A Double-Blind Randomised Placebo-Controlled Evaluation of Three Doses of Botulinum Toxin Type A (Dysport^®) in the Treatment of Spastic Equinovarus Deformity after Stroke

Abstract

Background/Objectives: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport^®) in post-stroke calf spasticity. Methods: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. Results: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002–0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators’ and patients’ assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. Conclusion: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.

Botulinum neurotoxins for post‐stroke spasticity in adults: A systematic review

“…23 In three studies global motor function was unchanged, as assessed by the Fugl-Meyer scale 21 and the Rivermead motor assessment. 25,27 Disability was not reduced in BoNT/B treated patients compared with placebo, as measured by the Jebsen test or nine-hole peg test. 28 Information on the frequency and severity of pain was available for eight studies, but these used different methods to assess and score pain; therefore, a metaanalysis could not be performed.…”

“…Concealment of treatment allocation was adequate in two trials 11,26 and unclear in the other nine. 7,10,21,[23][24][25][27][28][29] Blinding of patients and of the outcome assessor was poorly reported in four studies. 10,21,27,29 The Ashworth score was used as a primary outcome measure in all trials, but some trials used the scale as a continuous measure, 7,10,11,21,23,24,28 whereas others used it as a categorical measure.…”

“…10,21,27,29 The Ashworth score was used as a primary outcome measure in all trials, but some trials used the scale as a continuous measure, 7,10,11,21,23,24,28 whereas others used it as a categorical measure. [25][26][27]29 Overall, 29 (3.7%) patients were excluded by the studies after randomization or loss to follow-up: in one study 21 no indication of allocation (BoNT vs. placebo) was given for two dropouts; in the other trials there were 15 BoNT-treated dropouts and 12 placebo-treated dropouts. Five trials performed an intention-to-treat analysis.…”

“…23,24,26,28,29 Baseline spasticity was of comparable severity in the BoNT and placebo groups in seven trials, 11,21,23,24,26,27,29 whereas information on baseline clinical characteristics was considered insufficient in the other four studies. 7,10,25,28 Considering the potential relevance of concomitant drug treatments, rehabilitation, or devices, this information was not reported in seven trials, 7,11,21,24,[27][28][29] whereas one study indicated that no patient received concomitant therapy 23 and three studies reported no between-group differences. 10,25,26 In two studies, 23,29 all patients received a concomitant rehabilitation program.…”

“…In this dose-ranging study, BoNT was injected in the gastrocnemius muscle at the dose of 500, 1,000, or 1,500 Dysport U. 27 No significant reduction of spasticity occurred 4, 8, or 12 weeks after treatment, as measured by the number of patients who had at least a two-point reduction of the Ashworth score.…”