Restricted accessResearch articleFirst published online 2015-8
The efficacy of Botulinum Toxin A on improving ease of care in the upper and lower limbs: a systematic review and meta-analysis using the Grades of Recommendation,Assessment,Development and Evaluation approach
A systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach; evaluating Botulinum Toxin type A efficacy on improving ease of care in the upper/lower limb.
Data sources:
Pubmed, Cinahl, Amed, Embase and Cochrane databases. English Language. Search to July 2014.
Review methods:
All randomized, placebo controlled trials on adults with difficulty in caring for the upper/lower limb resulting from spasticity of any origin and treated with a single dose of Botulinum Toxin A. Evidence quality was assessed by GRADE.
Results:
A total of 32 studies were reviewed. Meta-analysis was carried out on 11 upper limb and three lower limb studies. Evidence quality for the upper limb was moderate. A significant result for Botulinum Toxin A was found at four to 12 weeks for the upper limb (SMD 0.80, CI 0.55, 1.06, p < 0.0001). The effects were maintained for up to six months (SMD 0.48, CI 0.34, 0.62, p < 0.0001). Evidence quality was very low for the lower limb. Meta-analysis was only possible for global assessment of benefit. No significant effect was found. (Patient: RR 1.37 CI (0.94, 2.00) p = 0.11; clinician: RR 1.06 (0.84, 1.34) p = 0.60.)
Conclusion:
Botulinum Toxin A improves ease of care in the upper limb for up to six months. No conclusion can be drawn for the lower limb.
GRADE working group. Grading quality of evidence and strength of recommendations. BMJ2004; 328: 1490–1497.
2.
BakerJPereiraG. The efficacy of Botulinum toxin A for spasticity and pain: a systematic review and meta analysis using the GRADE approach.Clin Rehabil2013; 27(12): 1084–1096.
3.
SheeanGL. Botulinum treatment of spasticity: why is it so difficult to show a functional benefit?Curr Opinion Neurol2001; 14: 771–776.
4.
ElovicEPBrashearAKaelinD. Repeated treatments with botulinum toxin type A produce sustained decreases in the limitations associated with focal upper limb poststroke spasticity for caregivers and patients. Arch Phys Med Rehabil2008; 89: 799–806.
5.
BarnesM. Botulinum toxin- mechanisms of action and clinical use in spasticity. J Rehabil Med2003; 41: 56–59.
6.
GraciesJ-M. Physiological effects of botulinum toxin in spasticity. Mov Disord2004; 19(S8): S120–S128.
7.
FrancisHPWadeDTTurner-Stokes. Does reducing spasticity translate into functional benefit? An exploratory meta-analysis. J Neurol Neurosurg Psychiatry2004; 75: 1547–1551.
8.
CardosoERodriguesBLucenaR. Botulinum toxin type A for the treatment of the upper limb spasticity after stroke – a meta analysis. Arq Neuropsiquiatr2005; 63(1): 30–33.
9.
RosalesRLChua-YapAS. Evidence based systematic review on the efficacy and safety of botulinum toxin A therapy in post stroke spasticity. J Neural Transm2008; 115: 617–623.
10.
SimpsonDMGraciesJ-MGrahamHK. 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. Neurology2008; 70: 1691–1698.
11.
WisselJWardAErztgaardPEuropean consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med2009; 41: 13–25.
12.
SheeanGLanninNATurner-StokesL. Botulinum toxin assessment, intervention and after-care for upper limb hypertonicity in adults: international consensus statement. Eur J Neurol2010; 17(S2): 74–93.
13.
GarcesKMcCormickAMcGahanLSkidmoreB. Botulinum toxin A upper and lower limb spasticity: a systematic review [Technology report no 51]. Ottawa: Canadian Coordinating Office for Health Technology Assessment, 2005.
14.
SinghJAFitzgeraldPM. Botulinum toxin for shoulder pain (review). The Cochrane Collaboration2011; 1: 1–51.
15.
FoleyNPereiraSSalterK. Treatment with Botulinum Toxin improves upper-extremity function post stroke: A systematic review and meta-analysis. Arch Phys Med Rehabil2013; 94: 977–989.
