Neuro-musculoskeletal simulation of instrumented contracture and spasticity assessment in children with cerebral palsy

BACKGROUND: Increased resistance in muscles and joints is an important phenomenon in patients with cerebral palsy (CP), and is caused by a combination of neural (e.g. spasticity) and non-neural (e.g. contracture) components. The aim of this study was to simulate instrumented, clinical assessment of the hamstring muscles in CP using a conceptual model of contracture and spasticity, and to determine to what extent contracture can be explained by altered passive muscle stiffness, and spasticity by (purely) velocity-dependent stretch reflex. METHODS: Instrumented hamstrings spasticity assessment was performed on 11 children with CP and 9 typically developing children. In this test, the knee was passively stretched at slow and fast speed, and knee angle, applied forces and EMG were measured. A dedicated OpenSim model was created with motion and muscles around the knee only. Contracture was modeled by optimizing the passive muscle stiffness parameters of vasti and hamstrings, based on slow stretch data. Spasticity was modeled using a velocity-dependent feedback controller, with threshold values derived from experimental data and gain values optimized for individual subjects. Forward dynamic simulations were performed to predict muscle behavior during slow and fast passive stretches. RESULTS: Both slow and fast stretch data could be successfully simulated by including subject-specific levels of contracture and, for CP fast stretches, spasticity. The RMS errors of predicted knee motion in CP were 1.1 ± 0.9° for slow and 5.9 ± 2.1° for fast stretches. CP hamstrings were found to be stiffer compared with TD, and both hamstrings and vasti were more compliant than the original generic model, except for the CP hamstrings. The purely velocity-dependent spasticity model could predict response during fast passive stretch in terms of predicted knee angle, muscle activity, and fiber length and velocity. Only sustained muscle activity, independent of velocity, was not predicted by our model. CONCLUSION: The presented individually tunable, conceptual model for contracture and spasticity could explain most of the hamstring muscle behavior during slow and fast passive stretch. Future research should attempt to apply the model to study the effects of spasticity and contracture during dynamic tasks such as gait. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12984-016-0170-5) contains supplementary material, which is available to authorized users

Understanding skeletal muscle in cerebral palsy: a path to personalized medicine?

Until recently, there has been little interest in understanding the intrinsic features associated with the pathomorphology of skeletal muscle in cerebral palsy (CP). Coupled with emerging evidence that challenges the role of spasticity as a determinant of gross motor function and in the development of fixed muscle contractures, it has become increasingly important to further elucidate the underlying mechanisms responsible for muscle alterations in CP. This knowledge can help clinicians to understand and apply treatment modalities that take these aspects into account. Thus, the inherent heterogeneity of the CP phenotype allows for the potential of personalized medicine through the understanding of muscle pathomorphology on an individual basis and tailoring treatment approaches accordingly. This review aims to summarize recent developments in the understanding of CP muscle and their relationship to musculoskeletal manifestations, in addition to proposing a treatment paradigm that incorporates this new knowledge

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch

BACKGROUND AND PURPOSE: To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. METHODS: During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. RESULTS: The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. CONCLUSIONS: A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.status: publishe

Human fetal amino acid metabolism at term gestation

Background: Knowledge on human fetal amino acid (AA) metabolism, largely lacking thus far, is pivotal in improving nutritional strategies for prematurely born infants. Phenylalanine kinetics is of special interest as is debate as to whether neonates will adequately hydroxylate phenylalanine to the semiessential AA tyrosine. Objective: Our aim was to quantify human fetal phenylalanine and tyrosine metabolism. Design: Eight fasted, healthy, pregnant women undergoing elective cesarean delivery at term received primed continuous stable-isotope infusions of [1-C-13] phenylalanine and [ring-D-4] tyrosine starting before surgery. Umbilical blood flow was measured by ultrasound. Maternal and umbilical cord blood was collected and analyzed by gas chromatography-mass spectrometry for phenylalanine and tyrosine enrichments and concentrations. Data are expressed as medians (25th-75th percentile). Results: Women were in a catabolic state for which net fetal AA uptake was responsible for >= 25%. Maternal and fetal hydroxylation rates were 2.6 (2.2-2.9) and 7.5 (6.2-15.5) mu mol phenylalanine/(kg.h), respectively. Fetal protein synthesis rates were higher than breakdown rates: 92 (84-116) and 73 (68-87) lmol phenylalanine/(kg.h), respectively, which indicated an anabolic state. The median metabolized fraction of available phenylalanine and tyrosine in the fetuswas < 20% for both AAs. Conclusions: At term gestation, fetuses still show considerable net AA uptake and AA accretion [converted to tissue approximate to 12 g/(kg.d)]. The low metabolic uptake (AA usage) implies a very large nutritional reserve capacity of nutrients delivered through the umbilical cord. Fetuses at term are quite capable of hydroxylating phenylalanine to tyrosine. Am J Clin Nutr 2009; 89: 153-60