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BMC Pediatrics

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Open Access 01-12-2015 | Study protocol

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol

Authors: Bernadette Gillick, Jeremiah Menk, Bryon Mueller, Gregg Meekins, Linda E. Krach, Timothy Feyma, Kyle Rudser

Published in: BMC Pediatrics | Issue 1/2015

Abstract

Background

Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies (http://www.cdc.gov/ncbddd/cp/data.html). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention . Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial –session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group.

Methods/design

A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8–21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques.

Discussion

Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime.

Trial registration

Clinicaltrials.gov, NCT02250092Registered 18 September 2014

Agrawal N, Johnston SC, Wu YW, Sidney S, Fullerton HJ. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke. 2009;40(11):3415–21. doi:10.1161/STROKEAHA.109.564633.CrossRefPubMedPubMedCentral

DeLuca S, Case Smith J, Stevenson R, Ramey S. Constraint-induced movement therapy (CIMT) for young children with cerebral palsy: Effects of therapeutic dosage. Journal of Pediatric Rehabilitation Medicine. 2012;5(2):133–42. doi:10.3233/PRM-2012-0206.PubMed

Eyre J, Smith M, Dabydeen L, Clowry G, Petacchi E, Battini R, et al. Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system? Ann Neurol. 2007;62(5):493–503. doi:10.1002/ana.21108.

Friel K, Chakrabarty S, Martin J. Pathophysiological mechanisms of impaired limb use and repair strategies for motor systems after unilateral injury of the developing brain. Dev Med Child Neurol. 2013;55 Suppl 4:27–31. doi:10.1111/dmcn.12303.CrossRefPubMed

Martin JH. The corticospinal system: from development to motor control. Neuroscientist. 2005;11:161–73.CrossRefPubMed

Staudt M, Gerloff C, Grodd W, Holthausen H, Niemann G, Krageloh-Mann I. Reorganization in congenital hemiparesis acquired at different gestational ages. Ann Neurol. 2004;56(6):854–63. doi:10.1002/ana.20297.CrossRefPubMed

Holmefur M, Krumlinde-Sundholm L, Bergstrom J, Eliasson AC. Longitudinal development of hand function in children with unilateral cerebral palsy. Developmental Medicine & Child Neurology. 2010;52(4):352–7.CrossRef

Charles J, Wolf S, Schneider J, Gordon A. Efficacy of a child-friendly form of constraint-induced movement therapy in hemiplegic cerebral palsy: A randomized control trial. Dev Med Child Neurol. 2006;48(8):635–42. doi:10.1017/S0012162206001356.CrossRefPubMed

Charles J, Gordon AM. A critical review of constraint-induced movement therapy and forced use in children with hemiplegia. Neural Plast. 2005;12:245–61. discussion 263–72.CrossRefPubMedPubMedCentral

10.

Juenger H, Linder-Lucht M, Walther M, Berweck S, Mall V, Staudt M. Cortical neuromodulation by constraint-induced movement therapy in congenital hemiparesis: an FMRI study. Neuropediatrics. 2007;38:130–6.CrossRefPubMed

11.

Reiss A, Wolf S, Hammel E, McLeod E, Williams E. Constraint-induced movement therapy (CIMT): Current perspectives and future directions. Stroke Research and Treatment. 2012;2012:159391–1. doi:10.1155/2012/159391.

12.

Gordon AM, Hung Y, Brandao M, Ferre CL, Kuo H, Friel K, et al. Bimanual training and constraint-induced movement therapy in children with hemiplegic cerebral palsy: A randomized trial. Neurorehabil Neural Repair. 2011;25(8):692–702. doi:10.1177/1545968311402508.

13.

Eliasson AC, Shaw K, Ponten E, Boyd R, Krumlinde-Sundholm L. Feasibility of a day-camp model of modified constraint-induced movement therapy with and without botulinum toxin A injection for children with hemiplegia. Phys Occup Ther Pediatr. 2009;29(3):311–33.CrossRefPubMed

14.

Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: State of the art 2008 RID A-5034-2009 RID A-3544-2009. Brain Stimul. 2008;1(3):206–23. doi:10.1016/j.brs.2008.06.004.

15.

Nair DN. Improving motor function in chronic stroke patients using simultaneous occupational therapy and tDCS. Stroke. 2008;39(2):542. doi:10.1161/STROKEAHA.107.496935.CrossRef

16.

San-Juan D, Calcaneo Jde D, Gonzalez-Aragon MF, Bermudez Maldonado L, Avellan AM, Argumosa EV, et al. Transcranial direct current stimulation in adolescent and adult rasmussen’s encephalitis. Epilepsy Behav. 2011;20(1):126–31. doi:10.1016/j.yebeh.2010.10.031.

17.

Mattai A, Miller R, Weisinger B, Greenstein D, Bakalar J, Tossell J, et al. Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia. Brain Stimulation. 2011;4(4):275–80. doi:10.1016/j.brs.2011.01.001.

18.

Young S, Bertucco M, Sheehan Stross R, Sanger T. Cathodal transcranial direct current stimulation in children with dystonia: A pilot open-label trial. J Child Neurol. 2013;28(10):1238–44. doi:10.1177/0883073812460092.CrossRefPubMed

19.

Gillick B, Feyma T, Menk J, Usset M, Vaith A, Wood T, et al. Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: Randomized controlled preliminary study. Phys Ther. 2015;95(3):337–49. doi:10.2522/ptj.20130565.

20.

Krishnan C, Santos L, Peterson M, Ehinger M. Safety of noninvasive brain stimulation in children and adolescents. Brain Stimulation. 2015;8(1):76–87. doi:10.1016/j.brs.2014.10.012.CrossRefPubMed

21.

Edwards D, Cortes M, Datta A, Minhas P, Wassermann EM, Bikson M. Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS. Neuroimage. 2013;74:266–75. doi:10.1016/j.neuroimage.2013.01.042.CrossRefPubMedPubMedCentral

22.

Bikson M, Rahman A, Datta A. Computational models of transcranial direct current stimulation. Clinical EEG and Neuroscience. 2012;43(3):176–83. doi:10.1177/1550059412445138.CrossRefPubMed

23.

Peterchev AV, Wagner TA, Miranda PC, Nitsche MA, Paulus W, Lisanby SH, et al. Fundamentals of transcranial electric and magnetic stimulation dose: Definition, selection, and reporting practices. Brain Stimulation. 2012;5(4):435–53. doi:10.1016/j.brs.2011.10.001.

24.

Fusco A, De Angelis D, Morone G, Maglione L, Paolucci T, Bragoni M, et al. The ABC of tDCS: Effects of anodal, bilateral and cathodal montages of transcranial direct current stimulation in patients with stroke-A pilot study. Stroke Res Treat. 2013;2013:837595–5. doi:10.1155/2013/837595.

25.

Manning KY, Fehlings D, Mesterman R, Gorter JW, Switzer L, Campbell C, et al. Resting state and diffusion neuroimaging predictors of clinical improvements following constraint-induced movement therapy in children with hemiplegic cerebral palsy. Journal of Child Neurology. 2015. doi:10.1177/0883073815572686.

26.

Gauthier LV, Mark VW, Taub E, McCullars A, Barghi A, Rickards T, et al. Motor recovery from constraint induced movement therapy is not constrained by extent of tissue damage following stroke. Restorative Neurology and Neuroscience. 2014;32(6):755–65. doi:10.3233/RNN-130366.

27.

McDougall J, Wright V, Rosenbaum P. The ICF model of functioning and disability: Incorporating quality of life and human development. Developmental Neurorehabilitation. 2010;13(3):204–11. doi:10.3109/17518421003620525.CrossRefPubMed

28.

Eliasson AC, Krumlinde-Sundholm L, Rosblad B, Beckung E, Arner M, Ohrvall AM, et al. Using the MACS to facilitate comunication about manual abilities of children with cerebral palsy. Developmental Medicine & Child Neurology. 2007;49:156–7.

29.

Krumlinde Sundholm L, Holmefur M, Kottorp A, Eliasson A. The assisting hand assessment: Current evidence of validity, reliability, and responsiveness to change. Dev Med Child Neurol. 2007;49(4):259–64. doi:10.1111/j.1469-8749.2007.00259.x.CrossRefPubMed

30.

Holmefur M, Krumlinde-Sundholm L, Eliasson AC. Interrater and intrarater reliability of the Assisting Hand Assessment. American Journal of Occupational Therapy. 2007;61:79–84.CrossRefPubMed

31.

Law M, Baptiste S, McColl M, Opzoomer A, Polatajko H, Pollock N. The canadian occupational performance measure: An outcome measure for occupational therapy. Can J Occup Ther. 1990;57(2):82–7.CrossRefPubMed

32.

Cup E, REIMER W, Thijssen M, VAN KM. Reliability and validity of the canadian occupational performance measure in stroke patients. Clin Rehabil. 2003;17(4):402–9.CrossRefPubMed

33.

Mathiowetz V, Weber K, Volland G, Kashman N. Reliability and validity of grip and pinch strength evaluations. J Hand Surg. 1984;9(2):222–6.CrossRef

34.

Frison L, Pocock SJ. Repeated measures in clinical trials: Analysis using mean summary statistics and its implications for design. Stat Med. 1992;11(13):1685–704. doi:10.1002/sim.4780111304.CrossRefPubMed

35.

Senn S. Change from baseline and analysis of covariance revisited. Stat Med. 2006;25(24):4334–44. doi:10.1002/sim.2682.CrossRefPubMed

36.

Gillick BT, Krach LE, Feyma T, Rich TL, Moberg K, Thomas W, et al. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: A randomized controlled trial. Dev Med Child Neurol. 2014;56(1):44–52. doi:10.1111/dmcn.12243.

37.

Gillick B, Krach L, Feyma T, Rich T, Moberg K, Menk J, et al. Safety of primed repetitive transcranial magnetic stimulation and modified constraint-induced movement therapy in a randomized controlled trial in pediatric hemiparesis. Arch Phys Med Rehabil. 2014. doi:10.1016/j.apmr.2014.09.012.

38.

Hahn C, Rice J, Macuff S, Minhas P, Rahman A, Bikson M. Methods for extra-low voltage transcranial direct current stimulation: Current and time dependent impedance decreases. Clinical Neurophysiology. 2013;124(3):551–6. doi:10.1016/j.clinph.2012.07.028.CrossRefPubMed

39.

Kessler SK, Minhas P, Woods AJ, Rosen A, Gorman C, Bikson M. Dosage considerations for transcranial direct current stimulation in children: A computational modeling study. PLoS ONE. 2013;8(9):e76112–2. doi:10.1371/journal.pone.0076112.

40.

Kirton A, Deveber G, Gunraj C, Chen R. Neurocardiogenic syncope complicating pediatric transcranial magnetic stimulation. Pediatr Neurol. 2008;39(3):196–7. Available.CrossRefPubMed

41.

Rossi S, Hallett M, Rossini PM, Pascual-Leone A, Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009;120(12):2008–39. doi:10.1016/j.clinph.2009.08.016.CrossRefPubMedPubMedCentral

42.

Bolognini N, Vallar G, Casati C, Latif LA, El-Nazer R, Williams J, et al. Neurophysiological and behavioral effects of tDCS combined with constraint-induced movement therapy in poststroke patients. Neurorehabil Neural Repair. 2011;25(9):819–29. doi:10.1177/1545968311411056.

43.

Schlaug G, Renga V, Nair D. Transcranial direct current stimulation in stroke recovery. Arch Neurol. 2008;65(12):1571–6. doi:10.1001/archneur.65.12.1571.CrossRefPubMedPubMedCentral

44.

Kirton A, Deveber G, Gunraj C, Chen R. Cortical excitability and interhemispheric inhibition after subcortical pediatric stroke: Plastic organization and effects of rTMS. Clin Neurophysiol. 2010;121(11):1922–9. doi:10.1016/j.clinph.2010.04.021.CrossRefPubMed

45.

Kobayashi Alvaro MPL. Transcranial magnetic stimulation in neurology. Lancet Neurology. 2003;2(3):145–56. doi:10.1016/S1474-4422(03)00321-1.CrossRef

46.

Kobayashi M, Hutchinson S, Theoret H, Schlaug G, Pascual-Leone A. Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements. Neurology. 2004;62:91–8.CrossRefPubMed

47.

Kimberley TJ, Borich MR, Prochaska KD, Mundfrom SL, Perkins AE, Poepping JM. Establishing the definition and inter-rater reliability of cortical silent period calculation in subjects with focal hand dystonia and healthy controls. Neurosci Lett. 2009;464(2):84–7. Available.CrossRefPubMedPubMedCentral

48.

Carey JR, Deng H, Gillick BT, Cassidy JM, Anderson DC, Zhang L, et al. Serial treatments of primed low-frequency rTMS in stroke: Characteristics of responders vs. nonresponders. Restorative Neurol Neurosci. 2014;32(2):323–35. doi:10.3233/RNN-130358.

Title: Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol
Authors: Bernadette Gillick
Jeremiah Menk
Bryon Mueller
Gregg Meekins
Linda E. Krach
Timothy Feyma
Kyle Rudser
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Pediatrics / Issue 1/2015
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-015-0498-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol

Abstract

Background

Methods/design

Discussion

Trial registration

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

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