Wang Shu, Hu Wei, Gao Yuan, Wang Anxin, Chen Ling, Liang Zhanhua, Zhang Shizhong, Long Hao, Li Weiguo, Niu Chaoshi, Liu Weiguo, Cai Guoen, Ji Yuchen, Tam Joseph, Xu Qin, Yang Anchao, Shi Lin, Zhang Hua, Han Chunlei, Zhu Guanyu, Bai Yutong, Jiang Lulu, Li Tao, Xue Shan, Wang Hongxiao, Li Yuexuan, Xiong Chi, Lozano Andres M, Ramirez-Zamora Adolfo, Zhang Wenbin, Meng Fangang, Zhang Jianguo
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
PLoS Med. 2025 Aug 1;22(8):e1004670. doi: 10.1371/journal.pmed.1004670. eCollection 2025 Aug.
Deep brain stimulation (DBS) has been increasingly introduced for patients with Parkinson's disease (PD). However, there has been extensive controversy regarding its surgical timing. This study aimed to evaluate surgical outcomes of DBS across different PD durations and identify key prognostic factors.
In this multicenter cohort study, patients with PD who underwent subthalamic DBS between 1/1/2011 and 12/31/2020 from seven representative Chinese national centers were included. Two-year follow-up data were analyzed, accordingly. These patients were classified into short (<5 years), mid (5-10 years), and long (≥10 years) PD duration groups. Primary assessments included part III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) at the off-medicine state, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), and Parkinson Disease Questionnaire-39 (PDQ-39) scales. Relative changes in scores were analyzed for within- and between-group comparisons, and prognostic factors were identified via multivariable linear regression. A total of 1,859 patients were screened, and 1,717 patients (749 females) were included for analysis. Respectively, 141, 978, and 598 patients underwent surgeries after short-, mid-, and long-duration. The scores of the MDS-UPDRS-III (off-medicine), HAM-A, HAM-D, and PDQ-39 significantly improved by 46.7% ± 14.1% (mean difference [MD] 25.1, 95% confidence interval [CI] [24.5, 25.7], P < 0.001), 54.4% ± 22.4% (MD 8.0, 95%CI [7.5, 8.5], P < 0.001), 43.4% ± 22.6% (MD 6.3, 95%CI [5.8, 6.8], P < 0.001), and 47.9% ± 17.8% (MD 28.0, 95%CI [27.0, 29.0], P < 0.001), respectively, and all the study groups achieved significant improvements (all P < 0.001). Notably, patients with mid-PD duration achieved greatest improvements in motor outcomes (versus short: MD 8.0%, 95%CI [4.7%, 11.3%], P = 0.008; versus long: MD 5.6%, 95%CI [2.8%, 9.4%], P = 0.01), neuropsychological evaluations (anxiety, versus long: MD 15.2%, 95%CI [12.3%, 18.1%], P = 0.002; depression, versus long: MD 19.1%, 95%CI [15.6%, 22.6%], P < 0.001), and quality of life (versus long: MD 7.6%, 95%CI [5.2%, 10.0%], P = 0.007). Levodopa response (short: adjusted β 0.42, 95% CI [0.30, 0.54], P < 0.001; mid: adjusted β 0.17, 95% CI [0.12, 0.22], P < 0.001; long: adjusted β 0.20, 95% CI [0.12, 0.28], P < 0.001) was a unified positive factor of motor response for all three groups. Higher MDS-UPDRS-III (off-medicine) scores (mid: adjusted β 0.10, 95% CI [0.05, 0.15], P < 0.001; long: adjusted β 0.30, 95% CI [0.23, 0.38], P < 0.001) were positively correlated with motor outcomes for the mid- and long-duration groups. Nevertheless, it was a negative factor for the short duration group (adjusted β -0.25, 95% CI [-0.36, -0.14], P < 0.001). The main limitation of this study is the nonrandomized observational nature introduced potential selection bias and imbalanced comparisons.
DBS significantly improved motor, neuropsychological, and quality-of-life outcomes across all PD durations, with the most substantial benefits observed in mid-duration (5-10 years) patients. While levodopa response was a consistent positive prognostic factor for motor response, caution is warranted for short-duration patients with rapidly progressive motor symptoms, as they exhibited less favorable outcomes.
脑深部电刺激术(DBS)已越来越多地应用于帕金森病(PD)患者。然而,其手术时机存在广泛争议。本研究旨在评估不同病程帕金森病患者接受DBS的手术效果,并确定关键的预后因素。
在这项多中心队列研究中,纳入了2011年1月1日至2020年12月31日期间来自中国七个有代表性的国家级中心接受丘脑底核DBS的帕金森病患者。相应地分析了两年的随访数据。这些患者被分为病程短(<5年)、病程中(5 - 10年)和病程长(≥10年)的帕金森病组。主要评估指标包括处于未服药状态时的运动障碍协会赞助修订的统一帕金森病评定量表(MDS - UPDRS - III)第三部分、汉密尔顿焦虑评定量表(HAM - A)、汉密尔顿抑郁评定量表(HAM - D)以及帕金森病问卷 - 39(PDQ - 39)量表。分析组内和组间比较时得分的相对变化,并通过多变量线性回归确定预后因素。共筛选出1859例患者,其中1717例患者(749例女性)纳入分析。分别有141例、978例和598例患者在病程短、病程中和病程长时接受手术。MDS - UPDRS - III(未服药)、HAM - A、HAM - D和PDQ - 39的得分分别显著改善了46.7%±14.1%(平均差[MD]25.1,95%置信区间[CI][24.5, 25.7],P < 0.001)、54.4%±22.4%(MD 8.0,95%CI[7.5, 8.5],P < 0.001)、43.4%±22.6%(MD 6.3,95%CI[5.8, 6.8],P < 0.001)和47.9%±17.8%(MD 28.0,95%CI[27.0, 29.0],P < 0.001),所有研究组均取得显著改善(所有P < 0.001)。值得注意的是,病程中期的帕金森病患者在运动结果(与病程短相比:MD 8.0%,95%CI[4.7%, 11.3%],P = 0.008;与病程长相比:MD 5.6%,95%CI[2.8%, 9.4%],P = 0.01)、神经心理学评估(焦虑,与病程长相比:MD 15.2%,95%CI[12.3%, 18.1%],P = 0.002;抑郁,与病程长相比:MD 19.1%,95%CI[15.6%, 22.6%],P < 0.001)以及生活质量(与病程长相比:MD 7.6%,95%CI[5.2%, 10.0%],P = 0.007)方面取得了最大改善。左旋多巴反应(病程短:调整后β 0.42,95%CI[0.30, 0.54],P < 0.001;病程中:调整后β 0.17,95%CI[0.12, 0.22],P < 0.001;病程长:调整后β 0.20,95%CI[0.12, 0.28],P < 0.001)是所有三组运动反应的统一积极因素。较高的MDS - UPDRS - III(未服药)得分(病程中:调整后β 0.10,95%CI[0.05, 0.15],P < 0.001;病程长:调整后β 0.30,95%CI[0.23, 0.38],P < 0.001)与病程中和病程长组的运动结果呈正相关。然而,对于病程短的组,它是一个负因素(调整后β - 0.25,95%CI[-0.36, -0.14],P < 0.001)。本研究的主要局限性在于非随机观察性质引入了潜在的选择偏倚和不平衡比较。
DBS在所有病程的帕金森病患者中均显著改善了运动、神经心理学和生活质量结果,在病程中期(5 - 10年)的患者中观察到的益处最为显著。虽然左旋多巴反应是运动反应一致的积极预后因素,但对于病程短且运动症状快速进展的患者需谨慎,因为他们的结果不太理想。