Brain Organization and Recovery in Perinatal Brain Injury.
Saiote, C., Sutter, E., Xenopoulos-Oddsson, A., Rao, R., Georgieff, M., Rudser, K., Peyton, C., Dean, D., McAdams, R. M., & Gillick, B. (2022). Study Protocol: Multimodal Longitudinal Assessment of Infant Brain Organization and Recovery in Perinatal Brain Injury. Pediatric physical therapy : the official publication of the Section on Pediatrics of the American Physical Therapy Association, 34(2), 268–276. https://pubmed.ncbi.nlm.nih.gov/35385465/
Intervention
Carton de Tournai A, Herman E, Gathy E, Ebner-Karestinos D, Araneda R, Dricot L, Macq B, Vandermeeren Y, Bleyenheuft Y. Baby HABIT-ILE intervention: study protocol of a randomised controlled trial in infants aged 6-18 months with unilateral cerebral palsy. BMJ Open. 2024 Feb 17;14(2):e078383. doi: 10.1136/bmjopen-2023-078383. PMID: 38367973; PMCID: PMC10875549.
Araneda R, Sizonenko SV, Newman CJ, Dinomais M, Le Gal G, Nowak E, Guzzetta A, Riquelme I, Brochard S, Bleyenheuft Y; Early HABIT-ILE group. 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. BMC Neurol. 2020 Apr 14;20(1):133. doi: 10.1186/s12883-020-01705-4. PMID: 32290815; PMCID: PMC7155331.
Gardas SS, Lysaght C, McMillan AG, Kantak S, Willson JD, Patterson CG, Surkar SM. Bimanual Movement Characteristics and Real-World Performance Following Hand-Arm Bimanual Intensive Therapy in Children with Unilateral Cerebral Palsy. Behav Sci (Basel). 2023 Aug 13;13(8):681. doi: 10.3390/bs13080681. PMID: 37622821; PMCID: PMC10451828.
Ferre, C. L., & Gordon, A. M. (2017). Coaction of individual and environmental factors: a review of intensive therapy paradigms for children with unilateral spastic cerebral palsy. Developmental medicine and child neurology, 59(11), 1139–1145. https://doi.org/10.1111/dmcn.13497
Evidence-based treatment approaches for children with unilateral spastic cerebral palsy are expanding and being modified to fit the constraints of families and the child receiving treatment. In this review, we first provide an overview of a theoretical framework that considers the intricate interactions between the individual child and the environment in which treatment is provided. Next, we describe intensive interventions that have strong support for their efficacy. We also highlight the heterogeneity with which children respond to these approaches. Individual characteristics that might affect responsiveness are summarized. We propose that a one-size-fits-all approach may not be as efficacious as approaches based on the specific brain damage and resulting development of the corticospinal tract. Finally, we review evidence suggesting that the environment can be structured to promote opportunities for intensive practice and self-generated movement-two important aspects of efficacious treatments. Emphasis is placed on intensive home programs delivered by caregivers.
What this paper adds: Considerable variability exists in how children with unilateral spastic cerebral palsy respond to intensive upper extremity therapies. Individual and environmental factors interact to shape responsiveness.
Dosage
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. doi: 10.1016/j.ridd.2014.10.050. Epub 2014 Nov 24. PMID: 25460215.
Brain wiring, CST and lesions
Jaspers, E., Byblow, W. D., Feys, H., & Wenderoth, N. (2016). The Corticospinal Tract: A Biomarker to Categorize Upper Limb Functional Potential in Unilateral Cerebral Palsy. Frontiers in pediatrics, 3, 112. https://doi.org/10.3389/fped.2015.00112
This review summarizes how early brain damage can cause dramatic deviations from the normal anatomy of sensory and motor tracts, resulting in unique "wiring patterns" of the sensorimotor system in CP. Based on the existing literature, we suggest that corticospinal tract (CST) anatomy and integrity constrains sensorimotor function of the upper limb and potentially also the response to treatment.
Simon-Martinez, C., Jaspers, E., Alaerts, K., Ortibus, E., Balsters, J., Mailleux, L., Blommaert, J., Sleurs, C., Klingels, K., Amant, F., Uyttebroeck, A., Wenderoth, N., & Feys, H. (2019). Influence of the corticospinal tract wiring pattern on sensorimotor functional connectivity and clinical correlates of upper limb function in unilateral cerebral palsy. Scientific reports, 9(1), 8230. https://doi.org/10.1038/s41598-019-44728-9
Motor and sensory functions were influenced by each of the investigated neurological factors. However, multiple regression analyses showed that motor function was predicted by the CST wiring (more preserved in individuals with contralateral CST (p < 0.01)), lesion extent, and damage to the basal ganglia and thalamus. Sensory function was predicted by the combination of a large and later lesion and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (p < 0.05). These novel insights contribute to a better understanding of the underlying pathophysiology of UL function and may be useful to delineate individualized treatment strategies.
Rich, T. L., Menk, J. S., Rudser, K. D., Feyma, T., & Gillick, B. T. (2017). Less-Affected Hand Function in Children With Hemiparetic Unilateral Cerebral Palsy: A Comparison Study With Typically Developing Peers. Neurorehabilitation and neural repair, 31(10-11), 965–976. https://doi.org/10.1177/1545968317739997
The less-affected hand in children with UCP underperformed the dominant hand of CTD. Limitations were greater in children with UCP ipsilateral motor pattern. Rehabilitation in the less-affected hand may be warranted. Bilateral hand function in future studies may help identify the optimal rehabilitation and neuromodulatory intervention.
Bilat vs CIMT Smorenburg, A. R., Gordon, A. M., Kuo, H. C., Ferre, C. L., Brandao, M., Bleyenheuft, Y., Carmel, J. B., & Friel, K. M. (2017). Does Corticospinal Tract Connectivity Influence the Response to Intensive Bimanual Therapy in Children With Unilateral Cerebral Palsy?. Neurorehabilitation and neural repair, 31(3), 250–260. https://doi.org/10.1177/1545968316675427
Conclusion: The efficacy of bimanual therapy on hand function in children with USCP appears to be independent of CST connectivity pattern.
In conclusion, this study showed that bimanual therapy can improve hand function of children with USCP irrespective of CST pattern and can therefore be provided to the general USCP population. Moreover, this study provided a new, objective way to determine CST pattern by using the LI, which may allow us to examine the relation between laterality and outcomes in a more comprehensive manner in children with USCP.
Motor learning
Hung YC, Gordon AM. . Motor learning of a bimanual task in children with unilateral cerebral palsyRes Dev Disabil. 2013;34(6):1891-1896. doi:10.1016/j.ridd.2013.03.008
Children with unilateral cerebral palsy (CP) have been shown to improve their motor performance with sufficient practice. However, little is known about how they learn goal-oriented tasks. In the current study, 21 children with unilateral CP (age 4-10 years old) and 21 age-matched typically developed children (TDC) practiced a simple bimanual speed stack task over 15 days of practice. Both groups demonstrated their ability to learn the current bimanual task, but their rate of improvement and learning pattern differed. Children with unilateral CP overall were slower and improved ~10% less than TDC. Most of the improvement occurred during the first 3 days for the TDC, whereas performance did not plateau until 6-8 days for the children with unilateral CP. This initial slower learning rate for children with unilateral CP was also confirmed by better fitting of the curve to an exponential function than the power law function (p<0.05). Therefore, when working with children with unilateral CP, sufficient practice is important (two to three times more than for TDC), and delayed improvement is expected.
Intervention approaches
The functional impact of unilateral upper limb impairment has been the focus of extensive research undertaken to improve motor performance and independence with daily activities [11].
As a result, upper limb interventions such as constraint-induced movement therapy (CIMT) and bimanual therapy have strong evidence supporting effectiveness in children with unilateral CP [2
However, not all children make clinically important change following these interventions [12]. We do not understand why a proportion of children with unilateral CP do not respond to evidence-based upper limb intervention [12]. As skilled task performance involves complex cognitive processes, it is reasonable to postulate that cognitive impairment may be associated with reduced ability of children to learn how to effectively use their two hands together to perform tasks
Holmefur M, Kits A, Bergstrom J, Krumlinde-Sundholm L, Flodmark O, Forssberg H, Eliasson AC. Neuroradiology can predict the development of hand function in children with unilateral cerebral palsy. Neurorehabil Neural Repair. 2013;27(1):72–78. [PubMed] [Google Scholar]
10. Arner M, Eliasson AC, Nicklasson S, Sommerstein K, Hagglund G. Hand function in cerebral palsy. Report of 367 children in a population-based longitudinal health care program. J Hand Surg Am. 2008;33(8):1337–1347. [PubMed] [Google Scholar]
11. Sakzewski L, Ziviani J, Boyd RN. Efficacy of upper limb therapies for unilateral cerebral palsy: A meta-analysis. Pediatrics. 2014;133(1):e175–e204. [PubMed] [Google Scholar]
12. Hoare B. Constraint therapy, the panacea for unilateral cerebral palsy? Dev Med Child Neurol. 2015;57(1):12–13. [PubMed
Early brain lesion and cognition in cerebral palsy
"Lesion to the brain in CP occurs in the early stages of development, either in the prenatal, perinatal or early postnatal periods (up to 2 years) [13]. Early brain injury impacts concomitantly on motor and cognitive development and function [14], yet the impact is not uniformly seen across these domains. Further, cognitive impacts may be realised only later in childhood due to the protracted nature of cognitive development, relative to motor skill development. In particular, higher-level cognitive skills develop in parallel to the extended neurodevelopment of the prefrontal regions of the brain [15], beginning in infancy [16] and continuing through the pre-school years [17], middle childhood [18] and into adolescence [19]."
For references and a good description of cognition in CP see Hoare, B., Ditchfield, M., Thorley, M., Wallen, M., Bracken, J., Harvey, A., Elliott, C., Novak, I., & Crichton, A. (2018). Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study. BMC neurology, 18(1), 63. https://doi.org/10.1186/s12883-018-1070-z
CIMT and Bimanual training
Gordon AM. To constrain or not to constrain, and other stories of intensive upper extremity training for children with unilateral cerebral palsy. Dev Med Child Neurol. 2011;53 Suppl 4:56-61. doi:10.1111/j.1469-8749.2011.04066.x
Impaired hand function is among the most functionally disabling symptoms of unilateral cerebral palsy. Evidence-based treatment approaches are generally lacking. However, recent approaches providing intensive upper extremity training appear promising. In this review, we first describe two such approaches, constraint-induced movement therapy (CIMT) and bimanual training (hand-arm bimanual intensive therapy). We then summarize findings across more than 100 participants in our CIMT/bimanual training studies since 1997. We show that (1) at high intensities, CIMT and bimanual training improve dexterity and bimanual upper extremity use; (2) bimanual training may allow direct practice of functionally meaningful goals, and such practice may transfer to unpracticed goals and improve bimanual coordination; (3) 90 hours of CIMT and bimanual training leads to greater improvements than 60 hours of the same treatments; (4) higher doses may be required for bimanual training; (5) increased dosing frequency and shaping may be needed for older children; and (6) combined CIMT/bimanual approaches may be useful, but require sufficient intensity. Together these findings suggest that dosage (treatment amount and frequency), more so than ingredients, may well be the key to successful training protocols, especially for older children. Such rehabilitation efforts should be 'child-friendly', and as least invasive as possible, especially because these approaches may be provided throughout development.
Sakzewski L, Gordon A, Eliasson AC. The state of the evidence for intensive upper limb therapy approaches for children with unilateral cerebral palsy. J Child Neurol. 2014;29(8):1077-1090. doi:10.1177/0883073814533150
Children with unilateral cerebral palsy experience difficulties with unimanual and bimanual upper limb function, impacting independence in daily life. Targeted upper limb therapies such as constraint-induced movement therapy, bimanual training, and combined approaches have emerged in the last decade. This article reviews the scientific rationale underpinning these treatments and current evidence to improve upper limb outcomes and goal attainment. Intensive models of therapy achieved modest to strong effects to improve upper limb function compared to usual care. Dose-matched comparisons of bimanual and unimanual training demonstrated similar gains in upper limb outcomes. The optimum timing, dose and impact of repeat episodes of intensive upper limb therapies require further investigation. Characteristics of children who achieve clinically meaningful outcomes remain unclear. Key components of intervention include collaborative goal setting with families and intensive repetitive, incrementally challenging, task practice. Choice of treatment approach should be governed by child/family goals and preferences, individual, and contextual factors.
Evidence
"Evidence for early interventions that involve active motor skill training has been growing slowly over the last 4 years. Two RCTs of GAME (Goals Activity Motor Enrichment; Morgan et al., 2014) intervention in infants aged 3–6 months with or at high risk of cerebral palsy demonstrated improved motor (Morgan et al., 2015, 2016b) and cognitive skills (Morgan et al., 2016b) after a minimum of 3 months intervention, when compared to standard care. GAME is a motor learning intervention that coaches and supports parents to train motor and cognitive skills through play, in an enriched environment. GAME is always delivered in the family home with practice carried out by parents throughout the week between face to face therapy sessions. A large multicenter single blind randomized controlled trial (n = 300) of GAME vs. standard care is currently being undertaken (ACTRN12617000006347).
About 20–30% of preterm infants with cerebral palsy will be diagnosed with unilateral cerebral palsy (Himpens et al., 2008; ACPR Group, 2018). High quality evidence exists for the use of constraint induced movement therapy (CIMT) in children with unilateral cerebral palsy (Novak et al., 2013) and there is early evidence to support the use of a modified version of CIMT for infants. A retrospective study of 72 infants with unilateral cerebral palsy confirmed that children who had received CIMT as an infant (baby-CIMT) were significantly more likely to have superior hand function at age two than those who did not, even when controlling for the type of lesion (Nordstrand et al., 2015). A recently published RCT (n = 37) confirmed that infants with unilateral cerebral palsy had better function of their affected hand after 36 h of baby-CIMT than infants who had received the same dose of infant massage (Eliasson et al., 2018). Bimanual therapy, a training intervention that targets using both hands together, is equally effective as CIMT at a matched dose in older children with hemiplegia however trials in infants are not yet published (Sakzewski et al., 2014). A randomized trial comparing baby CIMT with bimanual training is currently underway (Boyd et al., 2017)."
Finch-Edmondson, M., Morgan, C., Hunt, R. W., & Novak, I. (2019). Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy. Frontiers in physiology, 10, 15. https://doi.org/10.3389/fphys.2019.00015
Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialised world.1 Congenital hemiplegia, frequently termed unilateral cerebral palsy (UCP), is characterised by a unilateral or asymmetric brain injury occurring around the time of birth, impacting development of hand skills and motor abilities on one side. Cerebral palsy is the fifth most costly health condition.2 Therefore, early interventions that mitigate the brain injury and improve early hand function and later vocational and life outcomes are urgently needed. Children with congenital unilateral or asymmetric brain lesions frequently develop hemiplegia with major limitations in the use of their impaired hand, which results in poor bimanual coordination and impacts on the performance of daily activities in home, school and community life.
Currently, two very different intensive therapy approaches are used each with good evidence of improving outcomes for school-aged children with CP.3 Traditional upper limb therapy adopts a bimanual approach (BIM) which aims to improve the use of the impaired hand as an assisting hand in play and functional daily activities.4 More recently, modified constraint-induced movement therapy (mCIMT) has been introduced, which employs a unimanual approach whereby the unimpaired hand is constrained in a glove to encourage intensive unimanual training of the hemiplegic arm.5 There is speculation that BIM may benefit later bimanual coordination, whereas mCIMT may achieve earlier capability in the hemiplegic hand due to specificity of training. Other conclusions have been drawn from animal studies hypothesising that early mCIMT may have a deleterious effect on brain reorganisation (overlateralisation of corticospinal pathways), whereas equal training of both hands may reduce such an effect.4 To date, however, neither of these approaches have been tested or compared in a definitive randomised controlled trial (RCT) in very young infants with asymmetric brain lesions. This RCT, the Rehabilitation EArly for Congenital Hemiplegia (REACH) study, will directly compare an intensive infant friendly one-handed approach using mCIMT, called ‘Baby mCIMT’, to an equally intensive two-handed (bimanual) approach, called ‘Baby BIM,’ in very young infants with unilateral or asymmetric brain lesions and clinical signs of unilateral CP.
Boyd, R. N., Ziviani, J., Sakzewski, L., Novak, I., Badawi, N., Pannek, K., Elliott, C., Greaves, S., Guzzetta, A., Whittingham, K., Valentine, J., Morgan, C., Wallen, M., Eliasson, A. C., Findlay, L., Ware, R., Fiori, S., & Rose, S. (2017). REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia. BMJ open, 7(9), e017204. https://doi.org/10.1136/bmjopen-2017-017204
Evidence for mCIMT and bimanual upper limb rehabilitation in congenital hemiplegia
"Our meta-analysis reported the efficacy of interventions on improving upper limb dysfunction for school-aged children with hemiplegia.3 There was moderate to strong evidence that the original approach to CIMT (with a long cast on the unimpaired arm combined with intensive shaping) or modified CIMT (using a glove on the unimpaired hand with activity-based training) was more effective than usual care to improve the quality and efficiency of arm movement. When mCIMT was compared with an equal dose of bimanual therapy at school age, there were differential effects related to the specificity of training.8 It remains unclear, however, whether one approach is superior in infants as the majority of studies did not include children under 1 year of age. Despite the philosophical preference for very early intervention to optimise brain neuroplasticity, there is limited research on early upper limb rehabilitation for infants less than 12 months ca.9 It is important to test the efficacy of these two approaches to upper limb therapy in young infants where there is greater potential to harness neuroplasticity."
Boyd et al 2017