Center for Neurological Restoration, Cleveland Clinic Neurological Institute, Cleveland, OH, USA.
Centro de Trastornos del Movimiento, CETRAM, Santiago, Chile.
J Parkinsons Dis. 2022;12(6):1703-1725. doi: 10.3233/JPD-212986.
Parkinson's disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring.
帕金森病(PD)在某些情况下由遗传变异导致或促成,导致不同表型的表达。无论病因如何,随着疾病的进展,运动波动和/或左旋多巴诱导的运动障碍限制了药物治疗的效果。在疾病的晚期,设备辅助治疗是一种很好的替代方法,包括深部脑刺激(DBS)、左旋多巴-卡比多巴肠凝胶和持续皮下注射阿扑吗啡。候选者的选择和时机对这些治疗方法的成功至关重要。DBS 队列中的遗传筛查显示突变携带者的比例高于一般队列,这表明遗传因素可能影响晚期治疗的候选资格。单基因 PD 对设备治疗的反应尚未得到很好的确定,遗传信息对决策的贡献仍存在争议。本文综述了与设备辅助治疗相关的遗传依赖性反应的有限证据。要准确了解不同突变携带者对设备辅助治疗的充分性和反应,需要进行具有长期监测的特定研究。