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Levodopa And Physiotherapy Combined Aids Stroke Recovery

A combination of the neurotransmitter precursor levodopa and physiotherapy appears to improve motor recovery for stroke patients.

Dr. Klaus Scheidtmann and colleagues at the Neurological Hospital Bad Aibling, Bad Aibling, Germany, believe that because of minimal side effects, levodopa could be a possible add-on during stroke rehabilitation.

He and his colleagues point out that physiotherapy used to be the only way of improving motor function in patients with hemiplegia. However, administration of amphetamines in addition to exercise improves motor recovery in animal models, probably by increasing the concentration of norepinephrine in the central nervous system.

Their trial was designed to see whether levodopa could enhance the efficacy of physiotherapy after hemiplegia.

Systemic administration of norepinephrine might have potentially dangerous cardiovascular side effects, though no clinically important adverse events have been recorded, the clinicians said. However, physical and psychological dependence cannot be excluded, and this restricts its use.

To increase norepinephrine, but avoid these effects, levodopa is given orally; it is then metabolised to dopamine in the brain and converted to norepinephrine at a rate of up to 5 percent. In the periphery, metabolism is blocked by a decarboxylase inhibitor, which does not cross the blood-brain barrier.

Dr. Scheidtmann and colleagues enrolled 53 primary stroke patients in a prospective, randomised study. For the first three weeks, patients received single doses of 100 mg levodopa or placebo daily in combination with physiotherapy. For the second three weeks, patients had only physiotherapy.

Motor function was assessed every week by Rivermead motor assessment (RMA).

Motor recovery was substantially improved after three weeks in patients given levodopa (RMA improved by 6.4 points) compared with placebo (RMA 4.1) Result was independent of initial degree of impairment. The advantage of the levodopa group was maintained three weeks after levodopa administration was stopped.

At the end of the study, the total RMA score gain for the levodopa group was 8.2 points compared with 5.7 in the placebo group.

Dr. Friedemann Müller, one of the investigators in the study, said of the results: "A single dose of levodopa was well tolerated and, when given in combination with physiotherapy, was found to enhance motor recovery in patients with hemiplegia.

"This trend should be confirmed, and we need to establish long-term ceiling effects, which our short observation period did not allow us to judge. We should also ascertain to what extent the lesion size and amount of levodopa affect enhanced functional recovery."
Lancet 2001; 358: 787-90. "Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study"

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