Time course of motor recovery after stroke with and without levodopa: a post hoc 6-month longitudinal analysis of the ESTREL trial.
Publisher DOI
PubMed ID
42525438
Abstract
Introduction
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.Patients And Methods
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.Results
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.Conclusion
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.Clinical Trial Registration
NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.
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.Patients And Methods
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.Results
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.Conclusion
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.Clinical Trial Registration
NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1.
Date Issued
2026-07-06
Publication Type
Article
Subject(s)
Subjects
Fugl-Meyer Motor Assessment
•
dopamine agents
•
enhancement
•
levodopa
•
recovery of function
•
rehabilitation
Language(s)
en
Author(s)
Trüssel, Simon | |
Traenka, Christopher K | |
Polymeris, Alexandros | |
Enz, Lukas | |
Zietz, Annaelle | |
Altersberger, Valerian L | |
Wiesner, Karin | |
Katan, Mira | |
Goga, Irina | |
Engelter, Sophia | |
Rottenberger, Yannik | |
Schwarz, Anne | |
Michel, Patrik | |
Peters, Nils | |
Politz, Svetlana | |
Tarnutzer, Alexander | |
Schuster-Amft, Corina | |
Möller, J Carsten | |
Bujan, Bartosz | |
Sandor, Peter S | |
Gonzenbach, Roman | |
Mylius, Veit | |
Held, Jeremia | |
Schaedelin, Sabine | |
Ford, Gary A | |
Kaufmann, Josefin E | |
Gensicke, Henrik | |
Engelter, Stefan T |
Journal
European Stroke Journal
Publisher
Oxford University Press
ISSN
2396-9881
2396-9873
Access(Rights)
open.access