Background: OnabotulinumtoxinA (BoNT-A) can temporarily decrease spasticity following stroke, but whether there is an associated improvement in upper limb function is less clear. This study measured the benefit of adding weekly rehabilitation to a background of BoNT-A treatments for chronic upper limb spasticity following stroke. Methods: This was a multi-center clinical trial. Thirty-one patients with post-stroke upper limb spasticity were treated with BoNT-A. They were then randomly assigned to 24 weeks of weekly upper limb rehabilitation or no rehabilitation. They were injected up to two times, and followed for 24 weeks. The primary outcome was change in the Fugl–Meyer upper extremity score, which measures motor function, sensation, range of motion, coordination, and speed. Results: The ‘rehab’ group significantly improved on the Fugl–Meyer upper extremity score (Visit 1 = 60, Visit 5 = 67) while the ‘no rehab’ group did not improve (Visit 1 = 59, Visit 5 = 59; p = 0.006). This improvement was largely driven by the upper extremity “movement” subscale, which showed that the ‘rehab’ group was improving (Visit 1 = 33, Visit 5 = 37) while the ‘no rehab’ group remained virtually unchanged (Visit 1 = 34, Visit 5 = 33; p = 0.034). Conclusions: Following injection of BoNT-A, adding a program of rehabilitation improved motor recovery compared to an injected group with no rehabilitation.
While several blinded and open-label studies have demonstrated the ability of botulinum toxin to temporarily decrease spasticity following stroke, as measured by standard assessments such as the Modified Ashworth Scale [1
], the ability of botulinum toxin to improve upper limb function following stroke is less clear, with some studies [1
], though not all [2
], reporting functional improvement. Two recent meta-analyses of randomized controlled trials demonstrated that botulinum toxin treatment resulted in a moderate improvement in upper limb function [9
]. Despite large clinical trials [2
] and FDA approval, the exact timing, use of adjunct rehabilitation, and continuation of lifelong botulinum toxin treatment remains unclear [12
A recent Cochrane Review included three randomized clinical trials for post-stroke spasticity involving 91 participants [14
]. It aimed to determine the efficacy of multidisciplinary rehabilitation programs following treatment with botulinum toxin, and found some evidence supporting modified constraint-induced movement therapy and dynamic elbow splinting. There have been varied study designs exploring rehabilitation in persons after the injection of botulinum toxin or a placebo [13
], rehabilitation in persons after the injection of botulinum toxin or no injection [16
], or rehabilitation after the injection of botulinum toxin with no control condition [17
]. As the use of botulinum toxin expands and is beneficial in reducing spasticity and costs [18
], the benefit of adding upper limb rehabilitation continues to be questioned. We designed this multi-center, randomized, single-blind clinical trial to assess improvement in patient sensory and motor outcome following the injection of onabotulinumtoxinA (BoNT-A), comparing the effects of rehabilitation versus no rehabilitation, using the upper extremity portion of the Fugl–Meyer Assessment of Sensorimotor Recovery After Stroke [19
] as the primary outcome measure. While patients could not be blinded to their randomization to receive additional rehabilitation versus no rehabilitation, the assessments of all of the outcome measures were performed by evaluators blinded to rehabilitation assignment in this single-blind design.
Thirty-one patients with post-stroke upper limb spasticity were enrolled, with 29 completing the study (). The strokes occurred an average of 6 years prior to study entry, with a range of 6 months to 16½ years. The upper extremity postures treated included flexed elbow, pronated forearm, flexed wrist, flexed fingers, and clenched fist, and were evenly distributed between the treatment groups (the initial dose of BoNT-A administered was left up to the clinician’s judgment based on the amount of spasticity present, and did not differ between groups). One participant (‘no rehab’, injected at Visits 1 and 3A) left the study after Visit 3A due to a deterioration in general health and an inability to travel to study visits. A second participant (‘no rehab’, injected at Visits 1 and 3A) left the study after Visit 4 due to a fall with a broken affected wrist. All of the participants were injected at Visit 1, 19 were injected at Visit 3 (8 ‘rehab’; 11 ‘no rehab’), and 7 were injected at Visit 3A (3 ‘rehab’; 4 ‘no rehab’). Those participants who did not receive injections at Visits 3 or 3A had a level of spasticity that either did not meet the injection criteria due to an Ashworth score of <2 in the wrist (and/or fingers) or one that was felt to be too low to warrant injection. provides a description of each group with regard to age, sex, race, whether the stroke occurred in the dominant hemisphere, and clinical measures. At baseline, the treatment groups did not differ on any demographic or clinical variables. […]