16.
GuyattGHOxmanADVistGE. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ2008; 336: 924–926.
17.
Royal College of Physicians, British Society of Rehabilitation Medicine, Chartered Society of Physiotherapy, Association of Chartered Physiotherapists Interested in Neurology. Spasticity in adults: management using botulinum toxin. National guidelines. London: RCP, 2009.
18.
HarbourRMillerJ. A new system for grading recommendations in evidence based guidelines. BMJ2001; 323: 334–336.
19.
GuyattGHOxmanADKunzR. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol2011; 64: 395–400.
20.
GuyattGHOxmanADAklEA. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol2011; 64: 383–394.
21.
BalshemHHelfandMSchunemannHJ. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol2011; 64: 401–406.
22.
GuyattGHOxmanADVistG. GRADE guidelines: 4. Rating the quality of evidence – study limitations (risk of bias). J Clin Epidemiol2011; 64: 407–415.
23.
GuyattGHOxmanADMontoriV. GRADE guidelines: 5. Rating the quality of evidence – publication bias. J Clin Epidemiol2011; 64: 1277–1282.
24.
GuyattGHOxmanADKunzR. GRADE guidelines: 6. Rating the quality of evidence – imprecision. J Clin Epidemiol2011; 64: 1283–1293.
25.
GuyattGHOxmanADKunzR. GRADE guideline: 7. Rating the quality of evidence – inconsistency. J Clin Epidemiol2011; 64: 1294–1302.
26.
GuyattGHOxmanADKunzR. GRADE guidelines: 8. Rating the quality of evidence – indirectness. J Clin Epidemiol2011; 64: 1303–1310.
27.
GuyattGHOxmanADSultanS. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol2011; 64: 1311–1316.
HiggensJPTGreenS (eds). Cochrane Handbook for systematic reviews of Interventions. Version 5.1.0 (updated March2011). The Cochrane Collaboration, 2011, www.cochrane-handbook.org.
30.
BhaktaBBCozensJAChamberlainMA. 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 Psychiatry2000; 69: 217–221.
31.
BakheitAMOThilmanAFWardAB. A randomised, 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. Stroke2000; 31: 2402–2406.
32.
BakheitAMOPittockSMooreAP. 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. J Neurol2001; 8: 559–565.
33.
De BoerKSArwertHJDe GrootJH. Shoulder pain and external rotation in spastic hemiplegia do not improve by injection of botulinum toxin A into the subscapular muscle. J Neurol Neurosurg Psychiatry2008; 79: 581–583.
34.
YelnikAPColleFMBonanIVVicoutE. Treatment of shoulder pain in spastic hemiplegia by reducing spasticity of the subscapular muscle: a randomised, double blind, placebo controlled study of botulinum toxin A. J Neurol Neurosurg Psychiatry2007; 78: 845–848.
35.
MarcoEDuarteEVilaJ. Is botulinum toxin type A effective in the treatment of spastic shoulder pain in patients after stroke? A double blind randomized clinical trial. J Rehabil Med2007; 39: 440–447.
36.
KongK-HNeoJ-JChuaSG. A randomized controlled study of botulinum toxin A in the treatment of hemiplegic shoulder pain associated with spasticity. Clin Rehabil2007; 21: 28–35.
37.
RichardsonDSheeanGWerringD. Evaluating the role of botulinum toxin in the management of focal hypertonia in adults. J Neurol Neurosurg Psychiatry2000; 69: 499–506.
38.
SmithSJEllisEWhiteS. A double-blind, placebo-controlled study of botulinum toxin in upper limb spasticity after stroke or head injury. Clin Rehabil2000; 14: 5–13.
39.
MeythalerJMVogtleLBrunnerRC. A preliminary assessment of the benefits of the addition of botulinum toxin A to a conventional therapy program on the function of people with longstanding stroke. Arch Phys Med Rehabil2009; 90: 1453–1461.
40.
CousinsEWardARoffeC. Does low dose botulinum toxin help the recovery of arm function when given early after stroke? A phase II randomised controlled pilot study to estimate effect size. Clin Rehabil2010; 24:501–513.
41.
