Stroke: botulinum toxin had no clear effect on spasticity.

Clinical bottom line (level 1b-)

  1. Patients with poststroke upper extremity spasticity who are given botulinum toxin type A had no clear difference in mean change in Ashworth score at 16 weeks, than those given placebo.
Simpson et al: Neurology 1996; 46: 1306-1310
Expires December 2002

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: multicentre, USA

39 patients (aged range 29 to 76 years; mean 59, 57% female) At least nine months after stroke with an average elbow and wrist flexor tone of grade 2.5 or higher as measured by the Ashworth scale.

Excluded if
  • unstable clinical course within the last two months before study
  • unwilling to maintain ongoing spasticity treatments throughout the study
  • fixed contracture
  • previous treatment with botulinum toxin type A
  • neurolytic or surgical procedures in the study limb
  • neuromuscular disease


    • Control Group: (n = 10, 10 analysed): placebo
    Experimental Group: (n = 27, 27 analysed): low (75 units), medium (150 units) or high (300 units) of botulinum toxin type A injected into biceps (four sites), flexor carpi radialis (one site) and flexor carpi ulnaris (one site) with EMG guidance.
    The first four patients at each site received 75 units of botulinum or placebo, next four 150 units or placebo and the last four 300 units or placebo.
    95% followed for 16 weeks

    The evidence

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    mean change in Ashworth scores of the wrist (300 units) 0.40
    (1.10)     		0.40
    (0.50)     		0.00
    (-0.84 to 0.84)
    change in Ashworth score of the wrist (150 units) 0.40
    (1.10)     		0.00
    (0.70)     		0.40
    (-0.51 to 1.31)
    change in Ashworth score of the wrist (75 units) 0.40
    (1.10)     		0.10
    (0.60)     		0.30
    (-0.57 to 1.17)
    change in Ashworth score in elbow (300 units) 0.50
    (0.50)     		0.40
    (0.70)     		0.10
    (-0.48 to 0.68)
    change in Ashworth score of elbow (150 units) 0.50
    (0.50)     		0.20
    (0.40)     		0.30
    (-0.14 to 0.74)
    change in Ashworth score of elbow (75 units) 0.50
    (0.50)     		0.40
    (0.50)     		0.10
    (-0.39 to 0.56)

  • At 2, 4 and 6 weeks, change in Ashworth score of the wrist with 300 units of botulinum was both clinically and statistically significant.
  • At weeks 2 and 4, change in Ashworth score of the elbow was both clinically and statistically significant with 300 units of botulinum. At 6 weeks, the change was clinically significant.
  • There were no significant difference in adverse effects between the two groups, but numbers were not given.

    • Comments

    1. By measuring changes at specific joint, rather than in overall functional improvement, it is difficult to use the results of this study.
    2. There was no clear difference in baseline characteristics between the two groups.

    Citation

    1. Simpson DM, Alexander DN, O'Brien CF, et al: Botulinum toxin type A in the treatment of upper extremity spasticity: A randomized, double-blind, placebo-controlled trial. Neurology 1996; 46: 1306-1310
    Contributor: Clare Wotton and Bob Phillips, December 1999
    Reviewer:

    Clinical Question.
    Patient upper extremity spasticity after stroke
    Intervention or Exposure botulinum toxin
    Comparison placebo
    Outcome safety and efficacy