Synergic use of botulinum toxin injection and radial extracorporeal shockwave therapy in Multiple Sclerosis spasticity.

Synergic use of botulinum toxin injection and radial extracorporeal shockwave therapy in Multiple Sclerosis spasticity.


  • Cinzia Marinaro Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
  • Cosimo Costantino Department of Medicine and Surgery, University of Parma, Parma, Italy
  • Oriana d'Esposito Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
  • Marianna Barletta Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
  • Angelo Indino Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
  • Gerardo de Scorpio Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
  • Antonio Ammendolia Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy


Spasticity, Multiple Sclerosis, rESWT, BoNT-A


Background and aim: In Multiple Sclerosis (MS) spasticity worsen patient’s quality of life. Botulinum NeuroToxin TypeA (BoNT-A) is extensively used in focal spasticity, frequently combined with physical therapies. Radial extracorporeal shock waves (rESW) were already used in association with BoNT-A.  Considering that loss of efficacy and adverse events are determinants of BoNT-A treatment interruption, this study aimed to evaluate the possibility to prolong BoNT-A’s effect by using rESW in MS focal spasticity.

Methods: Sixteen MS patients with spasticity of triceps surae muscles were first subjected to BoNT-A therapy and, four months later, to 4 sections of rESWT. Patients were evaluated before, 30, 90 days after the end of the treatments, by using Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS) and kinematic analysis of passive and active ankle ROM.


Results: BoNT-A determined a significant reduction of spasticity evaluated by MAS with a reduction of positive effects after 4months (p<0.05); MTS highlighted the efficacy only 90 days after injection (p<0.05). rESWT decreased MAS values at the end and 30 days later the treatment (p<0.01); MTS values showed instead a prolonged effect (p<0.01). BoNT-A determined a gain of passive and active ankle ROM, persisting along with treatment and peaking the maximum value after rESWT (p<0.05). 

Conclusions: rESWT can prolong BoNT-A effect inducing significant reduction of spasticity and improvement in passive and active ankle ROM in MS patients. The use of rESWT following BoNT-A injection is useful to avoid some limitations and to prolong the therapeutic effects of BoNT-A therapy.


Dressler D, Bhidayasiri R, Bohlega S, Chana P, Chien HF, Chung TM, et al. Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy. J Neurol. 2018;265(4):856–62.

Cameron MH, Bethoux F, Davis N, Frederick M. Botulinum toxin for symptomatic therapy in multiple sclerosis. Curr Neurol Neurosci Rep. 2014 Aug 22;14(8):463.

Fonfria E, Maignel J, Lezmi S, Martin V, Splevins A, Shubber S, et al. The expanding therapeutic utility of botulinum neurotoxins. Toxins (Basel). 2018;10(5):1–27.

Naumann M, Boo LM, Ackerman AH, Gallagher CJ. Immunogenicity of botulinum toxins. J Neural Transm. 2013;120(2):275–90.

Picelli A, Smania N, Storti I, Munari D, Fontana C, Fiaschi A, et al. Immediate versus delayed electrical stimulation boosts botulinum toxin effect: A pilot study. Mov Disord. 2011 Aug 1;26(9):1785–6.

Santamato A, Notarnicola A, Panza F, Ranieri M, Micello MF, Manganotti P, et al. SBOTE study: Extracorporeal shock wave therapy versus electrical stimulation after botulinum toxin type a injection for post-stroke spasticity-a prospective randomized trial. Ultrasound Med Biol. 2013;39(2):283–91.

Stieger M, Schmid JP, Yawalkar N, Hunziker T. Extracorporeal shock wave therapy for injection site panniculitis in multiple sclerosis patients. Dermatology. 2015 Feb 17;230(1):82–6.

Marisa M, Riccardo M, Giacomo F, Giulia G, Franca D, Pietro F, et al. Pain and Muscles Properties Modifications After Botulinum Toxin Type A (BTX-A) and Radial Extracorporeal Shock Wave (rESWT) Combined Treatment. Endocrine, Metab Immune Disord - Drug Targets. 2019 Nov 11;19(8):1127–33.

Picelli A, La Marchina E, Gajofatto F, Pontillo A, Vangelista A, Filippini R, et al. Sonographic and clinical effects of botulinum toxin Type A combined with extracorporeal shock wave therapy on spastic muscles of children with cerebral palsy. Dev Neurorehabil. 2017 Apr 3;20(3):160–4.

Marinelli L, Mori L, Solaro C, Uccelli A, Pelosin E, Currà A, et al. Effect of radial shock wave therapy on pain and muscle hypertonia: A double-blind study in patients with multiple sclerosis. Mult Scler J. 2015;21(5):622–9.

Xiang J, Wang W, Jiang W, Qian Q. Effects of extracorporeal shock wave therapy on spasticity in post-stroke patients: A systematic review and meta-analysis of randomized controlled trials. J Rehabil Med. 2018;50(10):852–9.

Vidal X, Martí-Fàbregas J, Canet O, Roqué M, Morral A, Tur M, et al. Efficacy of radial extracorporeal shock wave therapy compared with botulinum toxin type A injection in treatment of lower extremity spasticity in subjects with cerebral palsy: A randomized, controlled, cross-over study. J Rehabil Med. 2020;52(6):jrm00076.

Ammendolia A, D’Esposito O, Barletta M, Dicorato R, Fratto L, Iocco M. Treatment of spasticity in multiple sclerosis: Botulinum toxin A injection versus radial shockwave therapy. Ann Phys Rehabil Med. 2018 Jul 1;61:e364–5.

Gracies JM. Pathophysiology of spastic paresis. I: Paresis and soft tissue changes. Vol. 31, Muscle and Nerve. Wiley-Blackwell; 2005. p. 535–51.

Romeo P, Lavanga V, Pagani D, Sansone V. Extracorporeal shock wave therapy in musculoskeletal disorders: A review. Med Princ Pract. 2013;23(1):7–13.

Leone JA, Kukulka CG. Effects of tendon pressure on alpha motoneuron excitability in patients with stroke. Phys Ther. 1988 Apr;68(4):475–80.

Latino P, Castelli L, Prosperini L, Marchetti MR, Pozzilli C, Giovannelli M. Determinants of botulinum toxin discontinuation in multiple sclerosis: a retrospective study. Neurol Sci. 2017 Oct 1;38(10):1841–8.

RCP. Royal College of Physicians, British Society of Rehabilitation Medicine, Chartered Society ofrPhysiotherapy, Association of Chartered Physiotherapists Interested in Neurology. Spasticity in adults: management using botulinum toxin. National guidelines. 2009.

Esquenazi A, Alfaro A, Ayyoub Z, Charles D, Dashtipour K, Graham GD, et al. OnabotulinumtoxinA for Lower Limb Spasticity: Guidance From a Delphi Panel Approach. PM R. 2017 Oct;9(10):960–8.

Meseguer-henarejos A-B, Sánchez-Meca J, López-Pina J-A, Carles-Hernández R. Inter- and intra-rater reliability of the Modified Ashworth Scale: a systematic review and meta-analysis. Eur J Phys Rehabil Med. 2017;(August):576–90.

Li F., Wu Y. LX. Test-retest reliability and inter-rater reliability of the Modified Tardieu Scale and the Modified Ashworth Scale in hemiplegic patients with stroke. Eur J Phys Rehabil Med. 2014;50(1):9–15.

Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004 Oct 2;10(5):589–95.

Dressler D, Bhidayasiri R, Bohlega S, Chahidi A, Chung TM, Ebke M, et al. Botulinum toxin therapy for treatment of spasticity in multiple sclerosis: review and recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders task force. J Neurol. 2017 Jan 27;264(1):112–20.

Jost WH, Kohl A, Brinkmann S, Comes G. Efficacy and tolerability of a botulinum toxin type a free of complexing proteins (NT 201) compared with commercially available botulinum toxin type a (BOTOX®) in healthy volunteers. J Neural Transm. 2005 Jun 3;112(7):905–13.

Paracka L, Kollewe K, Wegner F, Dressler D. Strategies to decrease injection site pain in botulinum toxin therapy. J Neural Transm. 2017 Oct 24;124(10):1213–6.

Lange O, Bigalke H, Dengler R, Wegner F, Degroot M, Wohlfarth K. Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: Much ado about nothing? Clin Neuropharmacol. 2009 Jul 1;32(4):213–8.

Picelli A, Santamato A, Chemello E, Cinone N, Cisari C, Gandolfi M, et al. Adjuvant treatments associated with botulinum toxin injection for managing spasticity: An overview of the literature. Annals of Physical and Rehabilitation Medicine. 2018 Sep 13;

Mills PB, Finlayson H, Sudol M, O’Connor R. Systematic review of adjunct therapies to improve outcomes following botulinum toxin injection for treatment of limb spasticity. Vol. 30, Clinical Rehabilitation. 2016. p. 537–48.

