Severity classification in cases of Collagen VI-related myopathy with Convolutional Neural Networks and handcrafted texture features

© 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Magnetic Resonance Imaging (MRI) is a non-invasive tool for the clinical assessment of low-prevalence neuromuscular disorders. Automated diagnosis methods might reduce the need for biopsies and provide valuable information on disease follow-up. In this paper, three methods are proposed to classify target muscles in Collagen VI-related myopathy cases, based on their degree of involvement, notably a Convolutional Neural Network, a Fully Connected Network to classify texture features, and a hybrid method combining the two feature sets. The proposed methods were evaluated on axial T1-weighted Turbo Spin-Echo MRI from 26 subjects, including Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy patients at different evolution stages. The hybrid model achieved the best cross-validation results, with a global accuracy of 93.8%, and F-scores of 0.99, 0.82, and 0.95, for healthy, mild and moderate/severe cases, respectively.info:eu-repo/semantics/acceptedVersio

Severity classification in cases of Collagen VI-related myopathy with Convolutional Neural Networks and handcrafted texture features

(C) 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Magnetic Resonance Imaging (MRI) is a non-invasive tool for the clinical assessment of low-prevalence neuromuscular disorders. Automated diagnosis methods might reduce the need for biopsies and provide valuable information on disease follow-up. In this paper, three methods are proposed to classify target muscles in Collagen VI-related myopathy cases, based on their degree of involvement, notably a Convolutional Neural Network, a Fully Connected Network to classify texture features, and a hybrid method combining the two feature sets. The proposed methods were evaluated on axial T1-weighted Turbo Spin-Echo MRI from 26 subjects, including Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy patients at different evolution stages. The hybrid model achieved the best cross-validation results, with a global accuracy of 93.8%, and F-scores of 0.99, 0.82, and 0.95, for healthy, mild and moderate/severe cases, respectively.info:eu-repo/semantics/acceptedVersio

ColVI myopathies: where do we stand, where do we go?

Collagen VI myopathies, caused by mutations in the genes encoding collagen type VI (ColVI), represent a clinical continuum with Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) at each end of the spectrum, and less well-defined intermediate phenotypes in between. ColVI myopathies also share common features with other disorders associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with important advances made in understanding its molecular pathogenesis. Indeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant-negative effects. Genotype-phenotype correlations have also started to emerge, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we present the current state of diagnosis and research in the field of ColVI myopathies. The past decade has provided significant advances, with the identification of altered cellular functions in animal models of ColVI myopathies and in patient samples. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle have recently been reported, thereby opening potential therapeutic avenues

Врожденные мышечные дистрофии: классификация и диагностика

Congenital muscular dystrophies (CMD) are a large group of genetically determined muscular diseases, initially defined by an early onset before the age of walking and dystrophic changes on myopathologic analyses. Currently, their definition is less restrictive with, a clinical continuum with limb-girdle muscular dystrophies, and closer histomorphological aspects with congenital myopathies. We distinguish 9 different forms of DMC, classified in 6 different groups depending on the location and/or function of the protein involved, on the control of 26 different genes. Ullrich's disease, UCMD (collagenopathy involving three different genes: COL6A1, COL6A2, COL6A3); secondary dystroglycanopathies (by abnormal glycosylation of alpha-dystroglycan involving 16 different genes); and DMC merosin negative, MDC1A, (merosinopathy secondary to mutations in a unique gene, LAMA2); represent the three most common forms. Rigid spine syndrome type 1, RSMD1 (selenopathy secondary to SEPN1 gene mutation) and L-CMD (laminopathy involving LMNA gene) are also part of the most current forms. Clinical features, plasmatic creatine kinase elevation or not, the presence or absence of clinical signs of central nervous system involvement, allow a first level of diagnostic pathway. According to these elements, muscle and/or cerebral MRI, muscle and/or skin biopsy will be discussed to guide the molecular investigations that will allow accurate diagnosis.Врожденные мышечные дистрофии (ВМД) составляют клинически и генетически чрезвычайно гетерогенную группу мышечных заболеваний. Изначально ВМД рассматривались как группа болезней с дебютом в раннем детском возрасте, до начала самостоятельной ходьбы, и наличием признаков дистрофии при патогистологическом исследовании. Сегодня ВМД подразделяют не столь строго. Так, имеется целый спектр клинических форм, включающий дистрофии поясов с более поздним дебютом игистологической картиной, сближающей их с врожденными миопатиями. Различают 9 форм ВМД, распределенных на 6 групп согласно локализации и/или функции нарушенного белка и соответствующего одному из 26 генов. Чаще всего встречаются следующие формы ВМД: болезнь Ульриха (коллагенопатия, связанная с патологией 3 генов: COL6A1, COL6A2, COL6A3); вторичные дистрогликанопатии (нарушение гликозилирования α-дистрогликана с вовлечением 16 генов) и мерозин-дефицитная ВМД (мерозинопатия, обусловленная мутацией одного гена LAMA2). К классическим формам ВМД также относятся синдром ригидного позвоночника 1-го типа (селенопатия вследствие мутации гена SEPN) и L-ВМД (ламинопатия, вовлекающая ген LMNA). Диагностический поиск определяется выявлением характерной клинической картины, наличием или отсутствием признаков поражения центральной нервной системы, нормальным или умеренно повышенным уровнем креатинфосфокиназы. Выбор молекулярного исследования для уточнения диагноза определяется результатами предварительного лабораторно-инструментального обследования, включающего магнитно-резонансную томографию мышц и/или головного мозга, биопсии мышцы и/или кожи

