Myogenic Disorders Research Articles

Progress and prospects of gene therapy clinical trials for the muscular dystrophies.

Clinical trials represent a critical avenue for new treatment development, where early phases (I, I/II) are designed to test safety and effectiveness of new therapeutics or diagnostic indicators. A number of recent advances have spurred renewed optimism toward initiating clinical trials and developing refined therapies for the muscular dystrophies (MD's) and other myogenic disorders. MD's encompass a heterogeneous group of degenerative disorders often characterized by progressive muscle weakness and fragility. Many of these diseases result from mutations in genes encoding proteins of the dystrophin-glycoprotein complex (DGC). The most common and severe form among children is Duchenne muscular dystrophy, caused by mutations in the dystrophin gene, with an average life expectancy around 25 years of age. Another group of MD's referred to as the limb-girdle muscular dystrophies (LGMDs) can affect boys or girls, with different types caused by mutations in different genes. Mutation of the α-sarcoglycan gene, also a DGC component, causes LGMD2D and represents the most common form of LGMD. Early preclinical and clinical trial findings support the feasibility of gene therapy via recombinant adeno-associated viral vectors as a viable treatment approach for many MDs. In this mini-review, we present an overview of recent progress in clinical gene therapy trials of the MD's and touch upon promising preclinical advances.

ELECTROMYOGRAPHIC STAGES OF DENERVATION/REINNERVATION PROCESS IN NEUROMUSCULAR DISEASES: NEED FOR REVISION

Analysis of motor unit potentials (MUPs) parameters registered by needle EMG electrodes is the key for understanding changes of the motor units in different neuromuscular disorders. The classification of MUPs changes known as electromyographic stages (EMGS) of the denervation/reinnervation process (DRP) is based on the analysis of myogenic, synaptic neurogenic and neuronal disorders. Current article focuses on pathogenesis of typical and atypical MUPs of low duration, decreased and increased amplitude, additionally muscle biopsy data and neurophysiological assessment of muscle fiber density, and мacro-EMG. The absence of primary neurogenic disturbances in inflammatory and non-inflammatory muscle diseases, as well as in neuro-muscular junction disorders, confirmed by single fiber EMG and мacro-EMG makes it impossible to discuss the concept of EMG stages in patients with these levels of pathology. The EMG stages concept can be applied for peripheral nerve and motor neuron disturbances only, reflecting the volume but not the efficiency of reinnervation.

Quantitative motor unit action potential analysis of supraspinatus, infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport horses.

Reference values for quantitative electromyography (QEMG) in shoulder and hindlimb muscles of horses are limited. To determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus (IS), deltoideus (DT) and biceps femoris (BF) muscles. Experimental observational study and retrospective case series. Seven adult healthy Royal Dutch sport horses underwent quantitative motor unit action potential analysis of each muscle using commercial electromyography equipment. Measurements were made according to published methods. One-way ANOVA was used to compare quantitative motor unit action potential variables between muscles, with post hoc testing according to Bonferroni, with significance set at P<0.05. The QEMG and clinical information from horses with lower motor neuron disorders (n = 7) or myopathy (n = 4) were summarised retrospectively. The 95% confidence intervals of duration, amplitude, phases, turns, area and size index of quantitative motor unit action potential were 8.7-10.4 ms, 651-867 μV, 3.2-3.7, 3.7-4.7, 1054-1457 μV·ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 μV, 3.3-3.7, 3.8-4.7, 1349-2204 μV·ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 μV, 2.9-3.7, 2.8-4.5, 380-1374 μV·ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 μV, 2.7-3.2, 2.6-3.1, 296-484 μV·ms and 0.2-0.5 for BF, respectively. Mean duration, amplitude, number of phases and turns, area and size index were significantly (P<0.01) higher in SS and IS than in DT and BF muscles. In addition, 4 of 7 normal horses had >15% polyphasic motor unit action potentials in SS and IS muscles. Differences between muscles should be taken into account when performing QEMG in order to be able to distinguish normal horses from horses with suspected neurogenic or myogenic disorders. These normal data provide the basis for objective QEMG assessment of shoulder and hindlimb muscles. Quantitative electromyography appears to be helpful in diagnosing neuropathies and discriminating these from myopathies.

Temporomandibular disorders in fibromyalgia syndrome: a short-communication

Fibromyalgia syndrome (FMS) is a chronic painful syndrome and the coexistence of a painful condition caused by Temporomandibular Disorders (TMD) and FMS has been frequently raised for several studies; however, a more likely hypothesis is that a set of FMS characteristics may lead to the onset of TMD symptoms and they are not merely coexisting conditions. Therefore, our aim is presenting a review of literature about the relation between fibromyalgia and the signs and symptoms of temporomandibular disorders. For this purpose, a bibliographic search was performed for the period of 1990–2013, in the Medline, Pubmed, Lilacs and Scielo databases, using the keywords fibromyalgia, temporomandibular disorders and facial pain. Here we present a set of findings in the literature showing that fibromyalgia can lead to TMD symptoms. These studies demonstrated greater involvement of the stomatognathic system in FMS and myogenic disorders of masticatory system are most commonly found in those patients. FMS appears to have a series of characteristics that constitute predisposing and triggering factors for TMD.

Disfunção temporomandibular na síndrome da fibromialgia: comunicação breve

Fibromyalgia syndrome (FMS) is a chronic painful syndrome and the coexistence of a painful condition caused by Temporomandibular Disorders (TMD) and FMS has been frequently raised for several studies, however, more likely hypothesis is that a set of FMS characteristics may lead to the onset of TMD symptoms and they are not merely coexisting conditions. Therefore, our aim is presenting a review of literature about the relation between fibromyalgia and the signs and symptoms of temporomandibular disorders. For this purpose, a bibliographic search was performed of the period of 1990‐2013, in the Medline, Pubmed, Lilacs and Scielo databases, using the keywords fibromyalgia, temporomandibular disorders and facial pain. Here we present a set of findings in the literature showing that fibromyalgia can lead to TMD symptoms. These studies demonstrated greater involvement of the stomatognathic system in FMS and myogenic disorders of masticatory system are the most commonly found in those patients. FMS appears to have a series of characteristics that constitute predisposing and triggering factors for TMD.

Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as variable biomarkers.

Cardiac characterization of sgca-null mice using high resolution echocardiography

Limb-girdle muscular dystrophy 2D (LGMD2D) is an inherited myogenic disorder belonging to the group of muscular dystrophies. Sgca-null mouse is a knock-out model of LGMD2D. Little is known about cardiac phenotype characterization in this model at different ages. We conducted a prospective study to characterize cardiac sgca-null mice phenotype using high resolution Doppler echocardiography at different ages. Conventional echocardiography was performed on anesthetised mice using a Vevo 770 (Visualsonics) with 30 MHz cardiac probe. Wild Type (WT) and sgca-null mice were scanned at 13, 15 and 17 months. From M-mode, we measured interventricular septal (IVS) wall thickness, posterior wall (PW) thickness, and end-left ventricular diameter in systolic and diastolic. From the above parameters, we calculated left ventricular (LV) shortening fraction (SF), LV ejection fraction (EF) and LV mass. At age 13 months, PW diastolic thickness was increased in sgca-null mice (0.89±0.14 mm vs 0.73±0.2 mm; P=0.020) and LV mass was higher in sgca-null mice (LV mass 205.2 mg vs 143 mg; P=0.001). We found also dilation of the LV (LVEDD: 4.84 mm vs 4.29 mm; P=0.019) in sgca-null mice. At age 15 months, dilation of the LV (LVEDD: 4.86 mm vs 4 mm; P=0.05) with an increase of the LV mass (165.7 mg vs 127.12; P=0.03) are found in sgca-null mice. At age 17 months, we found a decrease of the PW thickening (17% vs 30%; P=0.036).This work provides echocardiographic insights for the assessment of pharmaceutical therapies in sgca-null mice.

Abstract 18878: Development of a Unique Mode of Cardiac Remodeling in Muscular Dystrophy Patients

The muscular dystrophies (MD) represent an array of inherited myogenic disorders involving mutations and dysregulations of a variety of cytoskeleton or nuclear proteins. Many MD patients also develop a commitant cardiomyopathy. Despite the high incidence of end-stage cardiomyopathy in MD patients there is limited data regarding the mode of maladaptive cardiac remodeling that develops in these patients. In this retrospective study, we examined the hypothesis that MD patients with a cardiomyopathy develop a unique mode of cardiac remodeling as compared to patients with other forms of nonischemic cardiomyopathy. We examined the cardiac MRIs of 3 cohorts (N = 35 per cohort): patients with neuromuscular disorders with associated cardiomyopathy; patients with primary idiopathic nonischemic cardiomyopathy (NICM); and healthy patients from the Dallas Heart Study (DHS). The cardiac MRIs in each group were reviewed, assessing objective measurements of left ventricular ejection fraction (LVEF), mass (LVM), and end diastolic volume (LVEDV). LVM and LVEDV were indexed for body surface area. In addition, left ventricular concentricity 0.67 (LV Conc 0.67 = LVM / LVEDV 0.67 ), a surrogate marker for wall thickness known to decrease in advanced nonischemic heart failure, was computed for each patient. Despite a preserved ejection fraction in the neuromuscular cohort compared to the NICM cohort (58% vs. 30 %, p&lt;0.05), both displayed similar reduced LV Conc 0.67 (4.69 ± 1.05 and 5.16 ± 1.47) compared to the DHS cohort (7.27 ± 0.83). However, whereas the nonischemic cohort demonstrated hypertrophy with marked dilation (95.8 vs. 84.6 g/m 2 and 119.4 vs. 54.7 mL/m 2 , DHS comparison, p&lt;0.05), the neuromuscular cohort demonstrated a reduced cardiac mass (65.6 vs. 84.6 g/m 2 , p&lt;0.05) with only moderate dilation (74.5 vs. 54.7 mL/m 2 , p&lt;0.05) compared to the DHS population. In conclusion, our data suggests that MD patients develop a unique mode of cardiac remodeling and highlights that novel signaling pathways are involved in the development of cardiomyopathy in these patients.

Neuropsychological Profile of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an estimated prevalence of 1 in 3,500 male live births. This disease has long been associated with intellectual impairment. Research has shown that boys with DMD have variable intellectual performance, indicating the presence of specific cognitive deficits. The aim of the study was to use a battery of intelligence, learning, and memory tests to identify a neuropsychological profile in boys with DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old were evaluated using the Wechsler Intelligence Scale for Children-Third Edition, Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data were interpreted using means, standard deviations, percentages, and percentiles. Normative data were also used for further interpretation. The results showed that boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to be lower than Performance IQ (92.64). There was evidence of impaired performance on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension Indexes. Specific deficits in information processing, complex attention, immediate verbal memory span, verbal working memory, verbal comprehension, vocabulary, visuoconstruction ability, and verbal learning and encoding were observed. However, perceptional organization, general fund of information, abstract reasoning, visual discrimination and acuity, visual learning and memory, and verbal memory were adequate. The neuropsychological findings support the hypothesis that these children have specific cognitive deficits as opposed to a global intellectual deficit.

Cardiac asynchrony in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. Heart failure is a classical complication in this disease. Little data are available about systolic dyssynchrony in DMD. We sought to assess the prevalence of left ventricular dysfunction and systolic asynchrony in DMD patients using echocardiographic parameters. We performed electrocardiography and echocardiography for adult's patients with DMD. For systolic dyssynchrony assessment, echocardiography-Doppler was performed and completed by tissular Doppler imaging. 48 DMD were included in our study. Age ranged from 20 to 37years. QRS duration >120ms was present in 10 patients/48 and 1 patient disclosed a QRS duration >150ms. Left ventricular (LV) ejection fraction (EF) ranged from 10 to 62% with a median of 43%. Inter-ventricular asynchrony was found in 11.9% of patients with EF<35% and in 2.6% of patients with EF>35%. Intra-ventricular asynchrony was present in 6% of patients with EF<35%. We found a high prevalence of LV dysfunction in DMD. Systolic ventricular asynchrony seems frequent particularly in patients with EF<35%.

Study on BALB/c mice with EV71 infection by diverse inoculation routes

To study the characteristics of EV71 JN200804 strain infection in one-day old BALBI c mjce and to establish a animal model of EV71 infection , and to provide information and technical support for the evaluation of the EV71 vaccine and antiviral medicine. One-day old BALBic mice were infected with EV71 JN200804 strain through oral( PO) ,intracranial(IC) ,intraperitoneal (IP), intramuscular (IM) routes, respectively. All mice were sacrificed at paralysis of hind limbs and collected organs for viral isolation, RT -PCR and pathological examination, and the electrophysiology were detected before sacrifice. All mice infected through IC, IP and IM routes were paralyzed in hind limbs at 4-5 days and died at 7 days about, the hypokinesia and lethargy of mice were observed through PO routes. The viruses could be isolated and detected in the muscle from mice infected through IC, IP and IM routes and in the spinal cord through IC routes by viral isolation and RT-PCR. The neurogenic and myogenic disorders were detected by electromyography. Histopathologically, the varied pathologic changes were observed in the mouse cerebellum , spinal cord , muscle , heart, lung, liver and kidney. EV71 JN200804 strain can infect one-day old BALBI c mice and induce paralysis of hind limbs, its animal infection model may apply to study of EV71 infection pathogenesis and antiviral medicine, and evaluation of the EV71 vaccine.

Progressive Dysphagia in an Elderly Male

Dysphagia can result from a variety of causes, including central nervous and peripheral nervous system, myogenic, and structural disorders. A 76-year-old man underwent anterior cervical disketomy and fusion 10 years ago, with progressive dysphagia noted 2 years ago. Endoscopy showed an oropharyngeal tumor, and lateral plain film evaluation of the neck revealed a cervical plate extrusion. Removal of the instrumentation and tumor with primary closure of the pharyngeal perforation was performed, and dysphagia was resolved postoperatively. We report the case of an unusual presentation in the pharynx. We should not neglect this rare diagnosis, because it can progress to a life-threatening outcome.

Resveratrol Ameliorates Muscular Pathology in the Dystrophic mdx Mouse, a Model for Duchenne Muscular Dystrophy

Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. We previously showed that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and activator of the NAD(+)-dependent protein deacetylase SIRT1, delays the progression of heart failure and prolongs the lifespan of δ-sarcoglycan-deficient hamsters. Because a defect of dystroglycan complex causes muscular dystrophies, and δ-sarcoglycan is a component of this complex, we hypothesized that resveratrol might be a new therapeutic tool for muscular dystrophies. Here, we examined resveratrol's effect in mdx mice, an animal model of Duchenne muscular dystrophy. mdx mice that received resveratrol in the diet for 32 weeks (4 g/kg diet) showed significantly less muscle mass loss and nonmuscle interstitial tissue in the biceps femoris compared with mdx mice fed a control diet. In the muscles of these mice, resveratrol significantly decreased oxidative damage shown by the immunostaining of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine and suppressed the up-regulation of NADPH oxidase subunits Nox4, Duox1, and p47(phox). Resveratrol also reduced the number of α-smooth muscle actin (α-SMA)(+) myofibroblast cells and endomysial fibrosis in the biceps femoris, although the infiltration of CD45(+) inflammatory cells and increase in transforming growth factor-β1 (TGF-β1) were still observed. In C2C12 myoblast cells, resveratrol pretreatment suppressed the TGF-β1-induced increase in reactive oxygen species, fibronectin production, and expression of α-SMA, and SIRT1 knockdown blocked these inhibitory effects. SIRT1 small interfering RNA also increased the expression of Nox4, p47(phox), and α-SMA in C2C12 cells. Taken together, these findings indicate that SIRT1 activation may be a useful strategy for treating muscular dystrophies.

Masseter Tenomyositis

The masseter muscle is an integral part of the oral facial complex and one of the muscles of mastication. It functions with the other masticatory muscles in moving and posturing the mandible and in verbalizing, eating and swallowing. When a patient has temporomandibular dysfunction (TMD) or a myogenic disorder, the integrity of the masseter muscle can be compromised resulting in pain, malfunction, inflammation and/or swelling. A careful evaluation of the masseter muscles is necessary in facial pain patients since the pain can originate from a distant site and be referred to this area. One of the little known disorders involving the masseter and its tendinous origin is tenomyositis, in which an inflammation of the muscle and its tendon occurs. In this retrospective study, the charts of 114 consecutive patients (N=114) were evaluated to determine the prevalence of this disorder and the reported etiology.

Oculopharyngeal muscular dystrophy in Norway. Survey of a large Norwegian family.

Oculopharyngeal muscular dystrophy was first described by Taylor in 1915. A substantial number of cases have been reported from North America, the disorder being most frequent in Quebec, Canada. The onset of disease is in middle life, most often presenting with ptosis and a slight degree of ophthalmoplegia, followed some years later by dysphagia and often by proximal limb weakness. The course is slowly progressive, but the dysphagia may become severe and has caused death by starvation in several cases. The disorder is transmitted autosomally dominant in families. The present report describes a large Norwegian family with 13 affected members of whom we have examined eight. Transmission is autosomally dominant, mode of presentation may be either by ptosis or by dysphagia. In rare cases gait difficulties may be the presenting symptom. Electromyographic and muscle biopsy examinations demonstrate a primary myogenic disorder.

Complete atrioventricular block in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. It is characterized by progressive muscle wasting and weakness of variable distribution and severity. Heart is involved leading to heart failure. Conduction abnormalities are unusual. We report a case of complete atrio-ventricular block in a DMD patient.

