Journal of neuromuscular diseases最新文献

{"title":"Analysis of spinal muscular atrophy patients from the spinal muscular atrophy and muscular dystrophy registry of Pakistan.","authors":"Bisma Aziz, Ahmed A Arif, Kulsum Kazi, Salman Kirmani, Zeeshan Ansar, Asghar Nasir, Shahnaz Hamid Ibrahim, Khairunnisa Mukhtiar Ahmed, Zahra Hasan, Sara Khan","doi":"10.1177/22143602241301657","DOIUrl":"10.1177/22143602241301657","url":null,"abstract":"<p><p>BackgroundSpinal Muscular Atrophy (SMA) leads to motor neuron loss, with progressive muscle weakness and wasting. Nationwide registries for neuromuscular diseases are pivotal for assessing epidemiology, preparing for clinical trials, and for adopting standardized management guidelines.ObjectivesThis paper aims to present data gathered during the establishment of Pakistan's inaugural registry for genetically confirmed SMA cases.MethodsIn this retrospective study, 215 participants with genetically confirmed SMA were recruited. Telephonic interviews were conducted to collect data for the Muscular Disease Registry of Pakistan that was analyzed using STATA version 17.0.ResultsSMA type 1 was the most common type (71.2%, n = 153). Amongst patients who were tested for survival motor neuron (<i>SMN2</i>) copies, the majority (84.4%, n = 168) had two <i>SMN2</i> copies. SMA types were significantly associated with the ability to sit (p < 0.001) and walk (p < 0.001), and usage of a wheelchair (p = 0.0054). <i>SMN2</i> copy numbers were significantly associated with the ability to sit (p = 0.020) and walk (p = 0.031).ConclusionsThis study highlights the high prevalence of SMA genotypes and phenotypes associated with severe disease in our population. Our findings reiterate the challenging prognosis for Pakistani children with SMA and underscore the necessity of the development of nationwide newborn screening programs and making treatments available.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"260-270"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458277","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":"A rare case of myopathy with fatigability due to <i>PYROXD1</i> variation.","authors":"Dipti Baskar, Aneesha Thomas, Vijay Kumar Boddu, Rashmi Santhoshkumar, Ram Murthy Anjanappa, Saraswati Nashi, Kosha Srivastava, Kiran Polavarapu, Gautham Arunachal, Ananthapadmanabha Kotambail, Bhoomika Rao, Anita Mahadevan, Atchayaram Nalini, Seena Vengalil","doi":"10.1177/22143602241301635","DOIUrl":"10.1177/22143602241301635","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital myopathies are a group of heterogenous inherited muscle diseases. With advances in genetics, newer genes with novel features are being described. Pyridine nucleotide-disulfide oxidoreductase domain 1 (<i>PYROXD1</i>) related myopathy is an ultrarare congenital myopathy. Only few cases have been reported worldwide till now. We report the first interesting case of <i>PYROXD1</i> related myopathy from India.</p><p><strong>Methods: </strong>This is a retrospective study done from a quaternary neurology referral centre from southern India. All clinical, laboratory and electrophysiological data were collected from the medical records. Institutional ethics approval and informed consent from patient were obtained.</p><p><strong>Results: </strong>A 9 year-old-boy of non-consanguineous parentage presented with progressive fatigable proximo-distal weakness of upper and lower limbs with facial weakness from the age of 4 years. This was followed by chewing and swallowing difficulty. However speech was normal. There was profound proximal and distal joint hyperextensibility along with hip and ankle contractures. There was facial dysmorphism with high arched palate and retrognathism. Investigations showed normal serum creatine kinase levels. Nerve conduction studies showed axonal sensorimotor neuropathy. There was significant decremental response in tibialis anterior. Muscle biopsy showed both myopathic and neurogenic changes with novel findings of mitochondrial aggregates in subsarcolemmal and perinuclear regions. Next generation sequencing revealed a missense variant NM_024854.5:c.394C > T (NP_079130.2:p.Arg132Cys) of uncertain significance in exon 4 of <i>PYROXD1</i> gene.</p><p><strong>Conclusion: </strong>This is the first report of <i>PYROXD1</i> related myopathy from India. There were novel features of muscle fatigability, contractures, novel muscle biopsy features and a variant of uncertain significance expanding the phenotypic and genotypic spectrum of this rare myopathy.