TITLE: Botulinum Toxin for Spasticity: Clinical Effectiveness and … · Botulinum Toxin for Spasticity 4 Table 2: Summary of Included Studies on Botulinum Toxin for Spasticity in

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TITLE: Botulinum Toxin for Spasticity: Clinical Effectiveness and Guidelines

DATE: 07 April 2016 RESEARCH QUESTIONS

1. What is the clinical effectiveness of botulinum toxin for spasticity in adults? 2. What are the clinical guidelines regarding the use of botulinum toxin for spasticity in

adults? KEY FINDINGS

Eight systematic reviews, five systematic reviews with meta-analyses, and 15 randomized controlled trials were identified regarding botulinum toxin for spasticity in adults. In addition, seven evidence-based guidelines were identified regarding the use botulinum toxin for spasticity in adults. METHODS

A limited literature search was conducted on key resources including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, Canadian and major international health technology agencies, as well as a focused Internet search. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2011 and March 23, 2016. Internet links were provided, where available. The summary of findings was prepared from the abstracts of the relevant information. Please note that data contained in abstracts may not always be an accurate reflection of the data contained within the full article.

Botulinum Toxin for Spasticity 2

SELECTION CRITERIA

One reviewer screened citations and selected studies based on the inclusion criteria presented in Table 1.

Table 1: Selection Criteria

Population Adults with spasticity in any setting; adults in long-term care (residential care homes are a subgroup of interest)

Intervention Botulinum toxin

Comparator No comparator

Placebo

Alternate drug

Non-drug interventions (e.g., form of rehabilitation)

Outcomes Q1: Effectiveness, clinical benefit or harm, safety Q2:

Guidelines and recommendations for use and administration,

Guidelines and recommendations for follow-up and management of patients receiving botulinum toxin

Guidelines and recommendations regarding which patients should receive botulinum toxin

Study Designs Health technology assessment, systematic reviews, meta-analyses,

randomized controlled trials, non-randomized studies, and evidence-based guidelines

RESULTS

Rapid Response reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials and evidence-based guidelines. Eight systematic reviews, five systematic reviews with meta-analyses, and 15 randomized controlled trials were identified regarding botulinum toxin for spasticity in adults. In addition, seven evidence-based guidelines were identified regarding the use botulinum toxin for spasticity in adults. No heath technology assessments were identified, and non-randomized studies were not included due to the volume of systematic reviews and randomized controlled trials identified. Additional references of potential interest are provided in the appendix.

OVERALL SUMMARY OF FINDINGS

Eight systematic reviews,1,4-5,8-10,12-13 five systematic reviews with meta-analyses,2-3,6-7,11 and 15 randomized controlled trials (RCTs) 15-29 were identified regarding botulinum toxin for spasticity in adults. Most of the systematic reviews,1,4,10 systematic reviews with meta-analysis,2-3,6-7,11 and the RCTs12,14-22,24,26-28 provided evidence regarding the efficacy and safety associated with botulinum toxin (types A, B, or unspecified) for the treatment of either lower limb and upper limb spasticity or both. Conversely, there were a few studies that did not observe benefits in patients with spasticity treated with botulinum toxin or observed weak benefits;8,13,23,25 however, these


studies did observe improvements in some other movements upon treatment. One systematic review recommended instrument-guided injections of botulinum toxin for spasticity treatment,5 another systematic review discussed the potential benefits of chemodenervation with botulinum toxin,12 while another systematic review focused on which muscles were used for injection and the effectiveness therein.9 Detailed study characteristics are provided in Table 2.

Table 2: Summary of Included Studies on Botulinum Toxin for Spasticity in Adults

First

Author, Year

Study Characteristics

Botulinum

Toxin-Type, Doses

Outcomes Conclusions

Systematic Reviews and Meta-Analyses Dashtipour, 2016

1 SR

6 RCTs included

LL spasticity in various etiologies

ABO-BTX-A

500-2000 U (range)

Efficacy

Safety

Dosing practices

All studies showed statistically significant reduction in muscle tone

Generally well tolerated with most AEs considered un-related to tmt

Baker, 20152

SR and MA

LL spasticity 12 PL-controlled

RCTs included; various etiologies

MA of 6 UL and 6 LL studies

BTX-A

One dose (NR)

Relating to leg/arm spasticity o Active function

measures o QoL measures

BTX-A may improve active outcomes in UL

Baker, 20153

SR and MA Ease of care in UL

and LL

32 PL-controlled RCTs included

MA of 11 UL and 3 LL studies

BTX-A Dose NR

Efficacy regarding improving ease of care

BTX-A improves ease of care in UL for up to 6 months

No conclusions possible for LL

Dashtipour, 2015

4 SR

Tmt of UL spasticity 12 RCTs included

ABO-BTX-A

500 – 1500 U (range)

Efficacy

Safety Dosing practices

Strong evidence to support use of ABO for UL spasticity in stroke

ABO generally well tolerated with most AEs considered un-related to tmt

Grigoriu, 2015

5 SR Tmt of BTX-A on

focal spasticity and dystonia

10 studies included (7 RCTs)

BTX-A Dose NR

Effectiveness of instrument guided BTX-A in focal spasticity and dystonia

Results strongly recommend instrument guidance (ES or US) of BTX-A for spasticity tmt in adults and for tmt of focal dystonia such as spasmodic torticollis (EMG)

Baker, 20136

SR and MA 37 studies included

MA on 21 for spasticity

BTX-A Dose NR

Efficacy of BTX-A on spasticity

Use of BTX-A for UL and LL spasticity is supported by moderate quality evidence

Foley, 20137

SR and MA

Post-stroke spasticity in UL

16 RCTs (10 RCTs included in pooled

BTX-A

Dose NR

UL activity capacity or performance

BTX-A associated with moderate UL activity capacity or performance



First Author,

Year


Botulinum Toxin-Type,

Doses


analysis [n=1,000]) Intiso, 2013

8 SR

Post-stroke spasticity

16 RCTs included

BTX-A

Dose NR

Efficacy

Global functionality of activity daily living

After reduced spasticity there was some improvement in oriented-focused UL movements; however, significant benefit still in doubt

No improvement in global functionality of activity daily living

Nalysnyk, 2013

9 SR Adults with

spasticity

70 studies included (28 RCTs, 5 NRS, 37 single-arm)

ABO Dose NR

Injection patterns Most frequent muscles injected with ABO were wrist, elbow, finger flexors, and ankle plantar flexors

McIntyre, 2012

10 SR

BTX-A for reducing spasticity of LL in chronic stroke survivors

9 RCTs included (n=605)

BTX-A

Dose NR

Effectiveness Effective in reducing LL spasticity when initiated 6 months post-stroke

Wu, 201611

SR and MA

LL spasticity in stroke

7 RCTs (n=603) compared against PL or conventional therapy

BTX; unspecified type

Dose NR

Effectiveness BTX showed persistent clinical benefits in LL spasticity and Fugl-Meyer score

BTX could be a useful and safe strategy for LL spasticity post-stroke

Lui, 201512

SR Limb spasticity after

SCI

19 studies included (9 involving BTX; 10 involving phenol/alcohol)


Dose NR

Efficacy of chemodenervation

Chemodenervation with BTX may improve function and spasticity in patients with SCI

Phadke, 2014

13 SR Spasticity post-

stroke

Number of included studies NR


Dose NR

Impact of BTX treated spasticity on standing balance

Weak evidence for balance changes in post-stroke patients following BTX tmt

Randomized Controlled Trials

Elovic, 201614

PL-controlled

UL post-stroke spasticity

N=NR

Inco-BTX-A

1:1 400 U or PL

Efficacy

Tolerability

Significant improvement in UL spasticity and associated disability in patients post-stroke

AEs were mainly mild/moderated; inco-BTX-A well-tolerated

Gracies, 2015

15 DB, PL-controlled

Patients 6 months post-stroke or post-brain injury

ABO-BTX-A

1:1:1 500 U, 1000 U, or PL

Efficacy in UL on muscle tone, spasticity, active movement, and function

ABO-BTX-A provided tone reduction and clinical benefit in hemiparesis

AEs were mild or



First Author,

Year



Doses


N=243 o ABO-BTX-A

500 U (n=81) o ABO-BTX-A

1000 U (n=81) o PL (n=81)

Safety moderate; most common was mild muscle weakness

Nam, 201516

DB, active comparator

Post-stroke UL spasticity

N=197 o NABOTA

(n=99) o ONA-BTX-A

(n=98)

NABOTA

ONA-BTX-A

Efficacy

Safety

NABOTA was non-inferior in efficacy and safety for UL spasticity improvement compared to ONA-BTX-A

Seo, 201517

Active comparator

UL spasticity for stroke patients

N=196

Neuronox

ONA-BTX-A

Efficacy

Safety

Neuronox was equivalent to ONA-BTX-A with regard to efficacy and safety for treating UL spasticity in post-stroke patients

Tao, 201518

PL-controlled

Subacute stroke patients

N=23 o BTX-A (n=11) o PL (n=12)

Early, low dose electrical stimulation-guided BTX-A (200 U)

PL

Gait improvement

Spasticity improvement

Improvement in daily living activities

Early low-dose BTX-A may improve gait, spasticity, and daily living activities

Fietzek, 2014


Patients with stroke, traumatic brain injury or hypoxic encephalopathy and spastic pes equinovarus (unilateral or bilateral)

N=52

ONA-BTX-A (230 U or 460 U)

PL

Efficacy (muscular hypertonicity)

Given 3 months after lesions, ONA-BTX-A reduces muscular hypertonicity in spastic pes equines

Picelli, 201420

Double active comparator

Chronic stoke patients with spastic equinus

N=NR

ONA-BTX-A

Therapeutic ultrasound

TENS

Efficacy Results provide evidence that ONA-BTX-A is more effective for treating spasticity in this population that therapeutic ultrasound and TENS

Guarany, 2013

21 DB, active

comparator, crossover

Patients with clinically meaningful spasticity

N=57

BTX-A (Botox[R])

Prosigne[R] (new BTX serotype A)

Efficacy

Safety

Both Botox[R] and Prosigne[R] are comparable in efficacy and safety for 3 month tmt of spasticity

Yazdchi, DB, active BTX-A Efficacy In comparison with TZD,



First Author,

Year



Doses


201322

comparator Post-stroke UL

spasticity

N=68 o BTX-A (n=34) o TZD (n=34)

TZD Safety BTX-A was effective and safe in reducing post-stroke UL spasticity

Dunne, 2012

23 DB, PL-controlled Post-stroke with

plantarflexor overactivity

N=85 o ONA-BTX-A

200 U (n=28) o ONA-BTX-A

300 U (n=28) o PL (n=29)

ONA-BTX-A (at either 200 U or 300 U)

PL

Efficacy Safety

ONA-BTX-A did not alter local spasticity at 12 weeks; however, it did reduce spasms and improve gait quality

No detectable differences between 2 doses

ONA-BTX-A was safe and well-tolerated

Rosales, 2012

24 PL-controlled Asian patients with

post-stroke patients with UL spasticity

N=163 o BTX-A (n=80) o PL (n=93)

Very early use of: o BTX-A

(500 U) o PL

Effectiveness Safety

BTX-A 500 U, within 2-12 weeks of stroke) provided sustained reduction in UL spasticity when combined with rehabilitation in patients with mild-to moderate hypertonicity and voluntary movement

No differences in AS observed

Shaw, 201125

4 week therapy-controlled

Post-stroke patients with spasticity

N=333

BTX-A + 4-week therapy

4-week therapy

Impairment Activity limitation

Pain

BTX-A unlikely to be useful for spasticity post-stroke; however, may improve basic upper limb tasks and pain

Gracies, 2014


Post-stroke or traumatic brain injury hemiparetic patients with spastic UL muscles

N=24

Rima-BTX-B (10,000 U or 15,000 U)

PL

Efficacy

Safety

Rima-BTX-B (up to 15,000 U) improved active elbow extension and subject-perceived stiffness when injected into spastic UL muscles

Rima-BTX-B was well tolerated

Bollens, 2013

27 SB, active

comparator

Chronic stroke patients with spastic equinovarus of the foot

N=16 o Selective tibial

neurotomy (n=8)

o BTX (n=8)

Selective tibial neurotomy

BTX unspecified

Effectiveness Higher reduction in ankle stiffness was observed with selective tibial neurotomy

Both tmts induced improvement of ankle kinematics during gait

Neither induced muscle weakening

Lam, 201228

DB, PL-controlled Long-term care

patients

N=55

BTX-A PL

Primary outcome: decrease of care burden

Secondary

Patients treated with BTX-A had significant decrease in care burden

Improved scores on



First Author,

Year



Doses


outcomes: o Goal attainment

scale o Measure of

spasticity o Difficulty in

basic UL care

Safety

patient-centered outcomes were also improved with BTX-A tmt

No BTX-A AEs were observed

ABO-BTX-A = AboBotulinumtoxinA; AE = adverse event; BTX = botulinum toxin; BTX-A = botulinum toxin type A; DB = double blind; EMG = electromyogram; ES = electrical stimulation; LL = low er limb; MA = meta-analysis; NABOTA = new Botulinum toxin type A (DWP450); NR = not reported; NRS = non-randomized studies; ONA-BTX-A = onaBotulinum toxin A; PL = placebo; QoL = quality of life; RCT = randomized controlled trial; Rima-BTX-B = rimaBotulinumtoxinB; SB = single-blind; SCI = spinal cord injury; SR

= systematic review; TENS = transcutaneous electrical nerve stimulation ; tmt = treatment; TZD = tizanidine; UL = upper limb; US = ultrasonography.

Of the seven identified guidelines containing information on the use of botulinum toxin for spasticity in adults, three provided recommendations regarding its use in patients with acute or post-acute stroke,30,32,35 two provided statements regarding the lack of recommendations in patients with multiple sclerosis (MS),31,34 one guideline provided recommendations for patients with motor neuron disease (MND),33 and the last guideline provided a statement for making no recommendation for the use of botulinum toxin in patients with MND.29

For patients who have suffered a stroke, Health Quality Ontario and the Ministry of Health and Long-Term Care recommends the use of Clostridium botulinum toxin to, a) relieve spasticity when is causes pain or interferes with physical functioning or the maintenance of hand hygiene, b) treat hemiplegic shoulder pain thought to occur due to spasticity (by injecting into the subscapularis and pectoralis muscles), c) relieve pain related to both spasticity and inflammation or injury in a subset of patients experiencing both (and as dual therapy with steroidal injections), and d) treat focal spasticity and/or symptomatically distressing spasticity of the lower extremities in order to decrease pain, to improve gait, and to increase the patient’s range of motion (specifically relates to botulinum toxin A).30 The Heart and Stroke Foundation (HSF) echoes the aforementioned recommendation to chemodenervate using botulinum toxin in order to both decrease pain and increase range of motion in patients with focal and/or symptomatically distressing spasticity in the shoulder, arm, or hand.

32 In addition to being

beneficial in decreasing pain and increasing range of motion, the HSF also recommends the use of botulinum toxin for improving gait in patients with lower limb focal and/or symptomatically distressing spasticity.32 The Royal College of Physicians’ Intercollegiate Stroke Working Party35 recommends the use of intramuscular botulinum toxin in patients with progressing or persistent troublesome focal spasticity affecting one or more joints and who have an identifiable therapeutic goal. Botulinum toxin should be provided in the context of a specialist multidisciplinary team service (including rehabilitation or physical maintenance therapy) over two to 12 weeks post-injection, with a subsequent functional assessment provided three to four months post-injection.35

