Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial

R Araneda, S V Sizonenko, C J Newman, M Dinomais, G Le Gal, E Nowak, A Guzzetta, I Riquelme, S Brochard, Y Bleyenheuft, Early HABIT-ILE group, Julie Paradis, Daniela Ebner-Karestinos, Geoffroy Saussez, Anne Klöcker, Rodolphe Bailly, Sandra Bouvier, Josselin Demas, R Araneda, S V Sizonenko, C J Newman, M Dinomais, G Le Gal, E Nowak, A Guzzetta, I Riquelme, S Brochard, Y Bleyenheuft, Early HABIT-ILE group, Julie Paradis, Daniela Ebner-Karestinos, Geoffroy Saussez, Anne Klöcker, Rodolphe Bailly, Sandra Bouvier, Josselin Demas

Abstract

Background: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters.

Methods: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures.

Discussion: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE).

Trial registration: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

Keywords: Biomechanical changes; Cerebral palsy; Functional changes; Intensive training; Neuroplasticity; Randomized controlled trial; Toddlers.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT Flowchart. RCT, randomized controlled trial; CP, cerebral palsy; GMFCS, gross motor function classification system; AHA, assisting hand assessment; GMFM-66, gross motor function measure (66 items); MA-2, Melbourne assessment 2; PEDI-CAT, pediatric evaluation of disability inventory, computer adaptive test; YC-PEM, young children’s participation and environment measure; MPOC-20, measure of the process of care (20 items); COPM, Canadian occupational performance measure; DTI, diffusion tensor imaging; fMRI, functional magnetic resonance imaging; UE, upper extremities; LE, lower extremities

References

    1. Graham HK, Rosenbaum P, Paneth N, Dan B, Lin JP, Damiano DL, et al. Cerebral palsy. Nat Rev Dis Primers. 2016;2:15082. doi: 10.1038/nrdp.2015.82.
    1. Krageloh-Mann I, Cans C. Cerebral palsy update. Brain and Development. 2009;31(7):537–544. doi: 10.1016/j.braindev.2009.03.009.
    1. Weierink L, Vermeulen RJ, Boyd RN. Brain structure and executive functions in children with cerebral palsy: a systematic review. Res Dev Disabil. 2013;34(5):1678–1688. doi: 10.1016/j.ridd.2013.01.035.
    1. Chugani HT, Müller R-A, Chugani DC. Functional brain reorganization in children. Brain and Development. 1996;18(5):347–356. doi: 10.1016/0387-7604(96)00032-0.
    1. Brizzolara D, Pecini C, Brovedani P, Ferretti G, Cipriani P, Cioni G. Timing and type of congenital brain lesion determine different patterns of language lateralization in hemiplegic children. Neuropsychologia. 2002;40(6):620–632. doi: 10.1016/S0028-3932(01)00158-0.
    1. Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J, et al. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatr. 2017;171(9):897–907. doi: 10.1001/jamapediatrics.2017.1689.
    1. Reid LB, Rose SE, Boyd RN. Rehabilitation and neuroplasticity in children with unilateral cerebral palsy. Nat Rev Neurol. 2015;11(7):390–400. doi: 10.1038/nrneurol.2015.97.
    1. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005;47(8):571–576. doi: 10.1017/S001216220500112X.
    1. Novak I, McIntyre S, Morgan C, Campbell L, Dark L, Morton N, et al. A systematic review of interventions for children with cerebral palsy: state of the evidence. Dev Med Child Neurol. 2013;55(10):885–910. doi: 10.1111/dmcn.12246.
    1. Baud O, Daire JL, Dalmaz Y, Fontaine RH, Krueger RC, Sebag G, et al. Gestational hypoxia induces white matter damage in neonatal rats: a new model of periventricular leukomalacia. Brain Pathol. 2004;14(1):1–10. doi: 10.1111/j.1750-3639.2004.tb00492.x.
    1. Favrais G, van de Looij Y, Fleiss B, Ramanantsoa N, Bonnin P, Stoltenburg-Didinger G, et al. Systemic inflammation disrupts the developmental program of white matter. Ann Neurol. 2011;70(4):550–565. doi: 10.1002/ana.22489.
    1. Van Steenwinckel J, Schang AL, Sigaut S, Chhor V, Degos V, Hagberg H, et al. Brain damage of the preterm infant: new insights into the role of inflammation. Biochem Soc Trans. 2014;42(2):557–563. doi: 10.1042/bst20130284.
    1. Leviton A, Gressens P. Neuronal damage accompanies perinatal white-matter damage. Trends Neurosci. 2007;30(9):473–478. doi: 10.1016/j.tins.2007.05.009.
    1. Friel KM, Williams PT, Serradj N, Chakrabarty S, Martin JH. Activity-Based Therapies for Repair of the Corticospinal System Injured during Development. Front Neurol. 2014;5:229. doi: 10.3389/fneur.2014.00229.
    1. Martin JH, Friel KM, Salimi I, Chakrabarty S. Activity- and use-dependent plasticity of the developing corticospinal system. Neurosci Biobehav Rev. 2007;31(8):1125–1135. doi: 10.1016/j.neubiorev.2007.04.017.
    1. McKenzie IA, Ohayon D, Li H, de Faria JP, Emery B, Tohyama K, et al. Motor skill learning requires active central myelination. Science. 2014;346(6207):318–322. doi: 10.1126/science.1254960.
    1. Xiao L, Ohayon D, McKenzie IA, Sinclair-Wilson A, Wright JL, Fudge AD, et al. Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning. Nat Neurosci. 2016;19(9):1210–1217. doi: 10.1038/nn.4351.
    1. Eliasson AC, Nordstrand L, Ek L, Lennartsson F, Sjostrand L, Tedroff K, et al. The effectiveness of baby-CIMT in infants younger than 12 months with clinical signs of unilateral-cerebral palsy; an explorative study with randomized design. Res Dev Disabil. 2017;72:191–201. doi: 10.1016/j.ridd.2017.11.006.
    1. Eliasson AC, Shaw K, Berg E, Krumlinde-Sundholm L. An ecological approach of constraint induced movement therapy for 2-3-year-old children: a randomized control trial. Res Dev Disabil. 2011;32(6):2820–2828. doi: 10.1016/j.ridd.2011.05.024.
    1. 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. 2015:41–2. 10.1016/j.ridd.2015.05.003 86–93. Epub 2015/06/24. PubMed PMID: .
    1. 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):133–142. doi: 10.3233/prm-2012-0206.
    1. Taub E, Ramey SL, DeLuca S, Echols K. Efficacy of constraint-induced movement therapy for children with cerebral palsy with asymmetric motor impairment. Pediatrics. 2004;113(2):305–312. doi: 10.1542/peds.113.2.305.
    1. Ferre CL, Brandao MB, Hung YC, Carmel JB, Gordon AM. Feasibility of caregiver-directed home-based hand-arm bimanual intensive training: a brief report. Dev Neurorehabil. 2015;18(1):69–74. doi: 10.3109/17518423.2014.948641.
    1. Bleyenheuft Y, Gordon AM. Hand-arm bimanual intensive therapy including lower extremities (HABIT-ILE) for children with cerebral palsy. Phys Occup Ther Pediatr. 2014;34(4):390–403. doi: 10.3109/01942638.2014.932884.
    1. Bleyenheuft Y, Arnould C, Brandao MB, Bleyenheuft C, Gordon AM. Hand and arm bimanual intensive therapy including lower extremity (HABIT-ILE) in children with unilateral spastic cerebral palsy: a randomized trial. Neurorehabil Neural Repair. 2015;29(7):645–657. doi: 10.1177/1545968314562109.
    1. Bleyenheuft Y, Ebner-Karestinos D, Surana B, Paradis J, Sidiropoulos A, Renders A, et al. Intensive upper- and lower-extremity training for children with bilateral cerebral palsy: a quasi-randomized trial. Dev Med Child Neurol. 2017;59(6):625–633. doi: 10.1111/dmcn.13379.
    1. World Health O . ICF-CY, international classification of functioning, disability, and health : Children & Youth version. Geneva: World Health Organization; 2007.
    1. Van Cauwenberghe E, Gubbels J, De Bourdeaudhuij I, Cardon G. Feasibility and validity of accelerometer measurements to assess physical activity in toddlers. Int J Behav Nutr Phys Act. 2011;8:67. doi: 10.1186/1479-5868-8-67.
    1. Brandao MB, Mancini MC, Ferre CL, Figueiredo PRP, Oliveira RHS, Goncalves SC, et al. Does dosage matter? A pilot study of hand-arm bimanual intensive training (HABIT) dose and dosing schedule in children with unilateral cerebral palsy. Phys Occup Ther Pediatr. 2017:1–16. 10.1080/01942638.2017.1407014 Epub 2017/12/15PubMed PMID: .
    1. 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;37:9–16. doi: 10.1016/j.ridd.2014.10.050.
    1. Greaves S, Imms C, Dodd K, Krumlinde-Sundholm L. Development of the mini-assisting hand assessment: evidence for content and internal scale validity. Dev Med Child Neurol. 2013;55(11):1030–1037. doi: 10.1111/dmcn.12212.
    1. Krumlinde-Sundholm L, Holmefur M, Kottorp A, Eliasson AC. The assisting hand assessment: current evidence of validity, reliability, and responsiveness to change. Dev Med Child Neurol. 2007;49(4):259–264. doi: 10.1111/j.1469-8749.2007.00259.x.
    1. Gerber CN, Plebani A, Labruyere R. Translation, reliability, and clinical utility of the Melbourne assessment 2. Disabil Rehabil. 2017:1–9. 10.1080/09638288.2017.1386726 Epub 2017/10/14. PubMed PMID: .
    1. Auld ML, Ware RS, Boyd RN, Moseley GL, Johnston LM. Reproducibility of tactile assessments for children with unilateral cerebral palsy. Phys Occup Ther Pediatr. 2012;32(2):151–166. doi: 10.3109/01942638.2011.652804.
    1. Buitenhuis SM, Pondaag W, Wolterbeek R, Malessy MJA. Hand sensibility in healthy young children. Pediatr Neurol. 2018;86:52–56. doi: 10.1016/j.pediatrneurol.2018.04.007.
    1. Gottwald JM, Achermann S, Marciszko C, Lindskog M, Gredeback G. An Embodied Account of Early Executive-Function Development. Psychol Sci. 2016;27(12):1600–1610. doi: 10.1177/0956797616667447.
    1. Bleyenheuft Y, Paradis J, Renders A, Thonnard JL, Arnould C. ACTIVLIM-CP a new Rasch-built measure of global activity performance for children with cerebral palsy. Res Dev Disabil. 2017;60:285–294. doi: 10.1016/j.ridd.2016.10.005.
    1. Kramer JM, Liljenquist K, Coster WJ. Validity, reliability, and usability of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test for autism spectrum disorders. Dev Med Child Neurol. 2016;58(3):255–261. doi: 10.1111/dmcn.12837.
    1. Ko J. Sensitivity to functional improvements of GMFM-88, GMFM-66, and PEDI mobility scores in young children with cerebral palsy. Percept Mot Skills. 2014;119(1):305–319. doi: 10.2466/03.25.PMS.119c14z1.
    1. Khetani MA, Graham JE, Davies PL, Law MC, Simeonsson RJ. Psychometric properties of the Young Children's Participation and Environment Measure. Arch Phys Med Rehabil. 2015;96(2):307–316. doi: 10.1016/j.apmr.2014.09.031.
    1. Siebes RC, Maassen GH, Wijnroks L, Ketelaar M, van Schie PE, Gorter JW, et al. Quality of paediatric rehabilitation from the parent perspective: validation of the short measure of processes of care (MPOC-20) in the Netherlands. Clin Rehabil. 2007;21(1):62–72. doi: 10.1177/0269215506071280.
    1. Dedding C, Cardol M, Eyssen IC, Dekker J, Beelen A. Validity of the Canadian occupational performance measure: a client-centred outcome measurement. Clin Rehabil. 2004;18(6):660–667. doi: 10.1191/0269215504cr746oa.
    1. Almli CR, Rivkin MJ, McKinstry RC. The NIH MRI study of normal brain development (Objective-2): newborns, infants, toddlers, and preschoolers. Neuroimage. 2007;35(1):308–325. doi: 10.1016/j.neuroimage.2006.08.058.
    1. Dinomais M, Hertz-Pannier L, Groeschel S, Chabrier S, Delion M, Husson B, et al. Long term motor function after neonatal stroke: lesion localization above all. Hum Brain Mapp. 2015;36(12):4793–4807. doi: 10.1002/hbm.22950.
    1. Dinomais M, Hertz-Pannier L, Groeschel S, Delion M, Husson B, Kossorotoff M, et al. Does Contralesional hand function after neonatal stroke only depend on lesion characteristics? Stroke. 2016;47(6):1647–1650. doi: 10.1161/strokeaha.116.013545.
    1. Baek SO, Jang SH, Lee E, Kim S, Hah JO, Park YH, et al. CST recovery in pediatric hemiplegic patients: Diffusion tensor tractography study. Neurosci Lett. 2013;557(Pt B):79–83. doi: 10.1016/j.neulet.2013.10.047.
    1. Rose S, Guzzetta A, Pannek K, Boyd R. MRI structural connectivity, disruption of primary sensorimotor pathways, and hand function in cerebral palsy. Brain Connect. 2011;1(4):309–316. doi: 10.1089/brain.2011.0034.
    1. Lee D, Pae C, Lee JD, Park ES, Cho SR, Um MH, et al. Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy. Hum Brain Mapp. 2017;38(10):5292–5306. doi: 10.1002/hbm.23738.
    1. Saunders J, Carlson HL, Cortese F, Goodyear BG, Kirton A. Imaging functional motor connectivity in hemiparetic children with perinatal stroke. Hum Brain Mapp. 2018. 10.1002/hbm.24474 Epub 2018/11/18. PubMed PMID: .
    1. Davis RB, Õunpuu S, Tyburski D, Gage JR. A gait analysis data collection and reduction technique. Hum Mov Sci. 1991;10(5):575–587. doi: 10.1016/0167-9457(91)90046-Z.
    1. Hermens HJ, Freriks B, Disselhorst-Klug C, Rau G. Development of recommendations for SEMG sensors and sensor placement procedures. J Electromyogr Kinesiol. 2000;10(5):361–374. doi: 10.1016/S1050-6411(00)00027-4.
    1. Ransburg N, Reiser M, Munzert J, Jovanovic B, Schwarzer G. Concurrent anticipation of two object dimensions during grasping in 10-month-old infants: A quantitative analysis. Infant Behav Dev. 2017;48(Pt B):164–174. doi: 10.1016/j.infbeh.2017.04.003.
    1. Brochard S, Lempereur M, Mao L, Remy-Neris O. The role of the scapulo-thoracic and gleno-humeral joints in upper-limb motion in children with hemiplegic cerebral palsy. Clin Biomech (Bristol, Avon) 2012;27(7):652–660. doi: 10.1016/j.clinbiomech.2012.04.001.
    1. Sarcher A, Raison M, Leboeuf F, Perrouin-Verbe B, Brochard S, Gross R. Pathological and physiological muscle co-activation during active elbow extension in children with unilateral cerebral palsy. Clin Neurophysiol. 2017;128(1):4–13. doi: 10.1016/j.clinph.2016.10.086.
    1. Jaspers E, Feys H, Bruyninckx H, Klingels K, Molenaers G, Desloovere K. The arm profile score: a new summary index to assess upper limb movement pathology. Gait Posture. 2011;34(2):227–233. doi: 10.1016/j.gaitpost.2011.05.003.
    1. Ropars J, Lempereur M, Vuillerot C, Tiffreau V, Peudenier S, Cuisset JM, et al. Muscle Activation during Gait in Children with Duchenne Muscular Dystrophy. PLoS One. 2016;11(9):e0161938. doi: 10.1371/journal.pone.0161938.
    1. Bregou Bourgeois A, Mariani B, Aminian K, Zambelli PY, Newman CJ. Spatio-temporal gait analysis in children with cerebral palsy using, foot-worn inertial sensors. Gait Posture. 2014;39(1):436–442. doi: 10.1016/j.gaitpost.2013.08.029.
    1. Newman CJ, Bruchez R, Roches S, Jequier Gygax M, Duc C, Dadashi F, et al. Measuring upper limb function in children with hemiparesis with 3D inertial sensors. Childs Nerv Syst. 2017;33(12):2159–2168. doi: 10.1007/s00381-017-3580-1.
    1. Vickers AJ. The use of percentage change from baseline as an outcome in a controlled trial is statistically inefficient: a simulation study. BMC Med Res Methodol. 2001;1:6. doi: 10.1186/1471-2288-1-6.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir