Test-retest reliability of corticokinematic coherence in young children with cerebral palsy: An observational longitudinal study.

OBJECTIVES: To assess the test-retest reliability of the corticokinematic coherence (CKC), an electrophysiological marker of proprioception, in children with cerebral palsy (CP). METHODS: Electroencephalography (EEG) signals from 15 children with unilateral or bilateral CP aged 23 to 53 months were recorded in two sessions 3 months apart using 128-channel EEG caps. During each session, children's fingers were moved at 2 Hz by an experimenter, in separate recordings for the more-affected (MA) and less-affected (LA) hands. The CKC was computed at the electrode and source levels, at movement frequency F0 (2 Hz) and its first harmonic F1 (4 Hz). A two-way mixed-effects model intraclass-correlation coefficient (ICC) was computed for the maximum CKC strength across electrodes at F0 and F1 obtained during the two sessions. RESULTS: ICC of the CKC strength acquired from LA and MA hands pooled together were respectively 0.51 (95% CI: 0.30-0.68) at F0 and 0.96 (95% CI: 0.93-0.98) at F1. The mean distances separating the CKC peaks in the source space at the two evaluation times were in the order of a centimeter. CONCLUSION: CKC is a robust electrophysiologic marker to study the longitudinal changes in cortical processing of proprioceptive afferences in young children with CP.

Hand function after neonatal stroke: A graph model based on basal ganglia and thalami structure.

INTRODUCTION: Neonatal arterial ischemic stroke (NAIS) is a common model to study the impact of a unilateral early brain insult on developmental brain plasticity and the appearance of long-term outcomes. Motor difficulties that may arise are typically related to poor function of the affected (contra-lesioned) hand, but surprisingly also of the ipsilesional hand. Although many longitudinal studies after NAIS have shown that predicting the occurrence of gross motor difficulties is easier, accurately predicting hand motor function (for both hands) from morphometric MRI remains complicated. The hypothesis of an association between the structural organization of the basal ganglia (BG) and thalamus with hand motor function seems intuitive given their key role in sensorimotor function. Neuroimaging studies have frequently investigated these structures to evaluate the correlation between their volumes and motor function following early brain injury. However, the results have been controversial. We hypothesize the involvement of other structural parameters. METHOD: The study involves 35 children (mean age 7.3 years, SD 0.4) with middle cerebral artery NAIS who underwent a structural T1-weighted 3D MRI and clinical examination to assess manual dexterity using the Box and Blocks Test (BBT). Graphs are used to represent high-level structural information of the BG and thalami (volumes, elongations, distances) measured from the MRI. A graph neural network (GNN) is proposed to predict children's hand motor function through a graph regression. To reduce the impact of external factors on motor function (such as behavior and cognition), we calculate a BBT score ratio for each child and hand. RESULTS: The results indicate a significant correlation between the score ratios predicted by our method and the actual score ratios of both hands (p < 0.05), together with a relatively high accuracy of prediction (mean L1 distance < 0.03). The structural information seems to have a different influence on each hand's motor function. The affected hand's motor function is more correlated with the volume, while the 'unaffected' hand function is more correlated with the elongation of the structures. Experiments emphasize the importance of considering the whole macrostructural organization of the basal ganglia and thalami networks, rather than the volume alone, to predict hand motor function. CONCLUSION: There is a significant correlation between the structural characteristics of the basal ganglia/thalami and motor function in both hands. These results support the use of MRI macrostructural features of the basal ganglia and thalamus as an early biomarker for predicting motor function in both hands after early brain injury.

Changes Induced by Early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities in Young Children With Unilateral Cerebral Palsy: A Randomized Clinical Trial.

Importance: Intensive interventions are provided to young children with unilateral cerebral palsy (UCP), classically focused on the upper extremity despite the frequent impairment of gross motor function. Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) effectively improves manual dexterity and gross motor function in school-aged children. Objective: To verify if HABIT-ILE would improve manual abilities in young children with UCP more than usual motor activity. Design, Setting, and Participants: This prospective randomized clinical trial (November 2018 to December 2021), including 2 parallel groups and a 1:1 allocation, recruitment took place at European university hospitals, cerebral palsy specialized centers, and spontaneous applications at 3 sites: Brussels, Belgium; Brest, France; and Pisa, Italy. Matched (age at inclusion, lesion type, cause of cerebral palsy, and affected side) pairs randomization was performed. Young children were assessed at baseline (T0), 2 weeks after baseline (T1), and 3 months after baseline (T2). Health care professionals and assessors of main outcomes were blinded to group allocation. At least 23 young children (in each group) aged 12 to 59 months with spastic/dyskinetic UCP and able to follow instructions were needed. Exclusion criteria included uncontrolled seizures, scheduled botulinum toxin injections, orthopedic surgery scheduled during the 6 months before or during the study period, severe visual/cognitive impairments, or contraindications to magnetic resonance imaging. Interventions: Two weeks of usual motor activity including usual rehabilitation (control group) vs 2 weeks (50 hours) of HABIT-ILE (HABIT-ILE group). Main Outcomes and Measures: Primary outcome: Assisting Hand Assessment (AHA); secondary outcomes: Gross Motor Function Measure-66 (GMFM-66), Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and Canadian Occupational Performance Measure (COPM). Results: Of 50 recruited young children (26 girls [52%], median age; 35.3 months for HABIT-ILE group; median age, 32.8 months for control group), 49 were included in the final analyses. Change in AHA score from T0 to T2 was significantly greater in the HABIT-ILE group (adjusted mean score difference [MD], 5.19; 95% CI, 2.84-7.55; P < .001). Changes in GMFM-66 (MD, 4.72; 95% CI, 2.66-6.78), PEDI-CAT daily activities (MD, 1.40; 95% CI, 0.29-2.51), COPM performance (MD, 3.62; 95% CI, 2.91-4.32), and satisfaction (MD, 3.53; 95% CI, 2.70-4.36) scores were greater in the HABIT ILE group. Conclusions and Relevance: In this clinical trial, early HABIT-ILE was shown to be an effective treatment to improve motor performance in young children with UCP. Moreover, the improvements had an impact on daily life activities of these children. Trial registration: ClinicalTrials.gov Identifier: NCT04020354.

Assessing spino-cortical proprioceptive processing in childhood unilateral cerebral palsy with corticokinematic coherence.

OBJECTIVE: To develop an electrophysiological marker of proprioceptive spino-cortical tracts integrity based on corticokinematic coherence (CKC) in young children with unilateral cerebral palsy (UCP), in whom behavioral measures are not applicable. METHODS: Electroencephalography (EEG) signals from 12 children with UCP aged 19 to 57 months were recorded using 128-channel EEG caps while their fingers were moved at 2 Hz by an experimenter, in separate sessions for the affected and non-affected hands. The coherence between movement kinematics and EEG signals (i.e., CKC) was computed at the sensor and source (using a realistic head model) levels. Peaks of CKC obtained for the affected and non-affected hands were compared for location and strength. The relation between CKC strength on the lesion-side, the lesion-type (cortico-subcortical vs. subcortical) and the level of manual ability were studied with 2-way repeated-measures ANOVA. RESULTS: At the individual level, a significant CKC peak at the central area contralateral to the moved hand was found in all young children with their non-affected hand and in 8 out of 12 children with their affected hand. At the group level, CKC to the affected hand movements was weaker than CKC to the non-affected hand movements. This difference was influenced by the type of lesion, the effect being predominant in the subgroup (n = 5) with cortico-subcortical lesions. CONCLUSION: CKC is measurable with EEG in young children with UCP and provides electrophysiological evidence for altered proprioceptive spino-cortical tracts on the lesioned brain hemisphere, particularly in children with cortico-subcortical lesions.

Protocol of changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with bilateral cerebral palsy: a multisite randomized controlled trial.

