From INSERM 1127 (B.L., N.M., Y.A., M.V., C.K., M.-L.W.), Sorbonne Universités, Université Pierre et Marie Curie-Paris Université Paris 06 6, Unité Mixte de Recherche (UMR) S1127, Centre National de la Recherche Scientifique (CNRS), UMR 7225, Institut du Cerveau et de la Moelle Epinière, Paris, France; Department of Neurology (N.M., M.S.), Hôpital Universitaire de Bern, Switzerland; Clinical Investigation Centre (N.M., G.S.), Department of Neurology (V.C., D.G., M.V.), and Department of Neurosurgery (S.N., P.C., C.K.), Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris; and Department of Neurophysiology (M.-L.W.), CHU Charles Nicolle, Rouen University, France.
Neurology. 2019 May 28;92(22):e2559-e2570. doi: 10.1212/WNL.0000000000007562. Epub 2019 May 1.
To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS).
Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms "off" and "on" levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality.
Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery ("on" dopamine/"on" STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score).
We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.
在接受丘脑底核深部脑刺激 (STN-DBS) 治疗后进行长期随访的大型帕金森病 (PD) 患者队列中，描述疾病进展与死亡率的关系。
对 143 例连续 PD 患者在 STN-DBS 前和 STN-DBS 后 1、2、5 和 10 年进行运动和认知障碍评估。我们测量了“关”和“开”左旋多巴和 STN-DBS 时的运动症状，并记录了死亡原因。我们使用线性混合模型描述症状进展，包括治疗条件和时间之间的相互作用，以确定治疗如何改变疗效。我们使用联合模型将症状进展与死亡率联系起来。
手术后中位观察时间为 12 年，在此期间，运动迟缓和僵硬以及轴性症状恶化，术后 1-10 年分别平均增加 8.8（6.5）、1.8（3.1）和 5.4（4.1）分（“开”多巴胺/“开”STN-DBS）。随着时间的推移，对多巴胺能药物和 STN-DBS 的反应减弱，但除轴性症状外，所有药物均保持有效，预计 20 年后轴性症状两种治疗方法及其联合治疗均无效。认知状态显著下降。41 例患者死亡，术后中位死亡时间为 9 年。当前的轴性残疾程度是唯一显著预测死亡的症状（风险比 4.30 [SE 1.50]/每单位平方根转换的轴性评分）。
我们量化了 PD 患者的长期症状进展和多巴胺能药物和 STN-DBS 治疗效果的衰减，并将症状进展与死亡率联系起来。轴性残疾显著预测手术后个体死亡风险，这可能对 PD 的治疗策略规划有用。
