Comparative Effectiveness of Botulinum Toxin Injections and Extracorporeal Shockwave Therapy for Post-Stroke Spasticity: A Systematic Review and Network Meta-Analysis

Po-Cheng Hsu, Ke-Vin Chang, Yi-Hsiang Chiu, Wei-Ting Wu, Levent Özçakar, Po-Cheng Hsu, Ke-Vin Chang, Yi-Hsiang Chiu, Wei-Ting Wu, Levent Özçakar

Abstract

Background: The anti-spasticity efficacy of botulinum toxin (BoNT) injection has been well established for patients with chronic stroke; however, extracorporeal shock wave therapy (ESWT), i.e. focused shockwave (FSW) and radial shockwave (RSW), has recently been applied. We aimed to investigate the comparative effectiveness of BoNT vs. ESWT in the reduction of spasticity among stroke survivors.

Methods: PubMed, EMBASE, MEDLINE and Cochrane CENTRAL were searched from the earliest record to September 2021 for randomized controlled trials. Weighted mean differences (WMDs) on the reduction of the Modified Ashworth Scale before or at the 6th post-treatment week (short-term) and between the 7th and 12th weeks (mid-term) after the intervention were calculated. Ranking probabilities of the WMD were simulated to determine which treatment had the potential to possess the best effectiveness. inplasy.com registration: INPLASY202170018.

Findings: A total of 33 studies comprising 1,930 patients were enrolled. The network meta-analysis revealed that BoNT injections, FSW and RSW were better in spasticity reduction than the control treatment(s) at the short term, with WMDs of -0.69 (95% CI, -0.87 to -0.50), -0.36 (95% CI, -0.69 to -0.03) and -0.62 (95% CI, -0.84 to -0.40), respectively. Likewise, mid-term effects of BoNT injections, FSW and RSW also revealed superiority, with WMDs of -0.44 (95% CI, -0.62 to -0.26), -0.74 (95% CI, -1.26 to -0.23) and -0.79 (95% CI, -1.07 to -0.51), respectively. Ranking probability analysis revealed that RSW had the highest probability of being the best treatment for spasticity reduction at the short-term (62.2%) and mid-term (72.3%) periods during the follow up.

Interpretation: BoNT injections and ESWT are effective in alleviating post-stroke spasticity at the mid-term. The effectiveness of ESWT was comparable to BoNT injections, and RSW had the potential to be the best treatment for spasticity reduction among the three treatment options. More prospective trials incorporating head-to-head comparisons of BoNT injections vs. ESWT are needed to validate the role of ESWT in reducing post-stroke spasticity.

Funding: The current research project was supported by (1) National Taiwan University Hospital, Bei-Hu Branch; (2) Ministry of Science and Technology (MOST 106-2314-B-002-180-MY3 and 109-2314-B-002-114-MY3); 3) Taiwan Society of Ultrasound in Medicine.

Keywords: BoNT, botulinum toxin; CI, confidence interval; ESWT, extracorporeal shock wave therapy; FSW, focused shockwave; MAS, modified Ashworth scale; RSW, radial shockwave; WMD, weighted mean difference; chemodenervation; focused shockwave; hemiplegia; hypertonia; radial shockwave.

Conflict of interest statement

Each author certifies that he or she has no commercial associations

© 2021 The Author(s).

