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Meta-Analysis
. 2010 Jan 20;2010(1):CD003469.
doi: 10.1002/14651858.CD003469.pub4.

Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE)

Brian J Hoare  1 , Margaret A Wallen, Christine Imms, Elmer Villanueva, Hyam Barry Rawicki, Leeanne Carey
Affiliations
Meta-Analysis

Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE)

Brian J Hoare et al. Cochrane Database Syst Rev. .

Abstract

Background: Cerebral palsy (CP) is "a group of permanent disorders of the development of movement and posture causing activity limitation(s) that are attributed to non-progressive disturbance that occurred in the developing fetal or infant brain" (Rosenbaum 2007, p.9). The spastic motor type is the most common form of CP. Therapeutic management may include splinting/casting, passive stretching, facilitation of posture/movement, spasticity-reducing medication and surgery. Botulinum toxin-A (BoNT-A) is now used as an adjunct to these techniques in an attempt to reduce spasticity, improve range of movement and function.

Objectives: To assess the effectiveness of injections of BoNT-A or BoNT-A and occupational therapy in the treatment of the upper limb in children with CP.

Search strategy: We searched the Cochrane Controlled Trials Register/CENTRAL (The Cochrane Library, Issue 3, 2008), MEDLINE (1966 to August Week 1 2008), EMBASE (1980 to 2008 Week 28) and CINAHL (1982 to August Week 1 2008).

Selection criteria: All randomised controlled trials (RCTs) comparing BoNT-A injection or BoNT-A injection and occupational therapy in the upper limb(s) with other types of treatment (including no treatment or placebo) in children with CP.

Data collection and analysis: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity and rated for quality using the PEDro scale. Data were extracted and entered into RevMan 5.0.15.

Main results: Ten trials met the inclusion criteria. PEDro quality ratings ranged from 6/10 to 10/10. Concentration of BoNT-A ranged from 50U/1.0ml to 200U/1.0ml saline with doses of 0.5U to 16U/kg body weight and total doses of 220 to 410 Units (Botox(R)).A combination of BoNT-A and occupational therapy is more effective than occupational therapy alone in reducing impairment, improving activity level outcomes and goal achievement, but not for improving quality of life or perceived self-competence. When compared with placebo or no treatment, there is moderate evidence that BoNT-A alone is not effective.

Authors' conclusions: This systematic review found high level evidence supporting the use of BoNT-A as an adjunct to managing the upper limb in children with spastic CP. BoNT-A should not be used in isolation but should be accompanied by planned occupational therapy.Further research is essential to identify children most likely to respond to BoNT-A injections, monitor longitudinal outcomes, determine timing and effect of repeated injections and the most effective dosage, dilution and volume schedules. The most effective adjunct therapies including frequency and intensity of delivery also requires investigation.

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Conflict of interest statement

Brian Hoare ‐ In 2002 received a research grant from Allergan Australia to conduct an ongoing randomised controlled trial evaluating the effects of occupational therapy interventions following upper limb injection of BoNT‐A in children with cerebral palsy. These funds have been used to provide the BoNT‐A used in the research, payment of blinded outcome assessors and scorers and video editing for randomisation purposes. Brian Hoare has also received sponsorship from Allergan Australia to attend and teach at conferences and meetings but has no personal financial interest in Botox® or any related product.

Margaret Wallen ‐ In 2000 and 2003, Margaret Wallen was one member of a research group which received two separate grants from Allergan Australia to support a randomised controlled trial evaluating the effects of BoNT‐A and occupational therapy in children with cerebral palsy. The 2000 grant was used to provide the BONT‐A used in the research and payment of research staff to conduct the outcome assessments of study participants. The 2003 grant was used to support the statistical analysis of the RCT. Margaret Wallen has no personal or other financial interest in Botox or any related product.

Christine Imms ‐ is co‐investigator of a randomised controlled trial investigating the effect of repeat injections of BoNT‐A and occupational therapy in the upper limbs of children with hemiplegic cerebral palsy which has received support from Allergan Australia. In 2008, Christine Imms received a grant from Allergan Australia to present results of this trial at the American Academy of Cerebral Palsy and Developmental Medicine in Atlanta.

Barry Rawicki has received sponsorship from Allergan Australia to attend and teach at conferences and meetings but has no personal financial interest in Botox® or any related product.

Elmer Villanueva ‐ No competing interests.

Leeane Carey ‐ No competing interests

No author has a pecuniary interest in Allergan.

Figures

1.1
1.1. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 1 modified Tardieu scale ‐ Elbow flexors (change from baseline R2‐R1).
1.2
1.2. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 2 modified Tardieu scale ‐ Forearm pronators (change from baseline R2‐R1).
1.3
1.3. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 3 modified Tardieu scale ‐ Wrist flexors (change form baseline R2‐R1).
1.4
1.4. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 4 Elbow extension PROM (change from baseline).
1.5
1.5. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 5 Forearm supination PROM (change from baseline).
1.6
1.6. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 6 QUEST scores (change from baseline).
1.7
1.7. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 7 Melbourne Assessment (change from baseline).
1.8
1.8. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 8 PEDI raw scores ‐ Functional Skills (change from baseline).
1.9
1.9. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 9 PEDI scaled scores ‐ Functional Skills (change from baseline).
1.10
1.10. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 10 PEDI raw scores ‐ Caregiver Assistance (change from baseline).
1.11
1.11. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 11 PEDI scaled scores ‐ Caregiver Assistance (change from baseline).
1.12
1.12. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 12 WeeFIM (change from baseline).
1.13
1.13. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 13 Goal Attainment Scaling (change from baseline).
1.14
1.14. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 14 COPM Performance (change from baseline).
1.15
1.15. Analysis
Comparison 1 BoNT‐A vs Placebo/no treatment, Outcome 15 COPM Satisfaction (change from baseline).
2.1
2.1. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 1 modified Tardieu scale ‐ shoulder adductors (change from baseline R2‐R1).
2.2
2.2. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 2 modified Tardieu scale ‐ elbow flexors (change from baseline R2‐R1).
2.3
2.3. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 3 modified Tardieu scale ‐ forearm pronators (change from baseline R2‐R1).
2.4
2.4. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 4 modified Tardieu scale ‐ wrist flexors (change from baseline R2‐R1).
2.5
2.5. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 5 modified Ashworth scale ‐ shoulder adductors.
2.6
2.6. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 6 modified Ashworth scale ‐ elbow flexors.
2.7
2.7. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 7 modified Ashworth scale ‐ pronators.
2.8
2.8. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 8 modified Ashworth scale ‐ wrist flexors.
2.9
2.9. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 9 Wrist resonance Frequency 2Nm (change from baseline).
2.10
2.10. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 10 Wrist resonance Frequency 4Nm (change from baseline).
2.11
2.11. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 11 Supination AROM (change from baseline).
2.12
2.12. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 12 Wrist extension AROM (change from baseline).
2.13
2.13. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 13 Thumb abduction AROM (change from baseline).
2.14
2.14. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 14 Elbow extension PROM (change from baseline).
2.15
2.15. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 15 Forearm supination PROM (change from baseline).
2.16
2.16. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 16 Wrist extension PROM (change from baseline).
2.17
2.17. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 17 Palmar thumb abduction PROM (change from baseline).
2.18
2.18. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 18 Grip strength (change from baseline).
2.19
2.19. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 19 2‐point discrimination( change from baseline).
2.20
2.20. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 20 Melbourne Assessment (change from baseline).
2.21
2.21. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 21 QUEST scores (change from baseline).
2.22
2.22. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 22 AMPS ‐ Motor (change from baseline).
2.23
2.23. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 23 AMPS ‐ Process (change from baseline).
2.24
2.24. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 24 PDMS ‐ Fine motor Raw Score (change from baseline).
2.25
2.25. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 25 PDMS ‐ Fine motor Scaled Score (change from baseline).
2.26
2.26. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 26 PEDI raw score ‐ Functional Skills (change from baseline).
2.27
2.27. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 27 PEDI scaled score ‐ Functional Skills (change from baseline).
2.28
2.28. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 28 PEDI raw score ‐ Caregiver assistance (change from baseline).
2.29
2.29. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 29 PEDI scaled score ‐ Caregiver assistance (change from baseline).
2.30
2.30. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 30 Goal Attainment Scaling (change from baseline) ‐ Parent.
2.31
2.31. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 31 Goal Attainment Scaling (change from baseline) ‐ Therapist.
2.32
2.32. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 32 COPM Performance (change from baseline).
2.33
2.33. Analysis
Comparison 2 BoNT‐A/OT vs OT only, Outcome 33 COPM Satisfaction (change from baseline).
3.1
3.1. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 1 modified Tardieu scale ‐ Elbow Flexors (change from baseline).
3.2
3.2. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 2 modified Tardieu scale ‐ Pronators (change from baseline).
3.3
3.3. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 3 modified Tardieu scale ‐ Wrist Flexors (change from baseline).
3.4
3.4. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 4 Elbow extension PROM (change from baseline).
3.5
3.5. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 5 Forearm supination PROM (change from baseline).
3.6
3.6. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 6 Melbourne Assesment (change from baseline).
3.7
3.7. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 7 QUEST scores (change from baseline).
3.8
3.8. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 8 PEDI raw score ‐ Functional Skills (change from baseline).
3.9
3.9. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 9 PEDI scaled score ‐ Functional Skills (change from baseline).
3.10
3.10. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 10 PEDI raw score ‐ Caregiver Assistance (change from baseline).
3.11
3.11. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 11 PEDI scaled score ‐ Caregiver Assistance (change from baseline).
3.12
3.12. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 12 Goal Attainment Scaling (change from baseline).
3.13
3.13. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 13 COPM Performance (change from baseline).
3.14
3.14. Analysis
Comparison 3 BoNT‐A/OT vs BoNT‐A only, Outcome 14 COPM Satisfaction (change from baseline).
4.1
4.1. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 1 modified Tardieu scale ‐ Elbow flexors (change from baseline R2‐R1).
4.2
4.2. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 2 modified Tardieu scale ‐ Forearm pronators (change from baseline R2‐R1).
4.3
4.3. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 3 modified Tardieu scale ‐ Wrist flexors (change form baseline R2‐R1).
4.4
4.4. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 4 Elbow extension PROM (change from baseline).
4.5
4.5. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 5 Forearm supination PROM (change from baseline).
4.6
4.6. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 6 QUEST scores (change from baseline).
4.7
4.7. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 7 Melbourne Assessment (change from baseline).
4.8
4.8. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 8 PEDI raw scores ‐ Functional Skills (change from baseline).
4.9
4.9. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 9 PEDI scaled scores ‐ Functional Skills (change from baseline).
4.10
4.10. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 10 PEDI raw scores ‐ Caregiver Assistance (change from baseline).
4.11
4.11. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 11 PEDI scaled scores ‐ Caregiver Assistance (change from baseline).
4.12
4.12. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 12 Goal Attainment Scaling (change from baseline).
4.13
4.13. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 13 COPM Performance (change from baseline).
4.14
4.14. Analysis
Comparison 4 BoNT‐A/OT vs Placebo/no treatment, Outcome 14 COPM Satisfaction (change from baseline).
5.1
5.1. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 1 modified Tardieu scale ‐ Elbow Flexors (change from baseline).
5.2
5.2. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 2 modified Tardieu scale ‐ Pronators (change from baseline).
5.3
5.3. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 3 modified Tardieu scale ‐ Wrist flexors (change from baseline).
5.4
5.4. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 4 Elbow extension PROM (change from baseline).
5.5
5.5. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 5 Forearm supination PROM (change from baseline).
5.6
5.6. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 6 Melbourne Assesment (change from baseline).
5.7
5.7. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 7 QUEST scores (change from baseline).
5.8
5.8. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 8 PEDI raw score ‐ Functional Skills (change from baseline).
5.9
5.9. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 9 PEDI scaled score ‐ Functional Skills (change from baseline).
5.10
5.10. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 10 PEDI raw score ‐ Caregiver Assistance (change from baseline).
5.11
5.11. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 11 PEDI scaled score ‐ Caregiver Assistance (change from baseline).
5.12
5.12. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 12 Goal Attainment Scaling (change from baseline).
5.13
5.13. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 13 COPM Performance (change from baseline).
5.14
5.14. Analysis
Comparison 5 BoNT‐A only vs OT only, Outcome 14 COPM Satisfaction (change from baseline).
6.1
6.1. Analysis
Comparison 6 High dose BoNT‐A vs Low dose BoNT‐A, Outcome 1 Grip Strength (change from baseline).
6.2
6.2. Analysis
Comparison 6 High dose BoNT‐A vs Low dose BoNT‐A, Outcome 2 QUEST scores (change from baseline).
6.3
6.3. Analysis
Comparison 6 High dose BoNT‐A vs Low dose BoNT‐A, Outcome 3 PEDI ‐ functional skills (self care domain) (change from baseline).
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Update of

Comment in

References

References to studies included in this review

Boyd 2004 {unpublished data only}
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Greaves 2004 {unpublished data only}
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Kawamura 2007 {published and unpublished data}
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Koman 2007 {unpublished data only}
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Wallen 2007 {published and unpublished data}
    1. Wallen, M, A, O'Flaherty, S. J, Waugh, M‐C, A. Functional outcomes of intramuscular botulinum toxin tye A in the upper limbs of children with cerebral palsy: A phase II trial. Archives of Physical Medicine and Rehabilitation 2004;85:192‐200. - PubMed
    1. Wallen, M. A, O'Flaherty, S. J, Waugh, M‐C. A. Functional outcomes of intra‐muscular boutlinum toxin type A and occupational therapy in the upper limbs of children with cerebral palsy: A randomised controlled trial. Archives of Physical Medicine and Rehabilitation 2007;88:1‐10. - PubMed
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References to studies excluded from this review

Alahmar‐Bianchin 2007 {published data only}
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Autti‐Ramo 2000 {published data only}
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Autti‐Ramo 2001 {published data only}
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Chait 2002 {published data only}
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Chin 2003 {published data only}
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Delgado 2006 {unpublished data only}
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Desloovere 2007 {published data only}
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Fasoli 2008 {published data only}
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Freidman 2000 {published data only}
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Gibson 2007 {published data only}
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Gooch 1996 {published data only}
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Hoare 2004 {published data only}
    1. Hoare, B. J, Imms, C. Upper‐limb injections of botulinum toxin‐A in children with cerebral palsy: A critical review of the literature and clinical implications for occupational therapists. The American Journal of Occupational Therapy 2004;58(4):389‐97. - PubMed
Hurvitz 2000 {published data only}
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Hurvitz 2003 {published data only}
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Johnstone 2007 {published data only}
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Keren‐Capelovitch 2007 {published data only}
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Kim 2001 {published data only}
    1. Kim, H. S, Hwang, J. H, Lee, P. K, Jung, S. H, Park, H. D, Cho, E. H, Shim, J. S, Kim, J. M. The effects of botulinum toxin A on upper limb function in children with cerebral palsy. Journal of Korean Academic Rehabilitation Medicine 2001;25(4):594‐600.
Kolaski 2008 {published data only}
    1. Kolaski, K, Ajizian, S. J, Passmore, L, Pasutharnchat, N, Koman, L. A, Smith, B. P. Safety profile of multilevel chemical denervation procedures using phenol or botulinum toxin or both in a pediatric population. American Journal of Physical Medicine and Rehabilitation 2008;87:556‐566. [DOI: 10.1097/PHM.0b013e31817c115b] - DOI - PubMed
Lowe 2007 {published data only}
    1. Lowe, K, Novak, I, Cusick, A. Repeat injection of Botulinum toxin A is safe and effective for upper limb movement and function in children with cerebral palsy. Developmental Medicince and Child Neurology 2007;49(11):823‐829. - PubMed
Mackey 2006 {unpublished data only}
    1. Mackey, A. H, Walt, S. E, Miller, F, Waugh, M‐C, Stott, N. S. Three‐dimensional movement analysis following upper limb botulinum toxin A for children with hemiplegia. Archives of Physical Medicine and Rehabilitation 2006;87(2):207‐15.
Mall 1997 {published data only}
    1. Mall, V, Heinen, F, Linder, M, Philipsen, A, Korinthenberg, R. Treatment of cerebral palsy with botulinum toxin A: functional benefit and reduction of disability. Three case reports. Pediatric Rehabilitation 1;4:235‐7. - PubMed
O'Flaherty 2003 {published data only}
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Park 2006 {published data only}
    1. Park, E. S, Rha, D. W. Botulinum toxin type A injection for management of upper limb spastcity in children with cerebral palsy: a literature review. Yonsei Medical Journal 2006;47(5):589‐603. - PMC - PubMed
Reeuwijk 2006 {published data only}
    1. Reeuwijk, A, van Schie, P. E. M, Becher, J. G, Kwakkel, G. Effects of botulinum toxin type A on upper limb function in children with cerebral palsy: a systematic review. Clinical Rehabilitation 2006;20:375‐87. - PubMed
Romanini 2000 {published data only}
    1. Romanini, L, Villani, C, Chiozzi, F, Persiani, P. The spastic hand: treatment with botulinum toxin [La mano spastica: trattamento con tossina botulinica]. Riv.Chir.Riab.Mano Arto Sup 2000;38(1):113‐119.
Rosblad 2007 {published data only}
    1. Rosblad, B, Andersson, G, Petterson, K. Effects of botulinum toxin type A and a programme of functional activity to improve manaul ability in children and adolescents with cerebral palsy. Scandanavian Journal of Plastic and Reconstructive Surgery of the Hand 2007;41:250‐258. - PubMed
Sanger 2007 {published data only}
    1. Sanger, T. D, Kukke, S. N, Sherman‐Levine, S. Dystonia: An open‐label, dose‐escalation pilot study Botulinum toxin type B improves the speed of reaching in children with cerebral palsy. Journal of Child Neurology 2007;22:116‐122. - PubMed
Satila 2006 (a) {published data only}
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Satila 2006 (b) {published data only}
    1. Satila, H, Kotamaki, A, Koivikko, M, Autti‐Ramo, I. Upper limb function after botulinum toxin A treatment in cerebral palsy: Two years follow‐up of six cases. Pediatric Rehabilitation 2006;9(3):247‐58. - PubMed
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Waugh 2000 {published data only}
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Wong 2002 {published data only}
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Yang 2003 {published data only}
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References to studies awaiting assessment

Gibson 2009 {published data only}
    1. Gibson, N, Valentine, J, Pearce, A, Love, S, Chauvel, P, Blair, E. Preliminary results of using Botulinum Toxin A in the treatment of upper limb spasticity in children with cerebral palsy. 5th National Paediatric Physiotherapy Conference. Perth: Australian Journal of Phsyiotherapy (Suppl), 2003; Vol. 50, issue 2:S4‐S5. [http://ajp.physiotherapy.asn.au/AJP/50‐2/AustJPhysiotherv50i2Abstracts.pdf]
Kanellopoulos 2009 {published data only}
    1. Kanellopoulos, A. D, Mavrogenis, A. F, Mitsiokapa, E. A, Panagopoulos, D, Skouteli, H, Vrettos, S. G, Tzanos, G, Papagelopoulos, P. I. Long lasting benefits following the combination of static night upper extremity splinting with botulinum toxin A injections in cerebral palsy children. European Journal of Physical and Rehabilitation Medicine 2009;45:1‐6. - PubMed
Olesch 2009 {published data only}
    1. Greaves, S, Olesch, C, Imms, C, Reid, S, Reddihough, D, Graham, H. K. A randomised controlled trial of repeat injections of Botulinum toxin A in the upper extremity of young children with cerebral palsy. Developmental Medicine and Child Neurology 2008;50(suppl. 113):6.
Pearse 2009 {published data only}
    1. Pearse, J, Eyre, J. A, Gibson, M. Botulinum toxin injection of biceps brachii significantly increases the efficacy of occupational therapy in hemiplegic cerebral palsy: a randomised, double blinded, placebo controlled study. Developmental Medicine and Child Neurology 2009;51 (Suppl. 2):13.
    1. Pearse, J, Gibson, M, Eyre, J. Botulinum toxin injection of biceps brachii significantly increases the efficacy of occupational therapy in hemiplegic cerebral palsy: a randomised, double blinded,placebo controlled study. Developmental Medicine and Child Neurology 2008;50(Suppl. 114):23.
Rameckers 2009 {published data only}
    1. Rameckers, E. A. A, Speth, L. A. W. M, Duysens, J, Vles, J. S. H, Smits‐Engelsman, B. C. M. Long‐term effect of standardized functionaltherapy versus botulinum toxin‐A andstandardized functional therapy on manual isometric force generation in children with congenital spastic hemiplegia. Developmental Medicine and Child Neurology 2007;49(Suppl. 111):6.
    1. Rameckers, E. A. A, Speth, L. A. W. M, Duysens, J, Vles, J. S. H, Smits‐Engelsman, B. C. M. Botulinum toxin‐a in children with congenital spastic hemiplegia does not improve upper extremity motor‐related function over rehabilitation alone: a randomized controlled trial. Neurorehabilitation and Neural Repair 2009;23(3):218‐225. - PubMed
Redman 2008(a) {published data only}
    1. Redman, T. A, Finn, J. C, Bremner, A. P, Valentine, J. Effect of upper limb botulinum toxin‐A therapy on health‐related quality of life in children with hemiplegic cerebral palsy. Journal of Pediatrics and Child Health 2008;44(7‐8):409‐14. [DOI: 10.1111/j.1440-1754.2008.01319.x] - DOI - PubMed
Redman 2008(b) {published data only}
    1. Redman, T. A, Gibson, N, Finn, J. C, Bremner, A. P, Valentine, J, Thickbroom, G. W. Upper limb corticomotor projections and physiological changes that occur with botulinum toxin‐A therapy in children with hemiplegic cerebral palsy. European Journal of Neurology 2008;15(8):787‐791. - PubMed
    1. Redman, T, Gibson, N, Thickbroom, G, Valentine, J, Finn, J, Bremner, A. Motor pathway changes associated with upper limb botulinum toxin A therapy in children with hemiplegic cerebral palsy. Developmental Medicine and Child Neurology 2007;49(Suppl. 111):42.

References to ongoing studies

Ben‐Pazi 2008 {published data only}
    1. Ben‐Pazi, H. Improvement after Botulinum toxin injections to the arms in children with cerebral palsy. ClinicalTrials.gov. Israel: Shaare Zedek Medical Center, 2007. [ClinicalTrials.gov Identifier: NCT00549471]
Hoare 2008 {unpublished data only}
    1. Hoare B. J. Imms C. Carey L. Rawicki B. Botulinum toxin‐A and modified constraint induced movement therapy in the treatment of the upper limb in children with spastic hemiplegic cerebral palsy. http://www.anzctr.org.au/trial_view.aspx?ID=3. [http://www.anzctr.org.au/trial_view.aspx?ID=3] - PubMed
Sholas 2008 {published data only}
    1. Sholas, M. G, Yakusawa, A, Kahn, L, Cruz, E, Tann, B, Gaebler‐Spira, D. Randomized Double Masked Placebo Controlled Study of Upper Extremity Function with Botulinum Toxin A (Botox). http://www.ric.org/research/trials.php#extremity 2008.
Speth 2008 {published data only}
    1. Speth, L. M. Effect of botulinum toxin A injections and specific intensive rehabilitation therapy in children with hemiparetic cerebral palsy on upper limb functions and skills. http://www.srl.nl/default.asp?id=396&parent=0&template=algemeen.... 2008.

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