average physiological or clinical status when deep brain stimulation was turned off for 2 days, suggesting that deep brain stimulation had produced long-term neural reorganization in the motor system. (iii) However, there was considerable variation between patients. Those who had higher levels of plasticity when deep brain stimulation was 'on', had the best retention of clinical benefit when deep brain stimulation was stopped and vice versa. This may indicate that better plasticity is required for longer term retention of normal movement when deep brain stimulation is off. (iv) Patients with the highest plasticity 'on' deep brain stimulation were those who had been receiving stimulation with the least current drain. This suggests that it might be possible to 'shape' deep brain stimulation of an individual patient to maximize beneficial neurophysiological patterns that have an impact on clinical status. The results are relevant for understanding long-term consequences and management of deep brain stimulation in dystonia.