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TITLE: Constraint Induced Movement Therapy for Children: Update of Clinical Effectiveness and Guidelines
DATE: 16 June 2016
RESEARCH QUESTIONS
1. What is the clinical effectiveness of constraint induced movement therapy for children with
unilateral upper extremity impairment?
2. What are the evidence-based guidelines regarding the use of constraint induced movement therapy for children with unilateral upper extremity impairment?
3. What are the evidence-based guidelines regarding the optimal non-technology or non-drug based therapy for treatment of children with unilateral upper extremity impairment?
KEY FINDINGS
Five systematic reviews, 25 randomized controlled trials, and three evidence-based guidelines were identified regarding the use of constraint induced movement therapy for children with unilateral upper extremity impairment. METHODS
A limited literature search was conducted on key resources including Ovid Medline, PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, ECRI Institute, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit retrieval by publication type for research questions 1 and 2. For question 3, methodological filters were used to limit retrieval to systematic reviews, health technology assessments, meta-analyses and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2010 and May 30, 2016. Internet links were provided, where available.
Constraint Induced Movement Therapy for Children 2
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. SELECTION CRITERIA
One reviewer screened citations and selected studies based on the inclusion criteria presented in Table 1.
Table 1: Selection Criteria Population Pediatric patients with unilateral upper extremity impairment, including, but
not limited to cerebral palsy and pediatric stroke patients
Intervention Q1 and 2: Constraint Induced Movement Therapy (CIMT) Q3: CIMT, bimanual training, occupational or physical therapy, observational training, mirror therapy, casting
Excluding robotic or technology based therapies and drug or procedural therapies such as Botulinum toxin or blockades
Comparator Q1: Bimanual training, occupational or physical therapy, observational training, mirror therapy, casting;
Usual care; Q1 to 3: No comparator required
Outcomes Q1: Clinical effectiveness (e.g., upper extremity functional outcomes [e.g., hand function, functional skills, movement quality and efficiency, unimanual
capacity, bimanual performance], self-determined goal achievement, patient satisfaction, quality of life); Q2: Evidence-based guidelines regarding the use of CIMT including
appropriate indications as well as how it should be administered and by whom; Q3: Evidence-based guidelines regarding the use of non-technology, non-
drug-based therapy including which therapy is the most appropriate, who should be treated, how therapy should be administered and by whom
Study Designs Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, 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 (RCTs), non-randomized studies, and evidence-based guidelines. Five systematic reviews, 25 RCTs, and three evidence-based guidelines were identified regarding the use of constraint induced movement therapy (CIMT) for children with unilateral upper extremity impairment. No relevant health technology assessments were identified. Due to the large number of relevant studies identified, non-randomized studies have been included in the appendix with other references of potential interest.
Constraint Induced Movement Therapy for Children 3
OVERALL SUMMARY OF FINDINGS
Five systematic reviews1-5 and 25 RCTs6-30 were identified regarding the clinical effectiveness of CIMT for children with unilateral upper extremity impairment. The results of these studies generally indicate that CIMT was as, or more, effective than bimanual or conventional therapies.
The findings of these studies are summarized in Table 2.
Three evidence-based guidelines31-33 were identified. One guideline31 addresses the use of pediatric modified CIMT plus bimanual training (BMT) for children with unilateral upper extremity impairment; and two guidelines32,33 address optimal non-technology or non-drug based therapy, including CIMT, for treatment of children with unilateral upper extremity impairment.
The modified CIMT guideline from the Cincinnati Childrens Hospital31 provides three suggested treatment protocols. Treatment should be undertaken by a physiotherapist or occupational therapist trained in CIMT and BMT and the treatment protocol should be decided upon in
consultation with the primary caregivers of the child.31
For children with, or at risk for, cerebral palsy (CP) the guideline from the American Occupational Therapy Association32 recommends:
Use of constraint-induced movement therapy to improve motor performance in young
children with CP. Use of neurodevelopmental treatment for young children with CP to improve motor
performance.
Child-focused and context-focused intervention were equally likely to improve motor performance.
The guideline from National Institute for Health and Clinical Excellence33 addressing
management of spasticity and co-existing motor disorders and their early musculoskeletal
complications recommends a number of specific strategies including postural management strategies and active-use therapy, such as CIMT.33
Table 2: Summary of Included Studies
First Author, Year
Patient Population
Intervention and Comparator
Results and Authors Conclusions
Systematic Reviews Chen, 2014
1
27 RCTs
Children with CP CIMT vs conventional therapy
CIMT showed an overall beneficial effect when compared to conventional therapy.
The authors concluded CIMT was an effective intervention to improve arm function in children with CP.
Sakzewski,
20142
42 RCTs
evaluating 113 interventions
Children with
unilateral CP
Non-surgical upper
limb therapies
CIMT resulted in modest to strong
treatment effects when compared with usual care or equal doses of bimanual OT.
Tinderholt,
20143
Young children
with CP
Intensive motor
function and functional skills
Hand function and functional skills
outcomes from CIMT were examined in 6 SRs. The authors indicated that the
Constraint Induced Movement Therapy for Children 4
Table 2: Summary of Included Studies
First Author, Year
Patient Population
Intervention and Comparator
Results and Authors Conclusions
38 controlled studies
training results supported the existing evidence of CIMT.
Dong, 20134
Number of studies not
reported
Children with
unilateral CP
CIMT vs BMT CIMT and BMT both resulted in similar
improvements in overall performance and in bimanual and unimanual function of the affected arm.
Novak, 20135
166 articles
evaluating 64 interventions
Children with CP All interventions for CP
The authors graded the interventions from do it to do not do it. CIMT was rated as a do it therapy.
Randomized Controlled Trials Kirton, 2016
6 Children with
perinatal stroke hemiparesis
(n = 45)
Two weeks of daily
rTMS, CIMT, both, or neither added to intensive therapy
The addition of rTMS, CIMT, or both
resulted in a doubled chance of clinically significant improvement. QoL scores were improved.
Zafer, 20167 Children with
hemiplegic CP
(n = 20)
CIMT vs BMT Participants in the CIMT group had significantly greater improvement in functional status.
Gelkop, 20158 Children with
hemiplegic CP in an educational
setting (n = 12)
mCIMT vs HABIT Children in both treatment groups showed similar significant functional improvement. This improvement was maintained in both
groups at six month follow-up.
Xu, 20159 Children with
hemiplegic CP (n = 68)
CIMT vs
CIMT + electrical stimulation vs traditional OT
Functional outcomes (muscle recruitment
and coordination) of the wrist were more improved in the CIMT + electrical stimulation group.
Abdel-Kafy,
201410
Children with
congenital hemiparesis
(n = 30)
Child-friendly CIMT
vs conventional non-structured therapy group (control)
Upper extremity performance was more
greatly improved in the CIMT group as compared to the control group. This improvement was maintained at three
months follow-up.
Chen, 201411
Children with unilateral CP
(n = 47)
CIMT vs TR The authors reported larger effects in favour of CIMT on motor performance, daily function, and some aspects of
reaching control than in the TR group.
Chen, 201412
Children with unilateral CP
(n = 45)
Home-based CIMT vs TR (including unimanual and
bimanual training)
The CIMT group had significantly shorter reaction time and normalized movement time. The treatment group also showed
significantly greater improvement than the traditional group on measurement scales.
Choudhary, 2013
13
Children with hemiplegic CP
(n = 31)
mCIMT + conventional therapy
vs conventional therapy alone
The mCIMT group showed significant improvement in the affected upper limb vs
the control group. The functional improvement was maintained at eight weeks following treatment.
Constraint Induced Movement Therapy for Children 5
Table 2: Summary of Included Studies
First Author, Year
Patient Population
Intervention and Comparator
Results and Authors Conclusions
Deppe, 201314
Children with unilateral CP
(n = 47)
mCIMT vs intensive BMT
There was a significantly greater improvement in isolated motor functions
in the affected arm in the mCIMT group. The authors determined that children with more severe disability improved more
than those with less severe disability.
Kingels, 201315
Children with unilateral CP
(n = 51)
mCIMT vs mCIMT + IT
There were significant between group differences observed in the Assisting Hand Assessment in favour of the mCIMT
+ IT group. The authors suggested that younger children benefited from both approaches and older children benefited
most from the combined intervention.
de Brito, 201216
Children with hemiplegic CP
(n = 16)
CIMT vs HABIT Functional measures were significantly improved in both treatment groups.
Rostami, 201217
Children with spastic hemparetic CP
(n = 32)
VR vs mCIMT vs mCIMT + VR
Significantly greater improvements in amount of limb use, quality of movement, and speed and dexterity were observed in
the mCIMT + VR group. These improvements were maintained at 3 months follow-up.
Sakzewski,
201218
Children with
congenital hemiplegia
(n = 44)
CIMT vs BMT Significant within group improvements
were observed in both intervention groups; however, the two groups did not differ significantly from each other in
physical activity or skills scales.
Sakzewski, 2012
19
Children with unilateral CP
(n = 63)
CIMT vs BMT No changes in social or emotional well-being were reported in either group. Children and parents from both groups
reported a significant improvement in their or their child's feelings about functioning
Xu, 201220
Children with
hemiplegic CP (n = 68)
CIMT vs
CIMT + electrical stimulation vs OT
All three groups showed significant
improvements in range of motion, grip strength, and upper extremity functional test scores. The CIMT + electrical
stimulation group showed significantly greater improvements when compared to the other interventions.
Al-Oraibi, 201121
Children with
unilateral CP (n = 20)
CIMT vs NDT There was a significant improvement in
hand function in the CIMT group when compared with the NDT group.
Eliasson, 201122
Young children
with unilateral CP (n = 25)
Eco-CIMT vs
usual care
The authors determined there was a
significant treatment effect when Eco-CIMT was compared with the control.
Faccin, 201123
Children with
hemiplegic CP
mCIMT vs BMT vs
standard treatment
Paretic hand function was significantly
improved in both the mCIMT and BMT
Constraint Induced Movement Therapy for Children 6
Table 2: Summary of Included Studies
First Author, Year
Patient Population
Intervention and Comparator
Results and Authors Conclusions
(n = 105)
groups and not in the standard treatment group.
Gordon, 201124
Children with
hemiplegic CP (n = 42)
CIMT vs HABIT Both treatment groups showed similar
improvement in scale scores. Goal Attainment Scale scores were more improved in the HABIT group.
Lin, 201125
Children with CP
(n = 21)
CIMT vs
home-based control intervention
Significantly better results were observed
in grasping control, motor efficacy, and unilateral functional performance in the CIMT group. The results were maintained
at six month follow-up.
Sakzewski, 2011
26 Children with congenital hemiplegia
(n = 64)
CIMT vs BMT
Significant changes in the Canadian Occupational Performance Measure were observed in both groups at 3 weeks and
were maintained at 26 weeks. Minimal difference was reported between the two interventions.
Sakzewski,
201127
Children with
congenital hemiplegia
(n = 63)
CIMT vs BMT Unimanual capacity was significantly
greater in the CIMT group. There were no other significant differences reported after the interventions.
Taub, 201128
Children with congenital hemiparesis
(n = 20)
CIMT vs usual care Children in the CIMT group first exhibited emergence of more new classes of motor patterns and skills and had significantly
improved use of the more effected arm.
Wallen, 201129
Children with hemiplegic CP
(n = 50)
mCIMT vs intensive OT
No clinically or statistically significant differences in outcomes between groups
were identified. The authors concluded that mCIMT was not more effective than intensive OT.
de Brito, 201030
Children with CP
(n = 16)
CIMT vs usual care Functional skills and independence
following the intervention were significantly greater in the CIMT group.
BMT = bimanual therapy; CIMT = constraint-induced movement therapy; CP = cerebral palsy; HABIT = hand-arm bimanual intensive therapy; IT = intensive therapy; mCIMT = modif ied constraint-induced movement therapy; NDT = neurodevelopmental treatment; OT = occupational therapy; QoL = quality of life; rTMS = repetitive transcranial magnetic stimulation; SR = systematic
review ; TR = traditional rehabilitation; VR = virtual reality
Constraint Induced Movement Therapy for Children 7
REFERENCES SUMMARIZED
Health Technology Assessments
No literature identified. Systematic Reviews and Meta-analyses
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Constraint Induced Movement Therapy for Children 8
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Constraint Induced Movement Therapy for Children 9
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Constraint Induced Movement Therapy for Children 10
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Guidelines and Recommendations
31. Pediatric modified Constraint Induced Movement Therapy (mCIMT/BIT) Team CCHMC.
Evidence-based care guideline for pediatric constraint induced movement therapy [Internet]. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2014 Dec. 21 p. [cited 2016 Jun 15]. (Evidence-based care guideline). Available from: www.cincinnatichildrens.org/WorkArea/DownloadAsset.aspx?id=87897
32. Clark GF, Kingsley K. Occupational therapy practice guidelines for early childhood: birth
through 5 years. Bethesda (MD): American Occupational Therapy Association, Inc. (AOTA); 2013. See: Interventions for children with or at risk for cerebral palsy
33. National Collaborating Centre for Women's and Children's Health. Spasticity in children
and young people with non-progressive brain disorders. Management of spasticity and co-existing motor disorders and their early musculoskeletal complications. London (UK): National Institute for Health and Clinical Excellence (NICE); 2012 Jul. 54 p. (NICE clinical guideline; no. 145). https://www.nice.org.uk/guidance/cg145/resources/spasticity-in-under-19s-management-35109572514757 See: Specific Strategies
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21440700&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21401585&dopt=abstracthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674837http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21771948&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21923854&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=20530645&dopt=abstracthttp://www.cincinnatichildrens.org/WorkArea/DownloadAsset.aspx?id=87897https://www.nice.org.uk/guidance/cg145/resources/spasticity-in-under-19s-management-35109572514757https://www.nice.org.uk/guidance/cg145/resources/spasticity-in-under-19s-management-35109572514757
Constraint Induced Movement Therapy for Children 11
PREPARED BY:
Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca
http://www.cadth.ca/
Constraint Induced Movement Therapy for Children 12
APPENDIX FURTHER INFORMATION:
Previous CADTH Reports
34. Constraint-induced movement therapy for children: clinical effectiveness and clinical
practice guidelines [Internet]. Ottawa: CADTH; 2010 Oct 29. [cited 2016 Jun 15]. (Rapid response report: reference list). Available from: https://www.cadth.ca/sites/default/files/pdf/J0485_Constraint-Induced_Movement_Therapy_for_Children_final.pdf
Clinical Practice Guidelines Methodology Not Specified
35. Sunny Hill and BC Centre for Ability Pediatric Constraint Induced Movement Therapy
(CIMT) Guidelines Adaptation Working Group. BC pediatric constraint induced movement therapy (CIMT) guideline [Internet]. Vancouver (BC): Sunny HIll Health Centre for Children; 2012. [cited 2016 Jun 15]. (Evidence-based care guideline). Available from: http://www.childdevelopment.ca/Libraries/CIMT/CIMT_guideline_September_13_2012.sflb.ashx
Randomized Controlled Trials CIMT versus CIMT
Dosing 36. Case-Smith J, DeLuca SC, Stevenson R, Ramey SL. Multicenter randomized controlled
trial of pediatric constraint-induced movement therapy: 6-month follow-up. Am J Occup Ther. 2012 Jan;66(1):15-23. PubMed: PM22389937
37. DeLuca SC, Case-Smith J, Stevenson R, Ramey SL. Constraint-induced movement
therapy (CIMT) for young children with cerebral palsy: effects of therapeutic dosage. J Pediatr Rehabil Med. 2012;5(2):133-42. PubMed: PM22699104
Treatment Setting 38. Rostami HR, Malamiri RA. Effect of treatment environment on modified constraint-induced
movement therapy results in children with spastic hemiplegic cerebral palsy: a randomized controlled trial. Disabil Rehabil. 2012;34(1):40-4. PubMed: PM21851293
Non-Randomized Studies
39. Chen HC, Kang LJ, Chen CL, Lin KC, Chen FC, Wu KP. Younger children with cerebral
palsy respond better than older ones to therapist-based constraint-induced therapy at home on functional outcomes and motor control. Phys Occup Ther Pediatr. 2016 May;36(2):171-85. PubMed: PM26643052
https://www.cadth.ca/sites/default/files/pdf/J0485_Constraint-Induced_Movement_Therapy_for_Children_final.pdfhttps://www.cadth.ca/sites/default/files/pdf/J0485_Constraint-Induced_Movement_Therapy_for_Children_final.pdfhttp://www.childdevelopment.ca/Libraries/CIMT/CIMT_guideline_September_13_2012.sflb.ashxhttp://www.childdevelopment.ca/Libraries/CIMT/CIMT_guideline_September_13_2012.sflb.ashxhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=22389937&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=22699104&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21851293&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26643052&dopt=abstract
Constraint Induced Movement Therapy for Children 13
40. Komar A, Ashley K, Hanna K, Lavallee J, Woodhouse J, Bernstein J, et al. Retrospective analysis of an ongoing group-based modified constraint-induced movement therapy program for children with acquired brain Injury. Phys Occup Ther Pediatr. 2016 May;36(2):186-203. PubMed: PM26565125
41. Miller L, Ziviani J, Ware RS, Boyd RN. Does context matter? Mastery motivation and