Figures

Figure 1
Figure 1
Flow diagram for the study selection process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Figure 2
Figure 2
Forest plots of pairwise comparison in terms of MAS reduction (A) before or at the 6th week after intervention and (B) between the 7th and 12th weeks after interventions. WMD, weighted mean difference. CI, confidence interval represents the mean treatment effect. FSW, focused shockwave; RSW, radial shockwave; MAS, modified Ashworth scale. APMR, Archives of Physical Medicine and Rehabilitation; BoNT, botulinum toxin; CMRO, current medical research and opinion; EJPRM, European Journal of Physical and Rehabilitation Medicine.
Figure 3
Figure 3
Network plots of enrolled treatments in terms of the MAS reduction (A) before or at the 6th week after intervention and (B) between the 7th and 12th weeks after interventions. BoNT, botulinum toxin; FSW, focused shockwave; RSW, radial shockwave; MAS, modified Ashworth scale.
Figure 4
Figure 4
Forest plots of network comparisons in terms of MAS reduction (A) before or at the 6th week after intervention and (B) between the 7th and 12th weeks after interventions. CI, confidence interval represents the mean treatment effect. BoNT, botulinum toxin; FSW, focused shockwave; RSW, radial shockwave; MAS, modified Ashworth scale.
Figure 5
Figure 5
Ranking probabilities for different treatment options in terms of MAS reduction (A) before or at the 6th week after intervention and (B) between the 7th and 12th weeks after interventions. BoNT, botulinum toxin; FSW, focused shockwave; RSW, radial shockwave; MAS, modified Ashworth scale.

