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Showing papers in "Muscle & Nerve in 2011"


Journal ArticleDOI
TL;DR: The structure, composition, and mechanical properties of skeletal muscle ECM are reviewed; the cells that contribute to the maintenance of the ECMAreas for future study are proposed; and overview changes that occur with pathology are described.
Abstract: 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.

737 citations


Journal ArticleDOI
TL;DR: The need to use reference values for populations such as diabetics and active workers, where normative values differ from conventional cutoffs used to confirm suspected CTS, is presented and the value of needle electromyography (EMG) is examined.
Abstract: Carpal tunnel syndrome (CTS) is the most common nerve entrapment. Electrodiagnostic (EDX) studies are a valid and reliable means of confirming the diagnosis. This monograph addresses the various EDX techniques used to evaluate the median nerve at the wrist. It also demonstrates the limitations of EDX studies with a focus on the sensitivity and specificity of EDX testing for CTS. The need to use reference values for populations such as diabetics and active workers, where normative values differ from conventional cutoffs used to confirm suspected CTS, is presented. The value of needle electromyography (EMG) is examined.

316 citations


Journal ArticleDOI
TL;DR: Many patients deteriorate rapidly early in the disease, and PLEX is usually the preferred treatment, and long‐term outcomes are similar to those of patients with AChR‐Ab+ MG.
Abstract: Neuroscience Department, Catholic University, Largo F. Vito 1, 00168 Roma, ItalyAccepted 13 December 2010ABSTRACT: Introduction: Myasthenia gravis (MG) patientswith autoantibodies to muscle-specific tyrosine kinase (MuSK)represent a distinct subset of those with this disease. Treatmentand outcomes data in these patients are limited and conflicting.Methods: We reviewed 110 MuSK-MG patients from two largeclinics in Italy and the USA. Results: Thirty-nine to 49% ofpatients with generalized, acetylcholine receptor antibody(AChR-Ab)–negative MG had MuSK-MG. Eighty-five percentwere female, with disease onset typically in the fourth decade.Ocular and/or bulbar symptoms were present at onset in 79%of those studied. Eighty-five percent were MGFA class III orgreater, and crisis occurred in 28%. Plasma exchange (PLEX)produced improvement in 93%, whereas only 61% improved af-ter intravenous immunoglobulin. Long-term outcomes werecomparable to those of patients with AChR-Ab–positive MG.Conclusions: MuSK-MG has a marked female predominancewith frequent oculobulbar weakness and crises. Many patientsdeteriorate rapidly early in the disease, and PLEX is usually thepreferred treatment. Long-term outcomes are similar to those ofpatients with AChR-Ab

287 citations


Journal ArticleDOI
TL;DR: It is found that dyslipidemia is not an independent predictor of survival in ALS, and BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.
Abstract: Abnormal energy metabolism in amyotrophic lateral sclerosis (ALS) is an active area of research (reviewed by Dupuis et al.1). ALS patients lose weight as the disease progresses due to both dysphagia with decreased food intake and hypermetabolism, that is, increased energy expenditure. Recently, Dupuis et al. suggested that the abnormal energy balance in ALS is characterized by dyslipidemia and that the lipid ratio might be used as a separate prognostic marker.2 Subsequent studies regarding the role of lipid metabolism in ALS provided conflicting results. Chio et al. found no independent association between lipid levels and survival.3 Most recently, Dorst et al. reported prolonged life expectancy in ALS patients with hypercholesterolemia based on data from a German database.4 However, the association with hyperlipidemia was not significant after adjusting for body mass index (BMI) and age at onset. The aim of this study was to test whether cholesterol levels independently predict survival in a large series of ALS subjects. We hypothesized that cholesterol levels would change over time with disease progression and weight loss. Therefore, cholesterol levels were measured in 427 ALS subjects and they were measured repeatedly in a subset of subjects from three clinical trial databases.

260 citations


Journal ArticleDOI
TL;DR: Findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo.
Abstract: Introduction: Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist Methods: Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen-processed nerve allografts) were compared with nerve isografts and silicone nerve guidance conduits in a 14-mm rat sciatic nerve defect Results: All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration Detergent-processed allografts were similar to isografts at 6 weeks postoperatively, whereas AxoGen-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks postoperatively All acellular allografts promoted greater amounts of motor recovery compared with silicone conduits Conclusion: These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo Muscle Nerve, 2011

191 citations


Journal ArticleDOI
TL;DR: The suction‐modified Bergström needle muscle biopsy technique is safe and provides an adequate sample size for histologic, ultrastructural, DNA, and enzyme analysis.
Abstract: Introduction: Bergstrom needle muscle biopsies have been used by exercise physiologists for over 35 years but have been less accepted by neuromuscular clinicians due to size concerns. Methods: We retrospectively reviewed over 13,500 muscle Bergstrom needle biopsies done over a 21-year period to determine sampling success, patient/subject experience, and complications. We compared sample yield between two different needles (Bergstrom vs. UCH), with and without suction modifications. Results: Needle biopsies adequate for histology and enzymology were obtainable from the vastus lateralis, deltoid, biceps brachii, soleus, and medial gastrocnemius muscles, with a success rate of >99.9% and a minor complication rate of 0.15%. Approximately 450 muscle fibers were submitted for histologic assessment; suction modification and use of the Bergstrom vs. UCH needle were associated with larger sample size (P < 0.05). Conclusions: The suction-modified Bergstrom needle muscle biopsy technique is safe and provides an adequate sample size for histologic, ultrastructural, DNA, and enzyme analysis. Muscle Nerve, 2011

183 citations


Journal ArticleDOI
TL;DR: The current understanding of DMD cardiomyopathy has increased significantly over the past 10 years, but further research is required to improve cardiac treatment and outcomes in DMD.
Abstract: Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and occurs in 1 in 3500 male births. Improved survival due to improvements in clinical care of the musculoskeletal and respiratory systems has led to an increased incidence of cardiomyopathy. Cardiac-related deaths are now seen in approximately 20% of DMD patients. Our current understanding of DMD cardiomyopathy has increased significantly over the past 10 years, but further research is required to improve cardiac treatment and outcomes in DMD. This review provides a summary of the current literature and discussion of potential new therapies for DMD cardiomyopathy.

148 citations


Journal ArticleDOI
TL;DR: Ultrasonography of the ulnar nerve has been recommended as a useful additional test in ulnar neuropathy at the elbow (UNE).
Abstract: Introduction: Ultrasonography of the ulnar nerve has been recommended as a useful additional test in ulnar neuropathy at the elbow (UNE). Methods: We searched the literature and systemically reviewed all clinical trials in UNE. We also looked for articles about the normal sonoanatomy and spe- cific causes of UNE. Results: Seven of 14 clinical trials in UNE were suitable for further analysis. Ultrasonographic ulnar nerve size measurement appears to be a test with good diag- nostic accuracy. The most frequently reported abnormality was an increased cross-sectional area of the ulnar nerve at the elbow. However, several studies had methodological flaws. In addition, the ultrasonographic techniques and study designs dif- fered among the studies. There were a few other uncontrolled studies about the underlying causes of UNE. Discussion: The role of ultrasonography in UNE seems promising but could not be firmly established. More prospective studies are needed, and we make several recommendations for further research. Muscle Nerve 43: 627-635, 2011 The diagnosis of ulnar neuropathy at the elbow (UNE) may seem straightforward in the majority of cases. Clinicians will usually suspect an ulnar neu- ropathy when the characteristic symptoms and signs are present, and electrophysiological studies will eventually confirm the diagnosis. However, UNE has to be distinguished from other disorders and from ulnar neuropathy at other levels. Clinical signs indicating a lesion of the ulnar nerve above the level of the wrist (e.g., paresis of the flexor carpi ulnaris or flexor digitorum profundus muscles) are absent in many cases 1,2 and provocative clinical tests have a low diagnostic accuracy. 3 In addition, electrophysio- logical studies may be false negative or non-localiz- ing with sensitivities ranging from 37% to 86%. 4 Fur- thermore, the reliability of electrophysiological studies is undermined by a broad 95% confidence interval of the conduction velocity across the elbow owing to the accumulation of measurement errors. 5,6 Therefore, new laboratory tests are needed to improve the reliability of the diagnosis of UNE. 4 Ultrasonography of the ulnar nerve has been rec- ommended by several investigators as a good and reliable additional test in UNE. Using advanced ultrasonographic techniques, the ulnar nerve can be depicted with excellent resolution, and thickening may be revealed in patients with UNE. However, to our best knowledge, ultrasonography still has no de- finitive role in guidelines or practice parameters. As new and promising tests often become widely applied before they are critically appraised 7 we aimed to perform a more close and systematic review of the studies published so far. Ultrasonography in UNE requires detailed knowledge of the normal (sono-)anatomy, dynam- ics, and variations of the ulnar nerve and related structures. Therefore, we will first provide a synop- sis of the normal sonographic anatomy of the ul- nar nerve and then review ultrasonographic studies in the diagnosis of UNE and studies about underly- ing abnormalities in UNE.

117 citations


Journal ArticleDOI
TL;DR: Strength gains in the trained leg were due to enhanced agonist activation, whereas decreased coactivation may have affected strength changes in both legs.
Abstract: In this study we investigated the contribution of neural adaptations to strength changes after 4 weeks of unilateral isometric resistance training. Maximal and submaximal isometric knee extension contractions were assessed before and after training. Surface electromyography (EMG) data were collected from the agonist and antagonist muscles and normalized to evoked maximal M-wave and maximal knee flexor EMG, respectively. The interpolated twitch technique (ITT) was also used to determine activation at maximum voluntary force (MVF). MVF increased in the trained (+20%) and untrained (+8%) legs. Agonist EMG at MVF increased in the trained leg (+26%), although activation determined via the ITT was unchanged. In both legs the position of the force-agonist EMG relationship was unchanged, but antagonist coactivation was lower for all levels of agonist activation. Strength gains in the trained leg were due to enhanced agonist activation, whereas decreased coactivation may have affected strength changes in both legs.

107 citations


Journal ArticleDOI
TL;DR: The evidence on both sides is reviewed and it is concluded that ALN should be regarded as a toxic rather than nutritional neuropathy.
Abstract: Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction. Unfortunately, ALN is rarely discussed as a specific disease entity in textbooks because it is widely assumed to primarily reflect consequences of nutritional deficiency. This hypothesis is largely based on observations first made over eight decades ago when it was demonstrated that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN. In recent studies, failure of thiamine treatment to reverse ALN, together with new information demonstrating clinical and electrophysiological distinctions between ALN and nutritional deficiency neuropathies, suggests that alcohol itself may significantly predispose and enhance development of neuropathy in the appropriate clinical setting. We reviewed the evidence on both sides and conclude that ALN should be regarded as a toxic rather than nutritional neuropathy.

103 citations


Journal ArticleDOI
TL;DR: Albuterol is used to treat patients with EP AChE deficiency, Dok‐7 myasthenia, and β2‐laminin deficiency, and should spur controlled, prospective clinical trials of al buterol in these as well as other CMS.
Abstract: Introduction: Congenital myasthenic syndromes (CMS) are disabling but treatable disorders. Anticholinesterase therapy is effective in most of them, but is contraindicated in endplate (EP) acetylcholinesterase (AChE) deficiency, the slow-channel syndrome, Dok-7 myasthenia, and β2-laminin deficiency, and is not useful in CMS due to defects in muscle-specific kinase (MuSK), agrin, and plectin. EP AChE, Dok-7, and β2-laminin deficiencies respond favorably to ephedrine, but ephedrine can no longer be prescribed in the USA. Methods: We used albuterol, another sympathomimetic agent, to treat 3 patients with EP AChE deficiency and 15 with Dok-7 myasthenia. Response to therapy was evaluated by a 9-point questionnaire pertaining to activities of daily life. Results: Comparison of the pre- and posttreatment responses indicated a beneficial response to albuterol (P < 0.001) in both patient groups. The adverse effects of therapy were like those of ephedrine. Conclusion: Our observations should spur controlled, prospective clinical trials of albuterol in these as well as other CMS. Muscle Nerve, 2011

