Roediger Jan, Dembek Till A, Achtzehn Johannes, Busch Johannes L, Krämer Anna-Pauline, Faust Katharina, Schneider Gerd-Helge, Krause Patricia, Horn Andreas, Kühn Andrea A
Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Einstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Neurology, Faculty of Medicine, University of Cologne, Cologne, Germany.
Lancet Digit Health. 2023 Feb;5(2):e59-e70. doi: 10.1016/S2589-7500(22)00214-X. Epub 2022 Dec 15.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson's disease. However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We aimed to assess treatment effects of stimulation parameters suggested by a recently published algorithm (StimFit) based on neuroimaging data.
This double-blind, randomised, crossover, non-inferiority trial was carried out at Charité - Universitätsmedizin, Berlin, Germany, and enrolled patients with Parkinson's disease treated with directional octopolar electrodes targeted at the STN. All patients had undergone DBS programming according to our centre's standard of care (SoC) treatment before study recruitment. Based on perioperative imaging data, DBS electrodes were reconstructed and StimFit was applied to suggest optimal stimulation settings. Patients underwent motor assessments using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) during OFF-medication and in OFF-stimulation and ON-stimulation states under both conditions, StimFit and SoC parameter settings. Patients were randomly assigned (1:1) to receive either StimFit-programmed DBS first and SoC-programmed DBS second, or SoC-programmed DBS first and StimFit-programmed DBS second. The allocation schedule was generated using a computerised random number generator. Both the rater and patients were masked to the sequence of SoC and StimFit stimulation conditions. All patients who participated in the study were included in the analysis. The primary endpoint of this study was the absolute mean difference between MDS-UPDRS-III scores under StimFit and SoC stimulation, with a non-inferiority margin of 5 points. The study was registered at the German Register for Clinical Trials (DRKS00023115), and is complete.
Between July 10, 2020, and Oct 28, 2021, 35 patients were enrolled in the study; 18 received StimFit followed by SoC stimulation, and 17 received SoC followed by StimFit stimulation. Mean MDS-UPDRS-III scores improved from 47·3 (SD 17·1) at OFF-stimulation baseline to 24·7 (SD 12·4) and 26·3 (SD 12·4) under SoC and StimFit stimulation, respectively. Mean difference between motor scores was -1·6 (SD 7·1; 95% CI -4·0 to 0·9; superiority test p=0·20; n=35), establishing non-inferiority of StimFit stimulation at a margin of -5 points (non-inferiority test p=0·0038). In six patients (17%), initial programming of StimFit settings resulted in acute side-effects and amplitudes were reduced until side-effects disappeared.
Automated data-driven algorithms can predict stimulation parameters that lead to motor symptom control comparable to SoC treatment. This approach could significantly decrease the time necessary to obtain optimal treatment parameters.
Deutsche Forschungsgemeinschaft through NeuroCure Clinical Research Center and TRR 295.
丘脑底核（STN）的深部脑刺激（DBS）在控制帕金森病患者的运动症状方面非常有效。然而，正确选择刺激参数是治疗成功的关键，目前这一过程需要耗时且费力地反复试验。我们旨在评估基于神经影像数据的一种最近发表的算法（StimFit）所建议的刺激参数的治疗效果。
这项双盲、随机、交叉、非劣效性试验在德国柏林的夏里特大学医学中心进行，纳入了使用定向八极电极靶向STN进行治疗的帕金森病患者。所有患者在研究招募前均已根据我们中心的标准治疗（SoC）进行了DBS程控。基于围手术期影像数据，重建DBS电极并应用StimFit来建议最佳刺激设置。患者在药物未起效状态下以及在两种情况下（StimFit和SoC参数设置）的刺激关闭和刺激开启状态下，使用运动障碍协会支持的统一帕金森病评定量表第三部分（MDS-UPDRS-III）进行运动评估。患者被随机分配（1:1），先接受StimFit程控的DBS，后接受SoC程控的DBS，或者先接受SoC程控的DBS，后接受StimFit程控的DBS。分配方案使用计算机随机数生成器生成。评估者和患者均对SoC和StimFit刺激条件的顺序不知情。所有参与研究的患者均纳入分析。本研究的主要终点是StimFit和SoC刺激下MDS-UPDRS-III评分的绝对平均差异，非劣效界值为5分。该研究已在德国临床试验注册中心（DRKS00023115）注册，且已完成。
在2020年7月10日至2021年10月28日期间，35名患者纳入研究；18名患者先接受StimFit刺激，后接受SoC刺激，17名患者先接受SoC刺激，后接受StimFit刺激。在刺激关闭基线时，MDS-UPDRS-III平均评分从47.3（标准差17.1）分别改善至SoC刺激下的24.7（标准差12.4）和StimFit刺激下的26.3（标准差12.4）。运动评分的平均差异为-1.6（标准差7.1；95%置信区间-4.0至0.9；优效性检验p=0.20；n=35），确定了StimFit刺激在-5分的界值下的非劣效性（非劣效性检验p=0.0038）。6名患者（17%）在初始设置StimFit参数时出现急性副作用，刺激幅度降低直至副作用消失。
自动化的数据驱动算法可以预测出与SoC治疗相当的能控制运动症状的刺激参数。这种方法可以显著减少获得最佳治疗参数所需的时间。
德国研究基金会通过神经治疗临床研究中心和TRR 295提供资金。
