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Muscular dystrophies (MDs) are genetically heterogeneous diseases characterized by primary skeletal muscle atrophy. The collapse of muscle structure and irreversible degeneration of tissues promote the occurrence of comorbidities, including cardiomyopathy and respiratory failure. Mitochondrial dysfunction leads to inflammation, fibrosis, and adipogenic cellular infiltrates that exacerbate the symptomatology of MD patients. Gastrointestinal disorders and metabolic anomalies are common in MD patients and may be determined by the interaction between the intestine and its microbiota. Therefore, the gut–muscle axis is one of the actors involved in the spread of inflammatory signals to all muscles. In this review, we aim to examine in depth how intestinal dysbiosis can modulate the metabolic state, the immune response, and mitochondrial biogenesis in the course and progression of the most investigated MDs such as Duchenne Muscular Dystrophy (DMD) and Myotonic Dystrophy (MD1), to better identify gut microbiota metabolites working as therapeutic adjuvants to improve symptoms of MD. [ABSTRACT FROM AUTHOR]

We aim to develop a deep learning-based algorithm for automated segmentation of thigh muscles and subcutaneous adipose tissue (SAT) from T1-weighted muscle MRIs from patients affected by muscular dystrophies (MDs). From March 2019 to February 2022, adult and pediatric patients affected by MDs were enrolled from Azienda Ospedaliera Universitaria Pisana, Pisa, Italy (Institution 1) and the IRCCS Stella Maris Foundation, Calambrone-Pisa, Italy (Institution 2), respectively. All patients underwent a bilateral thighs MRI including an axial T1 weighted in- and out-of-phase (dual-echo). Both muscles and SAT were manually and separately segmented on out-of-phase image sets by a radiologist with 6 years of experience in musculoskeletal imaging. A U-Net1 and U-Net3 were built to automatically segment the SAT, all the thigh muscles together and the three muscular compartments separately. The dataset was randomly split into the on train, validation, and test set. The segmentation performance was assessed through the Dice similarity coefficient (DSC). The final cohort included 23 patients. The estimated DSC for U-Net1 was 96.8%, 95.3%, and 95.6% on train, validation, and test set, respectively, while the estimated accuracy for U-Net3 was 94.1%, 92.9%, and 93.9%. Both of the U-Nets achieved a median DSC of 0.95 for SAT segmentation. The U-Net1 and the U-Net3 achieved an optimal agreement with manual segmentation for the automatic segmentation. The so-developed neural networks have the potential to automatically segment thigh muscles and SAT in patients affected by MDs. [ABSTRACT FROM AUTHOR]

Cobblestone lissencephaly (C-LIS) (TYPE II) is a rare and severe neuronal migration disorder characterized by a smooth brain surface with overmigrated neurons and abnormal formation of cerebral convolutions or gyri during fetal development, resulting in a cobblestone appearance. C-LIS is associated with eye anomalies and muscular dystrophy. This case report presents a detailed clinical and neuroimaging analysis of a patient diagnosed with cobblestone lissencephaly (Type II). It reviews pertinent literature to enhance our understanding of this complex condition. We report a case of a 6-year-old female child with cobblestone lissencephaly (C-LIS) (Type II) severe developmental delays, hypotonia, and recurrent intractable seizures. Magnetic resonance imaging (MRI) revealed a characteristic cobblestone appearance on the brain surface, indicative of abnormal neuronal migration. In addition to the classic findings of Type II Cobblestone lissencephaly, the patient displayed ventriculomegaly and cerebellar hypoplasia, contributing to the overall neurological impairment observed. The literature review highlights the genetic basis of cobblestone lissencephaly, emphasizing the involvement of genes associated with glycosylation processes and basement membrane integrity. Neuroimaging findings, including MRI and computed tomography scans, are crucial for accurate diagnosis and prognostication. Early identification of cobblestone lissencephaly allows for appropriate counseling and management strategies. However, the prognosis remains guarded, and interventions primarily focus on supportive care and seizure management. This case report contributes to the knowledge of cobblestone lissencephaly, shedding light on the clinical spectrum and neuroimaging features associated with this rare disorder. To clarify the underlying genetic mechanisms and possible therapeutic pathways for better patient outcomes, more investigation is necessary.

• A critical literature review of case reports on statins-induced side effects in various hereditary myopathies. • Setting criteria to assess case reports of statin myotoxicity in hereditary myopathies. • Identification of myopathies with high risk for statin usage (MELAS and other mitochondrial disorders, myotonic dystrophy type 2, McArdle disease). • Suggesting practical management of hyperlipidemia in hereditary myopathies. Hyperlipidemia is not uncommon in patients with hereditary myopathies who get older and also in several conditions in which it is frequently observed. Thus, using the common cholesterol reducing medications of the stains group could be considered. However, the side effects of these drugs include myalgia, myopathy and rhabdomyolysis typically associated with high serum creatine kinase (CK). Because high CK levels are very frequently found in hereditary myopathies, physicians are reluctant to use statins in such patients. Reviewing the literature about statin side effects in hereditary myopathies does not provide a clear evidence about the true risk of these drugs. This review critically describes the reported cases of statin side effects in several genetic myopathies and suggests some guidelines for conditions that are contra indicated for statin usage (particularly in mitochondrial disorders, metabolic myopathies, myotonic dystrophy type 2). Possible solutions to the dilemma of whether to use statins in hereditary myopathies are discussed (prescribing other cholesterol lowering agents and a carefully monitored treatment initiation of statins). [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD), but there is significant cardiomyopathy phenotypic variability. Some patients demonstrate rapidly progressive disease and die at a young age while others survive into the fourth decade. Criteria to identify DMD subjects at greatest risk for early mortality could allow for increased monitoring and more intensive therapy. A risk score was created describing the onset and progression of left ventricular dysfunction and late gadolinium enhancement in subjects with DMD. DMD subjects prospectively enrolled in ongoing observational studies (which included cardiac magnetic resonance [CMR]) were used to validate the risk score. A total of 69 subjects had calculable scores. During the study period, 12 (17%) died from complications of DMD. The median risk score was 3 (IQR [2,5]; range [0,9]). The overall risk score applied at the most recent imaging age was associated with mortality at a median age of 17 years (IQR [16,20]) (HR 2.028, p < 0.001). There were no deaths in subjects with a score of less than two. Scores were stable over time. An imaging-based risk score allows risk stratification of subjects with DMD. This can be quickly calculated during a clinic visit to identify subjects at greatest risk of early death. [ABSTRACT FROM AUTHOR]

Skeletal muscle regeneration relies on the intricate interplay of various cell populations within the muscle niche--an environment crucial for regulating the behavior of muscle stem cells (MuSCs) and ensuring postnatal tissue maintenance and regeneration. This review delves into the dynamic interactions among key players of this process, including MuSCs, macrophages (MPs), fibro-adipogenic progenitors (FAPs), endothelial cells (ECs), and pericytes (PCs), each assuming pivotal roles in orchestrating homeostasis and regeneration. Dysfunctions in these interactions can lead not only to pathological conditions but also exacerbate muscular dystrophies. The exploration of cellular and molecular crosstalk among these populations in both physiological and dystrophic conditions provides insights into the multifaceted communication networks governing muscle regeneration. Furthermore, this review discusses emerging strategies to modulate the muscle-regenerating niche, presenting a comprehensive overview of current understanding and innovative approaches. [ABSTRACT FROM AUTHOR]

• Patient reported outcome measure for all limb girdle muscular dystrophies (LGMDs). • This outcome measure is specific to LGMD and measures 15 areas of disease burden. • This measure is designed for use in clinical trials to capture patient experience. Limb girdle muscular dystrophy (LGMD) is a debilitating disease and the fourth most common muscular dystrophy. This study describes the development of the LGMD-Health Index (LGMD-HI). Participants were aged >18 years and recruited from three LGMD registries and GRASP-LGMD consortium. The initial instrument, comprised of 16 thematic subscales and 161 items, underwent expert review resulting in item removal as well as confirmatory factor analysis followed by inter-rater reliability and internal consistency of the subscales. Following expert review, one subscale and 59 items were eliminated. Inter-rater reliability was assessed and five items were removed due to Cohen's kappa <0.5. The final subscales had high internal consistencies with an average Cronbach alpha of 0.92. Test re-test reliability of the final instrument was high (intraclass correlation coefficient=0.97). Known groups validity testing showed a statistically significant difference in LGMD-HI scores amongst subjects based on ambulation status (28.7 vs 50.0, p < 0.0001), but not sex, employment status, or genetic subtype. The final instrument is comprised of 15 subscales and 97 items. The LGMD-HI is a disease-specific, patient-reported outcome measure designed in compliance with published FDA guidelines. This instrument is capable of measuring burden of disease with no significant variation based on LGMD subtype. [ABSTRACT FROM AUTHOR]

The spectrum of canine muscular dystrophies has rapidly grown with the recent identification of several more affected breeds and associated mutations. Defects include those in genes and protein products associated with the sarcolemma (dystrophin deficient X-linked muscular dystrophy and sarcoglycan-deficient limb-girdle muscular dystrophy) and with the extracellular matrix (collagen 6, laminin α2, and α-dystroglycan-deficient congenital muscular dystrophies). With the increasing application of whole genome sequencing and whole exome sequencing, the clinical and pathological spectra associated with specific neuromuscular genetic defects are constantly evolving. In this report, we provide a brief overview of the current status of gene defects reported in canine muscular dystrophies. We also report the causative mutations for novel forms of X-linked muscular dystrophy in Brittany spaniels and in a French bulldog.

IntroductionThis research utilized data from the NHANES 2011–2018 study to investigate the connection between the Oxidative Balance Score (OBS) and muscular dystrophies.MethodsThis study is a cross-sectional, observational, secondary analysis utilizing data from the NHANES 2011-2018. Spearman’s correlation, chi-square tests, logistic regression, and restricted cubic spline plots were employed for statistical analyses.ResultsThis association remained significant after adjustment for various demographic and medical history factors (For continuous OBS: crude model, odds ratio [OR], 0.95, 95% confidence interval [CI:] 0.94, 0.97, p