Division of Clinical Neurosciences, Turku University Hospital, Hämeentie 11, POB 52, 20521, Turku, Finland.
Department of Neurology, University of Turku, Turku, Finland.
J Neurol. 2020 Apr;267(4):883-897. doi: 10.1007/s00415-019-09181-8. Epub 2019 Jan 18.
Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.
脑深部电刺激（DBS）是治疗伴有运动波动和运动障碍的帕金森病（PD）患者的有效方法。关键的 DBS 疗效研究是在 PD 患者的基因型未知的情况下进行的；然而，鉴于估计的单基因突变患病率约为 5-10%，最常见的是 LRRK2、PRKN、PINK1 和 SNCA，以及 GBA 等增加风险的遗传因素，适当的特征描述变得越来越重要。我们对报道了 221 例遗传 PD 患者 DBS 效果的 46 项研究进行了系统评价。结果表明，单基因 PD 患者的 DBS 获益因突变基因而异。最常见的 LRRK2 突变 p.G2019S 患者的预后效果极佳，PRKN 突变患者的预后效果良好，但更罕见的 LRRK2 p.R1441G 突变患者的预后效果较差。由于认知和神经精神症状的快速进展，SNCA、GBA 和 LRRK2 p.T2031S 突变患者的 DBS 整体获益可能受到影响。在存在其他突变的情况下，DBS 治疗的单基因 PD 患者的运动变化似乎与一般 PD 人群的运动变化相当。