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"293-300"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458273","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":"Newborn screening and rapid genomic diagnosis of neuromuscular diseases.","authors":"Tamara Dangouloff, Helena Lang, Noor Benmhammed, Laurent Servais","doi":"10.1177/22143602241296286","DOIUrl":"10.1177/22143602241296286","url":null,"abstract":"<p><p>BackgroundIn recent years, treatments have been approved for certain neuromuscular diseases. In some cases, early pre-symptomatic treatment is necessary for optimal response, and thus newborn screening is critical.ObjectiveTo review the current status of newborn screening programs for neuromuscular diseases and early diagnosis through genetic testing.MethodsFollowing the PRISMA guidelines, a literature search was performed on PubMed for screening of neuromuscular diseases; the search was conducted on literature available as of 1 May 2024.ResultsIncluded were 77 articles on newborn screening for seven diseases: spinal muscular atrophy (19 studies), Duchenne muscular dystrophy (15), Pompe disease (20), X-linked adrenoleukodystrophy (14), Krabbe disease (6), metachromatic leukodystrophy (2), and myotonic dystrophy 1 (1). Ten articles on rapid genomic diagnosis were identified.ConclusionSince 2021, newborn screening programs for neuromuscular diseases have been established, notably in X-linked adrenoleukodystrophy, spinal muscular atrophy, Pompe disease, and Duchenne Muscular Dystrophy. Even in diseases where treatment is currently not life-changing, such as Krabbe disease, new newborn screening programs continue to be implemented, especially in the USA. The use of genetic diagnostic tests does not yet appear to be widespread or at least not widely reported. As new treatments become available, genomic newborn screening programs will need to be rapidly and broadly implemented.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"157-172"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458283","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":"Rozanolixizumab in generalized myasthenia gravis: Pooled analysis of the Phase 3 MycarinG study and two open-label extensions.","authors":"Vera Bril, Artur Drużdż, Julian Grosskreutz, Ali A Habib, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, Tuan Vu, Marion Boehnlein, Bernhard Greve, Maryam Gayfieva, Franz Woltering, Thaïs Tarancón, John Vissing","doi":"10.1177/22143602241305511","DOIUrl":"10.1177/22143602241305511","url":null,"abstract":"<p><strong>Background: </strong>Myasthenia gravis (MG) is a chronic autoimmune disease causing fluctuating muscle weakness. The MycarinG study showed that rozanolixizumab, a neonatal Fc receptor inhibitor, provided clinically meaningful improvements in MG outcomes in patients with acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibody-positive generalized MG (gMG).</p><p><strong>Objective: </strong>We assessed efficacy and safety of 6-week rozanolixizumab treatment cycles in patients with gMG.</p><p><strong>Methods: </strong>Following MycarinG, eligible patients enrolled in the open-label extension Phase 3 studies MG0004 (NCT04124965) to receive up to 52 weekly rozanolixizumab infusions or MG0007 (NCT04650854) to receive cycles of 6 weekly rozanolixizumab infusions (initiated on symptom worsening at investigators' discretion). To assess the effect of repeated cyclical treatment, data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 (interim analysis). Efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC) and Quantitative Myasthenia Gravis (QMG) assessed in patients who received ≥2 symptom-driven treatment cycles. Treatment-emergent adverse events (TEAEs) were assessed in patients who received ≥1 cycle and had an (up to) 8-week follow-up period.</p><p><strong>Results: </strong>At data cut-off (July 8, 2022), 188/196 (95.9%) patients received ≥1 treatment cycle with a follow-up period (primary safety pool; MycarinG/MG0007) and 127 (64.8%) received ≥2 symptom-driven cycles (primary efficacy pool; MycarinG/MG0004 [first 6 weeks]/MG0007). Consistent and clinically meaningful improvements in MG-ADL, MGC and QMG scores, and high MG-ADL, MGC and QMG response rates, were observed at the end of the first symptom-driven cycle and subsequent cycles. TEAEs were experienced by 169/188 (89.9%) patients and were mostly mild to moderate. TEAEs did not increase with repeated cycles.</p><p><strong>Conclusions: </strong>Repeated cycles of rozanolixizumab resulted in consistent, clinically meaningful improvements across cycles in MG-specific outcomes with an acceptable safety profile, supporting rozanolixizumab as a treatment option for adults with AChR and MuSK autoantibody-positive gMG.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"218-230"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541818","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":"Systematic literature review of the impact of spinal muscular atrophy therapies on bulbar function.","authors":"Katlyn McGrattan, Katie Walsh, Lesa Mehl, Simarjeet Kaur, Keith W Dilly","doi":"10.1177/22143602241303373","DOIUrl":"10.1177/22143602241303373","url":null,"abstract":"<p><strong>Background: </strong>Improvement and maintenance of bulbar function are important goals of disease-modifying treatments (DMTs) for spinal muscular atrophy (SMA), but standardized and validated measures for assessing bulbar function do not exist, nor does a widely accepted definition of bulbar function in SMA. As such, the impact of DMTs on bulbar function has not yet been comprehensively evaluated.</p><p><strong>Objective: </strong>We conducted a systematic literature review (SLR) to identify evidence about the impact of DMTs for SMA on bulbar function.