Allison Brashear, M.D., principal investigator and first author of the article, said the results demonstrate a useful treatment for patients with functional disabilities from stroke.
"This is the first large trial to show that botulinum toxin type A improved function and muscle tone following a stroke," said Dr. Brashear, associate professor of neurology at the Indiana University School of Medicine. "A number of studies have demonstrated that botulinum toxin type A decreases muscle rigidity in spastic muscles and one small study has shown functional improvement from this therapy. However, use of the therapy has become common practice so the point of this clinical trial was to assess the effects of one-time treatment on a large, controlled group."
Stroke affects approximately 600 out of every 100,000 people in the United States, with nearly 70 percent of patients surviving the stroke. The prevalence of disabilities associated with stroke, including arm and hand spasticity, is high. Spasticity in upper limbs is especially debilitating because it can interfere with many daily activities, including personal hygiene and dressing.
Nineteen medical institutions were involved over the two-year period of the study. All of the 126 volunteers enrolled in the 12-week study had some degree of spasticity in their wrist or fingers after a stroke. The volunteers were randomized to either a placebo group or a group receiving one-time injections of 200 to 240 units of botulinum toxin type A.
The volunteers were asked to select one of four areas of disability as the principal target of treatment. That area was rated as moderate to severe on a four-point scale for determining degree of disability. The areas targeted for treatment by the patient pertained to perceived disability caused by the spasticity. They were personal hygiene, dressing, pain or limb position – all of which can be affected by a spastic or "frozen" limb. The rating was done at the initiation of the trial and at six weeks, at which time 40 of the 64 participants in the botulinum toxin type A group reported improvement in the selected area of disability. In the placebo group only 17 of the 62 participants reported improvement.
Significant improvement in wrist and finger flexors was observed in the majority of patients one week after the injection. The improvement was sustained at the 12-week follow-up. Participants also showed no adverse reactions to the botulinum toxin type A injections.
Following the conclusion of their participation in the clinical trial, 111 of the 126 participants volunteered to receive up to three additional treatments and each set of injections had positive effects that lasted for at least 12 weeks and, in some cases, as long as 18 to 24 weeks, the study reports.
"The findings suggest that botulinum toxin is useful in improving muscle tone, function and quality of life in patients with wrist and finger spasticity after a stroke," Dr. Brashear concludes.
Allergan, maker of Botox, supported the clinical trial.
In 1989, Botox therapy was approved by the U.S. Food and Drug Administration for the treatment of strabismus (crossed eyes) and blepharospasm (uncontrollable blinking). In December 2000, the FDA approved Botox for the treatment of abnormal head position and neck pain associated with cervical dystonia, a movement disorder characterized by involuntary muscle contractions. This past April, the FDA approved Botox® Cosmetic, botulinum toxin type A, for the temporary improvement in the appearance of moderate to severe forehead wrinkles in adult men and women age 65 or younger.
Journal
New England Journal of Medicine