Population-based incidence rates of 15 neuromuscular disorders: a nationwide capture-recapture study in the Netherlands.

Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders.

Perioperative Management of Paraneoplastic Necrotizing Myopathy in Thyroidectomy: A Case Report.

Perioperative management of patients with myopathies can be challenging due to the increased risk of malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis (AIR). However, currently, there is no evidence regarding the optimal anesthetic management for paraneoplastic necrotizing myopathy (PNM) (total intravenous anesthetic vs. volatile anesthetics). Here, I report a case where anesthesia was administered safely using volatile anesthetics. A 63-year-old female presented with PNM associated with papillary thyroid carcinoma, necessitating urgent thyroidectomy. The patient, previously diagnosed with anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibody-associated myopathy, exhibited progressive weakness and dysphagia, prompting suspicion of PNM. The patient's compromised respiratory status, attributed to tracheal compression by a large goiter, necessitated an urgent thyroidectomy. Anesthetic management considerations included the potential effect of HMGCR-M on respiratory muscles and the need for careful planning to mitigate postoperative complications. The patient underwent total thyroidectomy, left central compartment clearance, and tracheostomy. The surgery proceeded uneventfully, with meticulous monitoring and adjustment of anesthetic agents to maintain hemodynamic stability. Postoperatively, the patient recovered well, demonstrating complete resolution of neurological symptoms during a three-month follow-up. The case underscores the importance of recognizing paraneoplastic syndromes in the context of thyroid surgery and highlights potential challenges faced by anesthesiologists. Despite the lack of established safety data for anesthetic drugs in HMGCR-M necrotizing myopathy, the case demonstrates the successful use of sevoflurane and rocuronium.

Natural history of cardiac involvement in myotonic dystrophy type 1 - Emphasis on the need for lifelong follow-up.

BACKGROUND: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols. METHODS: Patients with genetically confirmed DM1 were identified. Data on patient characteristics, performed investigations (12 lead ECG, Holter monitoring and echocardiography), and clinical outcomes were retrospectively collected from electronic health records. RESULTS: We included 195 patients (52% men) with a mean age at baseline evaluation of 41 years (range 14-79). The overall prevalence of cardiac involvement increased from 42% to 66% after a median follow-up of 10.5 years. There was a male predominance for cardiac involvement at end of follow-up (74 vs. 44%, p < 0.001). The most common types of cardiac involvement were conduction abnormalities (48%), arrhythmias (35%), and left ventricular systolic dysfunction (21%). Only 17% of patients reported cardiac symptoms. The standard 12­lead ECG was the most sensitive diagnostic modality and documented cardiac involvement in 24% at baseline and in 49% at latest follow-up. However, addition of Holter monitoring and echocardiography significantly increased the diagnostic yield with 18 and 13% points at baseline and latest follow-up, respectively. Despite surveillance 35 patients (18%) died during follow-up; seven due to SCD. CONCLUSIONS: In patients with DM1 cardiac involvement was highly prevalent and developed during follow-up. These findings justify lifelong follow-up with ECG, Holter, and echocardiography. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

Diffusion tensor imaging reveals subclinical alterations in muscles of patients with Becker muscular dystrophy.

OBJECTIVES: Becker muscular dystrophy (BMD) is a relatively less investigated neuromuscular disease, partially overlapping the phenotype of Duchenne dystrophy (DMD). Physiopathological and anatomical patterns are still not comprehensively known, despite recent effort in the search of early biomarkers. Aim of this study was to selectively compare normal appearing muscles of BMD with healthy controls. METHODS: Among a pool of 40 BMD patients and 20 healthy controls, Sartorius and gracilis muscles were selected on the basis of a blinded clinical quantitative/qualitative evaluation, if classified as normal (0 or 1 on Mercuri scale) and subsequently segmented on diffusion tensor MRI scans with a tractographic approach. Diffusion derived parameters were extracted. RESULTS: Non-parametric testing revealed significant differences between normal and normal appearing BMD derived parameters in both muscles, the difference being more evident in sartorius. Bonferroni-corrected P-values (<.05) of Mann-Whitney test could discriminate between BMD and controls for standard deviation of all diffusion parameters (mean diffusivity, fractional anisotropy, axial and radial diffusivity) in both sartorius and gracilis, while in sartorius the significant difference was found also in the average values of the same parameters (with exception of RD). CONCLUSIONS: This method could identify microstructural alterations in BMD normal appearing sartorius and gracilis. ADVANCES IN KNOWLEDGE: Diffusion based MRI could be able to identify possible early or subclinical microstructural alterations in dystrophic patients with BMD.

Polymyositis: A Case Report.

Inflammatory myopathies are a group of diseases whose common pathway is immune-mediated muscle damage, one of which is polymyositis. The definition of polymyositis is controversial, with proponents advocating a definition based on immunohistochemical and histopathological findings in muscle biopsies, while other proponents advocate a definition based on clinical manifestations and histopathological findings. Polymyositis is a quite rare disease that is clinically characterized by progressive proximal muscle weakness with a symmetric distribution. Within the diagnostic approach, laboratory studies show elevation of sarcoplasmic enzymes; nerve conduction tests are performed, which may aid in distinguishing myopathic causes of weakness from neuropathic disorders; and muscle biopsy is considered the gold standard to diagnose inflammatory myopathy and to distinguish the subclasses. We report the case of a 61-year-old male patient who presented generalized symmetrical weakness, predominantly in the upper extremities, and dysphagia, whose laboratory studies, autoantibodies, and muscle biopsy were confirmatory of this entity.

Impairments and comorbidities in adults with cerebral palsy and spina bifida: a meta-analysis.

Introduction: Aging with a childhood-onset disability, such as cerebral palsy (CP), spina bifida (SB), and muscular diseases (MD), comes along with significant impairments and comorbidities. Despite the increasing evidence an overall picture is lacking. This study aimed to review the literature about adults with CP/SB/MD and impairments and comorbidities to perform a meta-analysis. Materials and methods: Embase, PubMed, Cinahl, and Google Scholar were searched (2000-2020). Search terms included adults with one of the aforementioned disabilities combined with impairments and comorbidities. If specific impairments or comorbidities were reported by at least four studies, these were included in the study. Pooled prevalence (95% Confidence Interval) of impairments/comorbidities were calculated. Results: The search yielded 7,054 studies of which 95 were included in the meta-analysis (64 CP, 31 SB, 0 MD). In total estimates were calculated for 26 (CP) and 11 (SB) outcomes. In adults with CP, pain [56.4% (95%CI 48.8-63.8)], deformities [44.2% (95%CI 12.9-78.4)], intellectual disability [37.2% (95%CI 26.7-48.3)], and fatigue [36.9% (95%CI 24.6-50.1)] were most prevalent; renal disease [3.0% (95%CI 2.1-4.2)] and stroke/rheumatic diseases {4.8% (95%CI 3.4-6.5; 4.8% (95%CI 1.5-9.9)] respectively} were least prevalent. For adults with SB, bladder incontinence [60.0% (95%CI 50.5-69.2)], bowel incontinence [49.2% (95%CI 34.5-64.0)], pain [44.1% (95%CI 27.4-61.5)], and sleeping problems [30.3% (95%CI 4.7-65.8)] were most prevalent; diabetes [4.8% (95%CI 2.8-7.3)] and renal disease [8.7% (95%CI 2.0-19.9)] were least prevalent. The included studies showed large heterogeneity. Conclusions: More research is needed to study health issues in adults with MD. Adults with CP or SB deal with a variety of health issues. More attention for the mental health of these adults is needed. There also is a need for accessible and adequate screening, preventive measures and clinical follow-up.

Dysregulation of Metabolism and Proteostasis in Skeletal Muscle of a Presymptomatic Pompe Mouse Model.

Pompe disease is a rare genetic metabolic disorder caused by mutations in acid-alpha glucoside (GAA) leading to pathological lysosomal glycogen accumulation associated with skeletal muscle weakness, respiratory difficulties and cardiomyopathy, dependent from the GAA residual enzyme activity. This study aimed to investigate early proteomic changes in a mouse model of Pompe disease and identify potential therapeutic pathways using proteomic analysis of skeletal muscles from pre-symptomatic Pompe mice. For this purpose, quadriceps samples of Gaa6neo/6neo mutant (Pompe) and wildtype mice, at the age of six weeks, were studied with three biological replicates for each group. The data were validated with skeletal muscle morphology, immunofluorescence studies and western blot analysis. Proteomic profiling identified 538 significantly upregulated and 16 significantly downregulated proteins in quadriceps muscles derived from Pompe animals compared to wildtype mice. The majority of significantly upregulated proteins were involved in metabolism, translation, folding, degrading and vesicular transport, with some having crucial roles in the etiopathology of other neurological or neuromuscular diseases. This study highlights the importance of the early diagnosis and treatment of Pompe disease and suggests potential add-on therapeutic strategies targeting protein dysregulations.