Texture Analysis of T1-weighted Turbo Spin-Echo MRI for the Diagnosis and Follow-up of Collagen VI-related Myopathy

Muscle texture analysis in Magnetic Resonance Imaging (MRI) has revealed a good correlation with typical histological changes resulting from neuromuscular disorders. In this research, we assess the effectiveness of several features in describing intramuscular texture alterations in cases of Collagen VI-related myopathy. A T1-weighted Turbo Spin-Echo MRI dataset was used (Nsubj = 26), consisting of thigh scans from subjects diagnosed with Ullrich Congenital Muscular Dystrophy or Bethlem Myopathy, with different severity levels, as well as healthy subjects. A total of 355 texture features were studied, including attributes derived from the Gray-Level Co-occurrence Matrix, the Run-Length Matrix, Wavelet and Gabor filters. The extracted features were ranked using the Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithm with Correlation Bias Reduction, prior to cross-validated classification with a Gaussian kernel SVM.info:eu-repo/semantics/acceptedVersionhttps://ieeexplore.ieee.org/document/9433942

Muscle histopathology in nebulin-related nemaline myopathy : ultrastrastructural findings correlated to disease severity and genotype

Peer reviewe

Muscle imaging in laminopathies: Synthesis study identifies meaningful muscles for follow-up

Introduction: Particular fibroadipose infiltration patterns have been recently described by muscle imaging in congenital and later onset forms of LMNA-related muscular dystrophies (LMNA-RD). Methods: Scores for fibroadipose infiltration of 23 lower limb muscles in 34 patients with LMNA-RD were collected from heat maps of 2 previous studies. Scoring systems were homogenized. Relationships between muscle infiltration and disease duration and age of onset were modeled with random forests. Results: The pattern of infiltration differs according to disease duration but not to age of disease onset. The muscles whose progression best predicts disease duration were semitendinosus, biceps femoris long head, gluteus medius, and semimembranosus. Discussion: In LMNA-RD, our synthetic analysis of lower limb muscle infiltration did not find major differences between forms with different ages of onset but allowed the identification of muscles with characteristic infiltration during disease progression. Monitoring of these specific muscles by quantitative MRI may provide useful imaging biomarkers in LMNA-RD. Muscle Nerve 58:812-817, 201

Correction to: Use of MFM-20 to monitor SMA types 1 and 2 patients treated with nusinersen.

peer reviewe

2024 update: European consensus statement on gene therapy for spinal muscular atrophy

Spinal muscular atrophy (SMA) is one of the most common genetic diseases and was, until recently, a leading genetic cause of infant mortality. Three disease-modifying treatments have dramatically changed the disease trajectories and outcome for severely affected infants (SMA type 1), especially when initiated in the presymptomatic phase. One of these treatments is the adeno-associated viral vector 9 (AAV9) based gene therapy onasemnogene abeparvovec (Zolgensma®), which is delivered systemically and has been approved by the European Medicine Agency for SMA patients with up to three copies of the SMN2 gene or with the clinical presentation of SMA type 1. While this broad indication provides flexibility in patient selection, it also raises concerns about the risk-benefit ratio for patients with limited or no evidence supporting treatment. In 2020, we convened a European neuromuscular expert working group to support the rational use of onasemnogene abeparvovec, employing a modified Delphi methodology. After three years, we have assembled a similar yet larger group of European experts who assessed the emerging evidence of onasemnogene abeparvovec's role in treating older and heavier SMA patients, integrating insights from recent clinical trials and real-world evidence. This effort resulted in 12 consensus statements, with strong consensus achieved on 9 and consensus on the remaining 3, reflecting the evolving role of onasemnogene abeparvovec in treating SMA

Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin β2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics