Background: Musculoskeletal modelling is used to assess musculoskeletal loading during gait. Linear scaling methods are used to personalize generic models to each participant's anthropometry. This approach introduces simplifications, especially when used in paediatric and/or pathological populations. This study aimed to compare results from musculoskeletal simulations using various models ranging from linear scaled to highly subject-specific models, i.e., including the participant's musculoskeletal geometry and electromyography data. Methods: Magnetic resonance images (MRI) and gait data of one typically developing child and three children with cerebral palsy were analysed. Musculoskeletal simulations were performed to calculate joint kinematics, joint kinetics, muscle forces and joint contact forces using four modelling frameworks: 1) Generic-scaled model with static optimization, 2) Generic-scaled model with an electromyography-informed approach, 3) MRI-based model with static optimization, and 4) MRI-based model with an electromyography-informed approach. Findings: Root-mean-square-differences in joint kinematics and kinetics between generic-scaled and MRI-based models were below 5° and 0.15 Nm/kg, respectively. Root-mean-square-differences over all muscles was below 0.2 body weight for every participant. Root-mean-square-differences in joint contact forces between the different modelling frameworks were up to 2.2 body weight. Comparing the simulation results from the typically developing child with the results from the children with cerebral palsy showed similar root-mean-square-differences for all modelling frameworks. Interpretation: In our participants, the impact of MRI-based models on joint contact forces was higher than the impact of including electromyography. Clinical reasoning based on overall root-mean-square-differences in musculoskeletal simulation results between healthy and pathological participants are unlikely to be affected by the modelling choice.

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.

Background:Children with cerebral palsy (CP) present with a pathological gait pattern due to musculoskeletal impairments, such as muscle weakness and altered bony geometry. However, the effect of these impairments on gait performance is still unknown. Research aim:This study aimed to explore the effect of hip muscle weakness and femoral deformities on the gait performance of CP and typical developing (TD) subjects. Methods:6400 musculoskeletal models were created by weakening the hip extensors, abductors, adductors and flexors from 0% to 75 % and increasing the femoral anteversion angle (FAA) and neck shaft angle (NSA) from 20° to 60° and 120° to 160°, respectively. One TD and five CP gait patterns were imposed to each model and muscle forces were calculated. The effect of weakness and bony deformities on the capability gap (CG) at the hip, i.e. the lack in hip moment generating capacity to perform the gait pattern, was investigated using regression analysis. Results:The CG of apparent equinus, stiff knee gait, TD gait, jump gait and true equinus increased with 0.080, 0.038, 0.015, 0.023 and 0.005 Nm/kg per 10 percent hip abductor weakness increase, with 0.211, 0.130, 0.056, 0.045 and 0.011 Nm/kg per 10 degrees FAA increase and with 0.163, 0.080, 0.036, 0.043 and 0.011 Nm/kg per 10 degrees NSA increase, respectively. Combined weakness and bony deformities explained 96 %, 85 %, 82 %, 65 %, 40 % and 35 % of the variance in the CG of apparent equinus, TD gait, stiff knee gait, jump gait, true equinus and crouch gait, respectively. Significance:The results suggest that surgical correction of femoral deformities is more likely to be effective than strength training of hip muscles in enhancing CP gait performance. Jump gait, true equinus and especially crouch were more robust, while apparent equinus and stiff knee gait were limited by hip weakness and femoral deformities.

Background: Children with cerebral palsy (CP) present altered gait patterns and electromyography (EMG) activity compared to typically developing children. To temporarily reduce muscular activity and to correct the abnormal muscle force balance, Botulinum Toxin type A (BTX-A) injections are used. Research question: What is the effect of BTX-A injections on dynamic muscle forces during gait, when calculated using an EMG-constrained approach?. Methods: Retrospective data of ten typically developing (TD) and fourteen children with spastic diplegic CP were used for musculoskeletal modeling and dynamic simulations of gait, before and after BTX-A treatment. Individual muscle forces were calculated using an EMG-constrained optimization, in which EMG of eight muscles was used as muscle excitation signal to constrain the muscle activation patterns. Paired t-tests were used to compare average modelled muscle forces in different phases of the gait cycle pre- and post-BTX-A, summarized in the muscle profile score. Two-sample t-tests were used to determine significant differences between TD and pre- and post-BTX-A modelled muscle forces. Results: For most muscles, the force was decreased in CP compared to TD children in all phases of the gait cycle, both before and after BTX-A treatment. Differences in muscle forces before and after BTX-A treatment were limited, with only few significant differences between pre- and post-BTX-A. Compared to a standard static optimization approach, imposing the EMG activity increased modelled muscle forces for most muscles. Significance: Our findings indicate that BTX-A treatment has a limited effect on the muscle balance in CP children. Besides that, the use of EMG-constrained optimization is recommended when studying muscle balance in children with CP.

Multi-scale simulations, combining muscle and joint contact force (JCF) from musculoskeletal simulations with adaptive mechanobiological finite element analysis, allow to estimate musculoskeletal loading and predict femoral growth in children. Generic linearly scaled musculoskeletal models are commonly used. This approach, however, neglects subject- and age-specific musculoskeletal geometry, e.g. femoral neck-shaft angle (NSA) and anteversion angle (AVA). This study aimed to evaluate the impact of proximal femoral geometry, i.e. altered NSA and AVA, on hip JCF and femoral growth simulations. Musculoskeletal models with NSA ranging from 120° to 150° and AVA ranging from 20° to 50° were created and used to calculate muscle and hip JCF based on the gait analysis data of a typically developing child. A finite element model of a paediatric femur was created from magnetic resonance images. The finite element model was morphed to the geometries of the different musculoskeletal models and used for mechanobiological finite element analysis to predict femoral growth trends. Our findings showed that hip JCF increase with increasing NSA and AVA. Furthermore, the orientation of the hip JCF followed the orientation of the femoral neck axis. Consequently, the osteogenic index, which is a function of cartilage stresses and defines the growth rate, barely changed with altered NSA and AVA. Nevertheless, growth predictions were sensitive to the femoral geometry due to changes in the predicted growth directions. Altered NSA had a bigger impact on the growth results than altered AVA. Growth simulations based on mechanobiological principles were in agreement with reported changes in paediatric populations.

Background: Many patients with cerebral palsy present a pathologic gait pattern, which presumably induces aberrant musculoskeletal loading that interferes with natural bone growth, causing bone deformations on the long term. Botulinum toxin interventions and single-event multilevel surgeries are used to restore the gait pattern, assuming that a normal gait pattern restores musculoskeletal loading and thus prevents further bone deformation. However, it is unknown if these interventions are able to restore musculoskeletal loading. Hence, we investigated the impact of botulinum toxin injections and single-event multilevel surgery on musculoskeletal loading. Methods: Gait data collected in 93 children with bilateral cerebral palsy, which included pre- and post multi-level botulinum toxin (49 children) and single-event multilevel surgery (44 children) assessments, and 15 typically developing children were retrospectively processed using a musculoskeletal modelling workflow to calculate joint angles, moments, muscle and joint contact force magnitudes and orientations. Differences from the typically developing waveform were expressed by a root-mean square difference were compared using paired t-tests for each intervention separately (alpha <0.05). Findings: Botulinum toxin induced significant changes in the joint angles, but did not improve the muscle and joint contact forces. Single-event multilevel surgery induced significant kinematic and kinetic changes, which were associated with improved muscle and joint contact forces. Interpretation: The present results indicate that botulinum toxin injections were not able to restore normal gait kinematics nor musculoskeletal loading, whereas single-event multilevel surgery did successfully restore both. Therefore, single-event multilevel surgery might be protective against the re-occurrence of bone deformation on the longer term.

Gait deficits in cerebral palsy (CP) are often treated with a single-event multi-level surgery (SEMLS). Selecting the treatment options (combination of bony and soft tissue corrections) for a specific patient is a complex endeavor and very often treatment outcome is not satisfying. A deterioration in 22.8% of the parameters describing gait performance has been reported and there is need for additional surgery in 11% of the patients. Computational simulations based on musculoskeletal models that allow clinicians to test the effects of different treatment options before surgery have the potential to drastically improve treatment outcome. However, to date, no such simulation and modeling method is available. Two important challenges are the development of methods to include patient-specific neuromechanical impairments into the models and to simulate the effect of different surgical procedures on post-operative gait performance. Therefore, we developed the SimCP framework that allows the evaluation of the effect of different simulated surgeries on gait performance of a specific patient and includes a graphical user interface (GUI) that enables performing virtual surgery on the models. We demonstrated the potential of our framework for two case studies. Models reflecting the patient-specific musculoskeletal geometry and muscle properties are generated based solely on data collected before the treatment. The patient's motor control is described based on muscle synergies derived from pre-operative EMG. The GUI is then used to modify the musculoskeletal properties according to the surgical plan. Since SEMLS does not affect motor control, the same motor control model is used to define gait performance pre- and post-operative. We use the capability gap (CG), i.e., the difference between the joint moments needed to perform healthy walking and the joint moments the personalized model can generate, to quantify gait performance. In both cases, the CG was smaller post- then pre-operative and this was in accordance with the measured change in gait kinematics after treatment.

Background: Selective dorsal rhizotomy aims to reduce spasticity in children with cerebral palsy. Early investigations indicated postoperative weakness, whereas more recent studies showed that selective dorsal rhizotomy either does not change or improves muscle strength. All previous studies assessed muscle strength in a static position, which did not represent the walking situation. The aim of this study was to analyze the influence of selective dorsal rhizotomy on muscle forces during gait. Methods: Motion capture data of 25 children with spastic cerebral palsy and 10 typically developing participants were collected. A musculoskeletal OpenSim model was used to calculate joint kinematics, joint kinetics and muscle forces during gait. Static optimization and an electromyography-informed approach to calculate muscle forces were compared. A Muscle-Force-Profile was introduced and used to compare the muscle forces during walking before and after a selective dorsal rhizotomy. Findings: Independent of the approach used (electromyography-informed versus static optimization), selective dorsal rhizotomy significantly normalized forces in spastic muscles during walking and did not reduce the contribution of non-spastic muscles. Interpretation: This study showed that selective dorsal rhizotomy improves dynamic muscle forces in children with cerebral palsy and leads to less gait pathology, as shown in the improvement in joint kinematics and joint kinetics. Individual muscle force analyses using the Muscle-Force-Profile extend standard joint kinematics and joint moment analyses, which might improve clinical-decision making in children with cerebral palsy in the future. The reference data of our participants and MATLAB code for the Muscle-Force-Profile are publicly available on simtk.org/projects/muscleprofile.