Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 2/2019

01-02-2019 | Stroke | Review Article

Botulinum Toxin Type A for the Treatment of Lower Limb Spasticity after Stroke

Authors: Andrea Santamato, Nicoletta Cinone, Francesco Panza, Sara Letizia, Luigi Santoro, Madia Lozupone, Antonio Daniele, Alessandro Picelli, Alessio Baricich, Domenico Intiso, Maurizio Ranieri

Published in: Drugs | Issue 2/2019

Login to get access

Abstract

Post-stroke lower limb spasticity impairs balance and gait leading to reduced walking speed, often increasing wheelchair use and caregiver burden. Several studies have shown that appropriate treatments for lower limb spasticity after stroke include injections of botulinum toxin type A (BoNT-A), phenol or alcohol, surgical correction and a rehabilitation program. In the present article, we review the safety and effectiveness of BoNT-A for the treatment of lower limb spasticity after stroke, with a focus on higher doses of BoNT-A. The cumulative body of evidence coming from the randomized clinical trials and open-label studies selected in the article suggest BoNT-A to be safe and efficacious in reducing lower limb spasticity after stroke. Studies of high doses of BoNT-A also showed a greater reduction of severe post-stroke spasticity. In stroke survivors with spasticity of the ankle plantar-flexor muscles, a combined approach between surgery and BoNT-A can be indicated. However, controversy remains about improvement in motor function relative to post-stroke spasticity reduction after BoNT-A treatment.
Literature
1.
Simpson DM, Gracies JM, Graham HK, Miyasaki JM, Naumann M, Russman B, Simpson LL, So Y. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1691–8.
2.
Wissel J, Ward AB, Erztgaard P, Bensmail D, Hecht MJ, Lejeune TM, Schnider P, Altavista MC, Cavazza S, Deltombe T, Duarte E, Geurts AC, Gracies JM, Haboubi NH, Juan FJ, Kasch H, Katterer C, Kirazli Y, Manganotti P, Parman Y, Paternostro-Sluga T, Petropoulou K, Prempeh R, Rousseaux M, Slawek J. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med. 2009;41:13–25.CrossRef
3.
Sheean GL. Botulinum treatment of spasticity: why is it so difficult to show a functional benefit? Curr Opin Neurol. 2001;14:771–6.CrossRef
4.
Deltombe T, Wautier D, De Cloedt P, Fostier M, Gustin T. Assessment and treatment of spastic equinovarus foot after stroke: guidance from the Mont-Godinne interdisciplinary group. J Rehabil Med. 2017;49:461–8.CrossRef
5.
Ward AB. Managing spastic foot drop after stroke. Eur J Neurol. 2014;21:1053–4.CrossRef
6.
Boudarham J, Hameau S, Pradon D, Bensmail D, Roche N, Zory R. Changes in electromyographic activity after botulinum toxin injection of the rectus femoris in patients with hemiparesis walking with a stiff-knee gait. J Electromyogr Kinesiol. 2013;23:1036–43.CrossRef
7.
Carda S, Bertoni M, Zerbinati P, Rossini M, Magoni L, Molteni F. Gait changes after tendon functional surgery for equinovarus foot in patients with stroke: assessment of temporo-spatial, kinetic, and kinematic parameters in 177 patients. Am J Phys Med Rehabil. 2009;88:292–301.CrossRef
8.
Farina S, Migliorini C, Gandolfi M, Bertolasi L, Casarotto M, Manganotti P, Fiaschi A. Smania N Combined effects of botulinum toxin and casting treatments on lower limb spasticity after stroke. Funct Neurol. 2008;23:87–91.PubMed
9.
Carda S, Invernizzi M, Baricich A, Cisari C. Casting, taping or stretching after botulinum toxin type A for spastic equinus foot: a single-blind randomized trial on adult stroke patients. Clin Rehabil. 2011;25:1119–27.CrossRef
