Muscle and Nerve

The compound 5‐azacytidine has been previously shown to convert cells of the rat embryonic fibroblastic cell line, C3H/10T1/2, into myoblasts, adipocytes, and chondrocytes. Rare, resident cells of bone marrow and periosteum, referred to as mesenchymal stem cells, have been shown to differentiate into a number of mesenchymal phenotypes including bone, cartilage, and adipocytes. Rat bone marrow‐derived mesenchymal stem cells were exposed to 5‐azacytidine beginning 24 h after seeding twice‐passaged cells into culture dishes. After an exposure of 24 h, long, multinucleated myotubes were observed in some of the dishes 7–11 days later. Cells containing Sudan black‐positive droplets in their cytoplasm were also observed. Thus, culture‐propagated rat bone marrow mesenchymal stem cells appear to have the capacity to be induced to differentiate in vitro into myogenic and adipocytic phenotypes, although nonmesenchymal cells (rat brain fibroblasts) cannot be so induced. Taken together, these observations provide support for the suggestion that mesenchymal stem cells in the bone marrow of postnatal organisms may provide a source for myoprogenitor cells which could function in clinically relevant myogenic regeneration. © 1995 John Wiley & Sons, Inc.

The factors limiting force production and exercise endurance time have been briefly described, together with some of the changes occurring at various sites within the muscle and central nervous system. Evidence is presented that, in fatigue of sustained maximal voluntary contractions (MVC) executed by well‐motivated subjects, the reduction in force generating capacity need not be due to a decline in central nervous system (CNS) motor drive or to failing neuromuscular transmission, but can be attributed solely to contractile failure of the muscles involved. However, despite this conclusion, both the integrated electromyogram (EMG) and the mean firing rate of individual motor units do decline progressively during sustained MVC. This, however, does not necessarily result in loss of force since the parallel slowing of muscle contractile speed reduces tetanic fusion frequency. It is suggested that the range of motoneuron firing rates elicited by voluntary effort is regulated and limited for each muscle to the minimum required for maximum force generation, thus preventing neuromuscular transmission failure and optimizing motor control. Such a CNS regulating mechanism would probably require some reflex feedback from the muscle.

To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine‐wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles. Muscle Nerve 27: 682–692, 2003

The severe Duchenne and milder Becker muscular dystrophy are both caused by mutations in the DMD gene. This gene codes for dystrophin, a protein important for maintaining the stability of muscle‐fiber membranes. In 1988, Monaco and colleagues postulated an explanation for the phenotypic difference between Duchenne and Becker patients in the reading‐frame rule: In Duchenne patients, mutations induce a shift in the reading frame leading to prematurely truncated, dysfunctional dystrophins. In Becker patients, in‐frame mutations allow the synthesis of internally deleted, but largely functional dystrophins. Currently, over 4700 mutations have been reported in the Leiden DMD mutation database, of which 91% are in agreement with this rule. In this study we provide an update of the mutational variability in the DMD gene, particularly focusing on genotype–phenotype correlations and mutations that appear to be exceptions to the reading‐frame rule. Muscle Nerve, 2006

The reported prevalence of diabetic polyneuropathy varies from 5 to 80%. This unsatisfactory state may relate to evaluation of different patient groups, different minimal criteria for the diagnosis of neuropathy, and different degrees of surveillance. To made matters worse, patients with polyneuropathy tend to be equated ignoring differences in severity. To remedy this situation, four recommendations are made: (1) population‐based patients should be studied, (2) nerve conduction should be used to set minimal criteria for neuropathy because the test is objective, sensitive, and repeatable, (3) validated tests of symptoms and deficits should also be used because clinical manifestations of neuropathy cannot be accurately inferred from electrophysiologic measurements, and (4) approaches to staging severity of neuropathy should be developed and used in expressing abnormality. To this end minimal criteria for the diagnosis of diabetic polyneuropathy have been proposed, and validated tests to assess neuropathic symptoms and sensory deficits have been developed. In this report we also propose a staging approach utilizing nerve conduction and neurologic history and examination and validated tests of neuropathic symptoms and deficits.

Mutations of different components of the dystrophin–glycoprotein complex (DGC) cause muscular dystrophies that vary in terms of severity, age of onset, and selective involvement of muscle groups. Although the primary pathogenetic processes in the muscular dystrophies have clearly been identified as apoptotic and necrotic muscle cell death, the pathogenetic mechanisms that lead to cell death remain to be determined. Studies of components of the DGC in muscle and in nonmuscle tissues have revealed that the DGC is undoubtedly a multifunctional complex and a highly dynamic structure, in contrast to the unidimensional concept of the DGC as a mechanical component in the cell. Analysis of the DGC reveals compelling analogies to two other membrane‐associated protein complexes, namely integrins and caveolins. Each of these complexes mediates signal transduction cascades in the cell, and disruption of each complex causes muscular dystrophies. The signal transduction cascades associated with the DGC, like those associated with integrins and caveolins, play important roles in cell survival signaling, cellular defense mechanisms, and regulation of the balance between cell survival and cell death. This review focuses on the functional components of the DGC, highlighting the evidence of their participation in cellular signaling processes important for cell survival. Elucidating the link between these functional components and the pathogenetic processes leading to cell death is the foremost challenge to understanding the mechanisms of disease expression in the muscular dystrophies due to defects in the DGC. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1575–1594, 2001

Small‐fiber neuropathy is a common disorder. It is often “idiopathic” and typically presents with painful feet in patients over the age of 60. Autoimmune mechanisms are often suspected, but rarely identified. Known causes of small‐fiber neuropathy include diabetes mellitus, amyloidosis, toxins, and inherited sensory and autonomic neuropathies. Occasionally, small‐fiber neuropathy is diffuse or multifocal. Depending on the type of small‐fiber neuropathy, autonomic dysfunction can be significant or subclinical. Diagnosis is made on the basis of the clinical features, normal nerve conduction studies, and abnormal specialized tests of small‐fiber function. These specialized studies include assessment of epidermal nerve fiber density as well as sudomotor, quantitative sensory, and cardiovagal testing. The sensitivities of these tests range from 59–88%. Each has certain advantages and disadvantages, and the tests may be complementary. Unless an underlying disease is identified, treatment is usually directed toward alleviation of neuropathic pain. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 173–188, 2002

We reviewed 180 electroneuromyographic (EMG) studies from patients with acute inflammatory demyelinating polyradiculoneuropathy. EMG criteria suggestive of demyelination were met during the first 5 weeks in 87% of patients; an additional 10% had indeterminate electrodiagnostic evaluations, and 3% demonstrated axonal degeneration only. Motor nerve conduction abnormalities initially predominated, with the nadir of abnormality occurring at week 3. Sensory nerve conduction abnormalities peaked during week 4 and were atypical for polyneuropathy, with 52% of patients having normal sural but abnormal median sensory studies, perhaps reflecting distal nerve involvement. Delayed sensory abnormalities may reflect, in part, secondary involvement related to increased intraneural edema accentuated by compression at sites of anatomic vulnerability. Fibrillation potentials and increased polyphasia appeared between weeks 2 and 5 in proximal and distal muscles simultaneously, which is consistent with either random axonal degeneration at any point along the axon or distal involvement. Resolution of conduction abnormalities began between weeks 6 and 10, with increased mean motor‐evoked amplitude best reflecting functional clinical recovery.

Multiple point stimulation (MPS) is described as a method of estimating the numbers of motor units in the median innervated thenar muscles of young and older control subjects. Stimulation at multiple sites along the course of the median nerve was employed to collect a sample of the lowest threshold, all‐or‐nothing surface‐recorded motor unit action potentials (S‐MUAPs). The average, negative peak area, and peak‐to‐peak amplitude of the sample of S‐MUAPs was determined and divided into the corresponding value for the maximal compound muscle action potential to derive the motor unit estimate (MUE). In 37 trials from 17 younger subjects (20—40 years), the mean MUE was 288 ± 95 SD based on negative peak area and, in 33 trials from 20 older subjects, mean values were 139 ± 68. In 23 young and older subjects, MPS was performed on at least two occasions and the MUEs were found to be highly correlated (r = 0.88). © 1993 John Wiley & Sons, Inc.

Introduction: The purpose of this study was to develop an evidence‐based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). Methods: Two questions were asked: (1) What is the accuracy of median nerve cross‐sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). Results: Neuromuscular ultrasound measurement of median nerve cross‐sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B). Muscle Nerve 46: 287–293, 2012