Background. Limited data are available about the effectiveness of early rehabilitation after stroke. Objective. This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome. Methods. Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand. Results. Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS. Conclusions. Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.

Disclosure StatementThis study was conceived and initiated by the investigators and supported by the Moody Foundation with additional support from Cephalon, Inc. Dr. Wilde has also received research support from Northstar Corporation. Dr. Masel has also received research support from and has participated in speaking engagements for Pfizer. Drs. Castriotta, Lai, Atanasov, and Kuna have reported no other financial conflicts of interest.

Background and Purpose-A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late (days to weeks) after brain injury in animals. A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke. To determine whether these findings extend to communication deficits subsequent to stroke, we administered dextroamphetamine, paired with speech/language therapy, to patients with aphasia. Methods-In a prospective, double-blind study, 21 aphasic patients with an acute nonhemorrhagic infarction were randomly assigned to receive either 10 mg dextroamphetamine or a placebo. Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions. Thirty minutes after drug/placebo administration, subjects received a 1-hour session of speech/language therapy. The Porch Index of Communicative Ability was used at baseline, at 1 week off the drug, and at 6 months after onset as the dependent language measure. Results-Although there were no differences between the drug and placebo groups before treatment (Pϭ0.807), by 1 week after the 10 drug treatments ended there was a significant difference in gain scores between the groups (Pϭ0.0153), with the greater gain in the dextroamphetamine group. The difference was still significant when corrected for initial aphasia severity and age. At the 6-month follow-up, the difference in gain scores between the groups had increased; however, the difference was not significant (Pϭ0.0482) after correction for multiple comparisons. Conclusions-Administration of dextroamphetamine paired with 10 1-hour sessions of speech/language therapy facilitated recovery from aphasia in a small group of patients in the subacute period after stroke. Neuromodulation with dextroamphetamine, and perhaps other drugs that increase central nervous system noradrenaline levels, may facilitate recovery when paired with focused behavioral treatment.