Personalisation of Plantarflexor Musculotendon Model Parameters in Children with Cerebral Palsy.

Neuromusculoskeletal models can be used to evaluate aberrant muscle function in cerebral palsy (CP), for example by estimating muscle and joint contact forces during gait. However, to be accurate, models should include representative musculotendon parameters. We aimed to estimate personalised parameters that capture the mechanical behaviour of the plantarflexors in children with CP and typically developing (TD) children. Ankle angle (using motion capture), torque (using a load-cell), and medial gastrocnemius fascicle lengths (using ultrasound) were measured during slow passive ankle dorsiflexion rotation for thirteen children with spastic CP and thirteen TD children. Per subject, the measured rotation was input to a scaled OpenSim model to simulate the torque and fascicle length output. Musculotendon model parameters were personalised by the best match between simulated and experimental torque-angle and fascicle length-angle curves according to a least-squares fit. Personalised tendon slack lengths were significantly longer and optimal fibre lengths significantly shorter in CP than model defaults and than in TD. Personalised tendon compliance was substantially higher in both groups compared to the model default. The presented method to personalise musculotendon parameters will likely yield more accurate simulations of subject-specific muscle mechanics, to help us understand the effects of altered musculotendon properties in CP.

MRI-based anatomical characterisation of lower-limb muscles in older women.

The ability of muscles to produce force depends, among others, on their anatomical features and it is altered by ageing-associated weakening. However, a clear characterisation of these features, highly relevant for older individuals, is still lacking. This study hence aimed at characterising muscle volume, length, and physiological cross-sectional area (PCSA) and their variability, between body sides and between individuals, in a group of post-menopausal women. Lower-limb magnetic resonance images were acquired from eleven participants (69 (7) y. o., 66.9 (7.7) kg, 159 (3) cm). Twenty-three muscles were manually segmented from the images and muscle volume, length and PCSA were calculated from this dataset. Personalised maximal isometric force was then calculated using the latter information. The percentage difference between the muscles of the two lower limbs was up to 89% and 22% for volume and length, respectively, and up to 84% for PCSA, with no recognisable pattern associated with limb dominance. Between-subject coefficients of variation reached 36% and 13% for muscle volume and length, respectively. Generally, muscle parameters were similar to previous literature, but volumes were smaller than those from in-vivo young adults and slightly higher than ex-vivo ones. Maximal isometric force was found to be on average smaller than those obtained from estimates based on linear scaling of ex-vivo-based literature values. In conclusion, this study quantified for the first time anatomical asymmetry of lower-limb muscles in older women, suggesting that symmetry should not be assumed in this population. Furthermore, we showed that a scaling approach, widely used in musculoskeletal modelling, leads to an overestimation of the maximal isometric force for most muscles. This heavily questions the validity of this approach for older populations. As a solution, the unique dataset of muscle segmentation made available with this paper could support the development of alternative population-based scaling approaches, together with that of automatic tools for muscle segmentation.

Stretching Interventions in Children With Cerebral Palsy: Why Are They Ineffective in Improving Muscle Function and How Can We Better Their Outcome?

Hyper-resistance at the joint is one of the most common symptoms in children with cerebral palsy (CP). Alterations to the structure and mechanical properties of the musculoskeletal system, such as a decreased muscle length and an increased joint stiffness are typically managed conservatively, by means of physiotherapy involving stretching exercises. However, the effectiveness of stretching-based interventions for improving function is poor. This may be due to the behavior of a spastic muscle during stretch, which is poorly understood. The main aim of this paper is to provide a mechanistic explanation as to why the effectiveness of stretching is limited in children with CP and consider clinically relevant means by which this shortcoming can be tackled. To do this, we review the current literature regarding muscle and tendon plasticity in response to stretching in children with CP. First, we discuss how muscle and tendon interact based on their morphology and mechanical properties to provide a certain range of motion at the joint. We then consider the effect of traditional stretching exercises on these muscle and tendon properties. Finally, we examine possible strategies to increase the effectiveness of stretching therapies and we highlight areas of further research that have the potential to improve the outcome of non-invasive interventions in children with cerebral palsy.

Semi-automatic methods for tracking the medial gastrocnemius muscle-tendon junction using ultrasound: a validation study.

NEW FINDINGS: What is the central question of this study? Is the proposed semi-automatic algorithm suitable for tracking the medial gastrocnemius muscle-tendon junction in ultrasound images collected during passive and active conditions? What is the main finding and its importance? The validation of a method allowing efficient tracking of the muscle-tendon junction in both passive and active conditions, in healthy as well as in pathological conditions. This method was tested in common acquisition conditions and the developed software made freely available. ABSTRACT: Clinically relevant information can be extracted from ultrasound (US) images by tracking the displacement of the junction between muscle and tendon. This paper validated automatic methods for tracking the location of muscle-tendon junction (MTJ) between the medial gastrocnemius and the Achilles tendon during passive slow and fast stretches, and active ankle rotations while walking on a treadmill. First, an automatic algorithm based on an optical flow approach was applied on collected US images. Second, results of the automatic algorithm were evaluated and corrected using a quality measure that indicated which critical images need to be manually corrected. US images from 12 typically developed (TD) children, 12 children with spastic cerebral palsy (SCP) and eight healthy adults were analysed. Automatic and semi-automatic tracking methods were compared to manual tracking using root mean square errors (RMSE). For the automatic tracking, RMSE was less than 3.1 mm for the slow stretch and 5.2 mm for the fast stretch, the worst case being for SCP. The tracking results in the fast stretch condition were improved (especially in SCP) by using the semi-automatic approach, with an RMSE reduction of about 30%. During walking, the semi-automatic method also reduced errors, with a final RMSE of 3.6 mm. In all cases, data processing was considerably shorter using the semi-automatic method (2 min) compared to manual tracking (20 min). A quick manual correction considerably improves tracking of the MTJ during gait and allows to achieve results suitable for further analyses. The proposed algorithm is freely available.

Resistance Training Combined With Stretching Increases Tendon Stiffness and Is More Effective Than Stretching Alone in Children With Cerebral Palsy: A Randomized Controlled Trial.

Aim: Stretching is often used to increase/maintain muscle length and improve joint range of motion (ROM) in children with cerebral palsy (CP). However, outcomes at the muscle (remodeling) and resulting function appear to be highly variable and often unsatisfactory. During passive joint rotation, the Achilles tendon lengthens more than the in-series medial gastrocnemius muscle in children with CP, which might explain the limited effectiveness of stretching interventions. We aimed to ascertain whether increasing tendon stiffness, by performing resistance training, improves the effectiveness of passive stretching, indicated by an increase in medial gastrocnemius fascicle length. Methods: Sixteen children with CP (Age median [IQR]: 9.6 [8.6, 10.5]) completed the study. Children were randomly assigned to a combined intervention of stretching and strengthening of the calf muscles (n = 9) or a control (stretching-only) group (n = 7). Medial gastrocnemius fascicle length at a resting ankle angle, lengthening during passive joint rotations, and tendon stiffness were assessed by combining dynamometry and ultrasound imaging. The study was registered on clinicaltrials.gov (NCT02766491). Results: Resting fascicle length and tendon stiffness increased more in the intervention group compared to the control group (median [95% CI] increase fascicle length: 2.2 [1.3, 4.3] mm; stiffness: 13.6 [9.9, 17.7] N/mm) Maximum dorsiflexion angle increased equally in both groups. Conclusion: This study provides proof of principle that a combined resistance and stretching intervention can increase tendon stiffness and muscle fascicle length in children with CP. This demonstrates that remodeling of muscle structure is possible with non-invasive interventions in spastic CP.

Medial gastrocnemius volume and echo-intensity after botulinum neurotoxin A interventions in children with spastic cerebral palsy.

AIM: This cross-sectional investigation evaluated whether recurrent botulinum neurotoxin A (BoNT-A) interventions to the medial gastrocnemius have an influence on muscle morphology, beyond Gross Motor Function Classification System (GMFCS) level. METHOD: A cohort of typically developing children (n=67; 43 males, 24 females; median age 9y 11mo [range 7y 10mo-11y 6mo]), a cohort of children with spastic cerebral palsy (CP) naive to BoNT-A interventions (No-BoNT-A; n=19; 10 males, nine females; median age 9y 3mo [range 8y 5mo-10y 10mo]) and a cohort of children with spastic CP with a minimum of three recurrent BoNT-A interventions to the medial gastrocnemius (BoNT-A; n=19; 13 males, six females; median age 9y 8mo [range 7y 3mo-10y 7mo]) were recruited. Three-dimensional freehand ultrasound was used to estimate medial gastrocnemius volume normalized to body mass and echo-intensity. RESULTS: Normalized medial gastrocnemius volume and echo-intensity significantly differed between the two spastic CP cohorts (p≤0.05), with the BoNT-A cohort having larger alterations. Associations between normalized medial gastrocnemius volume and echo-intensity were highest in the No-BoNT-A cohort, followed by the BoNT-A cohort. Multiple regression analyses revealed that both GMFCS level and BoNT-A intervention history were significantly associated with smaller normalized medial gastrocnemius volume and higher echo-intensity. INTERPRETATION: Recurrent BoNT-A interventions may induce alterations to medial gastrocnemius volume and echo-intensity beyond the natural history of the spastic CP pathology. WHAT THIS PAPER ADDS: In spastic cerebral palsy, medial gastrocnemius volumes are smaller and echo-intensities higher compared with typical development. Alterations after botulinum neurotoxin A intervention (BoNT-A) are larger than in no BoNT-A intervention. Gross Motor Function Classification System level and BoNT-A history significantly associate with medial gastrocnemius and echo-intensity alterations.

VOLUMEN DEL MÚSCULO GASTROCNEMIUS MEDIAL E INTENSIDAD DE LA ECOGRAFÍA DESPUÉS DE LA COLOCACIÓN DE NEUROTOXINA BOTULÍNICA (TIPO A), EN NIÑOS CON PARÁLISIS CEREBRAL ESPÁSTICA (PC): OBJETIVO: Esta investigación de corte transversal evaluó si la colocación recurrente de neurotoxina botulínica tipo A (BoNT-A) en el músculo gastrocnemius medial tienen una influencia en la morfología muscular, más allá del nivel del Sistema de Clasificación de la Función Motora Gruesa (GMFCS, siglas en ingles). MÉTODO: Una cohorte de niños con desarrollo tipico (n = 67; 43 varones, 24 mujeres; mediana de edad 9 años 11 meses [rango 7 años 10 meses -11 años 6 meses]), otra cohorte de niños con parálisis cerebral espástica (PC) que no habían recibido intervenciones de BoNT-A ( n = 19; 10 hombres, nueve mujeres; mediana de edad 9 años 3 meses [rango 8 años 5 meses -10 años 10 meses]) y una cohorte de niños con PC espástica con un mínimo de tres administraciones recurrentes de BoNT-A en el músculo gastrocnemius medial (BoNT-A; n = 19; 13 varones, seis mujeres; mediana de edad 9 años 8 meses [rango 7 años 3 meses - 10 años 7 meses]) fueron reclutados. Se usó ultrasonido tridimensional a mano alzada para estimar el volumen del músculo gastrocnemius medial normalizado a la masa corporal y la intensidad del eco. RESULTADOS: El volumen del músculo gastrocnemius medial normalizado y la intensidad del eco difirieron significativamente entre las dos cohortes de PC espástica (p≤0,05), la cohorte BoNT-A tuvo alteraciones mayores. Las asociaciones entre el volumen músculo gastrocnemius medial normalizado y la intensidad del eco fueron más altas en la cohorte No-BoNT-A, seguidas de la cohorte BoNT-A. Los análisis de regresión múltiple revelaron que tanto el nivel de GMFCS como el antecedente de intervención de BoNT-A se asociaron significativamente con un volumen del músculo gastrocnemius medial normalizado más pequeño y una mayor intensidad de eco. INTERPRETACIÓN: La colocación recurrentes de BoNT-A pueden inducir alteraciones en el volumen del músculo gastrocnemius medial y en la intensidad del eco más allá de la historia natural de la patología por PC espástica.

VOLUME E ECO-INTENSIDADE DO MÚSCULO GASTROCNÊMIO MEDIAL APÓS INTERVENÇÕES COM NEUROTOXINA BOTULÍNICA A EM CRIANÇAS COM PARALISIA CEREBRAL ESPÁSTICA: OBJETIVO: Esta investigação transversal avaliou se intervenções recorrentes com neurotoxina botulínica A (NTBo-A) no músculo gastrocnêmio medial têm influência na morfologia muscular, além do nível segundo o Sistema de Classificação da Função Motora Grossa (GMFCS). MÉTODO: Uma coorte de crianças com desenvolvimento típico (n=67; 43 do sexo masculino, 24 do sexo feminino; idade mediana 9a 11m [variação 7a 10m-11a 6m]), uma coorte de crianças com paralisia cerebral espástica (PC) que nunca recebeu intervenções com NTBo-A (No-NTBo-A; n=19; 10 do sexo masculino, nove do sexo feminino; idade mediana 9a 3m [variação 8a 5m-10a 10m]) e uma coorte de crianças com PC espástica com no mínimo três intervenções de NTBo-A no músculo gastrocnêmio medial (NTBo-A; n=19; 13 do sexo mascuino, seis do sexo feminino; idade mediana 9a 8m [variação 7a 3m-10a 7m]) foram recrutadas. Ultrassom tridimensional foi usado para estimar o volume do gastrocnêmio normalizado para a massa corporal e eco-intensidade. RESULTADOS: O volume normalizado e eco-intensidade do músculo gastrocnêmio medial diferiu significantemente entre as duas coortes de PC espástica (p≤0,05), com a coorte NTBo-A tendo maiores alteracões. Associações entre o volume normalizado do gastrocnêmio e eco-intensidade foram maiores na coorte No-NTBo-A, seguida pela coorte NTBo-A. Análises de regressão múltipla revelaram que tanto o nível GMFCS quanto a história de intervenção com NTBo-A foram significativamente associadas com menor volume normalizado do músculo gastrocnêmio medial e maior eco-intensidade. INTERPRETAÇÃO: Intervenções recorrentes com NTBo-A podem induzir alterações no volume e eco-intensidade do músculo gastrocnêmio medial, além da história natural da patologia da PC espástica.

The Relationship Between Medial Gastrocnemius Lengthening Properties and Stretch Reflexes in Cerebral Palsy.

Stretch reflex hyperactivity in the gastrocnemius of children with spastic cerebral palsy (CP) is commonly evaluated by passively rotating the ankle joint into dorsiflexion at different velocities, such as applied in conventional clinical spasticity assessments. However, surface electromyography (sEMG) collected from the medial gastrocnemius (MG) during such examination reveals unexplained heterogeneity in muscle activation between patients. Recent literature also highlights altered muscle tensile behavior in children with spastic CP. We aimed to document MG muscle and tendon lengthening during passive ankle motion at slow and fast velocity and explore its interdependence with the elicited hyperactive stretch reflex. The ankle of 15 children with CP (11 ± 3 years, GMFCS 9I 6II, 8 bilateral, 7 unilateral) and 16 typically developing children (TDC) was passively rotated over its full range of motion at slow and fast velocity. Ultrasound, synchronized with motion-analysis, was used to track the movement of the MG muscle-tendon junction and extract the relative lengthening of muscle and tendon during joint rotation. Simultaneously, MG sEMG was measured. Outcome parameters included the angular and muscle lengthening velocities 30 ms before EMG onset and the gain in root mean square EMG during stretch, as a measure of stretch reflex activity. Compared to slow rotation, the muscle lengthened less and stretch reflex activity was higher during fast rotation. These velocity-induced changes were more marked in CP compared to TDC. In the CP group, muscle-lengthening velocity had higher correlation coefficients with stretch reflex hyperactivity than joint angular velocity. Muscles with greater relative muscle lengthening during slow rotation had earlier and stronger stretch reflexes during fast rotation. These initial results suggest that ankle angular velocity is not representative of MG muscle lengthening velocity and is less related to stretch reflex hyperactivity than MG muscle lengthening. In addition, muscles that lengthened more during slow joint rotation were more likely to show a velocity-dependent stretch reflex. This interdependence of muscle lengthening and stretch reflexes may be important to consider when administering treatment. However, muscle and tendon lengthening properties alone could not fully explain the variability in stretch reflexes, indicating that other factors should also be investigated.

Medial Gastrocnemius Muscle-Tendon Junction and Fascicle Lengthening across the Range of Motion Analyzed in 2-D and 3-D Ultrasound Images.

Ultrasound imaging modalities offer a clinically viable method to visualize musculoskeletal structures. However, proper data comparison between investigations is compromised because of a lack of measurement error documentation and method standardization. This investigation analyzes the reliability and validity of extracting medial gastrocnemius belly and fascicle lengths and pennation angles in different ankle joint positions, across the full range of motion, in a cohort of 11 children with spastic cerebral palsy and 11 typically developed children. Each of these parameters was extracted from two consecutive acquisitions, using both 2-D and 3-D ultrasound images. The findings suggest that the muscle tendon junction extraction in 2-D images can be a suitable parameter for analyzing medial gastrocnemius muscle length in typically developed children and children with spastic cerebral palsy, although averaging over multiple measurements is recommended to reduce variability. More caution should be taken when performing analyses based on fascicle length.

Muscle and tendon lengthening behaviour of the medial gastrocnemius during ankle joint rotation in children with cerebral palsy.

NEW FINDINGS: What is the central question of this study? Which structures of the medial gastrocnemius muscle-tendon unit contribute to its lengthening during joint rotation and thus receive the stretching stimulus? What is the main finding and its importance? We show, for the first time, that muscle and tendon lengthen in a different manner in children with cerebral palsy compared with typically developing children during a similar amount of muscle-tendon unit lengthening or joint rotation. This indicates possible differences in mechanical muscle and tendon properties attributable to cerebral palsy, which are not evident by assessment of muscle function at the level of a joint. ABSTRACT: Children with cerebral palsy (CP) commonly present with reduced ankle range of motion (ROM) attributable, in part, to changes in mechanical properties of the muscle-tendon unit (MTU). Detailed information about how muscle and tendon interact to contribute to joint rotation is currently lacking but might provide essential information to explain the limited effectiveness of stretching interventions in children with CP. The purpose of this study was to quantify which structures contribute to MTU lengthening and thus receive the stretch during passive ankle joint rotation. Fifteen children with CP (age, in mean ± SD, 11.4 ± 3 years) and 16 typically developing (TD) children (age, in mean ± SD, 10.2 ± 3 years) participated. Ultrasound was combined with motion tracking, joint torque and EMG to record fascicle, muscle and tendon lengthening of the medial gastrocnemius during passive ankle joint rotations over the full ROM and a common ROM. In children with CP, relative to MTU lengthening, muscle and fascicles lengthened less (CP, 50.4% of MTU lengthening; TD, 63% of MTU lengthening; P < 0.04) and tendon lengthened more (CP, 49.6% of MTU lengthening; TD, 37% of MTU lengthening; P < 0.01) regardless of the ROM studied. Differences between groups in the amount of lengthening of the underlying structures during a similar amount of joint rotation and MTU displacement indicate possible differences in tissue mechanical properties attributable to CP, which are not evident by assessment at the level of a joint. These factors should be considered when assessing and treating muscle function in children with CP, for example during stretching exercises, because the muscle might not receive much of the applied lengthening stimulus.

Medial gastrocnemius muscle stiffness cannot explain the increased ankle joint range of motion following passive stretching in children with cerebral palsy.