10.
Baricich A, Carda S, Bertoni M, Maderna L, Cisari C. A single-blinded, randomized pilot study of botulinum toxin type A combined with non-pharmacological treatment for spastic foot. J Rehabil Med. 2008;40:870–2.CrossRef
11.
Perera S, Mody SH, Woodman RC, Studenski SA. Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc. 2006;54:743–9.CrossRef
12.
Slavinski J, Pradon D, Bensmail D, Roche N, Zory R. Energy cost of obstacle crossing in stroke patients. Am J Phys Med Rehab. 2014;93:1044–50.CrossRef
13.
Podsiadlo D, Richardson S. The timed up and go: a test of basic functional mobility for frail elderly persons. J Am Geriat Soc. 1991;39:142–8.CrossRef
14.
Das TK, Park DM. Effect of treatment with botulinum toxin on spasticity. Postgrad Med J. 1989;65:208–10.CrossRef
15.
Simpson DM, Hallett M, Ashman EJ, Comella CL, Green MW, Gronseth GS, Armstrong MJ, Gloss D, Potrebic S, Jankovic J, Karp BP, Naumann M, So YT, Yablon SA. 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.CrossRef
16.
Albanese A. Terminology for preparations of botulinum neurotoxins: what a difference a name makes. JAMA. 2011;305:89–90.CrossRef
17.
Santamato A, Panza F. Benefits and risks of non-approved injection regimens for botulinum toxins in spasticity. Drugs. 2017;77:1413–22.CrossRef
18.
Dressler D, Mander GJ, Fink K. Equivalent potency of Xeomin® and Botox®. Mov Disord. 2008;1(23 suppl):S20–1.
19.
Dressler D, Mander G, Fink K. Measuring the potency labelling of onabotulinumtoxinA (Botox®) and incobotulinumtoxinA (Xeomin®) in an LD50 assay. J Neural Transm. 2012;119:13–5.CrossRef
20.
Odergren T, Hjaltason H, Kaakkola S, Solders G, Hanko J, Fehling C, Marttila RJ, Lundh H, Gedin S, Westergren I, Richardson A, Dott C, Cohen H. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. 1998;64:6–12.CrossRef
21.
Frevert J. Content of botulinum neurotoxin in Botox®/Vistabel®, Dysport®/Azzalure®, and Xeomin®/Bocouture®. Drugs RD. 2010;10:67–73.CrossRef
22.
23.
Gracies JM, Esquenazi A, Brashear A, Banach M, Kocer S, Jech R, Khatkova S, Benetin J, Vecchio M, McAllister P, Ilkowski J, Ochudlo S, Catus F, Grandoulier AS, Vilain C, Picaut P. International AbobotulinumtoxinA adult lower limb spasticity study group. efficacy and safety of abobotulinumtoxinA in spastic lower limb: randomized trial and extension. Neurology. 2017;89:2245–53.
24.
Pittock SJ, Moore AP, Hardiman O, Ehler E, Kovac M, Bojakowski J, Al Khawaja I, Brozman M, Kanovský P, Skorometz A, Slawek J, Reichel G, Stenner A, Timerbaeva S, Stelmasiak Z, Zifko UA, Bhakta B, Coxon E. 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;15:289–300.CrossRef
25.
Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010;257:1330–7.CrossRef
26.
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;61:265–9.CrossRef
27.
Johnson CA, Burridge JH, Strike PW, Wood DE, Swain ID. 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;85:902–9.CrossRef
28.
Dunne JW, Gracies JM, Hayes M, Zeman B, Singer BJ, Multicentre Study Group. A prospective, multicentre, randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke. Clin Rehabil. 2012;26:787–97.
29.
Hesse S, Lücke D, Malezic M, Bertelt C, Friedrich H, Gregoric M, Mauritz KH. Botulinum toxin treatment for lower limb extensor spasticity in chronic hemiparetic patients. J Neurol Neurosurg Psychiatry. 1994;57:1321–4.CrossRef
30.
