Porta Mauro, Servello Domenico, Zekaj Edvin, Gonzalez-Escamilla Gabriel, Groppa Sergiu
Center for Movement Disorders and Tourette Syndrome, Galeazzi Hospital, Milan, Italy.
Functional Neurosurgery Unit, Galeazzi Hospital, Milan, Italy.
Front Neurosci. 2020 Jun 5;14:492. doi: 10.3389/fnins.2020.00492. eCollection 2020.
Deep brain stimulation (DBS) is an established therapy for the management of Parkinson's disease (PD). However, DBS is indicated as the disease progresses and motor complications derived from pharmacological therapy arise. Here, we evaluate the potential of DBS prior to levodopa (L-Dopa) in improving quality of life (QoL), challenging the state of the art for DBS therapy. We present data on clinical manifestation, decision finding during early indication to DBS, and trajectories after DBS. We further discuss current paradigms for DBS and hypothesize on possible mechanisms. Six patients, between 50 and 67 years old, presenting at least 5 years of PD symptoms, and without L-Dopa therapy initiation, received subthalamic nucleus (STN) DBS implantation. In the six PD cases, indication for DBS was not driven by motor complications, as supported by current guidelines, but by relevant QoL impairment and patient's reluctance to initiate L-Dopa treatment. All patients treated with STN-DBS prior to L-Dopa presented improvement in motor and non-motor symptoms and significant QoL improvement. All patients reduced the intake of dopamine agonists, and five are currently free from L-Dopa medication, with no reported adverse events. We introduce a multicenter observational study to investigate whether early DBS treatment may affect the natural course of PD. Early application of DBS instead of L-Dopa administration could have a pathophysiological basis and be prompted by a significant incline on QoL through disease progression; however, the clinical value of this proposed paradigm shift should be addressed in clinical trials aimed at modulating the natural course of PD.
深部脑刺激（DBS）是治疗帕金森病（PD）的一种既定疗法。然而，DBS适用于疾病进展且出现药物治疗引起的运动并发症时。在此，我们评估在左旋多巴（L-Dopa）治疗之前进行DBS对改善生活质量（QoL）的潜力，挑战DBS治疗的现有技术水平。我们展示了关于临床表现、DBS早期适应证决策以及DBS术后病程的数据。我们进一步讨论了当前的DBS范式并对可能的机制进行了假设。6例年龄在50至67岁之间、患有至少5年PD症状且未开始L-Dopa治疗的患者接受了丘脑底核（STN）DBS植入。在这6例PD病例中，DBS的适应证并非如当前指南所支持的那样由运动并发症驱动，而是由相关的QoL损害和患者不愿开始L-Dopa治疗所驱动。所有在L-Dopa治疗之前接受STN-DBS治疗的患者运动和非运动症状均有改善，QoL显著提高。所有患者减少了多巴胺激动剂的摄入量，5例目前无需服用L-Dopa药物，且未报告不良事件。我们开展了一项多中心观察性研究，以调查早期DBS治疗是否可能影响PD的自然病程。早期应用DBS而非L-Dopa给药可能有病理生理学基础，并可能因疾病进展导致QoL显著下降而促使采取这一措施；然而，这一提出的范式转变的临床价值应在旨在调节PD自然病程的临床试验中得到探讨。