For patients with MS, the National Institute for Health and Care Excellence (NICE) did not make specific recommendations regarding the use of botulinum toxin for the treatment of spasticity.31 Instead, they provided a statement affirming that it may have a place for use in patients with severe spasticity or complications from their spasticity under the care of specialized services.31 The Spanish Society of Neurology 34 also have stated that botulinum toxin A may be required in


selected cases of patients with MS; however, they did not provide any specific recommendations regarding its use for the treatment of spasticity. For patients with MND, Esquenazi et al.33 recommends the use of botulinum neurotoxin type A, Abo-A, and Ona-A (Level A evidence), and Inco-A (Level B evidence) for the treatment of upper limb spasticity. For lower limb spasticity, Esquenazi et al.33 recommends the use of botulinum neurotoxin Ona-A and Type A in aggregate (Level A), and Abo-A (Level C); however, there was insufficient identified evidence to recommend either Inco-A or Rima-B (a form of botulinum neurotoxin type B). While NICE29 made no specific recommendations regarding the use of botulinum toxin in patients with MND, they did state that patients may benefit from receiving botulinum toxin from a specialist for focal spasticity when they are not responding to other treatments.


REFERENCES SUMMARIZED

Health Technology Assessments

No literature identified. Systematic Reviews and Meta-analyses

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3. Baker JA, Pereira G. The efficacy of Botulinum Toxin A on improving ease of care in the

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5. Grigoriu AI, Dinomais M, Remy-Neris O, Brochard S. Impact of injection-guiding techniques on the effectiveness of botulinum toxin for the treatment of focal spasticity and dystonia: a systematic review. Arch Phys Med Rehabil. 2015 Nov;96(11):2067-78. PubMed: PM25982240

6. Baker JA, Pereira G. The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach. Clin Rehabil. 2013 Dec;27(12):1084-96. PubMed: PM23864518

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22. Yazdchi M, Ghasemi Z, Moshayedi H, Rikhtegar R, Mostafayi S, Mikailee H, et al. Comparing the efficacy of botulinum toxin with tizanidine in upper limb post stroke spasticity. Iran J Neurol [Internet]. 2013 [cited 2016 Apr 5];12(2):47-50. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829280 PubMed: PM24250901

http://www.ncbi.nlm.nih.gov/pubmed/26318836http://www.ncbi.nlm.nih.gov/pubmed/26233808http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452301http://www.ncbi.nlm.nih.gov/pubmed/26030192http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395709http://www.ncbi.nlm.nih.gov/pubmed/25931725http://www.ncbi.nlm.nih.gov/pubmed/24754350http://www.ncbi.nlm.nih.gov/pubmed/24722047http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585303http://www.ncbi.nlm.nih.gov/pubmed/23468866http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829280http://www.ncbi.nlm.nih.gov/pubmed/24250901


23. 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 Sep;26(9):787-97. PubMed: PM22308557

24. Rosales RL, Kong KH, Goh KJ, Kumthornthip W, Mok VC, Delgado-De Los Santos MM, et

al. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair. 2012 Sep;26(7):812-21. PubMed: PM22371239

25. Shaw LC, Price CI, van Wijck FM, Shackley P, Steen N, Barnes MP, et al. Botulinum

Toxin for the Upper Limb after Stroke (BoTULS) Trial: effect on impairment, activity limitation, and pain. Stroke. 2011 May;42(5):1371-9. PubMed: PM21415398

Botulinum Toxin B 26. Gracies JM, Bayle N, Goldberg S, Simpson DM. Botulinum toxin type B in the spastic arm:

a randomized, double-blind, placebo-controlled, preliminary study. Arch Phys Med Rehabil. 2014 Jul;95(7):1303-11. PubMed: PM24709034

Unspecified Botulinum Toxin 27. 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 Oct;27(8):695-703. PubMed: PM23757297

Long-Term Care Specified 28. Lam K, Lau KK, So KK, Tam CK, Wu YM, Cheung G, et al. Can botulinum toxin decrease

carer burden in long term care residents with upper limb spasticity? A randomized controlled study. J Am Med Dir Assoc. 2012 Jun;13(5):477-84. PubMed: PM22521630

