Introduction
Spasticity is a muscle control disorder characterized by tight or stiff muscles and an inability to control those muscles. It can result from various neurological conditions, with stroke and traumatic brain injury being common causes. The management of spasticity is crucial to improve the quality of life and functional ability of affected individuals. Botulinum neurotoxin (BoNT) is a well-established treatment for spasticity, particularly in the upper limbs. Despite its widespread use, questions remain regarding the optimal strategies for its injection. An international study published in BMJ Open has explored this matter, comparing two different BoNT injection techniques – one targeting neuromuscular junctions (NMJs) more specifically and the other reflecting current clinical practice. This news article delves into the study’s findings, its implications for therapy, and potential areas for further research.
Background of the Study
The study, “Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity,” DOI: 10.1136/bmjopen-2018-024340, assessed whether NMJ-targeted BoNT injections were non-inferior in efficacy compared to the current injection practices for upper limb spasticity. An open-label prospective evaluator-blinded design was employed across 20 medical centers in Denmark, Finland, Norway, and Sweden from 24 September 2012 to 11 March 2015.
Methodology
The participants included adults over 18 years of age suffering from upper limb spasticity post-stroke or traumatic brain injury. With a Modified Ashworth Scale (MAS) score of 2 or 3, these individuals had received at least two consecutive treatment cycles of BoNT-A, specifically abobotulinumtoxinA (aboBoNT-A), before requiring a retreatment of the same modality. Those requiring doses greater than 800 units of aboBoNT-A were excluded from the study.
A total of 88 patients were randomized into two groups to receive a single dose of aboBoNT-A (not exceeding 800 U). One group received the treatment following current clinical practice (employed at a concentration of 300 U/mL), while the other was administered as an NMJ-targeted injection at a lower concentration of 100 U/mL. The primary endpoint was the proportion of patients who experienced a reduction of at least one level in their MAS score at week four post-injection.
Main Findings
The study reported that in the intention-to-treat (ITT) population, 72.7% of participants in the current practice group were responders, compared to 56.8% in the NMJ-targeted group. However, the adjusted difference was not statistically significant (p=0.0986). Similarly, no significant difference was observed in the per-protocol (PP) population. The limited number of participants in the study meant that researchers could not conclusively determine non-inferiority. Nonetheless, they noted no statistical difference between the two techniques.
The authors stressed the need for larger studies to confirm whether both injection strategies offer comparable efficacy. The clinical trial registration number for this study is NCT01682148.
Implications for Practice
While the results did not establish non-inferiority due to sample size limitations, the lack of significant difference in efficacy between the two injection techniques indicates potential flexibility in treatment approaches. If further studies reinforce these findings, clinicians may have more options tailored to individual patient anatomy and response to treatment.
References
1. Pandyan AD, Gregoric M, Barnes MP, et al. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil 2005;27:2–6.
2. Wissel J, Manack A, Brainin M. Toward an epidemiology of poststroke spasticity. Neurology 2013;80:S13–S19.
3. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2016;86:1818–26.
4. Wissel J, Ward AB, Erztgaard P, et al. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med 2009;41:13–25.
5. Bakheit AM, Thilmann AF, Ward AB, et al. A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke. Stroke 2000;31:2402–6.
Keywords
1. Botulinum toxin efficacy
2. Upper limb spasticity treatment
3. Neuromuscular junction injections
4. BoNT-A therapy
5. Efficacy comparison of BoNT techniques
Conclusion
This study represents an important contribution to the ongoing effort to optimize treatment strategies for upper limb spasticity. While NMJ-targeted injection did not prove to be non-inferior within the scope of this study, the similar efficacy rates to current clinical practice may offer a promise of equally effective alternative approaches. Further research with larger participant groups is essential to confirm the results and potentially expand the therapeutic arsenal for spasticity management with an informed approach to BoNT injection targeting.