Dopamine in Stroke

Abstract & Commentary

Source: Scheidtmann K, et al. Lancet. 2001;358:787-790.

Twenty or more years ago, laboratory investigators found that rats suffering severe cerebral damage rapidly improved their motor behavior in response to systemically applied amphetamine. These findings led to human pharmacological trials incorporating amphetamine or methylphenidate along with vigorous physiotherapy, the latter factor being imperative. Each study up to now followed a different, institution-developed pattern. Crisostomo and colleagues (Ann Neurol. 1988;23:94-97) used only 1 oral dose of 10 mg amphetamine in 4 patients, 2 of whom increased arm and leg function moderately well and the other 2 only minimally. The 4 who did not take amphetamine developed essentially no improvement.

Walker-Batson and colleagues treated 10 hemiplegics with 10 mg amphetamine started between 16 and 30 days after stroke onset and repeated the agent every 4 days thenceforth (Stroke. 1995;26:2254-2259). Ten other hemiplegics received placebos in the same order. In the case of complications or a necessity to remove a person by either arm of the study, a substitute was obtained to replace the subject. Each person in each of the 2 groups was tested 1 week and evaluated again 1 year following the end of amphetamine treatment. At the end of 1 week and 1 year later the amphetamine group reported significant, permanent improvement (P = .047). The contribution appears to have provided the first good effort to facilitate specific, intentional skeletal motor activities beyond standard physiotherapy.

Grade and colleagues conducted a study similar to the above, blindly using methylphenidate for 3 weeks compared to a standard, double-blinded placebo (Arch Phys Med Rehabil. 1998;79:1047-1050). Five patients out of 11 finished methylphenidate 15 mg daily with the others tapering or on nonsurpassing lower amounts. Patients receiving methylphenidate showed less depression, more success in activity of daily life, and improved motor recovery. Compared to all caregivers, however, only the therapists directly identified particular patient’s singular improvement.

Scheidtmann and colleagues chose to use dopamine to ameliorate the degree of motor paralysis following severe cerebral infarction. Patients with aphasia were not chosen for this first effort.

Out of 53 randomized patients with severe dysfunctional cerebral hemispheric motor strokes, 22 were started and finished on levodopa/carbidopa. At the same time, 27 similar patients received placebos from the start. Each hemiplegic patient started with 1 week free of all drugs related to norepinephrine. For the next 3 weeks, 22 patients took levodopa-carbidopa 100 mg daily at least 30 minutes before physiotherapy. In the second week and onward, both groups received 1 hour of physiotherapy, 5 each week, but took no more levodopa. Among the stroke cohort, 39 of the 47 patients had either middle or (1) middle-anterior cerebral artery infarctions, and the remainder were strictocapsular or lacunar strokes. Following the seventh week, mean Rivermead motor assessment (RMA) indicated that the levodopa group both walked independently and had significant improvement of arm function compared to the nontreated patients. Almost all patients in both groups continued to improve after the sixth week. Also, the difference between the levodopa and nonlevodopa patients continued to remain more functional than the nonlevodopa patients (see Figures 1 and 2: click here).

Commentary

Considerable differences mark levodopa compared to the amphetamines, which exert their energy on behavioral activity and, sometimes, accentuate athletic function. Dopamine, however, has cofunctions with the basal ganglia as well as using about 1% of its function on neosynephrine receptors. This novel report shows a promising improvement for levodopa in cerebral function due to large strokes. The program needs to be duplicated but would seem to have a promising future in neuro-rehabilitation. —Fred Plum

Dr. Plum, University Professor, Weill Medical College, and Attending Neurologist, New York Presbyterian Hospital, is Editor of Neurology Alert.