Santamato A, Micello MF, Panza F, Fortunato F, Pilotto A, Giustini A, Testa A, Fiore P, Ranieri M, Spidalieri R. Safety and efficacy of incobotulinum toxin type A (NT 201-Xeomin) for the treatment of post-stroke lower limb spasticity: a prospective open-label study. Eur J Phys Rehabil Med. 2013;49:483–9.PubMed
31.
Mancini F, Sandrini G, Moglia A, Nappi G, Pacchetti C. A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot. Neurol Sci. 2005;26:26–31.CrossRef
32.
Pimentel LH, Alencar FJ, Rodrigues LR, Sousa FC, Teles JB. Effects of botulinum toxin type A for spastic foot in post-stroke patients enrolled in a rehabilitation program. Arq Neuropsiquiatr. 2014;72:28–32.CrossRef
33.
Picelli A, Bonetti P, Fontana C, Barausse M, Dambruoso F, Gajofatto F, Girardi P, Manca M, Gimigliano R, Smania N. Is spastic muscle echo intensity related to the response to botulinum toxin type A in patients with stroke? A cohort study. Arch Phys Med Rehabil. 2012;93:1253–8.CrossRef
34.
Picelli A, Tamburin S, Bonetti P, Fontana C, Barausse M, Dambruoso F, Gajofatto F, Santilli V, Smania N. Botulinum toxin type A injection into the gastrocnemius muscle for spastic equinus in adults with stroke: a randomized controlled trial comparing manual needle placement, electrical stimulation and ultrasonography-guided injection techniques. Am J Phys Med Rehabil. 2012;91:957–64.CrossRef
35.
Tok F, Balaban B, Yaşar E, Alaca R, Tan AK. The effects of onabotulinum toxin A injection into rectus femoris muscle in hemiplegic stroke patients with stiff-knee gait: a placebo-controlled, nonrandomized trial. Am J Phys Med Rehabil. 2012;91:321–6.CrossRef
36.
Roche N, Boudarham J, Hardy A, Bonnyaud C, Bensmail B. Use of gait parameters to predict the effectiveness of botulinum toxin injection in the spastic rectus femoris muscle of stroke patients with stiff knee gait. Eur J Phys Rehabil Med. 2015;51:361–70.PubMed
37.
Hameau S, Bensmail D, Robertson J, Boudarham J, Roche N, Zory R. Isokinetic assessment of the effects of botulinum toxin injection on spasticity and voluntary strength in patients with spastic hemiparesis. Eur J Phys Rehabil Med. 2014;50:515–23.PubMed
38.
Riley PO, Kerrigan DC. Torque action of two-joint muscles in the swing period of stiff-legged gait: a forward dynamic model analysis. J Biomech. 1998;31:835–40.CrossRef
39.
Sung DH, Bang HJ. Motor branch block of the rectus femoris: its effectiveness in stiff-legged gait in spastic paresis. Arch Phys Med Rehabil. 2000;81:910–5.CrossRef
40.
Goldberg SR, Anderson FC, Pandy MG, Delp SL. Muscles that influence knee flexion velocity in double support: implications for stiff knee gait. J Biomech. 2004;37:1189–96.CrossRef
41.
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;39:2803–8.CrossRef
42.
Rousseaux M, Daveluy W, Kozlowski O, Allart E. Onabotulinumtoxin-A injection for disabling lower limb flexion in hemiplegic patients. NeuroRehabilitation. 2014;35:25–30.PubMed
43.
Yelnik AP, Colle FM, Bonan IV, Lamotte DR. Disabling overactivity of the extensor hallucis longus after stroke: clinical expression and efficacy of botulinum toxin type A. Arch Phys Med Rehabil. 2003;84:147–9.CrossRef
44.
Suputtitada A. Local botulinum toxin type A injections in the treatment of spastic toes. Am J Phys Med Rehabil. 2002;81:770–5.CrossRef
45.
Royal College of Physicians. Guidance to good practice. Guidelines for the use of botulinum toxin (BTX) in the management of spasticity in adults. London: Royal College of Physicians; 2002.
46.
47.
Baricich A, Grana E, Carda S, Santamato A, Cisari C, Invernizzi M. High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis. J Neural Transm (Vienna). 2015;122:1283–7.CrossRef
