Magnetic Resonance Assessment of Hypertrophic and Pseudo-Hypertrophic Changes in Lower Leg Muscles of Boys with Duchenne Muscular Dystrophy and Their Relationship to Functional Measurements

Introduction

The primary objectives of this study were to evaluate contractile and non-contractile content of lower leg muscles of boys with Duchenne muscular dystrophy (DMD) and determine the relationships between non-contractile content and functional abilities.

Methods

Lower leg muscles of thirty-two boys with DMD and sixteen age matched unaffected controls were imaged. Non-contractile content, contractile cross sectional area and non-contractile cross sectional area of lower leg muscles (tibialis anterior, extensor digitorum longus, peroneal, medial gastrocnemius and soleus) were assessed by magnetic resonance imaging (MRI). Muscle strength, timed functional tests and the Brooke lower extremity score were also assessed.

Results

Non-contractile content of lower leg muscles (peroneal, medial gastrocnemius, and soleus) was significantly greater than control group (p<0.05). Non-contractile content of lower leg muscles correlated with Brooke score (r_s = 0.64-0.84) and 30 feet walk (r_s = 0.66-0.80). Dorsiflexor (DF) and plantarflexor (PF) specific torque was significantly different between the groups.

Discussion

Overall, non-contractile content of the lower leg muscles was greater in DMD than controls. Furthermore, there was an age dependent increase in contractile content in the medial gastrocnemius of boys with DMD. The findings of this study suggest that T₁ weighted MR images can be used to monitor disease progression and provide a quantitative estimate of contractile and non-contractile content of tissue in children with DMD.     

Foot center of pressure manipulation and gait therapy influence lower limb muscle activation in patients with osteoarthritis of the knee

Background

Foot center of pressure (COP) manipulation has been associated with improved gait patterns. The purpose of this study was to determine lower limb muscle activation changes in knee osteoarthritis patients, both immediately after COP manipulation and when COP manipulation was combined with continuous gait therapy (AposTherapy).

Methods

Fourteen females with medial compartment knee osteoarthritis underwent EMG analyzes of key muscles of the leg. In the initial stage, trials were carried out at four COP positions. Following this, gait therapy was initiated for 3 months. The barefoot EMG was compared before and after therapy.

Results

The average EMG varied significantly with COP in at least one phase of stance in all examined muscles of the less symptomatic leg and in three muscles of the more symptomatic leg. After training, a significant increase in average EMG was observed in most muscles. Most muscles of the less symptomatic leg showed significantly increased peak EMG. Activity duration was shorter for all muscles of the less symptomatic leg (significant in the lateral gastrocnemius) and three muscles of the more symptomatic leg (significant in the biceps femoris). These results were associated with reduced pain, increased function and improved spatiotemporal parameters.

Conclusions

COP manipulation influences the muscle activation patterns of the leg in patients with knee osteoarthritis. When combined with a therapy program, muscle activity increases and activity duration decreases.     

TEAD1-dependent expression of the FoxO3a gene in mouse skeletal muscle

Background  

TEAD1 (TEA domain family member 1) is constitutively expressed in cardiac and skeletal muscles. It acts as a key molecule of muscle development, and trans-activates multiple target genes involved in cell proliferation and differentiation pathways. However, its target genes in skeletal muscles, regulatory mechanisms and networks are unknown.     

Precocious Locomotor Behavior Begins in the Egg: Development of Leg Muscle Patterns for Stepping in the Chick

Background

The chicken is capable of adaptive locomotor behavior within hours after hatching, yet little is known of the processes leading to this precocious skill. During the final week of incubation, chick embryos produce distinct repetitive limb movements that until recently had not been investigated. In this study we examined the leg muscle patterns at 3 time points as development of these spontaneous movements unfolds to determine if they exhibit attributes of locomotion reported in hatchlings. We also sought to determine whether the deeply flexed posture and movement constraint imposed by the shell wall modulate the muscle patterns.

Methodology/Principal Findings

Synchronized electromyograms for leg muscles, force and video were recorded continuously from embryos while in their naturally flexed posture at embryonic day (E) 15, E18 and E20. We tested for effects of leg posture and constraint by removing shell wall anterior to the foot. Results indicated that by E18, burst onset time distinguished leg muscle synergists from antagonists across a 10-fold range in burst frequencies (1–10 Hz), and knee extensors from ankle extensors in patterns comparable to locomotion at hatching. However, burst durations did not scale with step cycle duration in any of the muscles recorded. Despite substantially larger leg movements after shell removal, the knee extensor was the only muscle to vary its activity, and extensor muscles often failed to participate. To further clarify if the repetitive movements are likely locomotor-related, we examined bilateral coordination of ankle muscles during repetitive movements at E20. In all cases ankle muscles exhibited a bias for left/right alternation.

Conclusions/Significance

Collectively, the findings lead us to conclude that the repetitive leg movements in late stage embryos are locomotor-related and a fundamental link in the establishment of precocious locomotor skill. The potential importance of differences between embryonic and posthatching locomotion is discussed.     

Development of mandibular,hyoid and hypobranchial muscles in the zebrafish: homologies and evolution of these muscles within bony fishes and tetrapods

Background  

During vertebrate head evolution, muscle changes accompanied radical modification of the skeleton. Recent studies have suggested that muscles and their innervation evolve less rapidly than cartilage. The freshwater teleostean zebrafish (Danio rerio) is the most studied actinopterygian model organism, and is sometimes taken to represent osteichthyans as a whole, which include bony fishes and tetrapods. Most work concerning zebrafish cranial muscles has focused on larval stages. We set out to describe the later development of zebrafish head muscles and compare muscle homologies across the Osteichthyes.     

Neuromuscular organization and aminergic modulation of contractions in the Drosophila ovary

Background  

The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies.     

The influence of the <Emphasis Type="Italic">PRKAG3</Emphasis> mutation on glycogen,enzyme activities and fibre types in different skeletal muscles of exercise trained pigs

Background  

AMP-activated protein kinase (AMPK) plays an important role in the regulation of glucose and lipid metabolism in skeletal muscle. Many pigs of Hampshire origin have a naturally occurring dominant mutation in the AMPK γ3 subunit. Pigs carrying this PRKAG3 (R225Q) mutation have, compared to non-carriers, higher muscle glycogen levels and increased oxidative capacity in m. longissimus dorsi, containing mainly type II glycolytic fibres. These metabolic changes resemble those seen when muscles adapt to an increased physical activity level. The aim was to stimulate AMPK by exercise training and study the influence of the PRKAG3 mutation on metabolic and fibre characteristics not only in m. longissimus dorsi, but also in other muscles with different functions.     

Assembly of the giant protein projectin during myofibrillogenesis in <Emphasis Type="Italic">Drosophila</Emphasis> indirect flight muscles

Background  

Projectin is a giant modular protein of Drosophila muscles and a key component of the elastic connecting filaments (C-filaments), which are involved in stretch activation in insect Indirect Flight Muscles. It is comparable in its structure to titin, which has been implicated as a scaffold during vertebrate myofibrillogenesis.     

Chromosome 4q;10q translocations; Comparison with different ethnic populations and FSHD patients

Background  

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by the weakness of facial, shoulder-girdle and upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated 3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous KpnI repeats, and inter-chromosomal translocation has been reported.     

Characterisation of the role of Vrp1 in cell fusion during the development of visceral muscle of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

In Drosophila muscle cell fusion takes place both during the formation of the somatic mesoderm and the visceral mesoderm, giving rise to the skeletal muscles and the gut musculature respectively. The core process of myoblast fusion is believed to be similar for both organs. The actin cytoskeleton regulator Verprolin acts by binding to WASP, which in turn binds to the Arp2/3 complex and thus activates actin polymerization. While Verprolin has been shown to be important for somatic muscle cell fusion, the function of this protein in visceral muscle fusion has not been determined.     

<Emphasis Type="Italic">Troponin T</Emphasis> isoform expression is modulated during Atlantic Halibut metamorphosis

Background  

Flatfish metamorphosis is a thyroid hormone (TH) driven process which leads to a dramatic change from a symmetrical larva to an asymmetrical juvenile. The effect of THs on muscle and in particular muscle sarcomer protein genes is largely unexplored in fish. The change in Troponin T (TnT), a pivotal protein in the assembly of skeletal muscles sarcomeres and a modulator of calcium driven muscle contraction, during flatfish metamophosis is studied.     

Fractional Anisotropy in Corpus Callosum Is Associated with Facilitation of Motor Representation during Ipsilateral Hand Movements

Background

Coactivation of primary motor cortex ipsilateral to a unilateral movement (M1_ipsilateral) has been observed, and the magnitude of activation is influenced by the contracting muscles. It has been suggested that the microstructural integrity of the callosal motor fibers (CMFs) connecting M1 regions may reflect the observed response. However, the association between the structural connectivity of CMFs and functional changes in M1_ipsilateral remains unclear. The purpose of this study was to investigate the relationship between functional changes within M1_ipsilateral during unilateral arm or leg movements and the microstructure of the CMFs connecting both homotopic representations (arm or leg).

Methods

Transcranial magnetic stimulation was used to assess changes in motor evoked potentials (MEP) in an arm muscle during unilateral movements compared to rest in fifteen healthy adults. Functional magnetic resonance imaging was then used to identify regions of M1 associated with either arm or leg movements. Diffusion-weighted imaging data was acquired to generate CMFs for arm and leg areas using the areas of activation from the functional imaging as seed masks. Individual values of regional fractional anisotropy (FA) of arm and leg CMFs was then calculated by examining the overlap between CMFs and a standard atlas of corpus callosum.

Results

The change in the MEP was significantly larger in the arm movement compared to the leg movement. Additionally, regression analysis revealed that FA in the arm CMFs was positively correlated with the change in MEP during arm movement, whereas a negative correlation was observed during the leg movement. However, there was no significant relationship between FA in the leg CMF and the change in MEP during the movements.

Conclusions

These findings suggest that individual differences in interhemispheric structural connectivity may be used to explain a homologous muscle-dominant effect within M1_ipsilateral hand representation during unilateral movement with topographical specificity.     

Filarioid nematodes in cattle,sheep and horses in Finland

Background  

In autumn 2006, Finnish meat inspection data revealed lesions in tendons, muscles and ligaments of bovine hind legs leading to partial condemnation of carcasses. In gross pathological examination at Finnish Food Safety Authority Evira, Oulu (now Fish and Wildlife Health) Research Unit, Onchocerca sp. (Filarioidea; Onchocercidae) nematodes were detected in lesions. Due to this, a pilot study was made in order to find out what filarioid nematodes do occur in cattle, horses and sheep in Finland.     

Knockdown and overexpression of Unc-45b result in defective myofibril organization in skeletal muscles of zebrafish embryos

Background  

Unc-45 is a myosin chaperone and a Hsp90 co-chaperone that plays a key role in muscle development. Genetic and biochemical studies in C. elegans have demonstrated that Unc-45 facilitates the process of myosin folding and assembly in body wall muscles. Loss or overexpression of Unc-45 in C. elegans results in defective myofibril organization. In the zebrafish Danio rerio, unc-45b, a homolog of C. elegans unc-45, is expressed in both skeletal and cardiac muscles. Earlier studies indicate that mutation or knockdown of unc-45b expression in zebrafish results in a phenotype characterized by a loss of both thick and thin filament organization in skeletal and cardiac muscle. The effects of unc-45b knockdown on other sarcomeric structures and the phenotype of Unc-45b overexpression, however, are poorly understood in vertebrates.     

Conduction in ulnar nerve bundles that innervate the proximal and distal muscles: a clinical trial

Background  

This study aims to investigate and compare the conduction parameters of nerve bundles in the ulnar nerve that innervates the forearm muscles and hand muscles; routine electromyography study merely evaluates the nerve segment of distal (hand) muscles.     

Postnatal development of depth-dependent collagen density in ovine articular cartilage

Background  

Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for the functions of adult AC. Collagen is the most abundant solid component and it affects the mechanical behaviour of AC. The current objective is to quantify the postnatal development of depth-dependent collagen density in sheep (Ovis aries) AC between birth and maturity. We use Fourier transform infra-red micro-spectroscopy to investigate collagen density in 48 sheep divided over ten sample points between birth (stillborn) and maturity (72 weeks). In each animal, we investigate six anatomical sites (caudal, distal and rostral locations at the medial and lateral side of the joint) in the distal metacarpus of a fore leg and a hind leg.     

Influence of maturation on anthropometry and body composition in Japanese junior high school students

Background

The purpose of this study was to examine maturity-related differences in anthropometry and body composition in Japanese youth within a single year.

Methods

Two hundred and ten Japanese youth aged from 13 to 13.99 years participated in this study. Their maturity status was assessed using a self-assessment of stage of pubic hair development. Bioelectrical impedance analysis was used to estimate percent body fat and lean body mass (LBM). Muscle thickness of the anterior thigh, posterior lower leg and rectus abdominis muscles were measured by ultrasound.

Results

For boys, height, body weight, and LBM in less mature groups were lower than that in more mature groups. The maturity-related differences were still significant after adjusting for chronological age. On the other hand, muscle thickness values in the lower extremity and abdomen differed among the groups at different stages of pubic hair development, whereas there was no maturity-related difference in the relative values corrected by LBM, except for those thickness values measured at the abdomen. For girls, only the muscle thickness at the anterior thigh and muscle thickness relative to LBM^1/3 at the posterior lower leg was significantly affected by maturity status, but significant maturity-related difference was not found after adjusting for chronological age.

Conclusions

At least for Japanese boys and girls aged 13 years, maturity status affected body size in boys, but not in girls, and the influence of maturation on the muscularity of the lower extremity and trunk muscles is less in both sexes.