Authors
Simon Trüssel, Christopher K Traenka, Alexandros Polymeris, Lukas Enz, Annaelle Zietz, Valerian L Altersberger, Karin Wiesner, Mira Katan, Philippe A Lyrer, Irina Goga, Sophia Engelter, Andreas R Luft, Yannik Rottenberger, Anne Schwarz, Friedrich Medlin, René M Müri, David Seiffge, Urs Fischer, Patrik Michel, Nils Peters, Georg Kägi, Svetlana Politz, Alexander Tarnutzer, Krassen Nedeltchev, Leo Bonati, Corina Schuster-Amft, J Carsten Möller, Bartosz Bujan, Peter S Sandor, Roman Gonzenbach, Veit Mylius, Carmen Lienert, Jeremia Held, Sabine Schaedelin, Lars G Hemkens, Gary A Ford, Josefin E Kaufmann, Henrik Gensicke, Stefan T Engelter
Published in
European stroke journal. Volume 11. Issue 7. Jul 06, 2026.
Abstract
Levodopa did not enhance early motor recovery at 3 months after stroke in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial. However, whether levodopa modifies the time course of recovery, leading to a delayed benefit remains unclear. Here, we examined levodopa's effects on the trajectories of motor recovery up to 6 months after stroke.
The ESTREL trial, a double-blind, randomised controlled clinical trial, compared a 39-day regimen of levodopa/carbidopa (100 mg/25 mg, 3×/day) to placebo alongside standardised task-oriented training. We longitudinally analysed Fugl-Meyer Motor Assessment (FMA) total scores (primary outcome), mRS and NIHSS (secondary outcomes) at baseline (0-7 days post stroke), 5 weeks, 3 and 6 months using linear mixed-effects models including timepoint, treatment allocation and their interaction.
In total, 576 of 610 (94%) participants (median age 73 years; 40% female) were analysed. FMA scores improved over time in both groups (P < .001), with no overall levodopa effect across visits (estimate 0.65 points, 95% CI, -3.3 to 4.6; P = .75). There was no indication that levodopa modified the recovery trajectory (χ2 = 0.52, df = 3, P = .91), and estimated levodopa-placebo differences in FMA changes across visit intervals were small, ranging from -0.7 to +0.8 points, with confidence intervals crossing zero. Secondary outcomes showed similar longitudinal improvement, without evidence of a treatment effect.
In this post hoc analysis of ESTREL participants with repeated FMA assessments, motor impairment improved from the first days after stroke up to 6 months. Levodopa added to task-oriented inpatient rehabilitation did not improve motor recovery or alter its trajectory over this period.
NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.
PMID:
42525438
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.
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