Does low-dose botulinum toxin help the recovery of arm function when given early after stroke? A phase II randomized controlled pilot study to estimate effect size

Objective: Spasticity after stroke may be associated with worse functional outcome. Our study aim is to establish whether a low dose of botulinum toxin, given early post stroke before clinically evident spasticity warrants treatment, will improve recovery of arm function. Design: A double-blind randomized placebo-controlled trial. Setting: An acute stroke unit. Subjects: Individuals recruited within three weeks of stroke onset with severe arm function deficits. Interventions: Injections of quarter and half standard dose botulinum toxin A to the upper limb, with a control of normal saline injections. Main measures: Arm function, active and passive movement, and spasticity at elbow and wrist were recorded at baseline, and at 4, 8, 12 and 20 weeks post intervention. A pre-planned subgroup analysis included only subjects with no arm function at baseline (Action Research Arm Test score = 0). Results: Thirty subjects were recruited, and 21 completed all assessments. Arm function scores improved in all three groups between baseline and week 20. There was no benefit for active treatment over control in the whole group analysis. In the subgroup analysis the active groups improved when compared with the control group and effect sizes for improvement in this subgroup were 0.6 and 0.5 for the quarter dose and half dose groups respectively. Conclusions: Individuals with no arm function within three weeks of stroke may benefit functionally from botulinum toxin. Using the effect size of 0.5, further studies would need a minimum of 101 participants in each group to confirm this finding.