Is Intermittent Abdominal Pressure Ventilation Still Relevant? A Multicenter Retrospective Pilot Study.

Non-invasive ventilatory support (NVS) is a technique used to reduce respiratory work in neuromuscular diseases, preventing the progression of respiratory failure. NVS is usually administered via a nasal or an oronasal mask, causing discomfort, especially in patients ventilated for more than 16 h/day. Intermittent abdominal pressure ventilation (IAPV) differs completely from conventional NVS and consists of a portable ventilator and a corset with Velcro closures as the interface. In our study, the practicability and efficacy of IAPV were studied in three Italian centers monitoring 28 neuromuscular patients using IAPV who were then retrospectively analyzed. The primary outcomes were an improvement in hypoxemia and the normalization of hypercapnia, and the secondary outcome was an improvement in quality of life. Data were collected at baseline (T0) and after two hours of ventilation (T1), with follow-ups at three months (T2) and six months (T3). Statistical significance was found for PaCO2 over time (F (2.42) = 7.63, p = 0.001) and PaO2 (W = 0.539, p = 0.033). The time of NVS usage also significantly affected the quality of life (F (2.14) = 6.90, p = 0.010), as seen when comparing T0 and T3. As an alternative ventilation method, IAPV is still relevant today and could become a key part of daytime support, especially for patients who do not tolerate standard daytime NVS with an oral interface.

Case report: Diagnostic clues for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy in pediatric patients.

Introduction: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is a recently recognized pathology, but appears less common in children and the characteristics of pediatric cases remain unclear. Case report: We report a pediatric case of anti-HMGCR myopathy accompanied by skin rash. Motor function and serum creatine kinase level normalized after combinational treatment including early intravenous immunoglobulin, methotrexate, and corticosteroid. Literature review: We searched PubMed and identified reports with detailed clinical information of 33 pediatric patients <18 years old with anti-HMGCR myopathy. Among these 33 patients and our own case, skin rash and maximum serum creatine kinase level >5,000 IU/L were observed in 44% (15 patients) and 94% (32 patients), respectively. Skin rash was present in 15 of the 22 patients (68%) ≥7 years old and none of the 12 patients (0%) <7 years old. Among the 15 patients with skin rash, 12 (80%) presented with erythematous rash. Conclusion: Erythematous skin rash may offer a clue to the diagnosis of anti-HMGCR myopathy in children with muscle weakness and serum creatine kinase level >5,000 IU/L in the absence of other myositis-specific antibodies, particularly in patients ≥7 years old. Our results suggest the importance of early anti-HMGCR testing in pediatric patients with these manifestations.

New Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii are Effective for Improving the Muscle Strength of Mice with Immobilization-Induced Muscular Atrophy.

Muscular atrophy is a muscle disease in which muscle mass and strength decrease due to aging, injury, metabolic disorders, or chronic conditions. Proteins in muscle tissue are degraded by the ubiquitin-proteasome pathway, and atrophy accelerates this pathway. Akkermansia muciniphila and Faecalibacterium prausnitzii strains are effective agents against metabolic and inflammatory diseases in next-generation probiotic research. In this study, we evaluated the efficacy of A. muciniphila strain EB-AMDK19 and F. prausnitzii strain EB-FPDK11 in a mouse model of muscular atrophy, since atrophy inhibits energy metabolism and immune activation. After oral administration of each strain for 4 weeks, the hind legs of the mice were fixed with a plaster cast to immobilize them for a week. As a result, the administration of EB-AMDK19 and EB-FPDK11 strains improved grip strength but did not increase muscle mass. At the molecular level, A. muciniphila and F. prausnitzii treatments decreased the expression levels of ubiquitin-proteasome genes, atrogin-1, MuRF, and cathepsin L. They increased the expression level of the mitochondrial biogenesis regulatory gene, PGC-1α. The effect of the strains was confirmed by a decrease in myostatin. Furthermore, A. muciniphila and F. prausnitzii modulated the immune function by enhancing ZO-1 and inhibiting IL-6. In particular, EB-AMDK19 promoted the expression of IL-10, an anti-inflammatory cytokine. These results suggest that A. muciniphila and F. prausnitzii may have beneficial effects on muscular atrophy, verified by newly isolated EB-AMDK19 and EB-FPDK11 as potential next-generation probiotics.

Transient receptor potential channel 6 in human skeletal muscle fibers: Investigation in fresh and conserved tissue samples.

Transient receptor potential channel 6 (TRPC6) channels constitute non-selective cation channels that are localized in the plasmalemma or sarcolemma, and have a leading permeability for the bivalent calcium ion. Animal models indicate an involvement of TRPC6 in malignant hyperthermia. The expression of TRPC6 in the sarcolemma has been demonstrated in the skeletal muscle fibers of mice. The importance of TRPC6 channels for the influx of calcium into the muscle cell has also been established. The presence of TRPC6 in tissues of human skeletal muscle is surmised. In order to confirm the presence of TRPC6 in human skeletal muscle, tissue samples of various skeletal muscles (Musculus deltoideus, pectoralis major, trizeps brachii and rectus femoris) from eight different human donors (n=8; six preserved cadavers and two non-preserved cadavers) were examined using immunohistochemistry. TRPC6 was found in all muscle fibers of all investigated bodies. Appropriate controls yielded the expected results. As demonstrated in animal studies and in studies of human cells, the presented results confirmed the presence of TRPC6 in human skeletal muscle tissue. Thus, TRPC6 is most likely important for calcium homeostasis and the proper function of human muscle fibers and may be a target for treatment in various muscular diseases.

Expanding the MYOD1 Phenotype: A Case Report of a Patient Diagnosed Whilst Pregnant.

A 38-year-old pregnant woman presented at 30 weeks gestation in respiratory distress with pre-eclampsia. This was on the background of slowly progressive dyspnoea over six years, with generalised weakness and previous surgery for ptosis and prognathia. After successful caesarean delivery at 31 weeks, the patient was found to have a homozygous likely pathogenic variant in the MYOD1 gene. This case presents a milder phenotype for MYOD1 congenital myopathy, usually associated with diaphragmatic defects, respiratory insufficiency and dysmorphic facies. It also highlights the difficulties of managing an undiagnosed patient through pregnancy.

Generation of Calpain-3 knock-out porcine embryos by CRISPR-Cas9 electroporation and intracytoplasmic microinjection of oocytes before insemination.

Limb girdle muscular dystrophy type R1 (LGMDR1) is an autosomal recessive myopathy described in humans resulting from a deficiency of calpain-3 protein (CAPN3). This disease lacks effective treatment and an appropriate model, so the generation of KO pigs by CRISPR-Cas9 offers a way to better understand disease ethology and to develop novel therapies. Microinjection is the main method described for gene editing by CRISPR-Cas9 in porcine embryo, but electroporation, which allows handling more embryos faster and easier, has also recently been reported. The objective of the current study was to optimize porcine oocyte electroporation to maximize embryo quality and mutation rate in order to efficiently generate LGMDR1 porcine models. We found that the efficiency of generating CAPN3 KO embryos was highest with 4 electroporation pulses and double sgRNA concentration than microinjection. Direct comparison between microinjection and electroporation demonstrated similar rates of embryo development and mutation parameters. The results of our study demonstrate that oocyte electroporation, an easier and faster method than microinjection, is comparable to standard approaches, paving the way for democratization of transgenesis in pigs.

An uncommon cause of myalgia: A case report on systemic lupus erythematous myopathy.

Introduction: Myositis in systemic lupus erythematous may present in a wide range of clinical spectrum. It can be part of an overlap syndrome, or mixed connective tissue disease or a musculoskeletal manifestation of systemic lupus erythematous itself. Case presentation: Here, we present a young girl with an underlying systemic lupus erythematous presented with the typical manifestation of severe proximal myopathy in the background of normal creatine kinase values. The diagnosis of systemic lupus erythematous myopathy was made after excluding other more common causes of myopathies which in itself is a very rare occurrence. Discussions: A normal creatine kinase values does not exclude systemic lupus erythematous myositis, but make the diagnosis more challenging. However, there are other parameters or diagnostic tools which can be used to exclude a myositis. Conclusion: This case elucidates the importance of history and physical examination in the face of some conflicting laboratory data.

Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.

