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[Limb-girdle muscular dystrophy; update].

Sixteen different forms of limb-girdle muscular dystrophies (LGMDs) have emerged from recent molecular genetic studies, six forms with a dominant trait and ten forms with a recessive trait. Among 1,420 Japanese patients with muscular dystrophy analyzed at NCNP, LGMD is the secondly largest category (19%) following dystrophinopathy (56%). Within LGMDs, the occurrence of LGMD2A (calpainopathy), LGMD2B (dysferlinopathy), and LGMD2C-F (sarcoglycanopathy) is 26%, 18%, and 6.6%, respectively, however, causative genes have not been specified in about 50% of the LGMD patients. LGMD2A patients show atr

[A case of chronic toluene poisoning with myopathic changes].

We reported a 27-year-old man, who had inhaled toluene vapor for 11 years and developed both polyneuropathy and myopathy. He gradually developed progressive muscular weakness in the limbs 2 months after the last inhalation and became nonambulant. Neurological examination revealed distal dominant muscular weakness and hypoactive deep tendon reflexes, especially in the legs. The cranial nerves were intact and neither sensory disturbances nor cerebellar signs were observed. Laboratory studies demonstrated mildly elevated serum CK value, but serum electrolytes and urinalysis were normal. Electromy

Thigh Muscle Changes in the ACL-Deficient Knee: A 4-Year Longitudinal MRI Study of 1,207 Patients.

BACKGROUND: Anterior cruciate ligament (ACL) injuries may lead to long-term neuromuscular and structural adaptations in thigh muscles. Although quadriceps dysfunction is well reported, chronic changes in other muscle groups, especially in nonoperatively managed ACL-deficient individuals, remain poorly understood. METHODS: The present cohort study utilized Osteoarthritis Initiative data to assess longitudinal thigh muscle changes in individuals with ACL tears confirmed on magnetic resonance imaging (MRI) and no history of reconstruction. A validated deep-learning model segmented muscle cross-s

Unravelling the impact of frontal lobe impairment for social dysfunction in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is an autosomal dominant multisystemic disorder affecting muscular and extra muscular systems, including the central nervous system. Cerebral involvement in myotonic dystrophy type 1 is associated with subtle cognitive and behavioural disorders, of major impact on socio-professional adaptation. The social dysfunction and its potential relation to frontal lobe neuropsychology remain under-evaluated in this pathology. The neuroanatomical network underpinning that disorder is yet to disentangle. Twenty-eight myotonic dystrophy type 1 adult patients (mean age: 46 years ol

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

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… Fig. 7 Transcriptomic analyses exhibited that the amiloride treatment improved glycolysis and ketone body oxidation in cachetic gastrocnemius. a Heat-map plot of relative transcription levels of muscular atrophy-related genes (n = 4). b Expressions of ACOT1, CD36, OXCT1, BDH2, and ACAT1 proteins. c Quantification … atrophy-related genes (n = 4). b Expressions of ACOT1, CD36, OXCT1, BDH2, and ACAT1 proteins. c Quantification of the expressed proteins (n = 4). …

Influence of Polystyrene Microplastics on Mitochondrial Oxidative Damage in Renal and Muscular Tissues of the Freshwater Fish.

Polystyrene microplastics (PS-MPs), an emerging environmental contaminant, have attracted significant concern in recent years. This study aimed to evaluate mitochondrial oxidative damage in renal and muscular tissues of the freshwater fish Anabas testudineus following exposure to environmentally relevant concentrations (13.6 mg L⁻1 and 23.6 mg L⁻1) of PS-MPs for 1, 7, and 15 days. Exposure to PS-MPs disrupted the antioxidant defense system within the mitochondrial compartments of renal and muscle tissues, leading to increased levels of hydrogen peroxide generation and lipid peroxidation. PS-MP

Involvement of Phosphate and the Consequences of Its High Consumption in Energy Metabolism and Muscle Functions.

Phosphate is an important element in energy metabolism and muscle function and is essential for numerous biological processes. This review emphasizes the implications of increased phosphate intake, particularly from processed foods supplemented with phosphate additives. These dietary habits raise substantial concerns regarding their potential health effects, including the exacerbation of metabolic disorders. Elevated phosphate levels disrupt the delicate balance between energy production and utilization, markedly influencing key metabolic processes in skeletal muscle. Excessive phosphate intak

Synthesis, Biological Activity, and Molecular Dynamics Simulations of LNA-Charge Neutral Linkages for Enhanced Splice-Switching Antisense Oligonucleotides.

Antisense oligonucleotides are promising therapeutic agents for a range of diseases, having found special clinical success for splice-switching genetic conditions such as spinal muscular atrophy and Duchenne muscular dystrophy. However, novel chemistries are still required to discover modifications which improve their druggable properties. For in vitro studies, thermal duplex stability, resistance to enzymatic degradation and gymnotic cellular activity are important, and biodistribution, toxicology and potency must be optimised for clinical progression. We investigate the combination of locked…

A shape-based functional index for objective assessment of pediatric motor function.

Clinical assessments for neuromuscular disorders, such as Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD), continue to rely on subjective measures to monitor treatment response and disease progression. We introduce a novel method using wearable sensors to objectively assess motor function during daily activities in 19 patients with DMD, 9 with SMA, and 13 age-matched controls. Pediatric movement data is complex due to confounding factors such as limb length variations in growing children and variability in movement speed. Our approach uses Shape-based Principal Component An…

Diaphragmatic morphological post-mortem findings in critically ill COVID-19 patients: an observational study.

Our study investigates the post-mortem findings of the diaphragm's muscular structural changes in mechanically ventilated COVID-19 patients. Diaphragm samples of the right side from 42 critically ill COVID-19 patients were analyzed and correlated with the type and length of mechanical ventilation (MV), ventilatory parameters, prone positioning, and use of sedative drugs. The mean number of fibers was 550±626. The cross-sectional area was 4120±3280 μm2, while the muscular fraction was 0.607±0.126. The overall population was clustered into two distinct populations (clusters 1 and 2). Cluster 1 s

mRNA-mediated delivery of gene editing tools to human primary muscle stem cells.

Muscular dystrophies are approximately 50 devastating, untreatable monogenic diseases leading to progressive muscle degeneration and atrophy. Gene correction of transplantable cells using CRISPR/Cas9-based tools is a realistic scenario for autologous cell replacement therapies to restore organ function in many genetic disorders. However, muscle stem cells have so far lagged behind due to the absence of methods to isolate and propagate them and their susceptibility to extensive ex vivo manipulations. Here, we show that mRNA-based delivery of SpCas9 and an adenine base editor results in up to >9

Emerging role of non-coding RNA in health and disease.

Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and … c.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA …

VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for adult survival in caenorhabditis elegans.

Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), two motor neuron diseases that often include alterations in energy metabolism. We have shown that C. elegans and Drosophila neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein domain (vMSP). Secreted vMSPs signal through Roundabout and Lar-like receptors expressed on striated muscle. The muscle signaling pathway localizes mitochondria to myofilaments, alters their fission/fusion balance, and promotes energy production. Here, we show that neuronal loss of …

[A case with severe respiratory muscle weakness due to chronic myositis associated with PBC].

We report a 37-year-old woman with slowly developing muscular weakness for 2 years following insidious stiffness of calf muscle. Serum CK was elevated up to 4,207 IU/l. She presented sleepiness, weakness of proximal and truncal muscles and systemic muscular atrophy. While she had not experienced dyspnea, her arterial blood gas analysis revealed extreme hypoxia and hypercapnea due to weakness of respiratory muscles. Echocardiogram showed thinness and hypokinesis of left ventricular wall, and arrhythmia was pointed out by holter ECG. Needle elctromyogram of the proximal muscles exhibited polypha…

Frequency and satisfaction of conventional and complementary or alternative therapies for neuromuscular disorders.

BACKGROUND: Causal therapies are not yet available for most neuromuscular diseases. Additionally, data on the use of complementary or altern … nsatisfactory - 2). RESULTS: Of 192 questionnaires analysed, the most common diagnoses were spinal muscular atrophy (n = 42; 21.9%), muscular dystrophies (n = 41; 21.4%) and myotonic dystrophies (n = 38; 19.8%). More than half (n = 112; 58.3%) used both conventional and CAM treatments. Physiotherapy (n = 165) was used most frequently within all treatments with co …

EMD missense variant causes X-linked isolated dilated cardiomyopathy with myocardial emerin deficiency.

Pathogenic variants in the EMD gene cause X-linked Emery-Dreifuss muscular dystrophy type 1 (EDMD1), typically presenting with joint contractures and skeletal muscle atrophy, followed by atrial arrhythmias, cardiac conduction defects, and atrial dilatation. Although an association with isolated dilated cardiomyopathy (DCM) has been suggested, evidence is currently insufficient to verify the gene-disease association. We investigated the causality of a missense variant, c.23C>G, p.Ser8Trp, in EMD in a large family with a history of DCM and suspected sudden cardiac death (SCD) in males. DCM was d

Identification of a novel heterozygous DYSF variant in a large family with a dominantly-inherited dysferlinopathy.

AIMS: Dysferlinopathy is an autosomal recessive muscular dystrophy, caused by bi-allelic variants in the gene encoding dysferlin (DYSF). Onset typically occurs in the second to third decade and is characterised by slowly progressive skeletal muscle weakness and atrophy of the proximal and/or distal muscles of the four limbs. There are rare cases of symptomatic DYSF variant carriers. Here, we report a large family with a dominantly inherited hyperCKaemia and late-onset muscular dystrophy. METHODS AND RESULTS: Genetic analysis identified a co-segregating novel DYSF variant [NM_003494.4:c.6207de

Growth Hormone Improves Adipose Tissue Browning and Muscle Wasting in Mice with Chronic Kidney Disease-Associated Cachexia.

Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. … erentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.

Regimen-dependent glucocorticoid effects improve muscle performance without altering CNS physiology in mdx mice.

Duchenne muscular dystrophy (DMD) is a multisystem disorder affecting striated muscle, metabolism and the central nervous system (CNS). Although glucocorticoids remain the standard therapy, muscle-centric evaluations typically fail to capture how dosing regimen and compound selection affect CNS and metabolic phenotypes. Here, we compared daily and weekly dosing of prednisolone and vamorolone in juvenile mdx mice over 6 weeks to determine how these variables influence multisystem outcomes. Multiorgan efficacy and adverse effects were quantified across behavioural, endocrine, metabolic, cardiova

Painless motor radiculopathy of the cervical spine: clinical and radiological characteristics and long-term outcomes after operative decompression.

OBJECTIVE Various neurological diseases are known to cause progressive painless paresis of the upper limbs. In this study the authors describe the previously unspecified syndrome of compression-induced painless cervical radiculopathy with predominant motor deficit and muscular atrophy, and highlight the clinical and radiological characteristics and outcomes after surgery for this rare syndrome, along with its neurological differential diagnoses. METHODS Medical records of 788 patients undergoing surgical decompression due to degenerative cervical spine diseases between 2005 and 2014 were asses…