therapy engagement of children with cerebral palsy. Phys Occup Ther Pediatr. 2016 May;36(2):155-70. PubMed: PM26565438
42. Psychouli P, Kennedy CR. Modified constraint-induced movement therapy as a home-
based intervention for children with cerebral palsy. 2016;Pediatr Phys Ther. 28(2):154-60. PubMed: PM26808960
43. DeLuca SC, Ramey SL, Trucks MR, Wallace DA. Multiple treatments of pediatric
constraint-induced movement therapy (pCIMT): a clinical cohort study. Am J Occup Ther. 2015 Nov;69(6):6906180010p1-9. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643376/ PubMed: PM26565094
44. Eliasson AC, Holmefur M. The influence of early modified constraint-induced movement therapy training on the longitudinal development of hand function in children with unilateral cerebral palsy. Dev Med Child Neurol. 2015 Jan;57(1):89-94. PubMed: PM25236758
45. Geerdink Y, Aarts P, van der Burg J, Steenbergen B, Geurts A. Intensive upper limb
intervention with self-management training is feasible and promising for older children and adolescents with unilateral cerebral palsy. Res Dev Disabil. 2015 Aug;43-44:97-105. PubMed: PM26164301
46. Nordstrand L, Holmefur M, Kits A, Eliasson AC. Improvements in bimanual hand function after baby-CIMT in two-year old children with unilateral cerebral palsy: A retrospective study. Res Dev Disabil. 2015 Jun;41-42:86-93. PubMed: PM26100242
47. Sakzewski L, Provan K, Ziviani J, Boyd RN. Comparison of dosage of intensive upper limb therapy for children with unilateral cerebral palsy: how big should the therapy pill be? Res Dev Disabil. 2015 Feb;37:9-16. PubMed: PM25460215
48. Thompson AM, Chow S, Vey C, Lloyd M. Constraint-induced movement therapy in children aged 5 to 9 years with cerebral palsy: a day camp model. Pediatr Phys Ther. 2015;27(1):72-80. PubMed: PM25521268
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26565125&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26565438&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26808960&dopt=abstracthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643376/http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26565094&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=25236758&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26164301&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26100242&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=25460215&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=25521268&dopt=abstract
Constraint Induced Movement Therapy for Children 14
49. Kwon JY, Chang WH, Chang HJ, Yi SH, Kim MY, Kim EH, et al. Changes in diffusion tensor tractographic findings associated with constraint-induced movement therapy in young children with cerebral palsy. Clin Neurophysiol. 2014 Dec;125(12):2397-403. PubMed: PM24746686
50. Lowes LP, Mayhan M, Orr T, Batterson N, Tonneman JA, Meyer A, et al. Pilot study of the
efficacy of constraint-induced movement therapy for infants and toddlers with cerebral palsy. Phys Occup Ther Pediatr. 2014 Feb;34(1):4-21. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162395 PubMed: PM23848499
51. McConnell K, Johnston L, Kerr C. Efficacy and acceptability of reduced intensity
constraint-induced movement therapy for children aged 9-11 years with hemiplegic cerebral palsy: a pilot study. Phys Occup Ther Pediatr. 2014 Aug;34(3):245-59. PubMed: PM24341455
52. Cimolin V, Beretta E, Piccinini L, Turconi AC, Locatelli F, Galli M, et al. Constraint-induced
movement therapy for children with hemiplegia after traumatic brain injury: a quantitative study. J Head Trauma Rehabil. 2012 May;27(3):177-87. PubMed: PM21522025
53. Reidy TG, Naber E, Viguers E, Allison K, Brady K, Carney J, et al. Outcomes of a clinic-
based pediatric constraint-induced movement therapy program. Phys Occup Ther Pediatr. 2012 Nov;32(4):355-67. PubMed: PM22731797
54. Sakzewski L, Ziviani J, Abbott DF, Macdonell RA, Jackson GD, Boyd RN. Equivalent
retention of gains at 1 year after training with constraint-induced or bimanual therapy in children with unilateral cerebral palsy. Neurorehabil Neural Repair. 2011 Sep;25(7):664-71. PubMed: PM21427273
55. Gillick BT, Koppes A. Gross motor outcomes in children with hemiparesis involved in a
modified constraint-induced therapy program. J Pediatr Rehabil Med. 2010;3(3):171-5. PubMed: PM21791848
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=24746686&dopt=abstracthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162395http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=23848499&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=24341455&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21522025&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=22731797&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21427273&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=21791848&dopt=abstract
Research QuestionsKey FindingsMethodsResultsOverall Summary of FindingsReferences SummarizedAppendix Further information:
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