Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging.

Computer models that estimate the force generation capacity of lower limb muscles have become widely used to simulate the effects of musculoskeletal surgeries and create dynamic simulations of movement. Previous lower limb models are based on severely limited data describing limb muscle architecture (i.e., muscle fiber lengths, pennation angles, and physiological cross-sectional areas). Here, we describe a new model of the lower limb based on data that quantifies the muscle architecture of 21 cadavers. The model includes geometric representations of the bones, kinematic descriptions of the joints, and Hill-type models of 44 muscle-tendon compartments. The model allows calculation of muscle-tendon lengths and moment arms over a wide range of body positions. The model also allows detailed examination of the force and moment generation capacities of muscles about the ankle, knee, and hip and is freely available at www.simtk.org.

Skeletal muscle architecture is defined as the arrangement of fibers in a muscle and functionally defines performance capacity. Architectural values are used to model muscle-joint behavior and to make surgical decisions. The two most extensively used human lower extremity data sets consist of five total specimens of unknown size, gender, and age. Therefore, it is critically important to generate a high-fidelity human lower extremity muscle architecture data set. We disassembled 27 muscles from 21 human lower extremities to characterize muscle fiber length and physiologic cross-sectional area, which define the excursion and force-generating capacities of a muscle. Based on their architectural features, the soleus, gluteus medius, and vastus lateralis are the strongest muscles, whereas the sartorius, gracilis, and semitendinosus have the largest excursion. The plantarflexors, knee extensors, and hip adductors are the strongest muscle groups acting at each joint, whereas the hip adductors and hip extensors have the largest excursion. Contrary to previous assertions, two-joint muscles do not necessarily have longer fibers than single-joint muscles as seen by the similarity of knee flexor and extensor fiber lengths. These high-resolution data will facilitate the development of more accurate musculoskeletal models and challenge existing theories of muscle design; we believe they will aid in surgical decision making.

The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property thathas clinical manifestations and alters muscle function. Here, we review the structure, composition, and mechanical properties of skeletal muscle ECM, describe the cells that contribute to the maintenance of the ECM and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure-function relationships. Detailed structure-function relationships of the ECM have yet to be defined and, as a result, we propose areas for future studies.

Non-technical summary Muscle spasticity, due to an upper motoneuron lesion, often leads to muscle contractures that limit range of motion and cause increased muscle stiffness. However, the elements responsible for this muscle adaption are unknown. Here we show that muscle tissue is stiffer in contracture compared to age-matched children, implicating the extracellular matrix (ECM). However, titin, the major load-bearing protein within muscle fibres, is not altered in contracture, and individual fibre stiffness is unaltered. Increased ECM stiffness is even more functionally significant given our finding of long in vivo sarcomeres which leads to much larger in vivo forces in muscle contracture. These results may lead to novel therapeutics for treating spastic muscle contracture.Abstract Cerebral palsy (CP) results from an upper motoneuron (UMN) lesion in the developing brain. Secondary to the UMN lesion, which causes spasticity, is a pathological response by musclenamely, contracture. However, the elements within muscle that increase passive mechanical stiffness, and therefore result in contracture, are unknown. Using hamstring muscle biopsies from pediatric patients with CP (n = 33) and control (n = 19) patients we investigated passive mechanical properties at the protein, cellular, tissue and architectural levels to identify the elements responsible for contracture. Titin isoform, the major load-bearing protein within muscle cells, was unaltered in CP. Correspondingly, the passive mechanics of individual muscle fibres were not altered. However, CP muscle bundles, which include fibres in their constituent ECM, were stiffer than control bundles. This corresponded to an increase in collagen content of CP muscles measured by hydroxyproline assay and observed using immunohistochemistry. In vivo sarcomere length of CP muscle measured during surgery was significantly longer than that predicted for control muscle. The combination of increased tissue stiffness and increased sarcomere length interact to increase stiffness greatly of the contracture tissue in vivo. These findings provide evidence that contracture formation is not the result of stiffening at the cellular level, but stiffening of the ECM with increased collagen and an increase of in vivo sarcomere length leading to higher passive stresses.