BACKGROUND: Major efforts have been made in the last decade to develop and improve therapies for proximal spinal muscular atrophy (SMA). The introduction of Nusinersen/Spinraza™ as an antisense oligonucleotide therapy, Onasemnogene abeparvovec/Zolgensma™ as an AAV9-based gene therapy and Risdiplam/Evrysdi™ as a small molecule modifier of pre-mRNA splicing have set new standards for interference with neurodegeneration. MAIN BODY: Therapies for SMA are designed to interfere with the cellular basis of the disease by modifying pre-mRNA splicing and enhancing expression of the Survival Motor Neuron (SMN) protein, which is only expressed at low levels in this disorder. The corresponding strategies also can be applied to other disease mechanisms caused by loss of function or toxic gain of function mutations. The development of therapies for SMA was based on the use of cell culture systems and mouse models, as well as innovative clinical trials that included readouts that had originally been introduced and optimized in preclinical studies. This is summarized in the first part of this review. The second part discusses current developments and perspectives for amyotrophic lateral sclerosis, muscular dystrophies, Parkinson's and Alzheimer's disease, as well as the obstacles that need to be overcome to introduce RNA-based therapies and gene therapies for these disorders. CONCLUSION: RNA-based therapies offer chances for therapy development of complex neurodegenerative disorders such as amyotrophic lateral sclerosis, muscular dystrophies, Parkinson's and Alzheimer's disease. The experiences made with these new drugs for SMA, and also the experiences in AAV gene therapies could help to broaden the spectrum of current approaches to interfere with pathophysiological mechanisms in neurodegeneration.

Importance of plasma ghrelin levels with special reference to nutritional metabolism and energy expenditure in pediatric patients with severe motor and intellectual disabilities.

BACKGROUND & AIMS: Nutritional metabolism is complex in pediatric patients with severe motor and intellectual disability (SMID), and therefore, appropriate estimation of the energy requirements is difficult. Focusing on ghrelin's role in energy metabolism regulation, we investigated plasma ghrelin levels in pediatric SMID patients and analyzed its nutritional significance as a regulatory marker of energy reserve. METHODS: Fasting plasma total, acyl, and des-acyl ghrelin levels in 40 patients with SMID, including cerebral palsy (CP) (n = 20) and muscular disease (MD) (n = 8), and healthy controls (n = 13) were investigated. The correlations of plasma ghrelin levels with anthropometry, blood nutritional markers, energy intake, and resting energy expenditure (REE) measured with indirect calorimetry were analyzed. A p value < 0.05 was considered significant. RESULTS: SMID patients had significantly higher acyl ghrelin, and lower body mass index (BMI), z-scores of body weight (BW), body height and BMI, and albumin than controls. CP patients had significantly higher total and acyl ghrelin, z-score of the mid-upper arm circumference (MUAC), retinol-binding protein, transthyretin, creatinine, and glucose than MD patients. Total and acyl ghrelin in CP patients and des-acyl ghrelin in MD patients had significant negative correlations with MUAC and upper arm fat area. In CP patients, total and acyl ghrelin had significant positive correlations with REE/BW (kcal/kg), and total ghrelin was predictive of REE/BW (r2 = 0.625, p < 0.0001). CONCLUSIONS: An increase in acyl ghrelin observed in SMID patients possibly indicates energy reserve deficiency. In CP patients, total and acyl ghrelin inversely reflected total body fat mass, resulting in strongly positive correlations with REE/BW. The measurement of plasma ghrelin may be useful to assess nutritional metabolism and energy reserve in pediatric SMID patients, such as CP and MD patients.

Descripción clínica de pacientes pediátricos con enfermedades neuromusculares en una muestra de población chilena / Clinical description of pediatric patients with neuromuscular diseases in a Chilean population sample

OBJETIVO: Describir clínica y diagnóstico de 152 pacientes pediátricos asistentes al policlínico del Programa de Enfermedades Neuromusculares (ENM) en un centro terciario de la Región Metropolitana, Chile. METODOLOGÍA: Revisión de fichas programa EMN (2012-2016). RESULTADOS: 49% niñas, mediana de edad: 9 años (rango, 0­18), consultan por alteraciones de la marcha, debilidad e hipotonía. Segmentos más afectados son músculo y nervio periférico (92%). Diagnósticos más frecuentes son neuropatías adquiridas (26,1%), distrofias musculares (14,8%) y trastornos miotónicos (12,7%). Comorbilidades más frecuentes son patología traumatológica (23,2%) y discapacidad intelectual (13,4%). Los pacientes con patología hereditaria tienen mayor chance de requerir ventilación mecánica (OR 15,4; IC 95% 1,9­119,2) y presentar morbilidad traumatológica (OR 4,1; IC 1,03­16,4) que los con patología adquiridas. Confirmación genético-molecular en 38,4% de los pacientes con patología hereditaria. CONCLUSIONES: El conocimiento de características clínicas y posibilidades de estudio de las ENM puede mejorar las estrategias de atención.