BACKGROUND: Cerebral palsy (CP), which is the leading cause of motor disability during childhood, can produce sensory and cognitive impairments at different degrees. Most recent therapeutic interventions for these patients have solely focused on upper extremities (UE), although more than 60% of these patients present lower extremities (LE) deficits. Recently, a new therapeutic concept, Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE), has been proposed, involving the constant stimulation of UE and LE. Based on motor skill learning principles, HABIT-ILE is delivered in a day-camp setting, promoting voluntary movements for several hours per day during 10 consecutive week days. Interestingly, the effects of this intervention in a large scale of youngsters are yet to be observed. This is of interest due to the lack of knowledge on functional, neuroplastic and biomechanical changes in infants with bilateral CP. The aim of this randomized controlled study is to assess the effects of HABIT-ILE adapted for pre-school children with bilateral CP regarding functional, neuroplastic and biomechanical factors. METHODS: This international, multicentric study will include 50 pre-school children with CP from 12 to 60 months of age, comparing the effect of 50 h (2 weeks) of HABIT-ILE versus regular motor activity and/or customary rehabilitation. HABIT-ILE presents structured activities and functional tasks with continuous increase in difficulty while the child evolves. Assessments will be performed at 3 period times: baseline, two weeks later and 3 months later. The primary outcome will be the Gross Motor Function Measure 66. Secondary outcomes will include Both Hands Assessment, Melbourne Assessment-2, Semmes-Weinstein Monofilament Test, algometry assessments, executive function tests, ACTIVLIM-CP questionnaire, Pediatric Evaluation of Disability Inventory (computer adaptative test), Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, neuroimaging and kinematics. DISCUSSION: The results of this study should highlight the impact of a motor, intensive, goal-directed therapy (HABIT-ILE) in pre-school children at a functional, neuroplastic and biomechanical level. In addition, this changes could demonstrated the impact of this intervention in the developmental curve of each child, improving functional ability, activity and participation in short-, mid- and long-term. NAME OF THE REGISTRY: Evaluation of Functional, Neuroplastic and Biomechanical Changes Induced by an Intensive, Playful Early-morning Treatment Including Lower Limbs (EARLY-HABIT-ILE) in Preschool Children With Uni and Bilateral Cerebral Palsy (HABIT-ILE). TRIAL REGISTRATION: NCT04017871 REGISTRATION DATE: July 12, 2019.

Mu rhythm: State of the art with special focus on cerebral palsy.

Various specific early rehabilitation strategies are proposed to decrease functional disabilities in patients with cerebral palsy (CP). These strategies are thought to favour the mechanisms of brain plasticity that take place after brain injury. However, the level of evidence is low. Markers of brain plasticity would favour validation of these rehabilitation programs. In this paper, we consider the study of mu rhythm for this goal by describing the characteristics of mu rhythm in adults and children with typical development, then review the current literature on mu rhythm in CP. Mu rhythm is composed of brain oscillations recorded by electroencephalography (EEG) or magnetoencephalography (MEG) over the sensorimotor areas. The oscillations are characterized by their frequency, topography and modulation. Frequency ranges within the alpha band (∼10Hz, mu alpha) or beta band (∼20Hz, mu beta). Source location analyses suggest that mu alpha reflects somatosensory functions, whereas mu beta reflects motor functions. Event-related desynchronisation (ERD) followed by event-related (re-)synchronisation (ERS) of mu rhythm occur in association with a movement or somatosensory input. Even if the functional role of the different mu rhythm components remains incompletely understood, their maturational trajectory is well described. Increasing age from infancy to adolescence is associated with increasing ERD as well as increasing ERS. A few studies characterised mu rhythm in adolescents with spastic CP and showed atypical patterns of modulation in most of them. The most frequent findings in patients with unilateral CP are decreased ERD and decreased ERS over the central electrodes, but atypical topography may also be found. The patterns of modulations are more variable in bilateral CP. Data in infants and young children with CP are lacking and studies did not address the questions of intra-individual reliability of mu rhythm modulations in patients with CP nor their modification after motor learning. Better characterization of mu rhythm in CP, especially in infants and young children, is warranted before considering this rhythm as a potential neurophysiological marker of brain plasticity.