A prospective, multicentre, randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke.

Objective: To examine the safety and efficacy of onabotulinumtoxinA (Botox) for plantarflexor overactivity following stroke.

Design: Double-blind randomized controlled trial, open-label extension phase.

Setting: Neurology rehabilitation facilities.

Subjects: Eighty-five subjects with lower limb hypertonia received 200 U (n = 28) or 300 U (n = 28) of onabotulinumtoxinA or saline (n = 29) injection.

Primary Measures: Plantarflexor Ashworth scores at 12 weeks post injection and adverse events. Secondary measures: self-reported spasm frequency and pain, physician rating of hypertonia severity, gait quality and active dorsiflexion.

Results: Differences were not seen between onabotulinumtoxinA groups; hence data were pooled. Incidence of adverse events was not different between groups (P = 0.61). Reduction in hypertonia was not different between groups at 12 weeks (P = 0.53); however for subjects with Ashworth scores of >3 at baseline, 14/31 in the onabotulinumtoxinA group demonstrated a reduction of >1 grade versus 1/17 receiving placebo injection (P = 0.01). Overall, onabotulinumtoxinA-injected subjects demonstrated significantly greater improvement in spasm frequency (22/54 versus 4/29, P = 0.01), pain reduction (8/54 versus 1/29, P = 0.02), active dorsiflexion (8/54 versus 1/29 P = 0.03) and gait quality (17/54 versus 6/29, P = 0.02) than controls. In the open-label phase, a second onabotulinumtoxinA injection was associated with greater hypertonia reduction (P = 0.005) and gait quality (P = 0.002) compared with single injection.

Conclusions: OnabotulinumtoxinA injection for ankle flexor overactivity after stroke was safe and well tolerated but did not alter local spasticity at 12 weeks; it did reduce spasms and improve gait quality. There were no detectable differences between higher and lower doses. A second injection may be associated with greater change.