Combining cyproheptadine hydrochloride with targeted muscle activation training to treat upper extremity stroke: a randomized, placebo-controlled trial.

OBJECTIVE: To examine a treatment for upper extremity impairment in stroke survivors that combines administration of cyproheptadine hydrochloride with repetitive practice focused on control of muscle activation patterns. DESIGN: Double-blind, randomized controlled trial. SETTINGS: Laboratory within free-standing rehabilitation hospital. PARTICIPANTS: A total of 94 stroke survivors with severe, chronic hand impairment were randomly assigned to one of four treatment groups. INTERVENTIONS: Participants received either placebo or cyproheptadine hydrochloride in identical pill form. Daily dosage of cyproheptadine/placebo was gradually increased from 8 mg/day to 24 mg/day over three weeks and then maintained over the next 6 weeks while participant completed 18 therapy sessions. Therapy consisted of either: (1) active practice of muscle activation patterns to play "serious" computer games or control a custom hand exoskeleton or (2) passive, cyclical finger stretching imposed by the exoskeleton. MAIN OUTCOME MEASURES: Hand control was evaluated with the primary outcome measure of time to complete the Graded Wolf Motor Function Test (GWMFT) and secondary outcome measures including finger strength and spasticity. RESULTS: Across the 88 participants who completed the study, a repeated measures ANOVA revealed a significant effect of GroupxEvaluation interaction on GWMFT (F=1.996, p=0.026). The three groups receiving cyproheptadine and/or actively practicing muscle activation pattern control exhibited significant reduction in mean time to complete the GWMFT tasks; roughly one-third of these participants experienced at least 10% reduction in completion time. Gains were maintained at the one-month follow-up evaluation. The group receiving placebo and passive stretching did not show improvement. No significant differences among groups were observed in terms of changes in strength or spasticity. CONCLUSIONS: Despite chronic, severe impairment, stroke survivors were able to complete the therapy focused on muscle activations and achieved statistically significant improvement in hand motor control. Cyproheptadine hydrochloride affords a potential complementary treatment modality for stroke survivors with hand impairment.

Use of an EMG-Controlled Game as a Therapeutic Tool to Retrain Hand Muscle Activation Patterns Following Stroke: A Pilot Study.

BACKGROUND/PURPOSE: To determine the feasibility of training with electromyographically (EMG) controlled games to improve control of muscle activation patterns in stroke survivors. METHODS: Twenty chronic stroke survivors (>6 months) with moderate hand impairment were randomized to train either unilaterally (paretic only) or bilaterally over 9 one-hour training sessions. EMG signals from the unilateral or bilateral limbs controlled a cursor location on a computer screen for gameplay. The EMG muscle activation vector was projected onto the plane defined by the first 2 principal components of the activation workspace for the nonparetic hand. These principal components formed the x- and y-axes of the computer screen. RESULTS: The recruitment goal (n = 20) was met over 9 months, with no screen failure, no attrition, and 97.8% adherence rate. After training, both groups significantly decreased the time to move the cursor to a novel sequence of targets (P = 0.006) by reducing normalized path length of the cursor movement (P = 0.005), and improved the Wolf Motor Function Test (WMFT) quality score (P = 0.01). No significant group difference was observed. No significant change was seen in the WMFT time or Box and Block Test. DISCUSSION/CONCLUSIONS: Stroke survivors could successfully use the EMG-controlled games to train control of muscle activation patterns. While the nonparetic limb EMG was used in this study to create target EMG patterns, the system supports various means for creating target patterns per user desires. Future studies will employ training with the EMG-controlled games in conjunction with functional task practice for a longer intervention duration to improve overall hand function.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A379).

Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke.

OBJECTIVES: The goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors. MATERIALS AND METHODS: A randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression. RESULTS: 89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial. CONCLUSIONS: Use of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance. REGISTRATION: Clinical Trial number: NCT02418949.