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Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

ABSTRACT: Physics-based simulations of walking have the theoretical potential to support clinical decision-making by predicting the functional outcome of treatments in terms of walking performance. Yet before using such simulations in clinical practice, their ability to identify the main treatment targets in specific patients needs to be demonstrated. In this study, we generated predictive simulations of walking with a medical imaging based neuro-musculoskeletal model of a child with cerebral palsy presenting crouch gait. We explored the influence of altered muscle-tendon properties, reduced neuromuscular control complexity, and spasticity on gait dysfunction in terms of joint kinematics, kinetics, muscle activity, and metabolic cost of transport. We modeled altered muscle-tendon properties by personalizing Hill-type muscle-tendon parameters based on data collected during functional movements, simpler neuromuscular control by reducing the number of independent muscle synergies, and spasticity through delayed muscle activity feedback from muscle force and force rate. Our simulations revealed that, in the presence of aberrant musculoskeletal geometries, altered muscle-tendon properties rather than reduced neuromuscular control complexity and spasticity were the primary cause of the crouch gait pattern observed for this child, which is in agreement with the clinical examination. These results suggest that muscle-tendon properties should be the primary target of interventions aiming to restore an upright gait pattern for this child. This suggestion is in line with the gait analysis following muscle-tendon property and bone deformity corrections. Future work should extend this single case analysis to more patients in order to validate the ability of our physics-based simulations to capture the gait patterns of individual patients pre- and post-treatment. Such validation would open the door for identifying targeted treatment strategies with the aim of designing optimized interventions for neuro-musculoskeletal disorders.

SUBMITTER: Falisse A

PROVIDER: S-EPMC7040166 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

Falisse Antoine A Pitto Lorenzo L Kainz Hans H Hoang Hoa H Wesseling Mariska M Van Rossom Sam S Papageorgiou Eirini E Bar-On Lynn L Hallemans Ann A Desloovere Kaat K Molenaers Guy G Van Campenhout Anja A De Groote Friedl F Jonkers Ilse I

Frontiers in human neuroscience 20200218

Physics-based simulations of walking have the theoretical potential to support clinical decision-making by predicting the functional outcome of treatments in terms of walking performance. Yet before using such simulations in clinical practice, their ability to identify the main treatment targets in specific patients needs to be demonstrated. In this study, we generated predictive simulations of walking with a medical imaging based neuro-musculoskeletal model of a child with cerebral palsy presen ...[more]

PMID: 32132911

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Project description:Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walking to predict gait adaptations due to these deficits. We trained a planar model containing 9 degrees of freedom and 18 musculotendon actuators to walk using a custom optimization framework through which we imposed simple objectives, such as minimizing cost of transport while avoiding falling and injury, and maintaining head stability. We first generated gaits at prescribed speeds between 0.50 m/s and 2.00 m/s that reproduced experimentally observed kinematic, kinetic, and metabolic trends for walking. We then generated a gait at self-selected walking speed; quantitative comparisons between our simulation and experimental data for joint angles, joint moments, and ground reaction forces showed root-mean-squared errors of less than 1.6 standard deviations and normalized cross-correlations above 0.8 except for knee joint moment trajectories. Finally, we applied mild, moderate, and severe levels of muscle weakness or contracture to either the soleus (SOL) or gastrocnemius (GAS) or both of these major plantarflexors (PF) and retrained the model to walk at a self-selected speed. The model was robust to all deficits, finding a stable gait in all cases. Severe PF weakness caused the model to adopt a slower, "heel-walking" gait. Severe contracture of only SOL or both PF yielded similar results: the model adopted a "toe-walking" gait with excessive hip and knee flexion during stance. These results highlight how plantarflexor weakness and contracture may contribute to observed gait patterns.

Project description:BackgroundChildren with cerebral palsy (CP) show progressive loss of ambulatory function characterized by kinematic deviations at the hip, knee, and ankle. Functional electrical stimulation (FES) can lead to more typical lower limb kinematics during walking by eliciting appropriately timed muscle contractions. FES-assisted walking interventions have shown mixed to positive results in improving lower limb kinematics through immediate correction of gait during the application of FES, or long-term, persisting effects of non-FES-assisted gait improvements following multi-week FES-assisted gait training, at the absence of stimulation, i.e., neurotherapeutic effects. It is unknown, however, if children with CP will demonstrate a neurotherapeutic response following FES-assisted gait training because of the CP population's heterogeneity in gait deviations and responses to FES. Identifying the neurotherapeutic responders is, therefore, important to optimize the training interventions to those that have higher probability of benefiting from the intervention.ObjectiveThe purpose of this case study was to investigate the relationship between immediate and neurotherapeutic effects of FES-assisted walking to identify responders to a FES-assisted gait training protocol.MethodsThe primary outcome was Gait Deviation Index (GDI) and secondary outcome was root mean squared error (RMSE) of the lower extremity joint angles in the sagittal plane between participants with CP and a typically developing (TD) dataset. Potential indicators were defined as immediate improvements from baseline during FES-assisted walking followed by neurotherapeutic improvements at the end of training.Case descriptionGait analysis of two adolescent female participants with spastic diplegia (Gross Motor Function Classification System level II and III) was conducted at the start and end of a 12-week FES-assisted treadmill training protocol. Participant 1 had scissoring crouch gait, while participant 2 had jump gait.OutcomesThe GDI showed both immediate (presence of FES) and neurotherapeutic (absence of FES after training period) improvements from baseline in our two participants. Joint angle RMSE showed mixed trends between immediate and neurotherapeutic changes from baseline. The GDI warrants investigation in a larger sample to determine if it can be used to identify responders to FES-assisted gait training.

Project description:Children with unilateral cerebral palsy (CP) walk independently although with an asymmetrical, more poorly coordinated pattern compared to their peers. While gait biomechanics in unilateral CP and their alteration from those without CP have been well documented, cortical mechanisms underlying gait remain inadequately understood. To the best of our knowledge, this is the first study utilizing electroencephalography (EEG) during treadmill gait in older children with and without CP. Lower limb surface electromyographic (EMG) data were collected and muscle synergy analyses performed to quantify motor output. Our primary goal was to evaluate the relationships between cortical and muscle activation within and across groups and hemispheres to provide novel insights into neural control of gait and how it may be disrupted by an early unilateral brain injury. Participants included 9 children with unilateral CP, mean age 16.0 ± 2.7 years, and 12 with typical development (TD), mean age 14.8 ± 3.0 years. EEG data were collected during a standing baseline and treadmill walking at self-selected speed. EMG of 16 lower limb muscles were also collected bilaterally and synchronized with EEG. No significant group differences were found in synergy number or structure across groups. Six cortical clusters were identified as having gait-related activation and all contained participants from both CP and TD groups; however, the percent of individuals per group appearing in different clusters varied. Notably, the cluster least represented in CP was the non-dominant motor region. Both groups showed mu-band ERD in the motor clusters during gait although sustained beta-band ERD was not evident in TD. The CP group showed greater cortical activation than TD during walking as measured by mu- and beta-ERD in the dominant and non-dominant motor and parietal regions and elevated low gamma-activity in the frontal and parietal areas, a unique finding in CP. CP showed greater bilateral motor EEG-EMG coherence in the gamma-band with the hallucis longus compared to TD. In summary, individuals with CP display increased cortical activation during gait possibly relating to differences in distal motor control of the more affected side. Strategies that iteratively reduce cortical activation while improving selective motor control are needed in CP.

Project description:BackgroundAltered motor control is common in cerebral palsy (CP). Understanding how altered motor control affects movement and treatment outcomes is important but challenging due to complex interactions with other neuromuscular impairments. While regression can be used to examine associations between impairments and movement, causal modeling provides a mathematical framework to specify assumed causal relationships, identify covariates that may introduce bias, and test model plausibility. The goal of this research was to quantify the causal effects of altered motor control and other impairments on gait, before and after single-event multi-level orthopedic surgery (SEMLS).MethodsWe evaluated the impact of SEMLS on change in Gait Deviation Index (ΔGDI) between gait analyses. We constructed our causal model with a Directed Acyclic Graph that included the assumed causal relationships between SEMLS, ΔGDI, baseline GDI (GDIpre), baseline neurologic and orthopedic impairments (Imppre), age, and surgical history. We identified the adjustment set to evaluate the causal effect of SEMLS on ΔGDI and the impact of Imppre on ΔGDI and GDIpre. We used Bayesian Additive Regression Trees (BART) and accumulated local effects to assess relative effects.ResultsWe prospectively recruited a cohort of children with bilateral CP undergoing SEMLS (N = 55, 35 males, age: 10.5 ± 3.1 years) and identified a control cohort with bilateral CP who did not undergo SEMLS (N = 55, 30 males, age: 10.0 ± 3.4 years). There was a small positive causal effect of SEMLS on ΔGDI (1.70 GDI points). Altered motor control (i.e., dynamic and static motor control) and strength had strong effects on GDIpre, but minimal effects on ΔGDI. Spasticity and orthopedic impairments had minimal effects on GDIpre or ΔGDI.ConclusionAltered motor control did have a strong effect on GDIpre, indicating that these impairments do have a causal effect on a child's gait pattern, but minimal effect on expected changes in GDI after SEMLS. Heterogeneity in outcomes suggests there are other factors contributing to changes in gait. Identifying these factors and employing causal methods to examine the complex relationships between impairments and movement will be required to advance our understanding and care of children with CP.

Dataset Information

Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

Publications

Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

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