LamKLauKKSoKK. Can botulinum toxin decrease carer burden in long term care residents with upper limb spasticity? A randomised controlled study. J Am Med Dir Assoc2012; 13: 477–484.
42.
RosalesRLKongKHGohKJ. Botulinum Toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: A randomised controlled trial. J Neurorehabil Neural Repair2012; 26(7): 812–821.
43.
MarciniakCMHarveyRLGagnonCM. Does Boutlinum Toxin Type A decrease pain and lessen disability in hemiplegic survivors of stroke with shoulder pain and spasticity?Am J Phys Med Rehabil2012; 91: 1007–1019.
44.
BrashearAGordonMFElovicE. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med2002; 347(6): 395–400.
45.
SimpsonDMGraciesJMYablonSA. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo controlled study. J Neurol Neurosurg Psychiatry2009; 80: 380–385.
46.
KajiROsakoYSuyamaK. Botulinum toxin type A in post-stroke upper limb spasticity. Curr Med Res Opinion2010; 26(8): 1983–1992.
47.
McCroryPTurner-StokesLBaguleyIJ. Botulinum toxin A for treatment of upper limb spasticity following stroke: a multi centre randomised placebo controlled study of the effects on quality of life and other person-centred outcomes. J Rehabil Med2009; 41: 536–544.
48.
ChildersMKBrashearAJozefczykP. Dose-dependent response to intramuscular botulinum toxin type A for upper limb spasticity in patients after stroke. Arch Phys Med Rehabil2004; 85: 1063–1069.
49.
SimpsonDMAlexanderDNO’BrienCF. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomised, double blind, placebo controlled trial. Neurology1996; 46: 1306–1310.
50.
BhaktaBBO’ConnorRJCozensJA. Associated Reactions after stroke: a randomised controlled trial of the effect of botulinum toxin type A. J Rehabil Med2008; 40: 36–41.
51.
HesseSMachHBehrendS. An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomised controlled trial. Clin Rehabil2011; 26(3): 239–245.
52.
RodgersHShawLPriceC. BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Health Technol Assess2010; 14(26): 1–141.
53.
HesseSReiterFKonradMJahnkeMT. Botulinum toxin type A and short term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomised, double blind, placebo controlled trial. Clin Rehabil1998; 12: 381–388.
54.
HymanNBarnesMBhaktaB. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomized, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry2000; 68: 707–712.
55.
PittockSJMooreAPHardimanO. A double blind randomized placebo controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke. Cerebrovasc Dis2003; 15: 289–300.
56.
VerplanckeDSnapeSSalisburyCF. A randomized controlled trial of botulinum toxin on lower limb spasticity following acute acquired severe brain injury. Clin Rehabil2005; 19: 117–125.
57.
GusevYIBanachMSimonowA. Efficacy and safety of Botulinum toxin Type A Toxin in Adductor spasticity due to Multiple Scelrosis. J Musculoskelet Pain2008; 16(3): 175–188.
58.
MaanumGJahnsenRStanghelleJK. Effects of botulinum toxin A in ambulant adults with spastic cerebral palsy: a randomised double blind placebo controlled trial. J Rehabil Med2011; 43: 338–347.
59.
KajiROsakoYSuyamaK. Botulinum toxin type A in post stroke lower limb spasticity: a multicenter, double blind, placebo controlled trial. J Neurol2010; 257: 1330–1337.
60.
BurbaudPWiartLDubosJL. A randomised, double blind, placebo controlled trial of botulinum tocin in the treatment of spastic foot in hemiparetic patients. J Neurol Neurosurg Psychiatry1996; 61(3): 265–269.
61.
SnowBJTsuiJKCBhattMH. Treatment of spasticity with botulinum toxin: a double blind study. Annals Neurol1990; 28(4): 512–515.
62.
CohenJ. Statistical power analysis for the behavioural sciences. 2nd ed.New York: Academic Press, 1988.
LiberatiAAltmanDTetzlaffJ. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med2009; 151(4): W65–W94.
66.
MooreAP. Botulinum toxin A (BoNT-A) for spasticity in adults. What is the evidence?Eur J Neurol2002; 9(S1): 42–47.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