Guidelines and Recommendations

29. National Clinical Guideline Centre. Motor neurone disease: assessment and management

[Internet]. London, United Kingdom: National Institute for Health and Care Excellence; 2016 Feb [cited 2016 Apr 5]. (NICE guideline NG42). Available from: https://www.nice.org.uk/guidance/ng42/evidence/full-guideline-2361774637 See: Section on Muscle stiffness, page 194

http://www.ncbi.nlm.nih.gov/pubmed/22308557http://www.ncbi.nlm.nih.gov/pubmed/22371239http://www.ncbi.nlm.nih.gov/pubmed/21415398http://www.ncbi.nlm.nih.gov/pubmed/24709034http://www.ncbi.nlm.nih.gov/pubmed/23757297http://www.ncbi.nlm.nih.gov/pubmed/22521630https://www.nice.org.uk/guidance/ng42/evidence/full-guideline-2361774637


30. Quality-based procedures: clinical handbook for stroke (acute and postacute) [Internet]. Toronto: Health Quality Ontario; 2015 December [cited 2016 Apr 5]. Available from: http://www.hqontario.ca/Portals/0/Documents/evidence/clinical-handbooks/community-stroke-20151802-en.pdf See: Section 9.40.1, pages 76 and 125 Section 9.47.4, pages 78 and 127 Section 9.47.6, pages 78 and 127 Section 9.54.1, pages 80 and 129

31. National Clinical Guideline Centre. Multiple sclerosis: management of multiple sclerosis in

primary and secondary care [Internet]. London, United Kingdom: National Institute for Health and Care Excellence; 2014 Oct [cited 2016 Apr 5]. (NICE clinical guideline 186). Available from: https://www.nice.org.uk/guidance/cg186/evidence/full-guideline-193254301

See: Section 9 Pharmacological management of MS symptoms, page 124 Table 48: Clinical evidence profile: Botulinum versus placebo, pages 149-151 Botulinum versus placebo, page 166 Botulinum Toxin not recommended, page 169

32. Dawson AS, Knox J, McClure A, Foley N, Teasell R. Chapter 5: stroke rehabilitation. In: Lindsay MP, Gubitz G, Bayley M, Phillips S, editors. Canadian best practice recommendations for stroke care [Internet]. 4th ed. Ottawa: Heart & Stroke Foundation; 2013 Jul 10 [cited 2016 Apr 6]. Available from: http://www.strokebestpractices.ca/wp-content/uploads/2010/10/Ch5_SBP2013_Stroke-Rehabilitation-_July-2013_FINAL-EN.pdf See 5.5.2 page 43, 5.6.2 page 53

33. Esquenazi A, Albanese A, Chancellor MB, Elovic E, Segal KR, Simpson DM, et al.

Evidence-based review and assessment of botulinum neurotoxin for the treatment of adult spasticity in the upper motor neuron syndrome. Toxicon. 2013 Jun 1;67:115-28. PubMed: PM23220492

34. Gold R, Oreja-Guevara C. Advances in the management of multiple sclerosis spasticity:

multiple sclerosis spasticity guidelines. Expert Rev Neurother. 2013 Dec;13(12 Suppl):55-9. PubMed: PM24289845

35. Intercollegiate Stroke Working Party. National clinical guideline for stroke [Internet]. 4th ed. London, United Kingdom: Royal College of Physicians; 2012 Sep [cited 2016 Apr 5]. Available from: https://www.rcplondon.ac.uk/guidelines-policy/stroke-guidelines See: Section on 6.10 Impaired tone – spasticity and spasms and Recommendations 6.10.1, page 87

PREPARED BY:

Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca

http://www.hqontario.ca/Portals/0/Documents/evidence/clinical-handbooks/community-stroke-20151802-en.pdfhttp://www.hqontario.ca/Portals/0/Documents/evidence/clinical-handbooks/community-stroke-20151802-en.pdfhttps://www.nice.org.uk/guidance/cg186/evidence/full-guideline-193254301http://www.strokebestpractices.ca/wp-content/uploads/2010/10/Ch5_SBP2013_Stroke-Rehabilitation-_July-2013_FINAL-EN.pdfhttp://www.strokebestpractices.ca/wp-content/uploads/2010/10/Ch5_SBP2013_Stroke-Rehabilitation-_July-2013_FINAL-EN.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23220492http://www.ncbi.nlm.nih.gov/pubmed/24289845https://www.rcplondon.ac.uk/guidelines-policy/stroke-guidelineshttp://www.cadth.ca/


APPENDIX – FURTHER INFORMATION:

Previous CADTH Reports

36. Botulinum toxin for spasticity in long-term care residents: clinical effectiveness and

guidelines [Internet]. Ottawa: CADTH; 2011 Dec 9 [cited 2016 Apr 5]. (Rapid response report: reference list). Available from: https://www.cadth.ca/media/pdf/htis/dec-2011/RA0560-000%20Botox%20for%20Pain%20Final.pdf

Randomized Controlled Trials – Injection Site or Technique Comparisons

37. Im S, Park JH, Son SK, Shin JE, Cho SH, Park GY. Does botulinum toxin injection site

determine outcome in post-stroke plantarflexion spasticity? Comparison study of two injection sites in the gastrocnemius muscle: a randomized double-blind controlled trial. Clin Rehabil. 2014 Jan 22;28(6):604-13. PubMed: PM24452704

38. Ploumis A, Varvarousis D, Konitsiotis S, Beris A. Effectiveness of botulinum toxin injection with and without needle electromyographic guidance for the treatment of spasticity in hemiplegic patients: a randomized controlled trial. Disabil Rehabil. 2014;36(4):313-8. PubMed: PM23672209

39. Santamato A, Micello MF, Panza F, Fortunato F, Baricich A, Cisari C, et al. Can botulinum

toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques. J Neurol Sci. 2014 Dec 15;347(1-2):39-43. PubMed: PM25263601

40. Picelli A, Tamburin S, Bonetti P, Fontana C, Barausse M, Dambruoso F, et al. 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 Nov;91(11):957-64. PubMed: PM23085706

Clinical Practice Guidelines – Unspecified Methodology 41. Semenko B, Thalman L, Ewert E, Delorme R, Hui S, Flett H, et al. An evidence based

occupational therapy toolkit for assessment and treatment of the upper extremity post stroke [Internet]. Winnipeg: Winnipeg Health Region Occupational Therapy Upper Extremity Working Group; 2015 Apr [cited 2016 Apr 5]. Available from: http://www.wrha.mb.ca/professionals/occupational-therapy/files/Stroke-UEToolkit.pdf See 8.1.7 page 39

https://www.cadth.ca/media/pdf/htis/dec-2011/RA0560-000%20Botox%20for%20Pain%20Final.pdfhttps://www.cadth.ca/media/pdf/htis/dec-2011/RA0560-000%20Botox%20for%20Pain%20Final.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24452704http://www.ncbi.nlm.nih.gov/pubmed/23672209http://www.ncbi.nlm.nih.gov/pubmed/25263601http://www.ncbi.nlm.nih.gov/pubmed/23085706http://www.wrha.mb.ca/professionals/occupational-therapy/files/Stroke-UEToolkit.pdf


42. Guidelines for the rehabilitation of patients with metastatic spinal cord compression (MSCC): assessment and care provision by occupational therapists and physiotherapists in the acute sector [Internet]. Belfast: Guidelines and Audit Implementation Network; 2014 Jan [cited 2016 Apr 5]. Available from: http://www.gain-ni.org/images/GAIN-Guidelines-for-Rehabilitation-of-Assessment-and-Care-Provision-by-Occupational-Therapists-and-Physiotherapists-in-the-Acute-Sector.PDF See pages 32, 57

43. Hertfordshire Medicines Management Committee. Botulinum toxin type A for focal

spasticity in adults. Recommended for restricted use [Internet]. Welwyn Garden City, United Kingdom: NHS Hertfordshire; 2012 Sep [cited 2016 Apr 5]. Available from: http://hertsvalleysccg.nhs.uk/uploads/file/Pharmacy/Local%20Decisions/Botulinum%20toxin%20for%20focal%20spasticity%20of%20upper%20limb%20201209(HMMC).pdf

44. Traumatic brain injury medical treatment guidelines [Internet]. Denver: State of Colorado,

Division of Workers' Compensation; 2012 Nov 26 [cited 2016 Apr 5]. Available from: https://www.colorado.gov/pacific/sites/default/files/MTG_Ex10_TBI.pdf See pages 86-87 e.

