Time course of motor recovery after stroke with and without levodopa: a post hoc 6-month longitudinal analysis of the ESTREL trial.
Trüssel S., Traenka CK., Polymeris A., Enz L., Zietz A., Altersberger VL., Wiesner K., Katan M., Lyrer PA., Goga I., Engelter S., Luft AR., Rottenberger Y., Schwarz A., Medlin F., Müri RM., Seiffge D., Fischer U., Michel P., Peters N., Kägi G., Politz S., Tarnutzer A., Nedeltchev K., Bonati L., Schuster-Amft C., Möller JC., Bujan B., Sandor PS., Gonzenbach R., Mylius V., Lienert C., Held J., Schaedelin S., Hemkens LG., Ford GA., Kaufmann JE., Gensicke H., Engelter ST.
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.