References

    1. Lance JW. The control of muscle tone, reflexes, and movement: Robert Wartenberg Lecture. Neurology. 1980;30(12):1303–1313.
    1. Trompetto C, Marinelli L, Mori L, et al. Pathophysiology of spasticity: implications for neurorehabilitation. Biomed Res Int. 2014;2014
    1. Sommerfeld DK, Eek EU, Svensson AK, Holmqvist LW, von Arbin MH. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke. 2004;35(1):134–139.
    1. Ward AB. A literature review of the pathophysiology and onset of post-stroke spasticity. Eur J Neurol. 2012;19(1):21–27.
    1. Bethoux F. Spasticity Management After Stroke. Phys Med Rehabil Clin N Am. 2015;26(4):625–639.
    1. Ghai A, Garg N, Hooda S, Gupta T. Spasticity - Pathogenesis, prevention and treatment strategies. Saudi J Anaesth. 2013;7(4):453–460.
    1. Chang E, Ghosh N, Yanni D, Lee S, Alexandru D, Mozaffar T. A Review of Spasticity Treatments: Pharmacological and Interventional Approaches. Critical Reviews in Physical and Rehabilitation Medicine. 2013;25(1-2):11–22.
    1. Anwar F, Ramanathan S, Khayer A. Complications of Peripheral Phenol Nerve and Motor Point Blocks in the Management of Spasticity. International Journal of Therapies and Rehabilitation Research. 2017;6(2)
    1. Andringa A, van de Port I, van Wegen E, Ket J, Meskers C, Kwakkel G. Effectiveness of Botulinum Toxin Treatment for Upper Limb Spasticity Poststroke Over Different ICF Domains: A Systematic Review and Meta-Analysis. Archives of physical medicine and rehabilitation. 2019;100(9):1703–1725.
    1. Roberts A. Surgical management of spasticity. J Child Orthop. 2013;7(5):389–394.
    1. Walewicz K, Taradaj J, Rajfur K, et al. The Effectiveness Of Radial Extracorporeal Shock Wave Therapy In Patients With Chronic Low Back Pain: A Prospective, Randomized, Single-Blinded Pilot Study. Clin Interv Aging. 2019;14:1859–1869.
    1. Gao J, Rubin JM, Chen J, O'Dell M. Ultrasound Elastography to Assess Botulinum Toxin A Treatment for Post-stroke Spasticity: A Feasibility Study. Ultrasound Med Biol. 2019;45(5):1094–1102.
    1. Stecco A, Stecco C, Raghavan P. Peripheral Mechanisms Contributing to Spasticity and Implications for Treatment. Current Physical Medicine and Rehabilitation Reports. 2014;2(2):121–127.
    1. El-Shamy SM, Eid MA, El-Banna MF. Effect of extracorporeal shock wave therapy on gait pattern in hemiplegic cerebral palsy: a randomized controlled trial. American journal of physical medicine & rehabilitation. 2014;93(12):1065–1072.
    1. Martinez IM, Sempere-Rubio N, Navarro O, Faubel R. Effectiveness of Shock Wave Therapy as a Treatment for Spasticity: A Systematic Review. Brain Sci. 2020;11(1)
    1. Wu YT, Yu HK, Chen LR, Chang CN, Chen YM, Hu GC. Extracorporeal Shock Waves Versus Botulinum Toxin Type A in the Treatment of Poststroke Upper Limb Spasticity: A Randomized Noninferiority Trial. Archives of physical medicine and rehabilitation. 2018;99(11):2143–2150.
    1. Cabanas-Valdes R, Serra-Llobet P, Rodriguez-Rubio PR, Lopez-de-Celis C, Llauro-Fores M, Calvo-Sanz J. The effectiveness of extracorporeal shock wave therapy for improving upper limb spasticity and functionality in stroke patients: a systematic review and meta-analysis. Clin Rehabil. 2020;34(9):1141–1156.
    1. Cabanas-Valdes R, Calvo-Sanz J, Urrutia G, Serra-Llobet P, Perez-Bellmunt A, German-Romero A. The effectiveness of extracorporeal shock wave therapy to reduce lower limb spasticity in stroke patients: a systematic review and meta-analysis. Top Stroke Rehabil. 2020;27(2):137–157.
    1. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777–784.
    1. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
    1. Dressler D, Benecke R. Pharmacology of therapeutic botulinum toxin preparations. Disabil Rehabil. 2007;29(23):1761–1768.
    1. McGrath S, Zhao X, Steele R, Thombs BD, Benedetti A, Collaboration DESD. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat Methods Med Res. 2020
    1. Marotta N, Demeco A, Moggio L, et al. Comparative effectiveness of breathing exercises in patients with chronic obstructive pulmonary disease. Complement Ther Clin Pract. 2020;41
    1. Mbuagbaw L, Rochwerg B, Jaeschke R, et al. Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev. 2017;6(1):79.
    1. Bae H, Lee J, Lee K. The effects of extracorporeal shock wave therapy on spasticity in chronic stroke patients. J Korean Acad Rehabil Med. 2010;34:663–669.
