Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke 1☆,

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Abstract

Childers MK, Brashear A, Jozefczyk P, Reding M, Alexander D, Good D, Walcott JM, Jenkins SW, Turkel C, Molloy PT. Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke. Arch Phys Med Rehabil 2004;85:1063–9.

Objective

To test the hypothesis that intramuscular (IM) botulinum toxin type A (BTX) reduces excessive muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke.

Design

Randomized, double-blind, placebo-controlled, multicenter, 24-week trial.

Setting

Six academic and 13 private US outpatient medical centers.

Participants

Ninety-one patients with a mean age of 60 years (range, 30–79y). Mean time elapsed from ischemic or hemorrhagic stroke to study enrollment was 25.8 months (range, 0.9–226.9mo).

Interventions

Up to 2 treatments of placebo, or 90, 180, or 360U of BTX. Concurrent splinting and physical therapy protocols were permitted, but no changes were allowed during the study.

Main outcome measures

Wrist, elbow, and finger flexor tone assessed by the Modified Ashworth Scale, physician and patient global assessments, pain, FIM instrument, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).

Results

Muscle tone decreased more with injections of BTX than with placebo in the wrist flexors at weeks 1, 2, 3, 6, and 9 (P≤.026); in the elbow flexors at weeks 1, 2, 3, 4, 5, and 9 (P≤.033); and in the finger flexors at weeks 1 and 3 (P≤.031). A dose-dependent response was generally observed in tone reduction but not in pain, FIM, or SF-36 measures.

Conclusions

IM BTX reduced muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke but did not appear to affect global quality of life or disability.

Section snippets

Study population

Patients were 21 to 80 years of age and weighed at least 60kg. Inclusion criteria consisted of (1) a stroke diagnosed by a neurologist, (2) occurrence of a stroke at least 6 weeks prior to study enrollment, (3) focal spasticity of an upper limb shown by excessive wrist flexor muscle tone score of 3 or higher (very severe) and elbow flexor tone score of 2 or more (severe) as measured by the Modified Ashworth Scale (MAS; table 1), and (4) ability to give informed consent and comply with study

Study population

Nineteen centers enrolled 91 participants (61 men, 30 women; mean age, 60y; range, 30.4–79.4y). Demographic characteristics are summarized in table 3. The mean time elapsed from stroke to study enrollment was 25.8 months (range, 0.9–226.9mo).

There was a significant difference among treatment groups for the type of stroke (P=.026), with more thrombotic strokes in the 90U (12/21, 57.1%), 360U (17/21, 81.0%), and placebo groups (15/26, 57.7%) than in the 180U group (7/23, 30.4%). The remaining

Discussion

The main findings from our multicenter study of patients who received 2 sets of IM injections of BTX for excessive upper-limb muscle tone after a stroke are as follows. First, IM BTX reduced excessive muscle tone in the elbow, wrist, and fingers. Second, the tone-reducing effects of BTX were dose dependent. And third, sustained benefit occurred when injections were repeated after 12 weeks.

Our findings are consistent with an earlier multicenter study23 that showed a single set of BTX injections

Conclusions

Data reported here support the hypothesis that IM BTX reduces excessive muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke.

Supplier

Acknowledgements

The BOTOX 133/134 Post-Stroke Spasticity Group is: Cynthia Comella, MD (Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL; Movement and Mobility Center, Des Plaines, IL); Mary Dombovy, MD (St. Mary’s Hospital, Rochester, NY); Gerard Francisco, MD (Kessler Institute for Rehabilitation, East Orange, NJ); Alvin Glass, MD (Kaiser Rehabilitation, Vallejo, CA); Richard Lazar, MD (Schwab Rehabilitation Hospital & Care Network, Chicago, IL); Erwin Montgomery, MD (University of Arizona, Tucson,

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    Copyright © 2004 American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.