Cabanas-Valdés R, Calvo-Sanz J, Urrùtia G, Serra-Llobet P, Pérez-Bellmunt A, Germán-Romero A. The effectiveness of extracorporeal shock wave therapy to reduce lower limb spasticity in stroke patients: a systematic review and meta-analysis. Topics in Stroke Rehabilitation. 2019. p. 1–21.

Lin Y, Wang G, Wang B. Rehabilitation treatment of spastic cerebral palsy with radial extracorporeal shock wave therapy and rehabilitation therapy. Medicine (Baltimore). 2018 Dec;97(51):e13828.

Wein T, Esquenazi A, Jost WH, Ward AB, Pan G, Dimitrova R. OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial. PM R. 2018;10(7):693–703.

Abdollahi I, Azarnia S, Dorebati SN, Salavati M. Inter-rater reliability of the modified Tardieu scale for the assessment of knee extensor spasticity in patient with multiple sclerosis. Koomesh. 2017 Jan 12;19(1):220–6.

Banky M, Williams G. Tardieu Scale. J Physiother. 2017;63(2):126.

Patrick E, Ada L. The Tardieu Scale differentiates contracture from spasticity whereas the Ashworts Scale is confounded by it. Clin Rehabil. 2006 Feb 1;20(2):173–81.

Alhusaini AAA, Dean CM, Crosbie J, Shepherd RB, Lewis J. Evaluation of spasticity in children with cerebral palsy using ashworth and tardieu scales compared with laboratory measures. J Child Neurol. 2010 Oct 10;25(10):1242–7.

Hoang PD, Gandevia SC, Herbert RD. Prevalence of joint contractures and muscle weakness in people with multiple sclerosis. Disabil Rehabil. 2014 Sep 18;36(19):1588–93.

Picelli A, Vallies G, Chemello E, Castellazzi P, Brugnera A, Gandolfi M, et al. Is spasticity always the same? An observational study comparing the features of spastic equinus foot in patients with chronic stroke and multiple sclerosis. J Neurol Sci. 2017 Sep;380:132–6.

Mori L, Marinelli L, Pelosin E, Currà A, Molfetta L, Abbruzzese G, et al. Shock Waves in the Treatment of Muscle Hypertonia and Dystonia. Biomed Res Int. 2014;2014.

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. Ann Rehabil Med. 2019;43(2):163–77.

Wu Y-T, Chang C-N, Chen Y-M, Hu G-C. 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. 2017;(August):1–27.

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 Jun;20(6):338–43.

Vetrano M, D’Alessandro F, Torrisi MR, Ferretti A, Vulpiani MC, Visco V. Extracorporeal shock wave therapy promotes cell proliferation and collagen synthesis of primary cultured human tenocytes. Knee Surgery, Sport Traumatol Arthrosc. 2011 Dec 27;19(12):2159–68.

Notarnicola A, Moretti B. The biological effects of extracorporeal shock wave therapy (eswt) on tendon tissue. Vol. 2, Muscles, ligaments and Tendons Journal. 2012.

Jeng B, Sandroff BM, Motl RW. Energetic cost of walking and spasticity in persons with multiple sclerosis with moderate disability. NeuroRehabilitation. 2018 Oct 31;Preprint(Preprint):1–7.

Harrison AR, Berbos Z, Zaldivar RA, Anderson BC, Semmer M, Lee MS, et al. Modulating neuromuscular junction density changes in botulinum toxin-treated orbicularis oculi muscle. Investig Ophthalmol Vis Sci. 2011;52(2):982–6.

Kenmoku T, Nemoto N, Iwakura N, Ochiai N, Uchida K, Saisu T, et al. Extracorporeal shock wave treatment can selectively destroy end plates in neuromuscular junctions. Muscle and Nerve. 2018 Mar;57(3):466–72.

Kenmoku T, Ochiai N, Ohtori S, Saisu T, Sasho T, Nakagawa K, et al. Degeneration and recovery of the neuromuscular junction after application of extracorporeal shock wave therapy. J Orthop Res. 2012;30(10):1660–5.




How to Cite

Synergic use of botulinum toxin injection and radial extracorporeal shockwave therapy in Multiple Sclerosis spasticity. Acta Biomed [Internet]. 2021 Jan. 28 [cited 2024 May 29];92(1):e2021076. Available from:

Most read articles by the same author(s)

<< < 1 2