NEW FINDINGS: What is the central question of this study? Can the increased range of motion seen acutely after stretching in children with cerebral palsy be explained by changes in the stiffness of the medial gastrocnemius fascicles? What is the main finding and its importance? We show, for the first time, that passive muscle and tendon properties are not changed acutely after a single bout of stretching in children with cerebral palsy and, therefore, do not contribute to the increase in range of motion. This contradicts common belief and what happens in healthy adults. ABSTRACT: Stretching is often used to increase or maintain the joint range of motion (ROM) in children with cerebral palsy (CP), but the effectiveness of these interventions is limited. Therefore, our aim was to determine the acute changes in muscle-tendon lengthening properties that contribute to increased ROM after a bout of stretching in children with CP. Eleven children with spastic CP [age 12.1 (3 SD) years, 5/6 hemiplegia/diplegia, 7/4 gross motor function classification system level I/II] participated. Each child received three sets of five × 20 s passive, manual static dorsiflexion stretches separated by 30 s rest, with 60 s rest between sets. Before and immediately after stretching, ultrasound was used to measure medial gastrocnemius fascicle lengthening continuously over the full ROM and an individual common ROM pre- to post-stretching. Simultaneously, three-dimensional motion of two marker clusters on the shank and the foot was captured to calculate ankle angle, and ankle joint torque was calculated from manually applied torques and forces on a six degrees-of-freedom load cell. After stretching, the ROM was increased [by 9.9 (12.0) deg, P = 0.005]. Over a ROM common to both pre- and post-measurements, there were no changes in fascicle lengthening or torque. The maximal ankle joint torque tolerated by the participants increased [by 2.9 (2.4) N m, P = 0.003], and at this highest passive torque the maximal fascicle length was 2.8 (2.4) mm greater (P = 0.009) when compared with before stretching. These results indicate that the stiffness of the muscle fascicles in children with CP remains unaltered by an acute bout of stretching.

Achilles tendon moment arm length is smaller in children with cerebral palsy than in typically developing children.

When studying muscle and whole-body function in children with cerebral palsy (CP), knowledge about both internal and external moment arms is essential since they determine the mechanical advantage of a muscle over an external force. Here we asked if Achilles tendon moment arm (MAAT) length is different in children with CP and age-matched typically developing (TD) children, and if MAAT can be predicted from anthropometric measurements. Sixteen children with CP (age: 10y 7m±3y, 7 hemiplegia, 12 diplegia, GMFCS level: I (11) and II (8)) and twenty TD children (age: 10y 6m±3y) participated in this case-control study. MAAT was calculated at 20° plantarflexion by differentiating calcaneus displacement with respect to ankle angle. Seven anthropometric variables were measured and related to MAAT. We found normalized MAAT to be 15% (∼7mm) smaller in children with CP compared to TD children (p=0.003). MAAT could be predicted by all anthropometric measurements with tibia length explaining 79% and 72% of variance in children with CP and TD children, respectively. Our findings have important implications for clinical decision making since MAAT influences the mechanical advantage about the ankle, which contributes to movement function and is manipulated surgically.

Neural Adaptations Associated with Interlimb Transfer in a Ballistic Wrist Flexion Task.

Cross education is the process whereby training of one limb gives rise to increases in the subsequent performance of its opposite counterpart. The execution of many unilateral tasks is associated with increased excitability of corticospinal projections from primary motor cortex (M1) to the opposite limb. It has been proposed that these effects are causally related. Our aim was to establish whether changes in corticospinal excitability (CSE) arising from prior training of the opposite limb determine levels of interlimb transfer. We used three vision conditions shown previously to modulate the excitability of corticospinal projections to the inactive (right) limb during wrist flexion movements performed by the training (left) limb. These were: (1) mirrored visual feedback of the training limb; (2) no visual feedback of either limb; and (3) visual feedback of the inactive limb. Training comprised 300 discrete, ballistic wrist flexion movements executed as rapidly as possible. Performance of the right limb on the same task was assessed prior to, at the mid point of, and following left limb training. There was no evidence that variations in the excitability of corticospinal projections (assessed by transcranial magnetic stimulation (TMS)) to the inactive limb were associated with, or predictive of, the extent of interlimb transfer that was expressed. There were however associations between alterations in muscle activation dynamics observed for the untrained limb, and the degree of positive transfer that arose from training of the opposite limb. The results suggest that the acute adaptations that mediate the bilateral performance gains realized through unilateral practice of this ballistic wrist flexion task are mediated by neural elements other than those within M1 that are recruited at rest by single-pulse TMS.