Remote central effects of botulinum toxin type A as adjuvant to intense occupational therapy in the early stage of stroke: A Type II fMRI randomised controlled trial

Introduction: Improvements in motor function following interventions incorporating botulinum toxin type A (BTX-A) remain controversial, with existing studies yielding contrasting results.1-3 The mechanisms underlying BTX-A remote central effects are still under investigation. It is hypothesized that the toxin administration strategy may play a role in producing such differing outcomes. We tested a strategy based on modulating muscle synergies. Aim: The aim of the study was to investigate the clinical and remote central effects of an occupational therapy intervention combined with adjunctive BTX-A compared to the same occupational therapy without the adjuvant application of the toxin. Methods: A two-group, parallel, pre-post, randomized controlled trial was performed. The clinical effects of occupational therapy when performed following BTX-A injections to disinhibit finger flexors (n=5) was compared to those of an equal dose of occupational therapy alone (n=6). Motor dexterity and function were assessed using the Fugl-Meyer Scale, Motor Index, Arm Activity Measure, 9-Hole Peg Test, and Box and Block Test, and differences were analysed using ANCOVA. Brain activity was examined using functional magnetic resonance imaging (fMRI), and between-group differences were analysed using contrast statistical parametric mapping. Results: Both groups started in statistically similar conditions. Both treatments provided significant clinical improvements compared to baseline. The total differences in change score on the Fugl-Meyer Scale and Motor Index were larger, though not significantly, in the toxin-treated group than in the control group (Figure). When the toxin is administered, activity in the brain is more localised and appears more in the right hemisphere in subjects in the toxin-treated group and more in the left in those in the control group. Conclusions: Functional improvements were observed in the toxin-treated group, but the effect size compared to the control group was too small to provide definitive results. Post-treatment contrast analysis of the fMRI scans suggests that the toxin reduces cortical and cerebellar overexcitation. Findings are limited by the small cohort size. Funding: FOE received Mexican Research Council CONACYT CB-2014-01-237251. Keywords: Neurorehabilitation; Botulinum toxin; fMRI; Stroke [Formula presented] References 1. Demetrios M, Khan F, Turner-Stokes L, Brand C, McSweeney S. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for post-stroke spasticity. Cochrane Database Syst Rev. 2013 Jun 5;(6):CD009689. 2. Shaw L, Rodgers H, Price C, et al; BoTULS Investigators. BoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Health Technol Assess. 2010; 14(26):1-142. 3. Shaw LC, Price CIM, van Wijck FMJ, et al; BoTULS Investigators. Botulinum toxin for the upper limb after stroke (BoTULS) trial: effect on impairment, activity limitation, and pain. Stroke. 2011;42(5):1371-1379.