During this year’s “Stroke Summer School 2021” in Basel, Switzerland, Stefan Engelter (Stroke Unit, University Hospital Basel, Switzerland) provided an overview of what is known about the use of dopamine in stroke rehabilitation and showed unpublished data from the Swiss Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial.
Brain plasticity is crucial in stroke rehabilitation
“Stroke rehabilitation is based on the principle of learning”, Dr Engelter started his presentation. There are various elements of motoric learning that are important in the rehabilitation process, including actively exercising, repetitions and breaks, goals, feedback and adjustments of goals and exercises. The ultimate goal of motoric learning in stroke rehabilitation is the establishment of new and optimised neuronal networks. By utilising the plasticity of the brain, pharmacological interventions might be able to enhance stroke recovery via the remodelling of these networks.
Dopamine as potential pharmacological intervention in stroke rehabilitation
Dopamine is a neurotransmitter that is connected to various brain performances, including attention, memory, motivation, drive and creativity. That is why its precursor molecule levodopa is already established in the treatment of Parkinson’s disease. “The question is: Is levodopa also useful in stroke rehabilitation?”, Dr Engelter asked during his talk. It has been previously shown in healthy subjects that levodopa can enhance word learning capacities and to improve balance on a straight line.1,2
New trial studying levodopa use
Conflicting results are currently published regarding dopamine use in stroke rehabilitation.3,4 However, Dr Engelter presented the results of an unpublished explorative meta-analysis that showed a small non-significant trend towards a better motor outcome with levodopa in a highly heterogeneous patient population. In that analysis, drug safety concerns were completely absent. Furthermore, Dr Engelter is involved in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) (clinicaltrials.gov: NCT03735901) randomised, placebo-controlled multicentre clinical trial in Switzerland. The study, which currently has a recruiting rate of 44.4% and will include 610 stroke patients, aims to identify potential patient-relevant enhancements of functional motor recovery with levodopa in addition to rehabilitative therapies. Patients are randomised to levodopa or placebo in addition to standardised therapy sessions according to the principles of motor learning. The primary outcome of the study is the in-between group difference in the Fugl-Meyer-Motor Assessment at 3 months.
Effectiveness of levodopa still to be shown
Dr Engelter continued his talk by presenting interim safety data from the ESTREL trial. A recent evaluation on 200 patients showed low percentages of pre-specified serious adverse events (SAEs), with arrhythmias being the most common event reported in 4.2% of patients, and hallucinations and confusion being the second most common events occurring in 1.4% of patients. Non-predefined SAEs included infection (25%), stroke (17.6%) and trauma (8.8%). “These interim safety data are encouraging, but effectiveness is still to be shown”, Dr Engelter concluded. More solid trial data is still required to ensure that the approach of adding dopamine in the stroke rehabilitation process is safe and effective.