Efficacy and Safety of Interventions for Cerebral Palsy: An Umbrella Review of 35 Meta-analyses
Main Article Content
Abstract
Background; At present, there is a shortage of strength and credibility of evidence regarding the efficacy and safety of intervention methods for individuals with cerebral palsy (CP).
Aim; To systematically evaluate the efficacy and safety of various intervention strategies for CP across physical, pharmacological, and biological domains through an umbrella review of meta-analyses.
Methods; PubMed, Web of Science, and Embase were systematically searched to identify peer-reviewed articles published prior to December 31, 2023. The study involved a meta-analysis of randomized controlled trials (RCTs) focusing on individuals diagnosed with CP who received interventions spanning physical (e.g., motor and stimulation therapies), pharmacological (e.g., botulinum toxin type A), and biological (e.g., stem cell therapy) domains. Two reviewers independently extracted data and assessed the quality of included studies using the AMSTAR tool. The GRADE system was used to evaluate the strength of evidence. The primary exclusion criteria were the absence of outcome measures related to efficacy and safety.
Results; This review encompasses 35 studies covering physical, biological, and pharmaceutical interventions, yielding a total of 31 outcome measures. The findings indicate that assistive technologies such as robot-assisted gait training, virtual-reality exercises, and hippotherapy, along with physical stimulation methods and stem cell therapy, positively influence multiple aspects of body functions and structures. Nevertheless, more comprehensive and stringent research is imperative to establish standardized therapeutic regimens. Type A botulinum toxin has proven effective in enhancing gait, albeit with safety concerns.
Conclusions; Our findings compared the effectiveness of multiple intervention methods for addressing various issues, yet further research is required to adopt more standardized approaches for evaluating the outcome measurements of these treatment plans. Future research should prioritize large-scale RCTs to validate these interventions and integrate multidisciplinary approaches to optimize functional outcomes in clinical practice.
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References
REFERENCE
[1] Colver A, Fairhurst C, Pharoah PO: Cerebral palsy. Lancet 2014, 383(9924): 1240-1249. https://doi.org/10.1016/S0140-6736(13)61835-8
[2] Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M: A report: the definition and classification of cerebral palsy - April 2006. Developmental Medicine and Child Neurology 2007, 49: 8-14. https://doi.org/10.1111/j.1469-8749.2007.tb12610.x
[3] Soares EG, Gusmao CHV, Souto DO: Effectiveness of aerobic exercise on functionality and quality of life of children and adolescents with cerebral palsy: A systematic review and meta-analysis. Developmental medicine and child neurology 2023. https://doi.org/10.1111/dmcn.15570
[4] McIntyre S, Taitz D, Keogh J, Goldsmith S, Badawi N, Blair E: A systematic review of risk factors for cerebral palsy in children born at term in developed countries. Developmental medicine and child neurology 2013, 55(6): 499-508. https://doi.org/10.1111/dmcn.12017
[5] Schwabe AL: Comprehensive Care in Cerebral Palsy. Physical medicine and rehabilitation clinics of North America 2020, 31(1): 1-13. https://doi.org/10.1016/j.pmr.2019.09.012
[6] Krigger KW: Cerebral palsy: an overview. American family physician 2006, 73(1): 91-100.
[7] A report: the definition and classification of cerebral palsy April 2006. Developmental medicine and child neurology 2007, 49(s109): 8-14. https://doi.org/10.1111/j.1469-8749.2007.tb12610.x
[8] Subspecialty Group of Rehabilitation tSoPCMA: Rehabilitation strategy and recommendation for motor dysfunction in children with cerebral palsy. Zhonghua Er Ke Za Zhi 2020, 58(2): 91-95. https://doi.org/10.3760/cma.j.issn.0578-1310.2020.02.005
[9] Herron MS, Wang L, von Bartheld CS: Prevalence and types of strabismus in cerebral palsy: A global and historical perspective based on a systematic review and meta-analysis. Ophthalmic epidemiology 2025, 32(2): 125-142. https://doi.org/10.1080/09286586.2024.2331537
[10] Gorter JW, Fehlings D, Ferro MA, Gonzalez A, Green AD, Hopmans SN, McCauley D, Palisano RJ, Rosenbaum P, Speller B et al: Correlates of mental health in adolescents and young adults with cerebral palsy: A cross-sectional analysis of the MyStory Project. Journal of Clinical Medicine 2022, 11(11). https://doi.org/10.3390/jcm11113060
[11] Eriksson E, Hägglund G, Alriksson-Schmidt AI: Pain in children and adolescents with cerebral palsy - a cross-sectional register study of 3545 individuals. Bmc Neurology 2020, 20(1). https://doi.org/10.1186/s12883-019-1597-7
[12] Damiano DL: Activity, activity, activity: rethinking our physical therapy approach to cerebral palsy. Physical therapy 2006, 86(11): 1534-1540. https://doi.org/10.2522/ptj.20050397
[13] Xue Y, Shi S, Zheng S, Yang Z, Xu J, Gong F: Therapeutic effect of scalp-based acupuncture and moxibustion as an adjunctive treatment on children with cerebral palsy comparing to conventional rehabilitation therapy: a systematic review and meta-analysis of randomized controlled trials. Transl Pediatr 2022, 11(5): 631-641. https://doi.org/10.21037/tp-22-85
[14] Novak I, Morgan C, Fahey M, Finch-Edmondson M, Galea C, Hines A, Langdon K, Namara MM, Paton MC, Popat H et al: State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy. Current neurology and neuroscience reports 2020, 20(2): 3. https://doi.org/10.1007/s11910-020-1022-z
[15] Pieper D, Antoine SL, Mathes T, Neugebauer EA, Eikermann M: Systematic review finds overlapping reviews were not mentioned in every other overview. Journal of clinical epidemiology 2014, 67(4): 368-375. https://doi.org/10.1016/j.jclinepi.2013.11.007
[16] Statistical power analysis for the behavioral sciences. Computers, Environment and Urban Systems 1990, 14(1): 71. https://doi.org/10.1016/0198-9715(90)90050-4
[17] Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, Porter AC, Tugwell P, Moher D, Bouter LM: Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC medical research methodology 2007, 7: 10. https://doi.org/10.1186/1471-2288-7-10
[18] Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, Ostinelli EG, Zangani C, Fornaro M, Estradé A et al: Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review. World psychiatry : official journal of the World Psychiatric Association (WPA) 2021, 20(2): 244-275. https://doi.org/10.1002/wps.20881
[19] Albavera-Hernández C, Rodríguez JM, Idrovo AJ: Safety of botulinum toxin type A among children with spasticity secondary to cerebral palsy: a systematic review of randomized clinical trials. Clinical rehabilitation 2009, 23(5): 394-407. https://doi.org/10.1177/0269215508099860
[20] Qu J, Zhou L, Zhang H, Han D, Luo Y, Chen J, Li L, Zou Z, He Z, Zhang M et al: Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis. Frontiers in Bioengineering and Biotechnology 2022, 10. https://doi.org/10.3389/fbioe.2022.1006845
[21] Poh TE, See VKY, Amini R, Amini F: Stem cell therapy in improving the motor function of patients with cerebral palsy: Systematic review with meta-analysis. Neurology Asia 2020, 25(4): 535-544.
[22] Eggenberger S, Boucard C, Schoeberlein A, Guzman R, Limacher A, Surbek D, Mueller M: Stem cell treatment and cerebral palsy: Systemic review and meta-analysis. World Journal of Stem Cells 2019, 11(10): 891-903. https://doi.org/10.4252/wjsc.v11.i10.891
[23] Zhang Y, Wu J, Xiao N, Li B: Hyperbaric Oxygen Therapy Is Beneficial for the Improvement of Clinical Symptoms of Cerebral Palsy: A Systematic Review and Meta-Analysis. Complementary medicine research 2022, 29(2): 158-171. https://doi.org/10.1159/000518785
[24] Li L-X, Zhang M-M, Zhang Y, He J: Acupuncture for cerebral palsy: a meta-analysis of randomized controlled trials. Neural Regeneration Research 2018, 13(6): 1107-1117. https://doi.org/10.4103/1673-5374.233455
[25] Wang Y, Zhang P, Li C: Systematic review and network meta-analysis of robot-assisted gait training on lower limb function in patients with cerebral palsy. Neurological Sciences 2023. https://doi.org/10.1007/s10072-023-06964-w
[26] Graham HK, Rosenbaum P, Paneth N, Dan B, Lin JP, Damiano DL, Becher JG, Gaebler-Spira D, Colver A, Reddihough DS et al: Cerebral palsy. Nature Reviews Disease Primers 2016, 2: 15082. https://doi.org/10.1038/nrdp.2015.82
[27] Tatla SK, Sauve K, Virji-Babul N, Holsti L, Butler C, Van Der Loos HF: Evidence for outcomes of motivational rehabilitation interventions for children and adolescents with cerebral palsy: an American Academy for Cerebral Palsy and Developmental Medicine systematic review. Developmental medicine and child neurology 2013, 55(7): 593-601. https://doi.org/10.1111/dmcn.12147
[28] Han Y, Park S: Effectiveness of virtual reality on activities of daily living in children with cerebral palsy: a systematic review and meta-analysis. PeerJ 2023, 11: e15964. https://doi.org/10.7717/peerj.15964
[29] Zai W, Xu N, Wu W, Wang Y, Wang R: Effect of task-oriented training on gross motor function, balance and activities of daily living in children with cerebral palsy: A systematic review and meta-analysis. Medicine 2022, 101(44): e31565. https://doi.org/10.1097/MD.0000000000031565
[30] Moon JH, Jung JH, Hahm SC, Cho HY: The effects of task-oriented training on hand dexterity and strength in children with spastic hemiplegic cerebral palsy: a preliminary study. J Phys Ther Sci 2017, 29(10): 1800-1802. https://doi.org/10.1589/jpts.29.1800
[31] Turkstra LS, Holland AL, Bays GA: The neuroscience of recovery and rehabilitation: what have we learned from animal research? Archives of physical medicine and rehabilitation 2003, 84(4): 604-612. https://doi.org/10.1053/apmr.2003.50146
[32] Bayona NA, Bitensky J, Salter K, Teasell R: The role of task-specific training in rehabilitation therapies. Topics in stroke rehabilitation 2005, 12(3): 58-65. https://doi.org/10.1310/BQM5-6YGB-MVJ5-WVCR
[33] Rossi F, Gianola S, Corvetti L: Regulation of intrinsic neuronal properties for axon growth and regeneration. Progress in neurobiology 2007, 81(1): 1-28. https://doi.org/10.1016/j.pneurobio.2006.12.001
[34] Levac D, Rivard L, Missiuna C: Defining the active ingredients of interactive computer play interventions for children with neuromotor impairments: a scoping review. Research in developmental disabilities 2012, 33(1): 214-223. https://doi.org/10.1016/j.ridd.2011.09.007
[35] Nudo RJ, Wise BM, SiFuentes F, Milliken GW: Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science (New York, NY) 1996, 272(5269): 1791-1794. https://doi.org/10.1126/science.272.5269.1791
[36] Chen Y-H, Wang H-Y, Liao C-D, Liou T-H, Escorpizo R, Chen H-C: Effectiveness of neuromuscular electrical stimulation in improving mobility in children with cerebral palsy: A systematic review and meta-analysis of randomized controlled trials. Clinical rehabilitation 2023, 37(1): 3-16. https://doi.org/10.1177/02692155221109661
[37] Tekgul H, Saz U, Yilmaz S, Polat M, Aktan G, Kose T, Kitis O, Gokben S: A transcranial magnetic stimulation study for the investigation of corticospinal motor pathways in children with cerebral palsy. Journal of Clinical Neuroscience 2020, 78: 153-158. https://doi.org/10.1016/j.jocn.2020.04.087
[38] Vanderthommen M, Duchateau J: Electrical stimulation as a modality to improve performance of the neuromuscular system. Exercise and Sport Sciences Reviews 2007, 35(4): 180-185. https://doi.org/10.1097/jes.0b013e318156e785
[39] Mooney JA, Rose J: A scoping review of neuromuscular electrical stimulation to improve gait in cerebral palsy: The arc of progress and future strategies. Frontiers in Neurology 2019, 10. https://doi.org/10.3389/fneur.2019.00887
[40] Sanger TD, Kukke SN, Sherman-Levine S: Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: An open-label, dose-escalation pilot study. Journal of Child Neurology 2007, 22(1): 116-122. https://doi.org/10.1177/0883073807299975
[41] O'Flaherty SJ, Janakan V, Morrow AM, Scheinberg AM, Waugh MCA: Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy. Developmental Medicine and Child Neurology 2011, 53(2): 125-130. https://doi.org/10.1111/j.1469-8749.2010.03814.x
[42] Sapienza M, Kapoor R, Alberghina F, Maheshwari R, McCracken KL, Canavese F, Johari AN: Adverse effects following botulinum toxin A injections in children with cerebral palsy. Journal of pediatric orthopedics Part B 2023, 32(5): 435-451. https://doi.org/10.1097/BPB.0000000000001055
[43] Akat A, Karaöz E: A systematic review of cell therapy modalities and outcomes in cerebral palsy. Molecular and cellular biochemistry 2025, 480(2): 891-922. https://doi.org/10.1007/s11010-024-05072-3
[44] Schiariti V, Sauve K, Klassen AF, O'Donnell M, Cieza A, Mâsse LC: 'He does not see himself as being different': the perspectives of children and caregivers on relevant areas of functioning in cerebral palsy. Developmental medicine and child neurology 2014, 56(9): 853-861. https://doi.org/10.1111/dmcn.12472
[45] Shikako-Thomas K, Lach L, Majnemer A, Nimigon J, Cameron K, Shevell M: Quality of life from the perspective of adolescents with cerebral palsy: "I just think I'm a normal kid, I just happen to have a disability". Quality of life research: an international journal of quality of life aspects of treatment, care and rehabilitation 2009, 18(7): 825-832. https://doi.org/10.1007/s11136-009-9501-3
[46] Abdelhaleem N, Taher S, Mahmoud M, Hendawy A, Hamed M, Mortada H, Magdy A, Raafat Ezz El-Din M, Zoukiem I, Elshennawy S: Effect of action observation therapy on motor function in children with cerebral palsy: a systematic review of randomized controlled trials with meta-analysis. Clinical rehabilitation 2021, 35(1): 51-63. https://doi.org/10.1177/0269215520954345
[47] Araújo PA, Starling JMP, Oliveira VC, Gontijo APB, Mancini MC: Combining balance-training interventions with other active interventions may enhance effects on postural control in children and adolescents with cerebral palsy: a systematic review and meta-analysis. Brazilian journal of physical therapy 2020, 24(4): 295-305. https://doi.org/10.1016/j.bjpt.2019.04.005
[48] Conner BC, Remec NM, Lerner ZF: Is robotic gait training effective for individuals with cerebral palsy? A systematic review and meta-analysis of randomized controlled trials. Clinical rehabilitation 2022, 36(7): 873-882. https://doi.org/10.1177/02692155221087084
[49] De Guindos-Sanchez L, Lucena-Anton D, Moral-Munoz JA, Salazar A, Carmona-Barrientos I: The effectiveness of hippotherapy to recover gross motor function in children with cerebral palsy: A systematic review and meta-Analysis. Children-Basel 2020, 7(9). https://doi.org/10.3390/children7090106
[50] de Lima Crispim TR, Neto MG, Crispim TRL, Dias RB, de Albuquerque MDM, Saquetto MB, Magalhães PAF: Addition of respiratory exercises to conventional rehabilitation for children and adolescents with cerebral palsy: a systematic review and meta-analysis. World journal of pediatrics : WJP 2023, 19(4): 340-355. https://doi.org/10.1007/s12519-022-00642-1
[51] Klaewkasikum K, Patathong T, Woratanarat P, Woratanarat T, Thadanipon K, Rattanasiri S, Thakkinstian A: Efficacy of conservative treatment for spastic cerebral palsy children with equinus gait: a systematic review and meta-analysis. Journal of orthopaedic surgery and research 2022, 17(1): 411. https://doi.org/10.1186/s13018-022-03301-3
[52] Liang X, Tan Z, Yun G, Cao J, Wang J, Liu Q, Chen T: Effectiveness of exercise interventions for children with cerebral palsy: A systematic review and meta-analysis of randomized controlled trials. Journal of rehabilitation medicine 2021, 53(4): jrm00176. https://doi.org/10.2340/16501977-2772
[53] Martins E, Cordovil R, Oliveira R, Letras S, Lourenco S, Pereira I, Ferro A, Lopes I, Silva CR, Marques M: Efficacy of suit therapy on functioning in children and adolescents with cerebral palsy: a systematic review and meta-analysis. Developmental medicine and child neurology 2016, 58(4): 348-360. https://doi.org/10.1111/dmcn.12988
[54] McLeod KL, Thorley M, Reedman SE, Chatfield MD, Sakzewski L: Effect of active motor learning interventions on gross motor function and mobility in children aged 2 to 6 years with bilateral cerebral palsy: A systematic review and meta-analysis. Pediatric physical therapy: the official publication of the Section on Pediatrics of the American Physical Therapy Association 2023, 35(4): 412-428. https://doi.org/10.1097/PEP.0000000000001041
[55] Merino-Andres J, Garcia de Mateos-Lopez A, Damiano DL, Sanchez-Sierra A: Effect of muscle strength training in children and adolescents with spastic cerebral palsy: A systematic review and meta-analysis. Clinical rehabilitation 2022, 36(1): 4-14. https://doi.org/10.1177/02692155211040199
[56] Qian G, Cai X, Xu K, Tian H, Meng Q, Ossowski Z, Liang J: Which gait training intervention can most effectively improve gait ability in patients with cerebral palsy? A systematic review and network meta-analysis. Frontiers in Neurology 2023, 13. https://doi.org/10.3389/fneur.2022.1005485
[57] Yang F-A, Lee T-H, Huang S-W, Liou T-H, Escorpizo R, Chen H-C: Upper limb manual training for children with cerebral palsy: A systematic review and network meta-analysis of randomized controlled trials. Clinical rehabilitation 2023, 37(4): 516-533. https://doi.org/10.1177/02692155221137698
[58] Chen Y, Fanchiang HD, Howard A: Effectiveness of Virtual Reality in Children With Cerebral Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Physical therapy 2018, 98(1): 63-77. https://doi.org/10.1093/ptj/pzx107
[59] Hao J, Huang B, Remis A, He Z: The application of virtual reality to home-based rehabilitation for children and adolescents with cerebral palsy: A systematic review and meta-analysis. Physiotherapy theory and practice 2023. https://doi.org/10.1080/09593985.2023.2184220
[60] Liu C, Wang X, Chen R, Zhang J: The effects of virtual reality training on balance, gross motor function, and daily living ability in children with cerebral palsy: Systematic review and meta-analysis. Jmir Serious Games 2022, 10(4). https://doi.org/10.2196/38972
[61] Liu W, Hu Y, Li J, Chang J: Effect of virtual reality on balance function in children with cerebral palsy: A systematic review and meta-analysis. Frontiers in public health 2022, 10: 865474. https://doi.org/10.3389/fpubh.2022.865474
[62] Arpino C, Vescio MF, De Luca A, Curatolo P: Efficacy of intensive versus nonintensive physiotherapy in children with cerebral palsy: a meta-analysis. International journal of rehabilitation research Internationale Zeitschrift fur Rehabilitationsforschung Revue internationale de recherches de readaptation 2010, 33(2): 165-171. https://doi.org/10.1097/MRR.0b013e328332f617
[63] Cai X, Qian G, Cai S, Wang F, Da Y, Ossowski Z: The effect of whole-body vibration on lower extremity function in children with cerebral palsy: A meta-analysis. PloS one 2023, 18(3): e0282604. https://doi.org/10.1371/journal.pone.0282604
[64] Kim H-J, Park J-W, Nam K: Effect of extracorporeal shockwave therapy on muscle spasticity in patients with cerebral palsy: systematic review and meta-analysis. European journal of physical and rehabilitation medicine 2019, 55(6): 761-771. https://doi.org/10.23736/S1973-9087.19.05888-X
[65] Ou CH, Shiue CC, Kuan YC, Liou TH, Chen HC, Kuo TJ: Neuromuscular electrical stimulation of upper limbs in patients with cerebral palsy: A systematic review and meta-analysis of randomized controlled trials. American journal of physical medicine & rehabilitation 2023, 102(2): 151-158. https://doi.org/10.1097/PHM.0000000000002058
[66] Saquetto M, Carvalho V, Silva C, Conceicao C, Gomes-Neto M: The effects of whole body vibration on mobility and balance in children with cerebral palsy: a systematic review with meta-analysis. Journal of musculoskeletal & neuronal interactions 2015, 15(2): 137-144.
[67] Sun Y-Y, Wang L, Peng J-l, Huang Y-j, Qiao F-q, Wang P: Effects of repetitive transcranial magnetic stimulation on motor function and language ability in cerebral palsy: A systematic review and meta-analysis. Frontiers in Pediatrics 2023, 11. https://doi.org/10.3389/fped.2023.835472
[68] Zhu Q, Gao G, Wang K, Lin J: Effect of functional electrical stimulation on gait parameters in children with cerebral palsy: A meta-analysis. Computational and mathematical methods in medicine 2022, 2022: 3972958. https://doi.org/10.1155/2022/3972958
[69] Pulay M, Nagy R, Kói T, Harnos A, Zimonyi N, Garami M, Gasparics Á, Hegyi P, Túri I, Feketéné Szabó É: The effect of additional whole-body vibration on musculoskeletal system in children with cerebral palsy: A systematic review and meta-analysis of randomized clinical trials. Journal of Clinical Medicine 2023, 12(21): 6759. https://doi.org/10.3390/jcm12216759
[70] Kumar D, Kumar R, Mudgal SK, Ranjan P, Kumar S: The effects of botulinum toxin and casting in spastic children with cerebral palsy: A systematic review and meta-analysis. Cureus 2023, 15(3): e36851-e36851. https://doi.org/10.7759/cureus.36851