Perhexiline maleate therapy may produce a polyneuropathy as well as other side effects in man. The Schwann-cell origin of the neuropathy is demonstrated by morphologic studies. Ultrastructural studies of muscle and nerve biopsies showed the presence of intracytoplasmic inclusions, primarily in Schwann cells, muscle fibers, and endothelial cells. These inclusions were polymorphic and varied from one cell type to another. They were frequently associated with calcium deposits, and their structure suggested a lysosomal origin. It was possible experimentally to reproduce similar inclusions in mice. Furthermore, numerous tubular aggregates were observed in intoxicated mouse muscle fibers.

Adult↗

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Morphometric analysis of mdx diaphragm muscle fibres. Comparison with hindlimb muscles.

Histological, histochemical and morphometric characteristics of diaphragm muscles from mdx and control mice were compared with those of hindlimb muscles [extensor digitorum longus (EDL), tibialis anterior (TA) and soleus (SA) muscles]. In contrast to mdx limb muscles, regeneration after muscle necrosis does not restore diaphragm muscle structure. In mdx mice at 270 days of age, 70-80% of fibres in hindlimb muscles had central nuclei, compared with only 35% in diaphragm muscle. At 270 days of age, mdx diaphragm muscle was characterized by perimysial and endomysial fibrosis; this latter feature was absent from mdx hindlimb muscles. Fibre diameter remained smaller than the control in mdx diaphragm muscle. We suggest that the similarity in muscle pathology between the diaphragms of mdx mice and in patients suffering from Duchenne muscular dystrophy (DMD) makes these an appropriate model for DMD, since respiratory failure is the leading cause of death in DMD patients.

Aging↗

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The role of the dystrophin-glycoprotein complex in the molecular pathogenesis of muscular dystrophies.

The dystrophin-glycoprotein complex is considered to be a major trans-sarcolemmal structure which provides a linkage between the subsarcolemmal actin cytoskeleton and the extracellular matrix component laminin. Recently, deficiency of the dystrophin-associated proteins has been shown to play an important role in the molecular pathogenesis of several forms of muscular dystrophy. These include Duchenne muscular dystrophy (DMD), symptomatic DMD carriers, Becker muscular dystrophy and severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype prevalent in North Africa. In Fukuyama-type congenital muscular dystrophy (FCMD), the finding of abnormal expression of the dystrophin-associated proteins may provide a clue to its molecular pathogenesis. These recent findings indicate that the linkage between the subsarcolemmal cytoskeleton and extracellular matrix via the dystrophin-glycoprotein complex is critical for maintaining the integrity of muscle cell function.

Child↗

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Malignant hyperthermia and central core disease: analysis of two families with heterogeneous clinical expression.

We report two families both presenting with malignant hyperthermia susceptibility and "core" or "core-like" changes in the muscle tissue. Combined analysis of the malignant hyperthermia phenotype and the histochemical findings demonstrates the complexity of their association and highly suggests genetic heterogeneity of malignant hyperthermia and central core diseases.

Adolescent↗

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Late-onset rod myopathy associated with monoclonal gammopathy.

A 31-yr-old woman presented with a severe and rapidly progressive myopathy affecting proximal limbs, neck flexors and respiratory muscles. Muscle biopsy revealed numerous atrophic fibres with marked structural alterations, without inflammatory infiltrate. By electron microscopy, atrophic fibres displayed many rods. A benign monoclonal gammopathy (IgG, lambda chain) was evident in serum. A sarcolemmal deposit of IgG, lambda chain was found by immunostaining. Plasmapheresis and immunosuppressive therapies produced a decrease in paraproteinemia and a partial clinical improvement. This observation is the third to associate monoclonal gammopathy with "late-onset rod myopathy". The pathogenetic role of paraproteinemia remains unclear.

Adult↗

PubMedDate not supplied

The permeability of the basal lamina at the neuromuscular junction. An ultrastructural study of rat skeletal muscle using particulate tracers.

Various macromolecular substances, such as toxins and antibodies, may interfere with neuromuscular transmission. The neuromuscular junction is also known to be a site for the uptake of macromolecular substances into the axon for subsequent transport to the central nervous system. The synaptic cleft of the neuromuscular junction is separated from the rest of the extracellular compartment of muscle by the basal lamina, the permeability properties of which are not known. The penetration of macromolecular substances of varying size into the synaptic cleft of the neuromuscular junction has been studied in rats. Four different tracers: Imferon (an iron-dextran measuring 11 X 7 X 7 nm), ferritin (a spherical iron-protein 12 nm in diameter), Imposil (an iron-dextran measuring 21 X 12 X 12 nm) and colloidal gold-protein (20-25 nm in diameter) were injected into the palmaris longus muscle. Fifteen and 120 min after injection, the distribution of these particulate tracers was studied by electron microscopy. Imferon and ferritin penetrated rapidly through the basal lamina along the muscle fibres and also into the synaptic cleft of the neuromuscular junction. The larger Imposil and colloidal gold particles were restricted from penetrating the basal lamina even after 2 h, and these particles were traced only occasionally within the synaptic cleft. The results indicate that the basal lamina of muscle acts as a diffusion barrier to large macromolecules, preventing them from entering the synaptic cleft.

Animals↗

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Functional recovery induced by satellite cell grafts in irreversibly injured muscles.

Grafting autologous cultured satellite cells in irreversibly injured rat extensor digitorum longus EDL muscle leads to myofiber regeneration at the grafting site. In this study, we investigated whether cell grafts induced functional improvement and correlated mechanophysiological findings with histological observations. In cell grafted muscles, the number of myofibers did not differ significantly between 2 wk and 3 mo, whereas no regenerating myofibers were observed in ungrafted controls. During this period, the total number of myofibers in the cell grafted muscles represented 48.2-51.9% of that in normal muscles. The mean diameter of regenerated myofibers increased with time, reaching a maximum (32 microns) at the second mo and remained smaller than that of normal myofibers (47 microns). Muscle function was measured by mechanophysiological recordings of muscle response to supramaximal electrical stimulation of the nerve in situ. Cell grafted muscles exhibited a progressive improvement of all contractile parameters. After 3 mo, a 4-fold increase in absolute values of twitch and tetanic tension outputs was measured in cell grafted muscles when compared to ungrafted controls. However, these parameters remained much lower than in normal muscles (23.4% and 22.3% of control, respectively). This study showed that myogenic cell grafts replace degenerated myofibers and form functional myofibers. Functional improvement observed, between 2 wk and 3 mo after cell grafting, correlated with the development, differentiation, and maturation of the regenerated myofibers rather than with an increase in the number of regenerated myofibers.

Animals↗

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Social identity and the International Classification of Handicaps: an evaluation of the consequences of facioscapulohumeral muscular dystrophy.

The objective of this study was to evaluate the consequences of facioscapulohumeral muscular dystrophy (FSH MD) using two different but complementary procedures: an analysis based on the three different dimensions of disablement developed by the WHO--impairment, disability, and handicap--and a study of the psychological repercussions on social identity. Sixty-eight individuals with FSH MD, with 68 members of a control group, responded to a battery of psychosocial questions. Individuals with muscular dystrophy were also studied with reference to the dimensions of impairment, disability and handicap. The results showed that there are close correlations among measures of the three dimensions of disablement. Evaluations made by people with muscular dystrophy of the seriousness of their own disablement are strongly linked to objective measures of impairment. Furthermore, we found that having muscular dystrophy does have certain consequences for an individual's self-identity, although the degree to which one's self-image is validated is to some extent independent of the seriousness of the illness.

Activities of Daily Living↗

PubMedDate not supplied