48.
Hesse S, Jahnke MT, Luecke D, Mauritz KH. Short-term electrical stimulation enhances the effectiveness of Botulinum toxin in the treatment of lower limb spasticity in hemiparetic patients. Neurosci Lett. 1995;201:37–40.CrossRef
49.
Santamato A, Panza F, Ranieri M, Frisardi V, Micello MF, Filoni S, Fortunato F, Intiso D, Basciani M, Logroscino G, Fiore P. Efficacy and safety of higher doses of botulinum toxin type A NT 201 free from complexing proteins in the upper and lower limb spasticity after stroke. J Neural Transm. 2013;120:469–76.CrossRef
50.
Santamato A, Panza F, Intiso D, Baricich A, Picelli A, Smania N, Fortunato F, Seripa D, Fiore P, Ranieri M. Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke. J Neurol Sci. 2017;378:182–6.CrossRef
51.
Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z. Diffusion, spread, and migration of botulinum toxin. Mov Disord. 2013;28:1775–83.CrossRef
52.
Bhatia KP, Münchau A, Thompson PD, Houser M, Chauhan VS, Hutchinson M, Shapira AH, Marsden CD. Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry. 1999;67:90–3.CrossRef
53.
Baizabal-Carvallo JF, Jankovic J, Pappert E. Flu-like symptoms following botulinum toxin therapy. Toxicon. 2011;58:1–7.CrossRef
54.
Roche N, Schnitzler A, Genet FF, Durand MC, Bensmail D. Undesirable distant effects following botulinum toxin type A injection. Clin Neuropharmacol. 2008;31:272280.CrossRef
55.
Pickett A. Dysport: pharmacological properties and factors that influence toxin action. Toxicon. 2009;54:683–9.CrossRef
56.
Ward AB, Wissel J, Borg J, Ertzgaard P, Herrmann C, Kulkarni J, Lindgren K, Reuter I, Sakel M, Säterö P, Sharma S, Wein T, Wright N, Fulford-Smith A. Functional goal achievement in post-stroke spasticity patients: the BOTOX® Economic Spasticity Trial (BEST). J Rehabil Med. 2014;46:504–13.CrossRef
57.
Leach E, Cornwell P, Fleming J, Haines T. Patient centered goal-setting in a subacute rehabilitation setting. Disabil Rehabil. 2010;32:159–72.CrossRef
58.
Sunnerhagen KS, Francisco GE. Enhancing patient–provider communication for long-term post-stroke spasticity management. Acta Neurol Scand. 2013;128:305–10.PubMed
59.
Baricich A, Cosenza L, Sandrini G, Paolucci S, Morone G, Santamato A, Baricich A, Cosenza L, Sandrini G, Paolucci S, Morone G, Santamato A. Development of a patient-centered questionnaire for post-stroke spasticity assessment: a reliability study. Funct Neurol. 2018;33:113–5.
60.
Rosales RL, Kong KH, Goh KJ, Kumthornthip W, Mok VC, Delgado-De Los Santos MM, Chua KS, Abdullah SJ, Zakine B, Maisonobe P, Magis A,Wong KS. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair. 2012;26:812–21.
61.
Fietzek UM, Kossmehl P, Schelosky L, Ebersbach G, Wissel J. Early botulinum toxin treatment for spastic pes equinovarus—a randomized double-blind placebo-controlled study. Eur J Neurol. 2014;21:1089–95.CrossRef
62.
Tao W, Yan D, Li JH, Shi ZH. Gait improvement by low-dose botulinum toxin A injection treatment of the lower limbs in subacute stroke patients. J Phys Ther Sci. 2015;27:759–62.CrossRef
63.
Kirazli Y, On AY, Kismali B, Aksit R. Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke: a randomized, double-blind trial. Am J Phys Med Rehabil. 1998;77:510–5.CrossRef
64.
Rousseaux M, Buisset N, Daveluy W, Kozlowski O, Blond SM. Comparison of botulinum toxin injection and neurotomy in patients with distal lower limb spasticity. Eur J Neurol. 2008;15:506–11.CrossRef
65.