45. Ells G. Botulinum toxin to manage spasticity in stroke rehabilitation and multiple sclerosis

[Internet]. Lewes, United Kingdom: East Sussex Downs and Weald Primary Care Trust; 2011 Feb 1 [cited 2016 Apr 5]. Available from: http://www.eastbournehailshamandseafordccg.nhs.uk/EasysiteWeb/getresource.axd?AssetID=366869&type=Full&servicetype=Attachment

46. Jabeen A, Kandadai RM, Kannikannan MA, Borgohain R. Guidelines for the use of

Botulinum toxin in movement disorders and spasticity. Ann Indian Acad Neurol [Internet]. 2011 Jul [cited 2016 Apr 5];14(Suppl 1):S31-S34. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152173 PubMed: PM21847327

Management Pathway 47. Spasticity management pathway [Internet]. Adelaide: Government of South Australia, SA

Health; 2013 Jan [cited 2016 Apr 5]. Available from: http://www.sahealth.sa.gov.au/wps/wcm/connect/c2e6a7804e5de262963df6fefb3fa04f/Spasticity+management+pathway-HealthReform-RCH-20130130.pdf?MOD=AJPERES&CACHEID=c2e6a7804e5de262963df6fefb3fa04f

http://www.gain-ni.org/images/GAIN-Guidelines-for-Rehabilitation-of-Assessment-and-Care-Provision-by-Occupational-Therapists-and-Physiotherapists-in-the-Acute-Sector.PDFhttp://www.gain-ni.org/images/GAIN-Guidelines-for-Rehabilitation-of-Assessment-and-Care-Provision-by-Occupational-Therapists-and-Physiotherapists-in-the-Acute-Sector.PDFhttp://www.gain-ni.org/images/GAIN-Guidelines-for-Rehabilitation-of-Assessment-and-Care-Provision-by-Occupational-Therapists-and-Physiotherapists-in-the-Acute-Sector.PDFhttp://hertsvalleysccg.nhs.uk/uploads/file/Pharmacy/Local%20Decisions/Botulinum%20toxin%20for%20focal%20spasticity%20of%20upper%20limb%20201209(HMMC).pdfhttp://hertsvalleysccg.nhs.uk/uploads/file/Pharmacy/Local%20Decisions/Botulinum%20toxin%20for%20focal%20spasticity%20of%20upper%20limb%20201209(HMMC).pdfhttps://www.colorado.gov/pacific/sites/default/files/MTG_Ex10_TBI.pdfhttp://www.eastbournehailshamandseafordccg.nhs.uk/EasysiteWeb/getresource.axd?AssetID=366869&type=Full&servicetype=Attachmenthttp://www.eastbournehailshamandseafordccg.nhs.uk/EasysiteWeb/getresource.axd?AssetID=366869&type=Full&servicetype=Attachmenthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152173http://www.ncbi.nlm.nih.gov/pubmed/21847327http://www.sahealth.sa.gov.au/wps/wcm/connect/c2e6a7804e5de262963df6fefb3fa04f/Spasticity+management+pathway-HealthReform-RCH-20130130.pdf?MOD=AJPERES&CACHEID=c2e6a7804e5de262963df6fefb3fa04fhttp://www.sahealth.sa.gov.au/wps/wcm/connect/c2e6a7804e5de262963df6fefb3fa04f/Spasticity+management+pathway-HealthReform-RCH-20130130.pdf?MOD=AJPERES&CACHEID=c2e6a7804e5de262963df6fefb3fa04fhttp://www.sahealth.sa.gov.au/wps/wcm/connect/c2e6a7804e5de262963df6fefb3fa04f/Spasticity+management+pathway-HealthReform-RCH-20130130.pdf?MOD=AJPERES&CACHEID=c2e6a7804e5de262963df6fefb3fa04f

Research questionSkey FINDINGSMethodsResultsOverall summary of findingsReferences summarizedAppendix – Further information: