Time course of motor recovery after stroke with and without levodopa: a post hoc 6-month longitudinal analysis of the ESTREL trial.
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.
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.
Authors
Trüssel Trüssel, Traenka Traenka, Polymeris Polymeris, Enz Enz, Zietz Zietz, Altersberger Altersberger, Wiesner Wiesner, Katan Katan, Lyrer Lyrer, Goga Goga, Engelter Engelter, Luft Luft, Rottenberger Rottenberger, Schwarz Schwarz, Medlin Medlin, Müri Müri, Seiffge Seiffge, Fischer Fischer, Michel Michel, Peters Peters, Kägi Kägi, Politz Politz, Tarnutzer Tarnutzer, Nedeltchev Nedeltchev, Bonati Bonati, Schuster-Amft Schuster-Amft, Möller Möller, Bujan Bujan, Sandor Sandor, Gonzenbach Gonzenbach, Mylius Mylius, Lienert Lienert, Held Held, Schaedelin Schaedelin, Hemkens Hemkens, Ford Ford, Kaufmann Kaufmann, Gensicke Gensicke, Engelter Engelter
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