INTRODUCTION: Neuromuscular diseases (NMS) represent a heterogeneous group of acquired and hereditary pathologies that affect the motor unit. There are few descriptive studies of patients with NMS in Chile and Latin America. OBJECTIVES: To clinically and epidemiologically characterize the pediatric population attending a polyclinic run using the NMS program of a hospital in the Metropolitan Region in Chile. Methodology: A review was made of database and clinical records of patients diagnosed with NMS between January 2012 and December 2016. RESULTS: A total of 142 patients, 51% of whom were male, with a median age 9 years (0-18 years), were included. The most frequent reasons for consultation were altered gait, decreased strength, and hypotonia. The most frequently affected segments were muscles and peripheral nerves (92% of the sample). The most frequent diagnoses were acquired neuropathies (26.1%), muscular dystrophies (14.8%), and myotonic disorders (12.7%). The most frequent comorbidities were traumatological pathologies (23.2%) and intellectual disabilities (13.4%). When comparing NMS with hereditary vs. acquired etiologies, those with hereditary etiologies had a higher risk of requiring mechanical ventilation (OR 15.4 [95%CI 1.9-119.2]) and having a traumatological disease (OR 4.1 [CI 1.03-16.4]) compared to those with acquired etiologies. For 38.4% of patients with hereditary etiologies, confirmation was obtained through molecular genetic testing. CONCLUSIONS: This study provides information on the frequency of NMS and their main comorbidities in a Chilean pediatric sample. These results provide information regarding current possibilities for studies and could aid in planning care for these patients in our country. Keywords: Neuromuscular disease, Muscular disease, Neuropathies, Neurological Diagnostic.

Combination of atorvastatin and gemfibrozil plus physical activity: an animal model of statin/fibrate-induced myopathy.

INTRODUCTION: Drug-induced myopathy is among the most common causes of muscle disease. Lipid-lowering drugs, primarily the statins as inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are a common cause of myopathy. Statin-fibrate combination potentially increases risk for myopathy and rhabdomyolysis. Blood levels of the enzymes creatine kinase (CK), aldolase and lactate dehydrogenase (LDH) increase during myopathy. Exercise may be a trigger for statin-associated muscle symptoms (SAMS). METHODS: In this study a model of myopathy induction was designed via combination of oral atorvastatin, gemfibrozil and exercise for ten days in rats. To maximise exercise, the rats were placed in a pool of water and allowed to swim before sinking in the last three days. Finally, the mean of swimming tolerance times and blood levels of creatine kinase, aldolase and lactate dehydrogenase were measured. RESULTS: The results showed a significantly (p < 0.05) decreased swimming tolerance time and elevated enzyme levels in rats receiving atorvastatin (ATV) and gemfibrozil (GMF) plus exercise compared with those rats in other groups. This animal model can be used to evaluate the effects of medication on reduction of statin/fibrate-induced myopathy.

Influence of Different Hardness Custom Foot Insoles in the Electromyography Activity Patterns of the Thigh and Hip Muscles during Motorcycling Sport: A Crossover Study.

: Nowadays, the use of insoles in sport practice have been recognized to decrease the foot and lower limb injury patterns. The aim of this study was to analyse the effect of four types of hardness insoles (HI) in the activity patterns of the hip and thigh muscles (HTM) in motoriders during motorcycling sport. The study was a crossover trial. Subjects were elite motoriders. The mean age was 33 ± 5.14 years. Electromyography (EMG) of hip and thigh muscles (HTM) data was registered via surface while subjects were riding on an elite motorcycle simulator. Subjects had to complete different tests with randomly hardest insoles (HI): 1: only polypropylene (58° D Shore); 2: Polypropylene (58° D Shore) with selective aluminium in hallux and metatarsal heads (60 HB Brinell hardness); 3: Ethylene vinyl acetate (EVA) (52° A Shore); and finally, 4: Ordinary EVA (25° A Shore) as the control. EMG patterns of the HTM, riding on an elite motorcycle simulator, showed the lowest peak amplitude with the insoles with polypropylene and selective aluminium. Using the hardest insoles in our study (selective aluminium) the EMG amplitude peaks decreased in all HTM.

Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Additionally, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.