Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Département de Neurologie, Clinical Research Center Neurosciences, Paris, France.
Sorbonne Université, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France.
Parkinsonism Relat Disord. 2020 Jul;76:56-62. doi: 10.1016/j.parkreldis.2020.04.002. Epub 2020 Jun 9.
Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated its efficacy on motor complications in advanced Parkinson's disease (PD) but does not modify disease progression. Genetic forms of PD have been associated with different cognitive progression profiles.
To assess the effect of PD-related genetic mutations on cognitive outcome after STN-DBS.
Patients with STN-DBS were screened for LRRK2, GBA, and PRKN mutations at the Pitié-Salpêtrière Hospital between 1997 and 2009. Patients with known monogenetic forms of PD from six other centers were also included. The Mattis Dementia Rating Scale (MDRS) was used to evaluate cognition at baseline and one-year post-surgery. The standardized Unified PD Rating Scale (UPDRS) evaluation On and Off medication/DBS was also administered. A generalized linear model adjusted for sex, ethnicity, age at onset, and disease duration was used to evaluate the effect of genetic factors on MDRS changes.
We analyzed 208 patients (131 males, 77 females, 54.3 ± 8.8 years) including 25 GBA, 18 LRRK2, 22 PRKN, and 143 PD patients without mutations. PRKN patients were younger and had a longer disease duration at baseline. A GBA mutation was the only significant genetic factor associated with MDRS change (β = -2.51, p = 0.009). GBA mutation carriers had a more pronounced post-operative MDRS decline (3.2 ± 5.1) than patients with LRRK2 (0.9 ± 4.8), PRKN (0.5 ± 2.7) or controls (1.4 ± 4.4). The motor response to DBS was similar between groups.
GBA mutations are associated with early cognitive decline following STN-DBS. Neuropsychological assessment and discussions on the benefit/risk ratio of DBS are particularly important for this population.
丘脑底核深部脑刺激（STN-DBS）已证明其对晚期帕金森病（PD）的运动并发症有效，但不会改变疾病进展。PD 的遗传形式与不同的认知进展特征相关。
评估 PD 相关基因突变对 STN-DBS 后认知结果的影响。
1997 年至 2009 年期间，在皮提-萨尔佩特里埃医院对 STN-DBS 患者进行了 LRRK2、GBA 和 PRKN 突变筛查。还纳入了来自其他六个中心的已知单基因形式 PD 的患者。使用 Mattis 痴呆评定量表（MDRS）在基线和术后一年评估认知。还进行了标准化的统一帕金森病评定量表（UPDRS）评估 ON 和 OFF 药物/刺激器。使用调整性别、种族、发病年龄和疾病持续时间的广义线性模型来评估遗传因素对 MDRS 变化的影响。
我们分析了 208 名患者（131 名男性，77 名女性，54.3±8.8 岁），包括 25 名 GBA、18 名 LRRK2、22 名 PRKN 和 143 名无突变的 PD 患者。PRKN 患者更年轻，基线时疾病持续时间更长。GBA 突变是唯一与 MDRS 变化显著相关的遗传因素（β=-2.51，p=0.009）。GBA 突变携带者术后 MDRS 下降更明显（3.2±5.1），而 LRRK2（0.9±4.8）、PRKN（0.5±2.7）或对照组（1.4±4.4）。各组之间 DBS 的运动反应相似。
GBA 突变与 STN-DBS 后早期认知下降有关。对于这一人群，神经心理学评估和关于 DBS 的获益/风险比的讨论尤为重要。