Bollens B, Gustin T, Stoquart G, Detrembleur C, Lejeune T, Deltombe T. A randomized controlled trial of selective neurotomy versus botulinum toxin for spastic equinovarus foot after stroke. Neurorehabil Neural Repair. 2013;27:695–703.CrossRef
66.
Picelli A, Dambruoso F, Bronzato M, Barausse M, Gandolfi M, Smania N. Efficacy of therapeutic ultrasound and transcutaneous electrical nerve stimulation compared with botulinum toxin type A in the treatment of spastic equinus in adults with chronic stroke: a pilot randomized controlled trial. Top Stroke Rehabil. 2014;21(Suppl 1):S8–16.CrossRef
67.
Wu T, Li JH, Song HX, Dong Y. Effectiveness of botulinum toxin for lower limbs spasticity after stroke: a systematic review and meta-analysis. Top Stroke Rehabil. 2016;23:217–23.CrossRef
68.
Baker JA, Pereira G. The efficacy of Botulinum Toxin A for limb spasticity on improving activity restriction and quality of life: a systematic review and meta-analysis using the GRADE approach. Clin Rehabil. 2016;30:549–58.CrossRef
69.
Gupta AD, Chu WH, Howell S, Chakraborty S, Koblar S, Visvanathan R, Cameron I, Wilson D. A systematic review: efficacy of botulinum toxin in walking and quality of life in post-stroke lower limb spasticity. Syst Rev. 2018;7:1.CrossRef
70.
Stoquart GG, Detrembleur C, Palumbo S, Deltombe T, Lejeune TM. Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study. Arch Phys Med Rehabil. 2008;89:56–61.CrossRef
71.
Hutin E, Pradon D, Barbier F, Gracies JM, Bussel B, Roche N. Lower limb coordination in hemiparetic subjects: impact of botulinum toxin injections into rectus femoris. Neurorehabil Neural Repair. 2010;24:442–9.CrossRef
72.
Robertson JV, Pradon D, Bensmail D, Fermanian C, Bussel B, Roche N. Relevance of botulinum toxin injection and nerve block of rectus femoris to kinematic and functional parameters of stiff knee gait in hemiplegic adults. Gait Posture. 2009;29:108–12.CrossRef
73.
Chan J, Winter A, Palit M, Sturt R, Graaff SD, Holland AE. Are gait and mobility measures responsive to change following botulinum toxin injections in adults with lower limb spasticity? Disabil Rehabil. 2013;35:959–67.CrossRef
74.
Baricich A, Picelli A, Molteni F, Guanziroli E, Santamato A. Post-stroke spasticity as a condition: a new perspective on patient evaluation. Funct Neurol. 2016;31:179–80.PubMedPubMedCentral
75.
Picelli A, Bonetti P, Fontana C, Barausse M, Dambruoso F, Gajofatto F, Tamburin S, Girardi P, Gimigliano R, Smania N. Accuracy of botulinum toxin type A injection into the gastrocnemius muscle of adults with spastic equinus: manual needle placement and electrical stimulation guidance compared using ultrasonography. J Rehabil Med. 2012;44:450–2.CrossRef
Metadata
Title
Botulinum Toxin Type A for the Treatment of Lower Limb Spasticity after Stroke
Authors
Andrea Santamato
Nicoletta Cinone
Francesco Panza
Sara Letizia
Luigi Santoro
Madia Lozupone
Antonio Daniele
Alessandro Picelli
Alessio Baricich
Domenico Intiso
Maurizio Ranieri
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Drugs / Issue 2/2019
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-018-1042-z

Other articles of this Issue 2/2019

Drugs 2/2019 Go to the issue

Adis Drug Evaluation

Brexpiprazole: A Review in Schizophrenia

Review Article

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

Therapy in Practice

Current and Emerging Treatment Strategies for Graves’ Orbitopathy

AdisInsight Report

Fexinidazole: First Global Approval

AdisInsight Report

Glasdegib: First Global Approval

Correction

Correction to: Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes