近日，瑞士巴塞尔大学Ashraf Eskandari团队研究了左旋多巴加入脑卒中康复方案对患者预后的影响。2025年9月22日出版的《美国医学会杂志》发表了这一最新研究成果。

左旋多巴增强多巴胺能信号传导，可能刺激神经可塑性，可能潜在地促进中风后的运动恢复。左旋多巴用于中风康复，尽管其有效性证据不一。

为了确定左旋多巴与安慰剂相比，在基于主动任务导向训练的标准化康复治疗之外，是否与急性卒中患者的运动恢复增强有关，研究组在瑞士的13个中风单位和中心以及11个合作康复中心进行了一项双盲、安慰剂对照的随机临床试验。在2019年6月14日（第一例患者，第一次就诊）至2024年8月27日（最后一例患者，最后一次就诊）期间，610例急性缺血性或出血性卒中伴临床意义偏瘫患者（即，在美国国立卫生研究院卒中量表中：运动臂、运动腿或肢体共济失调的总分≥3分）被1:1随机分配接受左旋多巴或安慰剂治疗。统计分析时间为2024年11月至2025年8月。

患者接受左旋多巴/卡比多巴(100mg / 25mg; n=307)或安慰剂(n=303)每天3次，持续39天，同时进行基于积极任务导向训练的标准化康复治疗。主要结局是3个月时Fugl-Meyer评估（FMA）总分（范围0-100分；越少表示运动功能越差；6分的差异被认为与患者相关）的调整后平均组间差异。

在610名参与者中（[IQR]年龄中位数为73[64-82]岁；252[41.3%]名女性；基线FMA总分中位数为34[14-54]），28名参与者在3个月内死亡，582名（95.4%）参与者符合初步分析。3个月时，左旋多巴组的中位（IQR） FMA总分为68（42-85）分，安慰剂组为64（44-83）分。左旋多巴组与安慰剂组FMA总分的平均差异为0.90分（95% CI, 3.78 ~ 1.98; P = 0.54）。左旋多巴组严重不良事件126例，安慰剂组129例；最常见的是感染（左旋多巴，n = 55；安慰剂，n = 44）。

研究结果表明，在这项随机临床试验中，在接受急性卒中住院康复的患者中，与安慰剂加标准化康复相比，左旋多巴加标准化康复在3个月时没有显著改善运动功能。这些结果不支持使用左旋多巴作为辅助康复治疗来增强急性中风后的运动恢复。

附：英文原文

Title: Levodopa Added to Stroke Rehabilitation: The ESTREL Randomized Clinical Trial

Author: Stefan T. Engelter, Josefin E. Kaufmann, Annaelle Zietz, Andreas R. Luft, Alexandros Polymeris, Valerian L. Altersberger, Karin Wiesner, Martina Wiegert, Jeremia P. O. Held, Yannik Rottenberger, Anne Schwarz, Friedrich Medlin, Ettore A. Accolla, Sandrine Foucras, Georg Kgi, Gian Marco De Marchis, Svetlana Politz, Matthias Greulich, Alexander A. Tarnutzer, Rolf Sturzenegger, Mira Katan, Urs Fischer, Krassen Nedeltchev, Janine Schr, Katrien Van Den Keybus Deglon, Pierre-André Rapin, Alexander Salerno, David J. Seiffge, Elias Auer, Julian Lippert, Leo H. Bonati, Corina Schuster-Amft, Szabina Gumann, Joelle N. Chabwine, Andrea Humm, J. Carsten Mller, Raoul Schweinfurther, Bartosz Bujan, Piotr Jedrysiak, Peter S. Sandor, Roman Gonzenbach, Veit Mylius, Dietmar Lutz, Carmen Lienert, Nils Peters, Patrik Michel, René M. Müri, Sabine Schdelin, Lars G. Hemkens, Gary A. Ford, Philippe A. Lyrer, Henrik Gensicke, Christopher Traenka, ESTREL Investigators, Krassen Nedeltchev, Timo Kahles, Sandra Clarke, Catharina Fritz-Rochner, Alexander Tarnutzer, Loric Berney, Manuela Buehrer, Karin Diserens, Alexandra Dos Reis Moreira, Grégoire Eberle, Ashraf Eskandari

Issue&Volume: 2025-09-22

Abstract:

Importance  Levodopa enhances dopaminergic signaling and may stimulate neuroplasticity, which could potentially enhance motor recovery after stroke. Levodopa is used in stroke rehabilitation despite mixed evidence for its effectiveness.

Objective  To determine whether levodopa compared with placebo, administered in addition to standardized rehabilitation based on active task-oriented training, is associated with enhanced motor recovery in patients with acute stroke.

Design, Setting, and Participants  A double-blind, placebo-controlled randomized clinical trial at 13 stroke units and centers and 11 collaborating rehabilitation centers in Switzerland. Between June 14, 2019 (first patient, first visit), and August 27, 2024 (last patient, last visit), 610 patients with acute ischemic or hemorrhagic stroke with clinically meaningful hemiparesis (ie, a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo. Statistical analyses were conducted from November 2024 to August 2025.

Intervention  Patients received levodopa/carbidopa (100 mg/25 mg; n=307) or placebo (n=303) 3 times daily for 39 days, alongside standardized rehabilitation therapy based on active task-oriented training.

Main Outcomes and Measures  The primary outcome was the adjusted mean between-group difference in the Fugl-Meyer Assessment (FMA) total score (range, 0-100 points; fewer points indicate worse motor function; 6-point difference considered patient-relevant) at 3 months.

Results  Among the 610 participants (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]), 28 participants died by 3 months, leaving 582 (95.4%) participants eligible for the primary analysis. At 3 months, the median (IQR) FMA total score was 68 (42-85) points in the levodopa group and 64 (44-83) points in the placebo group. The mean difference in the FMA total score between the levodopa and placebo groups was 0.90 points (95% CI, 3.78 to 1.98; P=.54). There were 126 serious adverse events in the levodopa group and 129 in the placebo group; the most common was infection (levodopa, n=55; placebo, n=44).

Conclusions and Relevance  In this randomized clinical trial, among patients receiving inpatient rehabilitation for acute stroke, levodopa added to standardized rehabilitation did not significantly improve motor function at 3 months compared with placebo plus standardized rehabilitation. These results do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke.

DOI: 10.1001/jama.2025.15185

Source: https://jamanetwork.com/journals/jama/fullarticle/2839112