Dataset Information

Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide.

ABSTRACT: Non-invasive brain stimulation has been increasingly investigated, mainly in adults, with the aims of influencing motor recovery after stroke. However, a consensus on safety and optimal study design has not been established in pediatrics. The low incidence of reported major adverse events in adults with and without clinical conditions has expedited the exploration of NIBS in children with paralleled purposes to influence motor skill development after neurological injury. Considering developmental variability in children, with or without a neurologic diagnosis, adult dosing and protocols may not be appropriate. The purpose of this paper is to present recommendations and tools for the prevention and mitigation of adverse events (AEs) during NIBS in children with unilateral cerebral palsy (UCP). Our recommendations provide a framework for pediatric NIBS study design. The key components of this report on NIBS AEs are (a) a summary of related literature to provide the background evidence and (b) tools for anticipating and managing AEs from four international pediatric laboratories. These recommendations provide a preliminary guide for the assessment of safety and risk mitigation of NIBS in children with UCP. Consistent reporting of safety, feasibility, and tolerability will refine NIBS practice guidelines contributing to future clinical translations of NIBS.

SUBMITTER: Gillick BT

PROVIDER: S-EPMC5864860 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide.

Gillick Bernadette T BT Gordon Andrew M AM Feyma Tim T Krach Linda E LE Carmel Jason J Rich Tonya L TL Bleyenheuft Yannick Y Friel Kathleen K

Frontiers in pediatrics 20180316

Non-invasive brain stimulation has been increasingly investigated, mainly in adults, with the aims of influencing motor recovery after stroke. However, a consensus on safety and optimal study design has not been established in pediatrics. The low incidence of reported major adverse events in adults with and without clinical conditions has expedited the exploration of NIBS in children with paralleled purposes to influence motor skill development after neurological injury. Considering developmenta ...[more]

PMID: 29616203

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Project description:Background: In children with unilateral cerebral palsy (uCP) virtually nothing is known on the relation between structural brain damage and upper limb (UL) kinematics quantified with three-dimensional movement analysis (3DMA). This explorative study aimed to (1) investigate differences in UL kinematics between children with different lesion timings, i.e., periventricular white matter (PWM) vs. cortical and deep gray matter (CDGM) lesions and (2) to explore the relation between UL kinematics and lesion location and extent within each lesion timing group. Methods: Forty-eight children (age 10.4 ± 2.7 year; 29 boys; 21 right-sided; 33 PWM; 15 CDGM) underwent an UL 3DMA during a reach-to-grasp task. Spatiotemporal parameters [movement duration, (timing of) maximum velocity, trajectory straightness], the Arm Profile Score (APS) and Arm Variable Scores (AVS) were extracted. The APS and AVS refer to the total amount of movement pathology and movement deviations of the wrist, elbow, shoulder, scapula and trunk respectively. Brain lesion location and extent were scored based on FLAIR-images using a semi-quantitative MRI-scale. Results: Children with CDGM lesions showed more aberrant spatiotemporal parameters (p < 0.03) and more movement pathology (APS, p = 0.003) compared to the PWM group, mostly characterized by increased wrist flexion (p = 0.01). In the CDGM group, moderate to high correlations were found between lesion location and extent and duration, timing of maximum velocity and trajectory straightness (r = 0.53-0.90). Lesion location and extent were further moderately correlated with distal UL movement pathology (wrist flexion/extension, elbow pronation/supination, elbow flexion/extension; r = 0.50-0.65) and with the APS (r = 0.51-0.63). In the PWM group, only a few and low correlations were observed, mostly between damage to the PLIC and higher AVS of elbow flexion/extension, shoulder elevation and trunk rotation (r = 0.35-0.42). Regression analysis revealed damage to the temporal lobe with lesion timing as interactor (27%, p = 0.002) and the posterior limb of the internal capsule (PLIC) (7%, p = 0.04) as the strongest predictors, explaining 34% of the variance in APS. Conclusion: UL kinematic deviations are more influenced by lesion location and extent in children with later (CDGM) versus earlier lesions (PWM), except for proximal movement pathology. Damage to the PLIC is a significant predictor for UL movement pathology irrespective of lesion timing.

Project description:IntroductionEarly brain injury, as found in children with unilateral cerebral palsy (CP), may cause deficits in higher-order cognitive tasks known as executive functions (EF). EF has been conceptualised as comprised of four distinct yet inter-related components: (1) attentional control, (2) cognitive flexibility, (3) goal setting and (4) information processing. The aim of this study was to examine EF in children with unilateral CP and compare their performance with a typically developing reference group (TDC). The potential laterality effects of unilateral CP on EF will be explored, as will the relationship between the cognitive measures of EF, behavioural manifestations of EF, psychological functioning and clinical features of unilateral CP.Methods and analysisThis cross-sectional study aims to recruit a total of 42 children with unilateral CP (21 right unilateral CP and 21 left unilateral CP) and 21 TDC aged between 8 and 16 years. Clinical severity will be described for gross motor function and manual ability. Outcomes for cognitive EF measureswill include subtests from the Wechsler Intelligence Scale for Children-Fourth Edition, Delis-Kaplan Executive Function System, Rey Complex Figure Test and the Test of Everyday Attention for Children. Behavioural manifestations of EF will be assessed using the Behaviour Rating Inventory of Executive Function, Parent and Teacher versions. Psychological functioning will be examined using the Strengths and Difficulties Questionnaire. Between-groups differences will be examined in a series of one-way analyses of covariance and followed up using linear comparisons. An overall composite of cognitive EF measures will be created. Bivariate correlations between the EF composite and psychological measures will be calculated.Ethics and disseminationThis protocol describes a study that, to our knowledge, is the first to examine multiple components of EF using a cohort of children with unilateral CP. Exploration of potential laterality effects of EF among children with a congenital, unilateral brain injury is also novel. Possible relationships between EF and psychological functioning will also be investigated. Ethics have been obtained through the University of Queensland School of Psychology Ethics Committee and the Queensland Children's Health Services Human Research Ethics Committee. Results will be disseminated in peer reviewed publications and presentations at national and international conferences. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000263998).

Project description:Combined non-invasive brain stimulation (NIBS) and rehabilitation interventions have the potential to improve function in children with unilateral cerebral palsy (UCP), however their effects on developing brain function are not well understood. In a proof-of-principle study, we used single-pulse transcranial magnetic stimulation (TMS) to measure changes in corticospinal excitability and relationships to motor performance following a randomized controlled trial consisting of 10 days of combined constraint-induced movement therapy (CIMT) and cathodal transcranial direct current stimulation (tDCS) applied to the contralesional motor cortex. Twenty children and young adults (mean age = 12 years, 9 months, range = 7 years, 7 months, 21 years, 7 months) with UCP participated. TMS testing was performed before, after, and 6 months after the intervention to measure motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration. The association between neurophysiologic and motor outcomes and differences in excitability between hemispheres were examined. Contralesional MEP amplitude decreased as hypothesized in five of five participants receiving active tDCS immediately after and 6 months after the intervention, however no statistically significant differences between intervention groups were noted for MEP amplitude [mean difference = -323.9 μV, 95% CI = (-989, 341), p = 0.34] or CSP duration [mean difference = 3.9 ms, 95% CI = (-7.7, 15.5), p = 0.51]. Changes in corticospinal excitability were not statistically associated with improvements in hand function after the intervention. Across all participants, MEP amplitudes measured in the more-affected hand from both contralesional (mean difference = -474.5 μV) and ipsilesional hemispheres (-624.5 μV) were smaller compared to the less-affected hand. Assessing neurophysiologic changes after tDCS in children with UCP provides an understanding of long-term effects on brain excitability to help determine its potential as a therapeutic intervention. Additional investigation into the neurophysiologic effects of tDCS in larger samples of children with UCP are needed to confirm these findings.

Project description:We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory-motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi-shell diffusion-weighted, T1-weighted and T2-FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting-modified FreeSurfer parcellations and multi-shell multi-tissue constrained spherical deconvolution-based anatomically-constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory-motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST-wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic-net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST-wiring pattern and age predicted sensory-motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM-lesions compared with PWM-lesions, with higher clustering coefficient (p = [<.001-.047], ηp2 =[0.09-0.27]), characteristic path length (p = .003, ηp2 =0.19) and local efficiency (p = [.001-.02], ηp2 =[0.11-0.21]), and a lower global efficiency with age (p = [.01-.04], ηp2 =[0.09-0.15]). No differences were found between CST-wiring groups. Overall, good predictions of sensory-motor function were obtained with elastic-net regression (R2 = .40-.87). CST-wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP.

Dataset Information

Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide.

Publications

Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide.

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