Alterations in regional shape on ipsilateral and contralateral cortex contrast in children with unilateral cerebral palsy and are predictive of multiple outcomes.
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ABSTRACT:
SUBMITTER: Pagnozzi AM
PROVIDER: S-EPMC6867510 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
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Alterations in regional shape on ipsilateral and contralateral cortex contrast in children with unilateral cerebral palsy and are predictive of multiple outcomes.
Pagnozzi Alex M AM Dowson Nicholas N Fiori Simona S Doecke James J Bradley Andrew P AP Boyd Roslyn N RN Rose Stephen S
Human brain mapping 20160603 10
Congenital brain lesions result in a wide range of cerebral tissue alterations observed in children with cerebral palsy (CP) that are associated with a range of functional impairments. The relationship between injury severity and functional outcomes, however, remains poorly understood. This research investigates the differences in cortical shape between children with congenital brain lesions and typically developing children (TDC) and investigates the correlations between cortical shape and func ...[more]
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Project description:Mirror movements (MM) can be a clinical manifestation of unilateral cerebral palsy (UCP) causing involuntary movements when attempting to use either hand for functional activities. Atypical development of the corticospinal tract (CST) contributes to impairments in observed motor movements and functional activities. However, little is known about the underlying neurophysiology and contribution of the CST to MM. The current case study characterizes MM in 13 children and young adults with UCP ranging in age from 7 to 19 years and includes clinical and neurophysiologic variables. Clinical profiles included MM of each hand (ie, Woods and Teuber), bimanual coordination and hand use (Assisting Hand Assessment [AHA]), and perception of performance (Canadian Occupational Performance Measure [COPM]). We measured the strength of motor-evoked potentials (MEP) elicited from single-pulse transcranial magnetic stimulation (TMS) of each hemisphere to create a ratio of hemispheric responses. Our sample included three types of CST circuitry: ipsilateral (n = 5), bilateral (n = 3), and contralateral (n = 4). The MEP ratio ranged from 0 to 1.45 (median 0.11) with greater MM observed in participants with ratios greater than 0.5. We observed a positive relationship between the MEP ratio and the more-affected MM score, meaning participants with larger ipsilateral responses from contralesional stimulation (eg, the contralesional hemisphere was stimulated with TMS resulting in an ipsilateral MEP response), as compared with contralateral responses, displayed greater MM than those that did not. There was no relationship between MM and function as measured by the AHA or COPM. These findings suggest a role of the contralesional hemisphere to MM, which could serve as a therapeutic target for interventions.
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Project description:BackgroundDetecting differences in upper limb use in children with unilateral cerebral palsy (UCP) is challenging and highly dependent on examiner experience. The recent introduction of technologies in the clinical environment, and in particular the use of wearable sensors, can provide quantitative measurement to overcome this issue. This study aims to evaluate ActiGraph GT3X+ as a tool for measuring asymmetry in the use of the two upper limbs (ULs) during the assessment with a standardized clinical tool, the Assisting Hand Assessment (AHA) in UCP patients aged 3-25 years compared to age-matched typically developing (TD) subjects.MethodsFifty children with UCP and 50 TD subjects were assessed with AHA while wearing ActiGraphs GT3X+ on both wrists. The mean activity of each hand (dominant and non-dominant, MADH and MANDH, respectively) and the asymmetry index (AI) were calculated. Two linear mixed model analyses were carried out to evaluate how dependent actigraphic variables (i.e. MANDH and AI) varied by group (TD vs UCP) and among levels of manual ability based on Manual Ability Classification System (MACS). In both models age, sex, side of hemiplegia, presence/absence of mirror movements were specified as random effects.ResultsThe MANDH was significantly lower in UCP compared to TD, while the AI was significantly higher in UCP compared to TD. Moreover, in UCP group there were significant differences related to MACS levels, both for MANDH and AI. None of the random variables (i.e. age, sex, side, presence/absence of mirror movements) showed significant interaction with MANDH and AI.ConclusionsThese results confirm that actigraphy could provide, in a standardized setting, a quantitative description of differences between upper limbs activity.Trial registrationClincalTrials.gov, NCT03054441 . Registered 15 February 2017.
| S-EPMC6387534 | biostudies-literature
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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.
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Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.
2012-11-21 | E-GEOD-31243 | biostudies-arrayexpress
Project description:BackgroundSpinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons.ResultsThe expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury.Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response.ConclusionsThis analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.
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| S-EPMC6850156 | biostudies-literature
Project description:Background: Motor Imagery (MI) refers to mental simulation of a motor action without producing any overt movement. Previous studies showed that children with Unilateral Cerebral Palsy (UCP) are impaired in implicit MI, as demonstrated by the performance of Hand Laterality Judgment tasks. The aim of this study was to examine the specificity of explicit MI deficits in UCP children. Methods: A group of UCP children (n = 10; aged 9-14) performed a mental chronometry task consisting in grasping an object and placing it into a container, or in imagining to perform the same action. As control, a group of typically developing (TD) children, matched by age, performed the same task. Movement durations for executed and imagined trials were recorded. A subgroup of 7 UCP children and 10 TD children also underwent a session of functional MRI to examine the activation of parieto-frontal areas typically associated to MI processes, during the imagination of reaching-grasping actions performed with the paretic hand. Results: Behavioral results revealed the existence of a correlation between executed and imagined movement durations both in TD and UCP groups. Moreover, the regression analysis in TD children showed that higher scores in mental chronometry tasks were positively correlated to increased bilateral activation of the intraparietal sulcus (IPS), superior parietal lobule (SPL), and dorsal premotor (PMd) cortex. A similar analysis revealed in the UCP group a positive correlation between a higher score in the mental chronometry task and bilateral activations of IPS, and to activation of contralesional, right PMd, and putamen during imagination of grasping movements. Conclusions: These results provide new insights on the relationship between MI capacity and motor deficits in UCP children, suggesting the possibility of the use of explicit MI training to improve patient's upper limb motor functions.
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