Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity - a randomized double-blind placebo controlled study

Anupam Datta Gupta, Renuka Visvanathan, Ian Cameron, Simon A Koblar, Stuart Howell, David Wilson, Anupam Datta Gupta, Renuka Visvanathan, Ian Cameron, Simon A Koblar, Stuart Howell, David Wilson

Abstract

Background: Post-stroke lower limb spasticity (PSLLS) has a prevalence of 28-37%. PSLLS can cause difficulty in walking and reduce quality of life (QOL). Post stroke spasticity impairs the ability to intervene to improve walking ability. Botulinum Toxin A (BT) is an effective intervention for focal spasticity, but its use is currently restricted in many countries by their reimbursement system stating that the evidence for improvement in walking and quality of life (QOL) is not robust for treatment in the lower limb. This randomized control trial (RCT) will investigate the effectiveness of BT in modifying spasticity, and improving functioning (mobility, walking, activities of daily living (ADL's) and QOL.

Methods/design: A double-blind placebo-controlled trial injection will assess the effect of BT compared with a placebo (normal saline) in a sample of n = 94 patients. Following treatment of spasticity measured by Modified Ashworth Scale (MAS), the primary outcome of gait velocity will be measured by i) Gait Rite (Electronic Walkway); ii) walking by 2 Min Walk Test; iii) balance by Berg Balance Scale; mobility by iv) Timed Up and Go (TUG); v) lower limb function by ABILICO; vi) patient related goal by Goal Attainment Scale (GAS); vii) QOL by SF 12 (Rand version); viii) activities of daily living by the Functional Autonomy Measurement System (SMAF). There will be an associated health economic analysis.

Discussion: The study methodology is based on our systematic review 2026 studies, which concluded the evidence for improving mobility following use of BT to reduce spasticity was not robust. The results of this study could establish the use of BT in improving gait and lower limb function in PSLLS. This study could provide the evidence needed for reimbursement schemes to consider and changes to its funding policy for BT in PSLLS.

Trial registration: The trial is registered with the Australia New Zealand Clinical Trails Registry (ANZCTR)- ANZCTRN12617001603303 . Registered 07/12/2017.

Keywords: Botulinum toxin; Lower limb spasticity; Quality of life; Stroke; Walking.

Conflict of interest statement

Ethics approval and consent to participate

The Hospital Research Ethics Committee has approved the study and all the participants will provide written informed consent.

Consent for publication

Not applicable.

Competing interests

Authors declare no financial or non-financial interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study Design- Randomized Controlled Trial

References

    1. Stinear CM, Barber PA, Petoe M, Anwar S, Byblow WD. The PREP algorithm predicts potential for upper limb recovery after stroke. Brain. 2012;135:2527–2535. doi: 10.1093/brain/aws146.
    1. stats.
    1. Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8:741–754. doi: 10.1016/S1474-4422(09)70150-4.
    1. Zorowitz RD, Gillard PJ, Brainin M. Poststroke spasticity-sequelae and burden on stroke survivors and caregivers. Neurology. 2013;80(Suppl 2):S27–S34.
    1. Sunnerhagen KS, Olver J, Francisco GE. Assessing and treating functional impairment in post-stroke spasticity. Neurology. 2013(Suppl 2):80, S35–S44.
    1. Lance JW. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, editors. Spasticity: disordered motor control. Miami: year book medical: Publishers; 1980. p. 485–94.
    1. Stroke Smart. Spasticity: how to tone it down after a stroke. . Accessed 10 Mar 2017.
    1. Langhammer B, Lindmark B. Functional exercise and physical fitness post stroke: the importance of exercise maintenance for motor control and physical fitness after stroke. Stroke Res Treat. 2012;2012:1–9. doi: 10.1155/2012/864835.
    1. Nudo R. Recovery after brain injury: mechanisms and principles. Front Human Neurosci. 2013;7:1–14. doi: 10.3389/fnhum.2013.00887.
    1. Moore A. P. Botulinum toxin A (BoNT-A) for spasticity in adults. What is the evidence? European Journal of Neurology. 2002;9(s1):42–47. doi: 10.1046/j.1468-1331.2002.0090s1042.x.
    1. Teasell R, Foley N, Pereira S, Sequeira K, et al. Evidence to practice: outline toxin in the treatment of spasticity post stroke. Stroke Rehab. 2012;19(2):115–121. doi: 10.1310/tsr1902-115.
    1. Gupta AD, Chu WH, Howell S, Chakrabarty S, Koblar S, Visvanathan R, Cameron I, Wilson D. Efficacy of botulinum toxin on walking and quality of life in post-stroke lower limb spasticity. Syst Rev. 2018;7:1–9. doi: 10.1186/s13643-017-0670-9.
    1. Burbaud P, Wiart L, Dubos JL, Gaujard E, Debelleix X, Joseph PA, Mazaux JM, Bioulac B, Barat M, Lagueny A. A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients. J Neurol Neurosurg Psychiatry. 1996;61(3):265–269. doi: 10.1136/jnnp.61.3.265.
    1. Pittock SJ, et al. A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type a (Dysport) in the treatment of spastic equinovarus deformity after stroke. Cerebrovasc Dis. 2003;15(4):289–300. doi: 10.1159/000069495.
    1. Johnson CA, et al. The effect of combined use of botulinum toxin type a and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation. Arch Phys Med Rehabil. 2004;85(6):902–909. doi: 10.1016/j.apmr.2003.08.081.
    1. Kaji R, et al. Botulinum toxin type a in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010;257(8):1330–1337. doi: 10.1007/s00415-010-5526-3.
    1. Tao Wu, Yan Dong, Li Jian-Hua, Shi Zhao-Hong. Gait improvement by low-dose botulinum toxin A injection treatment of the lower limbs in subacute stroke patients. Journal of Physical Therapy Science. 2015;27(3):759–762. doi: 10.1589/jpts.27.759.
    1. Kosak M, Smith T. Comparison of the 2-, 6-, and 12-minute walk tests in patients with stroke. J of Rehabil Res Dev. 2005;42(1):103–108. doi: 10.1682/JRRD.2003.11.0171.
    1. Singer JC, Nishihara K, Mochizuki G. Does Poststroke lower-limb spasticity influence the recovery of standing balance control? A 2-year multilevel growth model. Neurorehabil Neural Rep. 2016;30(7):626–634. doi: 10.1177/1545968315613862.
    1. Hafsteinsdóttir TB, Rensink M, Schuurmans M. Clinimetric properties of the timed up and go test for patients with stroke: a systematic review. Top Stroke Rehabil. 2014;21(3):197–210. doi: 10.1310/tsr2103-197.
    1. Caty GD, Detrembleur C, Bleyenheuft C, Deltombe T, Lejeune TM. Effect of simultaneous botulinum toxin injections into several muscles on impairment, activity, participation, and quality of life among stroke patients presenting with a stiff knee gait. Stroke. 2008;39:2803–2808. doi: 10.1161/STROKEAHA.108.516153.
    1. Mullins D, Winter A, Fini N, Dixon C, Aldous S, Palit M, Holland AE. Frequency and characteristics of goal attainment following BoNTA injection for management of spasticity. Disabil Rehabil. 2016;38(19):1927–1933. doi: 10.3109/09638288.2015.1107781.
    1. Wales K, Clemson L, Lannin N, Cameron I. Functional assessments used by occupational therapists with older adults at risk of activity and participation limitations: a systematic review. PLoS One. 2016;11(2):e0147980. doi: 10.1371/journal.pone.0147980.
    1. .
    1. Rand D, Eng JJ, Tang P, Jeng J, Hung C. How active are people with stroke? Use of Accelerometersto assess physical activity. Stroke. 2009;40:163–168. doi: 10.1161/STROKEAHA.108.523621.
    1. Turkel C, et al. Pooled analysis of the safety of botulinum toxin type a in the treatment of poststroke spasticity. Arch Phys Med Rehabil. 2006;87:786–792. doi: 10.1016/j.apmr.2006.02.015.
    1. Naumann M, Jankovic J. Safety of botulinum toxin type a: a systematic review and meta-analysis. Curr Med Res Opin. 2004;20:981–990. doi: 10.1185/030079904125003962.
    1. Bakheit AM, 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;31:2402–2406. doi: 10.1161/01.STR.31.10.2402.
    1. Crowner B, et al. Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature. Clin Neuropharmacol. 2010;33(5):243–247. doi: 10.1097/WNF.0b013e3181f5329e.
    1. Dressler D. Clinical relevance of botulinum toxin antibodies. Nervenarzt. 2008;79(Suppl 1):36–40.
    1. Joffe H, Yardley L. Content and thematic analysis. In: Marks DF, Yardley L, editors. Research methods for clinical and Health Psychology. London: Sage Publications Ltd; 2004. pp. 56–68.
    1. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3:77–101. doi: 10.1191/1478088706qp063oa.
    1. Fusch PI, Ness LR. Are we there yet? Data saturation in qualitative research. Qual Rep. 2015;20:1408–1416.
    1. Bohannon RW, Andrews AW, Smith MB. Rehabilitation goals of patients with hemiplegia. Int J Rehabil Res. 1988;11(2):181–183. doi: 10.1097/00004356-198806000-00012.
    1. Esquenazi A. Falls and fractures in older post-stroke patients with spasticity: consequences and drug treatment considerations. Clin Geriatr. 2004;12:1–9.
    1. Esquenazi A. The human and economic burden of post stroke spasticity and muscle Overactivity. JClin Outcome Management. 2011;18:607–614.
    1. Wade DT, Skilbeck CE, Wood VA, Langton Hewer R. Long-term survival after stroke. Age Ageing. 1984;13(2):76–82. doi: 10.1093/ageing/13.2.76.
    1. Newman AB, Simonsick EM, Naydeck BL, et al. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA. 2006;295(17):2018–2016. doi: 10.1001/jama.295.17.2018.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa