CHU de Grenoble, Pavillon de neurology, Grenoble Cedex 9, France.
Brain. 2012 May;135(Pt 5):1463-77. doi: 10.1093/brain/aws078. Epub 2012 Apr 15.
Addictions to dopaminergic drugs or to pleasant behaviours are frequent and potentially devastating neuropsychiatric disorders observed in Parkinson's disease. They encompass impulse control disorders, punding and dopamine dysregulation syndrome. A relationship with dopaminergic treatment is strongly suggested. Subthalamic stimulation improves motor complications and allows for drastic reductions in medication. This treatment might, therefore, be considered for patients with behavioural addictions, when attempts to reduce dopaminergic medication have failed. However, conflicting data have reported suppression, alleviation, worsening or new onset of behavioural addictions after subthalamic stimulation. Non-motor fluctuations are also a disabling feature of the disease. We prospectively investigated behaviour in a cohort of 63 patients with Parkinson's disease, before and 1 year after subthalamic stimulation using the Ardouin scale, with systematic evaluation of functioning in overall appetitive or apathetic modes, non-motor fluctuations, dopaminergic dysregulation syndrome, as well as behavioural addictions (including impulse control disorders and punding) and compulsive use of dopaminergic medication. Defined drug management included immediate postoperative discontinuation of dopamine agonists and reduction in levodopa. Motor and cognitive statuses were controlled (Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, frontal score). After surgery, the OFF medication motor score improved (-45.2%), allowing for a 73% reduction in dopaminergic treatment, while overall cognitive evaluation was unchanged. Preoperative dopamine dysregulation syndrome had disappeared in 4/4, behavioural addictions in 17/17 and compulsive dopaminergic medication use in 9/9 patients. New onset of levodopa abuse occurred in one patient with surgical failure. Non-motor fluctuations were significantly reduced with improvements in off-dysphoria (P ≤ 0.001) and reduction in on-euphoria (P ≤ 0.001). There was an inversion in the number of patients functioning in an overall appetitive mode (29 before versus 2 after surgery, P ≤ 0.0001) to an overall apathetic mode (3 before versus 13 after surgery, P < 0.05). Two patients attempted suicide. Improvement in motor fluctuations is linked to the direct effect of stimulation on the sensory-motor subthalamic territory, while improvement in dyskinesias is mainly explained by an indirect effect related to the decrease in dopaminergic drugs. Our data suggest that non-motor fluctuations could similarly be directly alleviated through stimulation of the non-motor subthalamic territories, and hyperdopaminergic side effects might improve mainly due to the decrease in dopaminergic medication. We show an overall improvement in neuropsychiatric symptomatology and propose that disabling non-motor fluctuations, dopaminergic treatment abuse and drug-induced behavioural addictions in Parkinson's disease may be considered as new indications for subthalamic stimulation.
药物成瘾或愉快行为成瘾是帕金森病中常见且潜在破坏性的神经精神障碍，包括冲动控制障碍、打桩和多巴胺失调综合征。这与多巴胺治疗有很强的关系。丘脑下刺激改善运动并发症，并允许大幅度减少药物治疗。因此，当尝试减少多巴胺药物治疗失败时，对于有行为成瘾的患者，可以考虑进行这种治疗。然而，有矛盾的数据报告称，丘脑下刺激后会出现行为成瘾的抑制、缓解、恶化或新发病。非运动波动也是该疾病的一种致残特征。我们前瞻性地使用 Ardour 量表在 63 名帕金森病患者的队列中，在丘脑下刺激前后一年评估行为，系统评估整体食欲或冷漠模式、非运动波动、多巴胺失调综合征以及行为成瘾（包括冲动控制障碍和打桩）和多巴胺药物的强迫使用。定义的药物管理包括术后立即停止使用多巴胺激动剂和减少左旋多巴。控制运动和认知状态（统一帕金森病评定量表、Mattis 痴呆评定量表、额叶评分）。手术后，“关”药物运动评分改善（-45.2%），允许多巴胺治疗减少 73%，而整体认知评估保持不变。术前多巴胺失调综合征在 4/4 例患者中消失，17/17 例行为成瘾和 9/9 例强迫使用多巴胺药物得到改善。手术失败的 1 例患者出现左旋多巴滥用的新发病例。非运动波动显著减少，出现“关”时抑郁（P≤0.001）和“开”时欣快（P≤0.001）减少。总体上患者处于食欲模式的数量发生反转（术前 29 例，术后 2 例，P≤0.0001），而处于冷漠模式的数量增加（术前 3 例，术后 13 例，P<0.05）。有 2 例患者试图自杀。运动波动的改善与刺激对感觉运动丘脑下区的直接作用有关，而运动障碍的改善主要与减少多巴胺药物的间接作用有关。我们的数据表明，非运动波动也可以通过刺激非运动丘脑下区直接缓解，而高多巴胺能副作用的改善主要是由于减少多巴胺药物治疗。我们观察到神经精神症状的整体改善，并提出帕金森病中的致残性非运动波动、多巴胺治疗滥用和药物诱导的行为成瘾可能被视为丘脑下刺激的新适应证。