Journal ArticleDOI
TL;DR: High‐resolution ultrasound has been used to evaluate several neuromuscular conditions, but it has only been used on a limited basis in amyotrophic lateral sclerosis patients, and not to assess their peripheral nerves.
Abstract: Introduction: High-resolution ultrasound has been used to evaluate several neuromuscular conditions, but it has only been used on a limited basis in amyotrophic lateral sclerosis (ALS) patients. It has not been used to assess their peripheral nerves. This study was designed to use neuromuscular ultrasound to investigate nerve cross-sectional area and muscle thickness in ALS. Methods: Twenty individuals with ALS and 20 matched controls underwent neuromuscular ultrasound to measure the cross-sectional area of their median and sural nerves and the thickness of their biceps/brachialis muscle complex. Results: The cross-sectional area of the median nerve in the mid-arm was smaller in the ALS group than in controls (10.5 mm2 vs. 12.7 mm2, P = 0.0023), but no difference was seen in the sural nerve (4.5 mm2 vs. 5.0 mm2, P = 0.1927). The ALS group also had thinner biceps/brachialis than controls (2.1 cm vs. 2.9 cm, P = 0.0007). Conclusions: Neuromuscular ultrasound demonstrates nerve and muscle atrophy in ALS and should be further explored as a disease biomarker. Muscle Nerve 44: 346–351, 2011

Journal ArticleDOI
TL;DR: Composite sum scores of normal deviates (from percentiles corrected for applicable variables) of sensitive NC attributes and with modifications, RDNS and AAN criteria performed acceptably for diagnosis of DSPN.
Abstract: Introduction: In this study we aimed to deter- mine which criteria are valid for nerve conduction (NC) diagno- sis of typical diabetic sensorimotor polyneuropathy (DSPN). Methods: Eight criteria were assessed from among diabetes databases, the Rochester Diabetic Neuropathy Study (RDNS, N ¼ 456), and in healthy subjects (RDNS-HS, N ¼ 330). Results: In the RDNS, the most frequent abnormal attributes (� 2.5th/� 97.5th percentile) are: fibular motor nerve conduction velocity (MNCV; 26.3%); sural sensory nerve conduction veloc- ity (SNAP; 25.4%); tibial MNCV (24.8%); ulnar MNCV (21.3%); fibular F latency (16.9%); and ulnar F latency (16.0%). Normal deviate (from percentiles) composite scores of NC included: representative of neurophysiological abnormalities; sensitive and specific for diagnosis and useful for epidemiological sur- veys; randomized trials; and medical practice. By contrast, abnormality of one or more attributes in any nerve or abnormally of two most sensitive attributes performed poorly. Conclusions: Composite sum scores of normal deviates (from percentiles corrected for applicable variables) of sensitive NC attributes and with modifications, RDNS and AAN criteria per- formed acceptably for diagnosis of DSPN. Muscle Nerve 44: 340-345, 2011

Journal ArticleDOI
TL;DR: The concomitant improvement of mean fiber CV supports the hypothesis of an effect of caffeine on motor unit recruitment, and improves muscle performance during short‐duration maximal dynamic contractions.
Abstract: Introduction: In this study we tested the hypothe- sis that caffeine supplementation improves neuromuscular func- tion, which has both nutritional and clinical relevance. Methods: Fourteen male subjects (mean 6 SD: 23.8 6 2.8 years) volun- teered in a double-blind, repeated-measures study with placebo (PLA) or caffeine (CAFF) (6 mg kg � 1 ). Maximal voluntary iso- metric contractions (MVCs), evoked maximal twitch, and maxi- mal isokinetic contractions during elbow flexion were assessed. Mechanical and electromyographic (EMG) signals from the biceps brachii muscle were recorded, and muscle fiber conduc- tion velocity (CV) was calculated to evaluate changes in the muscle force-velocity relationship and muscle fiber recruitment. Results: The torque-angular velocity curve was enhanced after CAFF supplementation. This was supported by a concomitant increase of CV values (8.7% higher in CAFF). Conclusions: Caffeine improves muscle performance during short-duration maximal dynamic contractions. The concomitant improvement of mean fiber CV supports the hypothesis of an effect of caf- feine on motor unit recruitment. Muscle Nerve 000: 000-000, 2011

Journal ArticleDOI
TL;DR: Activity‐dependent therapies promote axonal regeneration and functional recovery and may improve sensory–motor coordination and restoration of adequate circuitry at the spinal level.
Abstract: Introduction: Lesions of peripheral nerves cause loss of motor and sensory function and also lead to hyperreflexia and hyperalgesia. Activity-dependent therapies promote axonal regeneration and functional recovery and may improve sensory–motor coordination and restoration of adequate circuitry at the spinal level. Methods: We compared the effects of passive (bicycle) and active (treadmill) exercise on nerve regeneration and modulation of the spinal H reflex after transection and repair of the rat sciatic nerve. Animals were evaluated during 2 months using electrophysiological, functional, and histological methods. Results: Moderate exercise for 1 hour/day, either active treadmill walking or passive cycling, improved muscle reinnervation, increased the number of regenerated axons in the distal nerve, and reduced the increased excitability of spinal reflexes after nerve lesion. Discussion: Maintenance of denervated muscle activity and afferent input, by active or passive exercise, may increase trophic factor release to act on regenerating axons and to modulate central neuronal plasticity. Muscle Nerve, 2011

Journal ArticleDOI
TL;DR: The aim of this analysis was to examine the performance of the Myasthenia Gravis–specific Activities of Daily Living scale (MG‐ADL) during a multicenter scale validation study.
Abstract: Introduction: The aim of this analysis was to examine the performance of the Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) during a multicenter scale validation study. Methods: Consecutive MG patients were assessed with several MG outcome measures, including the MG-ADL. Statistical tests included descriptive analysis, Pearson correlation, and sensitivity/specificity. Results: Eighty-seven patients completed the MG-ADL, MG Composite (MGC), and MG 15-item Quality of Life scale (MG-QOL15) on the first visit, and 76 returned for the second visit. At the first visit, there was a strong positive correlation between MG-ADL and MGC (r ¼ 0.85, P < 0.0001) and MG-QOL15 (r ¼ 0.76, P < 0.0001). Cor- relation of the delta MG-ADL score and physician impression of change between the visits was strong (r ¼ 0.70, P < 0.0001). A 2-point improvement in the MG-ADL best predicted clinical improvement. Test-retest analysis demonstrated a high reliabil- ity coefficient. Conclusions: The MG-ADL correlates strongly with newer, validated MG outcome measures. A 2-point improvement in the MG-ADL indicates clinical improvement. The MG-ADL is useful as a research tool and in routine clinical management. Muscle Nerve 44: 727-731, 2011

Journal ArticleDOI
TL;DR: Findings support a role for TGF‐β1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice and suggest suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies.
Abstract: Fibrosis is a pathological feature observed in patients with Duchenne muscular dystrophy (DMD) and in mdx mice, the experimental model of DMD. We evaluated the effect of suramin, a transforming growth factor-beta 1 (TGF-β1) blocker, on fibrosis in mdx mice. mdx mice (6 months old) received suramin for 7 weeks. Suramin- and saline-treated (control) mdx mice performed exercise on a treadmill to worsen disease progression. Immunoblotting showed an increase of TGF-β1 in mdx diaphragm, limb, and cardiac muscles. Suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle. Suramin protected limb muscles against damage and reduced the exercise-induced loss of strength over time. These findings support a role for TGF-β1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice. Suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies.

Journal ArticleDOI
TL;DR: Findings suggest neuromuscular ultrasound is potentially helpful for the assessment of individuals undergoing treatment for CTS, as typical changes can be expected after successful treatment injection.
Abstract: Introduction: Neuromuscular ultrasound is a painless, radiation-free, high-resolution imaging modality for assessment of the peripheral nervous system. The purpose of this study was to use neuromuscular ultrasound to assess the changes that occur in the median nerve after steroid injection for carpal tunnel syndrome (CTS). Methods: Ultrasound and nerve conduction studies were performed at baseline and 1 week, 1 month, and 6 months after steroid injection in 19 individuals (29 wrists) with CTS. Results: Significant changes were noted in median nerve cross-sectional area (P < 0.001), mobility (P = 0.001), and vascularity (P = 0.042) at the distal wrist crease after steroid injection, and the nerve cross-sectional area correlated with symptom score and electrodiagnostic parameters. Changes in the ultrasonographic parameters were seen within 1 week of injection. Conclusions: These findings suggest neuromuscular ultrasound is potentially helpful for the assessment of individuals undergoing treatment for CTS, as typical changes can be expected after successful treatment injection. Muscle Nerve 44: 25–29, 2011

Journal ArticleDOI
TL;DR: The MG‐QOL15 is considered to be most useful for informing the clinician about the patient's perception and tolerance of MG‐related dysfunction and more objective measures, such as the MG Composite, should also be used to follow disease severity.
Abstract: The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with myasthenia gravis (MG)-related dysfunction. The aims of this study were to determine the usefulness of the MG-QOL15 for following individuals with MG and to guide clinical researchers who plan to use the MG-QOL15. We assessed sensitivity and specificity for detecting clinical change and evaluated test-retest reliability. Sensitivities and specificities of various cut-points of change in scores are presented. Also presented are means and standard deviations of MG-QOL15 scores for all patients and for subgroups of patients. The test-retest reliability coefficient was 98.6%. The MG-QOL15 has an acceptable longitudinal construct validity. We consider this instrument to be most useful for informing the clinician about the patient's perception and tolerance of MG-related dysfunction. More objective measures, such as the MG Composite, should also be used to follow disease severity.

Journal ArticleDOI
TL;DR: The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated.
Abstract: Introduction The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs. Methods We performed a retrospective analysis of 189 ALS patients from our ALS outpatient database to investigate the different spreading patterns of UMN and LMN affection in disease progression in relation to the onset region. Results The body region with the highest UMN involvement at onset in general also had the highest frequency of LMN signs and vice versa. This is in line with the hypothesis of a focal onset of disease, which then spreads to adjacent areas. However, there was a great variation between ALS phenotypes. Discussion These observations support the hypothesis of focal damage of a localized group of motor neurons, which then spreads to adjacent motor neurons. Muscle Nerve, 2011

Journal ArticleDOI
TL;DR: A simple method to quantify myotube formation using micrographs of Jenner–Giemsa‐stained C2C12 cultures and the sum of the darkest tones was used as a measure of myotubes density.
Abstract: Introduction: C2C12 myoblasts undergo in vitro myogenesis to form protein-rich multinucleated myotubes. Determining the fraction of total nuclei incorporated into myo- tubes is a commonly used method to quantify the extent of dif- ferentiation, but it is labor-intensive and susceptible to operator bias. Methods: We have developed a simple method to quantify myotube formation using micrographs of Jenner-Giemsa- stained C2C12 cultures. Because myotubes are darkly stained by Jenner-Giemsa dyes, the extent of myotube formation corre- lates with an increase in pixels attributed to the darkest tones. Thus, image histograms were obtained from photographs using ImageJ software, and the sum of the darkest tones was used as a measure of myotube density. Results: Measurements of myotube density mirrored those of fusion index during C2C12 differentiation and after treatment with prostaglandin D2, an in- hibitor of C2C12 myogenesis. Conclusions: We propose this inexpensive, quick, and unbiased method to quantify C2C12 dif- ferentiation as a complement of the fusion index analysis. Muscle Nerve 44: 366-370, 2011

Journal ArticleDOI
TL;DR: The effects of downhill or horizontal treadmill running on the magnetic resonance imaging (MRI) transverse relaxation time constant (T2) in mdx mice is compared.
Abstract: Introduction—This study compared the effects of downhill or horizontal treadmill running on the magnetic resonance imaging (MRI) transverse relaxation time constant (T2) in mdx mice. Methods—Mice underwent either downhill (n=11 mdx, n=6 controls) or horizontal running (n=9, mdx only) on a treadmill. MRI was conducted prior to exercise, immediately afterwards (~20 min), 24, and 48 hours following exercise. Results—A higher percentage of pixels with elevated T2 in the lower hindlimb muscles was observed in the mdx mice compared to controls both pre-exercise (p < 0.001) and at each time point following downhill running (p < 0.05), but not with horizontal running. The medial compartment muscles appeared to be the most susceptible to increased T2. Discussion—Downhill running provides a stimulus for inducing acute changes in muscle T2 in mdx mice. MRI is a non-invasive approach for examining acute muscle damage and recovery in multiple muscle groups simultaneously.

Journal ArticleDOI
TL;DR: It is suggested that clinically relevant doses of doxorubicin cause respiratory muscle weakness and that the loss of function depends, in part, on the route of administration.
Abstract: Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While undergoing treatment, patients exhibit frequent symptoms that suggest respiratory muscle weakness. Cancer patients can receive doxorubicin chemotherapy through either intravenous (IV) or intraperitoneal (IP) injections. We hypothesized that respiratory muscle function would be depressed in a murine model of chemotherapy. We tested this hypothesis by treating C57BL/6 mice with a clinical dose of doxorubicin (20 mg/kg) via IV or IP injection. Three days later we measured contractile properties of muscle fiber bundles isolated from the diaphragm. Doxorubicin consistently depressed diaphragm force with both methods of administration (P < 0.01). Doxorubicin IP exaggerated the depression in diaphragm force and stimulated tissue inflammation and muscle fiber injury. These results suggest that clinically relevant doses of doxorubicin cause respiratory muscle weakness and that the loss of function depends, in part, on the route of administration.

Journal ArticleDOI
TL;DR: Serum IL‐17 concentrations were higher in generalized MG compared with controls and correlated with anti‐acetylcholinesterase receptor antibody titers, indicating whether levels depend on the severity of MG.
Abstract: It has been suggested that interleukin-17 (IL-17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL-17. The aim of this study was to measure the concentration of IL-17 and determine whether levels depend on the severity of MG. Serum IL-17 concentrations were measured in 25 patients. IL-17 concentrations were higher in generalized MG compared with controls and correlated with anti-acetylcholinesterase receptor antibody titers.

Journal ArticleDOI
TL;DR: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC‐1α/G93A DL mice may contribute to neuronal protection.
Abstract: Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor c coactivator 1a (PGC-1a) would have a beneficial effect on this disease. Methods: PGC-1a transgenic mice were crossed with SOD1 mutant G93A DL mice. Results: We observed a moder- ate but non-significant increase in average lifespan in PGC-1a/ G93A DL mice, as compared with G93A DL mice (292 6 3 days vs. 274 6 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower ( � increase in duration) in the PGC-1a/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions. Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astro- cytes of the PGC-1a/G93A DL mice may contribute to neuronal protection. Muscle Nerve 44: 947-956, 2011

Journal ArticleDOI
TL;DR: It is found that paclitaxel produces early sensory dysfunction and leads to persistent neuropathy and significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies.
Abstract: Paclitaxel is used in the adjuvant treatment of breast cancer. It induces disabling and potentially long-lasting sensory neuropathy. This study systematically and prospectively investigated sensory function, using clinical grading scales, quantitative sensory testing, and neurophysiological and nerve excitability studies in 28 patients with early-stage breast cancer. After administration of 529 ± 41 mg/m(2) paclitaxel, 71% of patients developed neuropathic symptoms by 6 weeks of treatment. Early and progressive increases in stimulus threshold (P < 0.05) and reduction in sensory amplitudes from 47.0 ± 3.3 μV to 42.4 ± 3.4 μV (P < 0.05) occurred by 4 weeks, with a further reduction by final treatment (33.7 ± 3.0 μV, P < 0.001). The majority of patients (63%) did not experience recovery of neuropathic symptoms at follow-up. Axonal disruption did not relate to membrane conductance dysfunction. We found that paclitaxel produces early sensory dysfunction and leads to persistent neuropathy. Importantly, significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies.

Journal ArticleDOI
TL;DR: These findings suggest that when diabetic individuals face a new challenging situation that induces a higher demand for muscle strength and propulsion, the necessary range of motion and neuromuscular control around distal joints are insufficient.
Abstract: Introduction: Changes in gait cadence caused by challenging situations in daily life might induce higher demand for strength and propulsion in diabetic neuropathic (DN) sub- jects. Methods: Forty-six subjects (healthy and DN) walked at two cadences (self-selected and 25% higher). Kinematic and electromyographic data were obtained from lower limbs and compared across the gait cycle. Results: DN subjects showed a delayed peak in plantarflexor activity along the whole cycle (irre- spective of cadence) compared with healthy subjects. However, during the imposed cadence, DN individuals showed reduced ankle range of motion along the entire cycle compared with the self-selected condition and healthy individuals walking at both cadences (P ¼ 0.002). Conclusions: These findings suggest that when diabetic individuals face a new challenging situation that induces a higher demand for muscle strength and propul- sion, the necessary range of motion and neuromuscular control around distal joints are insufficient. Muscle Nerve 44: 258-268, 2011 The biomechanical pattern of gait is highly repeti- tive, cyclic, and has low variation across steps as well as across days. 1 This feature allows us to use gait analysis as an experimental model to investi- gate the influence of the environment, such as real-life challenges and perturbations, and biology, such as neuromuscular diseases. These two factors might impair both the coordinated harmonic action of the lower limbs and the neuromuscular strategies adopted for the control of locomotion. Diabetic neuropathy (DN) impairs both the soma- tosensory and motor control systems, 2,3 and affects the amount and quality of the sensory information that is essential for the complexity involved in gait generation and control. 4 The regularity of normal gait allows for the establishment of basic biome- chanical criteria to distinguish between normal and pathologic patterns of movement, such as gait patterns in DN individuals.

Journal ArticleDOI
TL;DR: Older age, longer duration of statin use, diabetes, stroke, and lower body mass index were associated with increased risk of developing muscle complications and adverse reactions to statins may be more common than previously reported.
Abstract: Introduction: The aim of the study was to investigate the prevalence and risk factors of muscle complications among patients using statins. Methods: We conducted a prospective comparative study on 345 patients receiving statins and compared the findings with an age- and gender-matched control group of 85 subjects. Univariate and multivariate analyses with logistic regression models were used to study the association of different patient and disease characteristics with muscle complications. Results: Adverse reactions were reported by 21% of patients and 5.9% of controls (P = 0.0013). Objective weakness was found in 15% of the patients who reported muscle symptoms (3.2% of the total cohort), but not in controls. Older age, longer duration of statin use, diabetes, stroke, and lower body mass index were associated with increased risk of developing these symptoms. Conclusions: Adverse reactions to statins may be more common than previously reported, and they may be affected by specific patient and disease characteristics. Muscle Nerve 2011

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TL;DR: The results indicate that knee position significantly affects quadriceps force steadiness and activation strategies, and this finding may have important implications for designing a force control testing protocol and interpreting test results.
Abstract: Introduction: In this study we investigated the effect of knee position on quadriceps force steadiness and activation strategies. Methods: Quadriceps force steadiness was evaluated in 22 volunteers at two knee positions by testing their ability to regulate submaximal force. Muscle activation strategies were studied in both time and frequency domains using surface electromyography. Results: Quadriceps force fluctuations and the associated agonist and antagonist activity were significantly higher at 90° than at 30° of flexion (P 0.05). Conclusions: The results indicate that knee position significantly affects quadriceps force steadiness and activation strategies. This finding may have important implications for designing a force control testing protocol and interpreting test results. Muscle Nerve, 2011

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TL;DR: It is concluded that the PPT is a valid and reliable tool to quantify functional impairment caused by CTS and can be a useful outcome measure in young and middle‐aged patients.
Abstract: There is a paucity of validated tests to quantify hand function impairment due to carpal tunnel syndrome (CTS). The aim of this study was to test the validity and reliability of the Purdue Pegboard Test (PPT) in CTS patients. We compared 190 CTS patients with 122 healthy, age-matched controls. CTS severity was determined based on electrophysiologic parameters and the Levine Self-Assessment Questionnaire. The time to complete the PPT and the test-retest reliability were tested. The test-retest reliability was high with an intraclass correlation coefficient of 0.91. Compared to healthy controls, the CTS patients were significantly slower. Although the functional performance generally declined with increasing severity of electrophysiologic abnormalities, the correlation between hand function decline and symptom severity in the young and middle-aged groups was low. We conclude that the PPT is a valid and reliable tool to quantify functional impairment caused by CTS. It can be a useful outcome measure in young and middle-aged patients.