Journal of neuromuscular diseases最新文献

{"title":"A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6.","authors":"Esmee S B van Kleef, Karlijn Bouman, Joery P F Molenaar, Josine M de Winter, Floor A M Duijkers, Filip Eftimov, Corien C Verschuuren-Bemelmans, Tineke van der Laan, Benno Küsters, Edoardo Malfatti, Erik-Jan Kamsteeg, Baziel G M van Engelen, Coen A C Ottenheijm, Jonne Doorduin, Nicol C Voermans","doi":"10.3233/JND-230196","DOIUrl":"https://doi.org/10.3233/JND-230196","url":null,"abstract":"<p><strong>Background: </strong>Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant.</p><p><strong>Objective: </strong>To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene.</p><p><strong>Results: </strong>We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier.</p><p><strong>Conclusions: </strong>The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies.","authors":"Lauren Hinkley, Rotem Orbach, Justin Park, Rachel Alvarez, Gustavo Dziewczapolski, Carsten G Bönnemann, A Reghan Foley","doi":"10.3233/JND-240048","DOIUrl":"https://doi.org/10.3233/JND-240048","url":null,"abstract":"<p><strong>Background: </strong>LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency.</p><p><strong>Objective: </strong>While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized.</p><p><strong>Methods: </strong>We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: \"Sit\" for those patients who attained that ability to remain seated and \"Walk\" for those patients who attained the ability to walk independently by 3.5 years of age.</p><p><strong>Results: </strong>Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life.</p><p><strong>Conclusions: </strong>This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life Expectancy and Causes of Death in Patients with Myotonic Dystrophy Type 2.","authors":"Manon J Damen, Otto G Muilwijk, Tom B G Olde Dubbelink, Baziel G M van Engelen, Nicol C Voermans, Alide A Tieleman","doi":"10.3233/JND-240089","DOIUrl":"https://doi.org/10.3233/JND-240089","url":null,"abstract":"<p><strong>Background: </strong>Myotonic Dystrophy type 2 (DM2) is a dominantly inherited multisystem disease caused by a CCTG repeat expansion in intron 1 of the CNBP gene. Although in the last two decades over 1500 patients with DM2 have been diagnosed worldwide, our clinical impression of a reduced life expectancy in DM2 has not been investigated previously.</p><p><strong>Objective: </strong>The aim of this observational study was to determine the life expectancy and the causes of death in patients with genetically confirmed DM2.</p><p><strong>Methods: </strong>We identified the data of all deceased patients with DM2 in the Dutch neuromuscular database between 2000 and 2023. Ages and causes of death and the patients' clinical features during lifetime were determined. Age of death in DM2 was compared to the general population by using life tables with prognostic cohort life expectancy (CLE) and period life expectancy (PLE) data of the Dutch electronic database of statistics (CBS StatLine).</p><p><strong>Results: </strong>Twenty-six deceased patients were identified in the Dutch DM2 cohort (n = 125). Median age of death in DM2 (70.9 years) was significantly lower compared to sex- and age-matched CLE (78.1 years) and PLE (82.1 years) in the Netherlands. Main causes of death were cardiac diseases (31%) and pneumonia (27%). Seven patients (27%) had a malignancy at the time of death.</p><p><strong>Conclusion: </strong>These results provide new insights into the phenotype of DM2. Life expectancy in patients with DM2 is reduced, possibly attributable to multiple causes including increased risk of cardiac disease, pneumonia, and malignancies. The occurrence of a significantly reduced life expectancy has implications for clinical practice and may form a basis for advanced care planning, including end-of-life care, to optimize quality of life for patients with DM2 and their family. Research in larger cohorts should be done to confirm these findings and to ascertain more about the natural course in DM2.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E-Health & Innovation to Overcome Barriers in Neuromuscular Diseases. Report from the 3rd eNMD Congress: Pisa, Italy, 29-30 October 2021.","authors":"Erika Schirinzi, Mario Alessandro Bochicchio, Hanns Lochmüller, John Vissing, Jordie-Diaz-Manerae, Teresinha Evangelista, Jean-Philippe Plançon, Luca Fanucci, Marco Marini, Alessandro Tonacci, Michelangelo Mancuso, Sandrine Segovia-Kueny, Antonio Toscano, Corrado Angelini, Benedikt Schoser, Sabrina Sacconi, Gabriele Siciliano","doi":"10.3233/JND-230091","DOIUrl":"https://doi.org/10.3233/JND-230091","url":null,"abstract":"<p><p>Neuromuscular diseases (NMDs), in their phenotypic heterogeneity, share quite invariably common issues that involve several clinical and socio-economical aspects, needing a deep critical analysis to develop better management strategies. From diagnosis to treatment and follow-up, the development of technological solutions can improve the detection of several critical aspects related to the diseases, addressing both the met and unmet needs of clinicians and patients. Among several aspects of the digital transformation of health and care, this congress expands what has been learned from previous congresses editions on applicability and usefulness of technological solutions in NMDs. In particular the focus on new solutions for remote monitoring provide valuable insights to increase disease-specific knowledge and trigger prompt decision-making. In doing that, several perspectives from different areas of expertise were shared and discussed, pointing out strengths and weaknesses on the current state of the art on topic, suggesting new research lines to advance technology in this specific clinical field.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis","authors":"E. Landfeldt, A. Alemán, S. Abner, R. Zhang, C. Werner, I. Tomazos, N. Ferizovic, H. Lochmüller, J. Kirschner","doi":"10.3233/jnd-230220","DOIUrl":"https://doi.org/10.3233/jnd-230220","url":null,"abstract":"Objective: The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). Methods: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included “Duchenne muscular dystrophy” as a Medical Subject Heading or free text term, in combination with variations of the term “predictor”. Risk of bias was assessed using the Newcastle–Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model. Results: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40–0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3–7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49–50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias. Conclusion: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140675873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy.","authors":"Michael Rabbia, M. Ormazabal, H. Staunton, Klaas Veenstra, Damien Eggenspieler, M. Annoussamy, L. Servais, Paul Strijbos","doi":"10.3233/jnd-230188","DOIUrl":"https://doi.org/10.3233/jnd-230188","url":null,"abstract":"Background\u0000Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in patients aged ≥4 years.\u0000\u0000\u0000Objective\u0000To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]).\u0000\u0000\u0000Methods\u0000SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6-11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures.\u0000\u0000\u0000Results\u0000SV95C change at Week 24 was -0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong (r = 0.611-0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong (r = 0.443-0.678).∥.\u0000\u0000\u0000Conclusions\u0000Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140698295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts of the 17th UK Neuromuscular Translational Research Conference, 17th and 18th April 2024.","authors":"","doi":"10.3233/jnd-249001","DOIUrl":"https://doi.org/10.3233/jnd-249001","url":null,"abstract":"","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy for Patients With Duchenne Muscular Dystrophy.","authors":"C. Zaidman, N. Goedeker, Amal A Aqul, Russell J. Butterfield, Anne M. Connolly, Ronald G Crystal, Kara E Godwin, Kan N Hor, Katherine D. Mathews, Crystal M. Proud, Elizabeth Kula Smyth, A. Veerapandiyan, Paul B Watkins, J. R. Mendell","doi":"10.3233/JND-230185","DOIUrl":"https://doi.org/10.3233/JND-230185","url":null,"abstract":"BACKGROUND\u0000Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy. Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMD gene.\u0000\u0000\u0000OBJECTIVE\u0000Evidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec.\u0000\u0000\u0000METHODS\u0000An interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. Consensus was defined as a majority (≥58% ; 7/12) of panelists either agreeing or disagreeing.\u0000\u0000\u0000RESULTS\u0000Panelists agreed that the choice of baseline assessments should be informed by individual clinical indications, the treating provider's judgment, and prescribing information. Corticosteroid dosing for treatment of TRAEs should be optimized by considering individual risk versus benefit for each indication. In all cases involving patients with a confirmed TRAE, consultations with appropriate specialists were suggested.\u0000\u0000\u0000CONCLUSIONS\u0000The Delphi Panel established consensus considerations for the evaluation and management of potential TRAEs for patients receiving delandistrogene moxeparvovec, including vomiting, acute liver injury, myocarditis, and immune-mediated myositis.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140713341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Physical Activity/Heart Rate Variability Data Obtained Using a Wearable Device and Timed Motor Functional Tests in Patients with Duchenne Muscular Dystrophy: A Pilot Study.","authors":"A. Nakamura, Tsuyoshi Matsumura, Yasuhiro Takeshima, Satoshi Kuru, Manami Imazaki, Hidenori Nonomura, Hisanobu Kaiya","doi":"10.3233/jnd-230142","DOIUrl":"https://doi.org/10.3233/jnd-230142","url":null,"abstract":"Background\u0000Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disease. Clinical evaluation of DMD uses patient-intensive motor function tests, and the recent development of wearable devices allows the collection of a variety of biometric information, including physical activity.\u0000\u0000\u0000Objective\u0000In this study, we examined differences in physical activity and heart rate variability (HRV) between patients with DMD and healthy subjects using a wearable device, and investigated any association between these parameters and motor function in patients with DMD.\u0000\u0000\u0000Methods\u0000Participants were 7 patients with DMD and 8 healthy males, whose physical activity and HRV were provided by a wearable device. These data were used to investigate the relationship between both physical activity and HRV parameters and timed motor functional tests [Time to stand from supine, 10-meter walking time (10MWT), North Star Ambulatory Assessment (NSAA), and 6-minute walking test (6MWT)] in patients with DMD.\u0000\u0000\u0000Results\u0000Results of 24-hours physical activity, fat burning, total number of steps and active distance, average step rate, average exercise intensity during walking, exercise, degree of forward lean during walking, maximum heart rate, normalized low frequency power (LF norm), and maximum exercise intensity in patients with DMD were lower than those in control subjects. Physical activity and HRV parameters did not correlate with the time to stand from supine. The 10MWT positively correlated with average heart rate, while NSAA negatively correlated with average heart rate, total frequency power (TF), and very low frequency power (VLF) during arousal. The 6MWT negatively correlated with ratio LF/high frequency power (HF).\u0000\u0000\u0000CONCLUSIONS\u0000Physical activity and HRV indices that differ from those of normal children and that correlate with motor function assessment may serve as digital biomarkers.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140735586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Alteration Patterns in Children with Duchenne Muscular Dystrophy: A Machine Learning Approach to Magnetic Resonance Imaging.","authors":"D. Peruzzo, Tommaso Ciceri, Sara Mascheretti, Valentina Lampis, Filippo Arrigoni, Nivedita Agarwal, Alice Giubergia, Filippo Maria Villa, Alessandro Crippa, Maria Nobile, Elisa Mani, Annamaria Russo, Maria Grazia D'Angelo","doi":"10.3233/JND-230075","DOIUrl":"https://doi.org/10.3233/JND-230075","url":null,"abstract":"Background\u0000Duchenne Muscular Dystrophy (DMD) is a genetic disease in which lack of the dystrophin protein causes progressive muscular weakness, cardiomyopathy and respiratory insufficiency. DMD is often associated with other cognitive and behavioral impairments, however the correlation of abnormal dystrophin expression in the central nervous system with brain structure and functioning remains still unclear.\u0000\u0000\u0000Objective\u0000To investigate brain involvement in patients with DMD through a multimodal and multivariate approach accounting for potential comorbidities.\u0000\u0000\u0000Methods\u0000We acquired T1-weighted and Diffusion Tensor Imaging data from 18 patients with DMD and 18 age- and sex-matched controls with similar cognitive and behavioral profiles. Cortical thickness, structure volume, fractional anisotropy and mean diffusivity measures were used in a multivariate analysis performed using a Support Vector Machine classifier accounting for potential comorbidities in patients and controls.\u0000\u0000\u0000Results\u0000the classification experiment significantly discriminates between the two populations (97.2% accuracy) and the forward model weights showed that DMD mostly affects the microstructural integrity of long fiber bundles, in particular in the cerebellar peduncles (bilaterally), in the posterior thalamic radiation (bilaterally), in the fornix and in the medial lemniscus (bilaterally). We also reported a reduced cortical thickness, mainly in the motor cortex, cingulate cortex, hippocampal area and insula.\u0000\u0000\u0000Conclusions\u0000Our study identified a small pattern of alterations in the CNS likely associated with the DMD diagnosis.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}