Deep brain stimulation surgical timing, outcomes, and prognostic factors in patients with Parkinson’s disease: A Chinese retrospective multicenter cohort study

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BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

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