A predictive mathematical model of muscle forces for children with cerebral palsy.
Ontology highlight
ABSTRACT: Aim
The purpose of this study was to determine if our previously developed muscle model could be used to predict forces of the quadriceps femoris and triceps surae muscles of children with spastic diplegic cerebral palsy (CP).Method
Twenty-two children with CP (12 males, 10 females; mean age 10y, SD 2y, range 7-13y; Gross Motor Function Classification System levels II and III) participated. A physiologically based mathematical model with four free parameters is presented.Results
For individuals with CP, the model predicted well the force profile throughout each contraction and both peak force and force-time integral responses to a wide range of stimulation frequencies (5-100Hz) and different stimulation patterns (constant-, variable-, and doublet-frequency trains) both for nonfatigued and fatigued muscles.Interpretation
The significance of this work is the insight the model can provide into the physiology of muscle in CP. Additionally, the model can potentially be applied clinically to design optimal electrical stimulation patterns for interventions to address impairments in strength and function in individuals with CP, such as functional electrical stimulation-assisted cycling.
SUBMITTER: Lee SC
PROVIDER: S-EPMC7935412 | biostudies-literature | 2009 Dec
REPOSITORIES: biostudies-literature
Publications
A predictive mathematical model of muscle forces for children with cerebral palsy.
Lee Samuel C K SC Ding Jun J Prosser Laura A LA Wexler Anthony S AS Binder-Macleod Stuart A SA
Developmental medicine and child neurology 20090824 12
<h4>Aim</h4>The purpose of this study was to determine if our previously developed muscle model could be used to predict forces of the quadriceps femoris and triceps surae muscles of children with spastic diplegic cerebral palsy (CP).<h4>Method</h4>Twenty-two children with CP (12 males, 10 females; mean age 10y, SD 2y, range 7-13y; Gross Motor Function Classification System levels II and III) participated. A physiologically based mathematical model with four free parameters is presented.<h4>Resu ...[more]
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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: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.
2012-11-21 | GSE31243 | GEO
Project description:Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP 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 CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits.Biopsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10) and typically developing patients (n = 10) undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP 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 and muscle specific networks.The majority of altered transcripts were related to increased extracellular matrix expression in CP and 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 development of novel therapies.
| S-EPMC3431909 | biostudies-literature
Project description:Cerebral palsy is a neuromusculoskeletal disorder associated with muscle weakness, altered muscle architecture, and progressive musculoskeletal symptoms that worsen with age. Pathological changes at the level of the whole muscle have been shown; however, it is unclear why this progression of muscle impairment occurs at the cellular level. The process of muscle regeneration is complex, and the interactions between cells in the muscle milieu should be considered in the context of cerebral palsy. In this work, we built a coupled mechanobiological model of muscle damage and regeneration to explore the process of muscle regeneration in typical and cerebral palsy conditions, and whether a reduced number of satellite cells in the cerebral palsy muscle environment could cause the muscle regeneration cycle to lead to progressive degeneration of muscle. The coupled model consisted of a finite element model of a muscle fiber bundle undergoing eccentric contraction, and an agent-based model of muscle regeneration incorporating satellite cells, inflammatory cells, muscle fibers, extracellular matrix, fibroblasts, and secreted cytokines. Our coupled model simulated damage from eccentric contraction followed by 28 days of regeneration within the muscle. We simulated cyclic damage and regeneration for both cerebral palsy and typically developing muscle milieus. Here we show the nonlinear effects of altered satellite cell numbers on muscle regeneration, where muscle repair is relatively insensitive to satellite cell concentration above a threshold, but relatively sensitive below that threshold. With the coupled model, we show that the fiber bundle geometry undergoes atrophy and fibrosis with too few satellite cells and excess extracellular matrix, representative of the progression of cerebral palsy in muscle. This work uses in silico modeling to demonstrate how muscle degeneration in cerebral palsy may arise from the process of cellular regeneration and a reduced number of satellite cells.
| S-EPMC8429491 | biostudies-literature
Project description:Background: Walking problems in children with cerebral palsy (CP) can in part be explained by limited selective motor control. Muscle synergy analysis is increasingly used to quantify altered neuromuscular control during walking. The early brain injury in children with CP may lead to a different development of muscle synergies compared to typically developing (TD) children, which might characterize the abnormal walking patterns. Objective: The overarching aim of this review is to give an overview of the existing studies investigating muscle synergies during walking in children with CP compared to TD children. The main focus is on how muscle synergies differ between children with CP and TD children, and we examine the potential of muscle synergies as a measure to quantify and predict treatment outcomes. Methods: Bibliographic databases were searched by two independent reviewers up to 22 April 2019. Studies were included if the focus was on muscle synergies of the lower limbs during walking, obtained by a matrix factorization algorithm, in children with CP. Results: The majority (n = 12) of the 16 included studies found that children with CP recruited fewer muscle synergies during walking compared to TD children, and several studies (n = 8) showed that either the spatial or temporal structure of the muscle synergies differed between children with CP and TD children. Variability within and between subjects was larger in children with CP than in TD children, especially in more involved children. Muscle synergy characteristics before treatments to improve walking function could predict treatment outcomes (n = 3). Only minimal changes in synergies were found after treatment. Conclusions: The findings in this systematic review support the idea that children with CP use a simpler motor control strategy compared to TD children. The use of muscle synergy analysis as a clinical tool to quantify altered neuromuscular control and predict clinical outcomes seems promising. Further investigation on this topic is necessary, and the use of muscle synergies as a target for development of novel therapies in children with CP could be explored.
| S-EPMC7343959 | biostudies-literature
Project description:AimTo determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP).MethodIn this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns.ResultsSynergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high.InterpretationThe similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.
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Project description:Muscle weakness is a common clinical symptom in children with spastic cerebral palsy (SCP). It is caused by impaired neural ability and altered intrinsic capacity of the muscles. To define the contribution of decreased muscle size to muscle weakness, two cohorts were recruited in this cross-sectional investigation: 53 children with SCP [median age, 8.2 (IQR, 4.1) years, 19/34 uni/bilateral] and 31 children with a typical development (TD) [median age, 9.7 (IQR, 2.9) years]. Muscle volume (MV) and muscle belly length for m. rectus femoris, semitendinosus, gastrocnemius medialis, and tibialis anterior were defined from three-dimensional freehand ultrasound acquisitions. A fixed dynamometer was used to assess maximal voluntary isometric contractions for knee extension, knee flexion, plantar flexion, and dorsiflexion from which maximal joint torque (MJT) was calculated. Selective motor control (SMC) was assessed on a 5-point scale for the children with SCP. First, the anthropometrics, strength, and muscle size parameters were compared between the cohorts. Significant differences for all muscle size and strength parameters were found (p ≤ 0.003), except for joint torque per MV for the plantar flexors. Secondly, the associations of anthropometrics, muscle size, gross motor function classification system (GMFCS) level, and SMC with MJT were investigated using univariate and stepwise multiple linear regressions. The associations of MJT with growth-related parameters like age, weight, and height appeared strongest in the TD cohort, whereas for the SCP cohort, these associations were accompanied by associations with SMC and GMFCS. The stepwise regression models resulted in ranges of explained variance in MJT from 29.3 to 66.3% in the TD cohort and from 16.8 to 60.1% in the SCP cohort. Finally, the MJT deficit observed in the SCP cohort was further investigated using the TD regression equations to estimate norm MJT based on height and potential MJT based on MV. From the total MJT deficit, 22.6-57.3% could be explained by deficits in MV. This investigation confirmed the disproportional decrease in muscle size and muscle strength around the knee and ankle joint in children with SCP, but also highlighted the large variability in the contribution of muscle size to muscle weakness.
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Project description:Muscle spasticity is characterized by exaggerated stretch reflexes and affects about 85% of the children with cerebral palsy. However, the mechanisms underlying spasticity and its influence on gait are not well understood. Here, we first aimed to model the response of spastic hamstrings and gastrocnemii in children with cerebral palsy to fast passive stretches. Then, we evaluated how the model applied to gait. We developed three models based on exaggerated proprioceptive feedback. The first model relied on feedback from muscle fiber length and velocity (velocity-related model), the second model relied on feedback from muscle fiber length, velocity, and acceleration (acceleration-related model), and the third model relied on feedback from muscle force and its first time derivative (force-related model). The force-related model better reproduced measured hamstrings and gastrocnemii activity during fast passive stretches (coefficients of determination (R2): 0.73 ± 0.10 and 0.60 ± 0.13, respectively, and root mean square errors (RMSE): 0.034 ± 0.031 and 0.009 ± 0.007, respectively) than the velocity-related model (R2: 0.46 ± 0.15 and 0.07 ± 0.13, and RMSE: 0.053 ± 0.051 and 0.015 ± 0.009), and the acceleration-related model (R2: 0.47 ± 0.15 and 0.09 ± 0.14, and RMSE: 0.052 ± 0.050 and 0.015 ± 0.008). Additionally, the force-related model predicted hamstrings and gastrocnemii activity that better correlated with measured activity during gait (cross correlations: 0.82 ± 0.09 and 0.85 ± 0.06, respectively) than the activity predicted by the velocity-related model (cross correlations: 0.49 ± 0.17 and 0.71 ± 0.22) and the acceleration-related model (cross correlations: 0.51 ± 0.16 and 0.67 ± 0.20). Our results therefore suggest that force encoding in muscle spindles in combination with altered feedback gains and thresholds underlie activity of spastic muscles during passive stretches and gait. Our model of spasticity opens new perspectives for studying movement impairments due to spasticity through simulation.
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Project description:When treating children with Cerebral Palsy (CP), computational simulations based on musculoskeletal models have a great potential in assisting the clinical decision-making process towards the most promising treatments. In particular, predictive simulations could be used to predict and compare the functional outcome of a series of candidate interventions. In order to be able to benefit from these predictive simulations however, it is important to know how much information about the post-treatment patient's motor control could be gathered from data available before the intervention. Within this paper, we quantified how much of the muscle activity measured after a treatment could be explained by subject-specific muscle synergies computed from EMG data collected before the intervention. We also investigated whether generic synergies could be used, in case no EMG data is available when running predictive simulations, to reproduce both pre- and post-treatment muscle activity in children with CP. Subject-specific synergies proved to be a good indicator of the patient's post-treatment motor control, explaining on average more than 85% of the post-treatment muscle activity, compared to an average of 94% when applied to the original pre-treatment data. Generic synergies explained 84% of the pre-treatment and 83% of the post-treatment muscle activity on average, but performed relatively well for patients with low selective motor control and poorly in patients with more selectivity. Our results suggest that subject-specific muscle synergies computed from pre-treatment EMG data could be used with confidence to represent the post-treatment motor control of children with CP during walking. In addition, when performing simulations involving patients with a low selective motor control, generic synergies could be a valid alternative.
| S-EPMC7015404 | biostudies-literature
Project description:BackgroundRespiratory muscle weakness and its relation to other impairments in children with cerebral palsy (CP) have been shown in the latest studies. The effects of inspiratory muscle training (IMT) in this population have not been comprehensively investigated so far.ObjectivesTo investigate the effects of IMT on trunk control, pulmonary functions, respiratory muscle strength, daily living activities, exercise capacity and quality of life in children with CP.MethodsThis was a prospective-randomized controlled trial. Twenty-five children with CP were randomly assigned to the treatment (n=13) or the control group (n=12). The treatment group received IMT at 30% of maximal inspiratory pressure (MIP) and the control group received sham therapy (5% of MIP) for 6 weeks. Also, both groups received routine conventional physical therapy (stretching, strengthening, and functional exercises, etc.) for 6 weeks. The primary outcome measure was trunk control. Secondary outcome measures were pulmonary function, respiratory muscle strength, daily living activities, functional exercise capacity and quality of life.ResultsThe treatment group had better outcome for trunk control (3.87, 95% CI 3.72-4.02). Also, respiratory muscle strength, daily living activities, functional exercise capacity and quality of life were significantly improved in the treatment group compared with controls. No improvements were observed in the pulmonary function test scores between the groups.ConclusionInspiratory muscle training improves trunk control, respiratory muscle strength, daily living activities, functional exercise capacity and quality of life in children with CP and it can be included in the physiotherapy and rehabilitation programs.
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