Muscle engraftment of myogenic progenitor cells following intraarterial transplantation

Cell-based therapy continues to be a promising avenue for the treatment of Duchenne muscular dystrophy (DMD), an X-linked skeletal muscle-wasting disease. Recently, we demonstrated that freshly isolated myogenic progenitors contained within the adult skeletal muscle side population (SP) can engraft into dystrophic fibers of nonirradiated mdx(5cv) mice after intravenous transplantation. Engraftment rates, however, have not been therapeutically significant, achieving at most 1% of skeletal muscle myofibers expressing protein from donor-derived nuclei. To enhance the engraftment of transplanted myogenic progenitors, an intraarterial delivery method was adapted from a previously described procedure. Cultured, lentivirus-transduced skeletal muscle SP cells, derived from mdx(5cv) mice, were transplanted into the femoral artery of noninjured mdx(5cv) mice. Based on the expression of microdystrophin or green fluorescent protein (GFP) transgenes in host muscle, sections of the recipient muscles exhibited 5%-8% of skeletal muscle fibers expressing donor-derived transgenes. Further, donor muscle SP cells, which did not express any myogenic markers prior to transplant, expressed the satellite cell transcription factor, Pax7, and the muscle-specific intermediate filament, desmin, after extravasation into host muscle. The expression of these muscle-specific markers indicates that progenitors within the side population can differentiate along the myogenic lineage after intraarterial transplantation and extravasation into host muscle. Given that femoral artery catheterization is a common, safe clinical procedure and that the transplantation of cultured adult muscle progenitor cells has proven to be safe in mice, our data may represent a step toward the improvement of cell-based therapies for DMD and other myogenic disorders.

1125. AAV-Mediated Myostatin Propeptide Gene Delivery Results in Growth and Hypertrophy of Skeletal but Not Cardiac Muscles

Muscular dystrophies are inherited myogenic disorders characterized by progressive muscle wasting and weakness. Because of the lack of effective treatment with traditional pharmaceutical agents, gene therapy and stem-cell therapy have been vigorously explored. Besides gene replacement therapy, a different form of gene therapy, i.e., expression of |[ldquo]|booster genes|[rdquo]|, has been investigated, aiming at alleviating the secondary deficiencies in muscular dystrophies rather than the primary ones. Blockade of myostatin is one of such strategies. Myostatin is a member of the TGF-beta family and a negative regulator of skeletal muscle growth. Studies using transgenic mice or antagonist antibody against myostatin showed promotion of muscle growth and amelioration of muscular dystrophy. However, gene delivery of myostatin inhibitors has not been reported.

Quantitative Electromyographic Examination in Myogenic Disorders of 6 Horses

Electromyographic needle examination (EMG), including the semiautomatic quantitative analysis of motor unit action potential (MUAP), is an important diagnostic tool for myopathy in humans. The diagnostic possibilities of this technique have not been fully explored in horses; however, recent studies have shown that MUAP analysis can be performed in conscious horses. To determine the diagnostic possibilities of EMG in horses, we compared the EMG results of the subclavian muscle, the triceps, and the lateral vastus muscle in 6 equine patients thought to have myogenic disorders with those in 7 normal control horses. The EMG results were compared with the results of the histopathologic examination of the lateral vastus muscle in patients and controls. Histopathologic examination showed muscle disease in 3 patients. In the patient group, several types of abnormal spontaneous activities were observed (mainly fibrillation potentials and positive sharp waves), and the MUAPs of the patient group had a markedly shorter duration and lower amplitude than those of the control group. In the subclavian muscle, triceps, and lateral vastus muscle of affected horses, the MUAP duration was 5.0 +/- 0.4 (mean +/- SD), 3.9 +/- 0.3, and 4.7 +/- 1.1 milliseconds, respectively. The MUAP amplitude was 217 +/- 55, 150 +/- 74, and 180 +/- 54 microV; the number of phases was 2.4 +/- 0.2, 2.5 +/- 0.3, and 2.3 +/- 0.1; and the number of turns was 2.6 +/- 0.2, 2.4 +/- 0.2, and 2.8 +/- 0.5, respectively. In conclusion, it appears that the EMG may be a more sensitive method than other techniques for examining muscle biopsies for diagnosis of early-stage myopathy in horses.

Quantitative Electromyographic Examination in Myogenic Disorders of 6 Horses

Quantitative Electromyographic Examination in Myogenic Disorders of 6 Horses