    1. Duan HY, Li ZL, Xu GX, Liu FQ Z.H.Y. Efficacy of extracorporeal shock wave in treatment of spasticity of biceps brachii in stroke patients. Journal of Jilin University Medicine Edition. 2017;40(01):151–154.
    1. Dymarek R, Taradaj J, Rosinczuk J. The Effect of Radial Extracorporeal Shock Wave Stimulation on Upper Limb Spasticity in Chronic Stroke Patients: A Single-Blind, Randomized, Placebo-Controlled Study. Ultrasound Med Biol. 2016;42(8):1862–1875.
    1. Fouda KZ, Sharaf MA. Efficacy of Radial Shock Wave Therapy on Spasticity in Stroke Patients. International Journal of Health and Rehabilitation Sciences. 2015;4(1):19–26.
    1. Guo J, Qian S, Wang Y, Xu A. Clinical study of combined mirror and extracorporeal shock wave therapy on upper limb spasticity in poststroke patients. International journal of rehabilitation research Internationale Zeitschrift fur Rehabilitationsforschung Revue internationale de recherches de readaptation. 2019;42(1):31–35.
    1. Kim SH, Ha KW, Kim YH, et al. Effect of Radial Extracorporeal Shock Wave Therapy on Hemiplegic Shoulder Pain Syndrome. Annals of rehabilitation medicine. 2016;40(3):509–519.
    1. Lee CH, Lee SH, Yoo JI, Lee SU. Ultrasonographic Evaluation for the Effect of Extracorporeal Shock Wave Therapy on Gastrocnemius Muscle Spasticity in Patients With Chronic Stroke. PM R. 2019;11(4):363–371.
    1. Li TY, Chang CY, Chou YC, et al. Effect of Radial Shock Wave Therapy on Spasticity of the Upper Limb in Patients With Chronic Stroke: A Prospective, Randomized, Single Blind, Controlled Trial. Medicine. 2016;95(18):e3544.
    1. Tabra SAA, Zaghloul MI, Alashkar DS. Extracorporeal shock wave as adjuvant therapy for wrist and hand spasticity in post-stroke patients: a randomized controlled trial. Egyptian Rheumatology and Rehabilitation. 2021;48(1)
    1. Taheri P, Vahdatpour B, Mellat M, Ashtari F, Akbari M. Effect of Extracorporeal Shock Wave Therapy on Lower Limb Spasticity in Stroke Patients. Arch Iran Med. 2017;20(6):338–343.
    1. Tirbisch L. Effets des ondes de choc radiales sur la spasticité du triceps sural de patients hémiplégiques en phase subaiguë : un essai contrôlé randomisé. Kinésithérapie, la Revue. 2015;15:62–69. 164-165.
    1. Wu YT, Chang CN, Chen YM, Hu GC. Comparison of the effect of focused and radial extracorporeal shock waves on spastic equinus in patients with stroke: a randomized controlled trial. Eur J Phys Rehabil Med. 2018;54(4):518–525.
    1. XU G, YAN Z, ZHANG Y, et al. Therapeutic effect of slow stretching training combined with extracorporeal shock wave on biceps brachii spasticity in stroke patients. Journal of Jilin University Medicine Edition. 2018;44(2):374–378.
    1. Yoon SH, Shin MK, Choi EJ, Kang HJ. Effective Site for the Application of Extracorporeal Shock-Wave Therapy on Spasticity in Chronic Stroke: Muscle Belly or Myotendinous Junction. Annals of rehabilitation medicine. 2017;41(4):547–555.
    1. Yoldas Aslan S, Kutlay S, Dusunceli Atman E, Elhan AH, Gok H, Kucukdeveci AA. Does extracorporeal shock wave therapy decrease spasticity of ankle plantar flexor muscles in patients with stroke: A randomized controlled trial. Clin Rehabil. 2021
    1. Bakheit AM, Pittock S, Moore AP, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. Eur J Neurol. 2001;8(6):559–565.
    1. 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(10):2402–2406.
    1. Bhakta BB, Cozens JA, Chamberlain MA, Bamford JM. Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial. J Neurol Neurosurg Psychiatry. 2000;69(2):217–221.
    1. Childers MK, Brashear A, Jozefczyk P, et al. Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke. Archives of physical medicine and rehabilitation. 2004;85(7):1063–1069.
    1. Hesse S, Reiter F, Konrad M, Jahnke MT. Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial. Clin Rehabil. 1998;12(5):381–388.
    1. Jahangir AW, Tan HJ, Norlinah MI, et al. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after stroke. Med J Malaysia. 2007;62(4):319–322.
    1. Kaji R, Osako Y, Suyama K, et al. Botulinum toxin type A in post-stroke upper limb spasticity. Curr Med Res Opin. 2010;26(8):1983–1992.
    1. Kaji R, Osako Y, Suyama K, 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.
    1. Kerzoncuf M, Viton JM, Pellas F, et al. Poststroke Postural Sway Improved by Botulinum Toxin: A Multicenter Randomized Double-blind Controlled Trial. Archives of physical medicine and rehabilitation. 2020;101(2):242–248.
    1. Marciniak CM, Harvey RL, Gagnon CM, et al. Does botulinum toxin type A decrease pain and lessen disability in hemiplegic survivors of stroke with shoulder pain and spasticity?: a randomized, double-blind, placebo-controlled trial. American journal of physical medicine & rehabilitation. 2012;91(12):1007–1019.
    1. Marco E, Duarte E, Vila J, et al. Is botulinum toxin type A effective in the treatment of spastic shoulder pain in patients after stroke? A double-blind randomized clinical trial. Journal of rehabilitation medicine. 2007;39(6):440–447.
    1. Prazeres A, Lira M, Aguiar P, Monteiro L, Vilasboas I, Melo A. Efficacy of physical therapy associated with botulinum toxin type A on functional performance in post-stroke spasticity: A randomized, double-blinded, placebo-controlled trial. Neurol Int. 2018;10(2):7385.
    1. Shaw L, Rodgers H, Price C, et al. 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):1–113. iii-iv.
    1. Hesse S, Mach H, Frohlich S, Behrend S, Werner C, Melzer I. An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial. Clin Rehabil. 2012;26(3):237–245.
    1. McCrory P, Turner-Stokes L, Baguley IJ, et al. Botulinum toxin A for treatment of upper limb spasticity following stroke: a multi-centre randomized placebo-controlled study of the effects on quality of life and other person-centred outcomes. Journal of rehabilitation medicine. 2009;41(7):536–544.
    1. Rosales RL, Balcaitiene J, Berard H, et al. Early AbobotulinumtoxinA (Dysport(R)) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study. Toxins (Basel) 2018;10(7)
    1. Wolf SL, Milton SB, Reiss A, Easley KA, Shenvi NV, Clark PC. Further assessment to determine the additive effect of botulinum toxin type A on an upper extremity exercise program to enhance function among individuals with chronic stroke but extensor capability. Archives of physical medicine and rehabilitation. 2012;93(4):578–587.
    1. Bensmail D, Hanschmann A, Wissel J. Satisfaction with botulinum toxin treatment in post-stroke spasticity: results from two cross-sectional surveys (patients and physicians) Journal of Medical Economics. 2014;17(9):618–625.
    1. Simpson DM, Alexander DN, O'Brien CF, et al. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial. Neurology. 1996;46(5):1306–1310.
    1. Dressler D, Altavista MC, Altenmueller E, et al. Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity. J Neural Transm (Vienna) 2021;128(3):321–335.
    1. Dietz V, Sinkjaer T. Spastic movement disorder: impaired reflex function and altered muscle mechanics. Lancet Neurol. 2007;6(8):725–733.
    1. Gaverth J, Sandgren M, Lindberg PG, Forssberg H, Eliasson AC. Test-retest and inter-rater reliability of a method to measure wrist and finger spasticity. Journal of rehabilitation medicine. 2013;45(7):630–636.
    1. Manganotti P, Amelio E. Long-term effect of shock wave therapy on upper limb hypertonia in patients affected by stroke. Stroke. 2005;36(9):1967–1971.
    1. Amelio E, Manganotti P. Effect of shock wave stimulation on hypertonic plantar flexor muscles in patients with cerebral palsy: a placebo-controlled study. Journal of rehabilitation medicine. 2010;42(4):339–343.
    1. Gracies JM. Pathophysiology of spastic paresis. I: Paresis and soft tissue changes. Muscle Nerve. 2005;31(5):535–551.
    1. Altındag O, Gursoy S. Effect of Shock Wave Therapy on Spasticity: A Single-Institution Experience. Türkiye Fiziksel Tip ve Rehabilitasyon Dergisi. 2014;60(1):95–96.
    1. Oh JH, Park HD, Han SH, Shim GY, Choi KY. Duration of Treatment Effect of Extracorporeal Shock Wave on Spasticity and Subgroup-Analysis According to Number of Shocks and Application Site: A Meta-Analysis. Annals of rehabilitation medicine. 2019;43(2):163–177.
    1. Bellows S, Jankovic J. Immunogenicity Associated with Botulinum Toxin Treatment. Toxins (Basel) 2019;11(9)
    1. Kaya CS, Yilmaz EO, Akdeniz-Dogan ZD, Yucesoy CA. Long-Term Effects With Potential Clinical Importance of Botulinum Toxin Type-A on Mechanics of Muscles Exposed. Front Bioeng Biotechnol. 2020;8:738.
    1. Tugnoli V, Eleopra R, Quatrale R, Capone JG, Sensi M, Gastaldo E. Botulism-like syndrome after botulinum toxin type A injections for focal hyperhidrosis. Br J Dermatol. 2002;147(4):808–809.
    1. Banky M, Ryan HK, Clark R, Olver J, Williams G. Do clinical tests of spasticity accurately reflect muscle function during walking: A systematic review. Brain Inj. 2017;31(4):440–455.

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