</p><p><strong>Methods: </strong>We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to conduct this review. Embase^® and MEDLINE^® databases were searched through August 10, 2023. Eligible studies included patients with SMA who were treated with any DMT and reported bulbar function outcomes. Non-English studies were excluded.</p><p><strong>Results: </strong>We identified 51 studies (across 83 publications) that evaluated SMA DMTs and bulbar function for more than 1600 patients. The ability to feed orally, the ability to tolerate liquids, and the need for nutrition support were commonly reported. Most infants treated with any DMT before SMA symptom onset preserved bulbar function. Infants, children, and adults treated after SMA symptom onset experienced variable results in terms of bulbar function outcomes.</p><p><strong>Conclusions: </strong>The definition and assessment of bulbar function are not standardized. Therefore, the tools, scales, methods, and timing used for bulbar function assessments varied among studies. Larger prospective studies using standardized and age-based assessments with longer follow-up periods are needed to assess the clinical stability of bulbar function for patients with SMA who receive DMTs.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"195-217"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458303","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":"Plasma-derived protein and imaging biomarkers distinguish disease severity in oculopharyngeal muscular dystrophy.","authors":"Ian C Smith, Marcos L Sampaio, Gerd Melkus, Kaitlynn Meier-Ross, Shaoni Chakraborty, Cameron Stotts, Pierre R Bourque, Hanns Lochmuller, Bernard Brais, Othmane Ayoub, Theodore J Perkins, Mireille Khacho, Jodi Warman-Chardon","doi":"10.1177/22143602241304990","DOIUrl":"10.1177/22143602241304990","url":null,"abstract":"<p><strong>Background: </strong>Oculopharyngeal muscular dystrophy (OPMD) is a rare, late-onset, slowly progressive neuromuscular disorder characterized by ptosis, dysphagia, and proximal limb weakness. Emerging clinical trials require rapidly accessible and sensitive biomarkers to evaluate OPMD disease progression and potential response to future treatments.</p><p><strong>Objective: </strong>This cross-sectional study was designed to identify candidate circulating protein and imaging biomarkers of OPMD severity for future use in clinical trials.</p><p><strong>Methods: </strong>Twenty-five individuals with OPMD (age 63.3 ± 10.5 years; GCN copy number of 13 in <i>PABPN1</i>) were assessed using the 7k SOMAScan assay to profile the plasma proteome, and MRI to quantify replacement of muscle by fat. OPMD severity was first categorized using the clinical presence/absence of limb weakness, and protein signals were considered distinguishing if they differed by more than 30% between subgroups and had statistically significant <i>P</i>-values after correcting for multiple comparisons. Distinguishing proteins were contrasted with age-matched controls (<i>n </i>= 10). OPMD severity was also treated as a continuous variable using fat fraction of the soleus muscle, and proteins were considered distinguishing if the slope of relationship between protein signal and soleus fat fraction differed significantly from zero after correcting for multiple comparisons. Pathway analyses were conducted using Metascape and the Database for Annotation, Visualization, and Integrated Discovery webtools.</p><p><strong>Results: </strong>Eighteen plasma proteins distinguished OPMD on both indicators of severity. Pathway analyses identified skeletal muscle tissue, phagocytosis/engulfment, and extracellular matrix organization as enriched ontology clusters in OPMD with limb weakness. The most distinguishing plasma protein signals (ACTN2, MYOM2, CA3, APOBEC2, MYL3, and PDLIM3) were over 200% higher in OPMD with limb weakness than OPMD without limb weakness as well as controls, and correlated strongly with percent of fatty replacement of soleus (<i>r </i>= 0.89 ± 0.04).</p><p><strong>Conclusions: </strong>The candidate biomarkers identified contribute to the ongoing search for sensitive and accessible biomarkers of OPMD progression, prognosis, and monitoring.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"244-259"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458294","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":"Long-term safety of cyclical rozanolixizumab in patients with generalized myasthenia gravis: Results from the Phase 3 MycarinG study and an open-label extension.","authors":"Ali A Habib, Artur Drużdż, Julian Grosskreutz, Renato Mantegazza, Sabrina Sacconi, Kimiaki Utsugisawa, Tuan Vu, John Vissing, Maryam Gayfieva, Irene Pulido-Valdeolivas, Thaïs Tarancón, Franz Woltering, Vera Bril","doi":"10.1177/22143602241308181","DOIUrl":"10.1177/22143602241308181","url":null,"abstract":"<p><strong>Background: </strong>Generalized myasthenia gravis (gMG) is a rare, chronic, fluctuating and heterogeneous autoimmune disease requiring lifelong treatment. The Phase 3 MycarinG study demonstrated the efficacy and safety of one 6-week cycle of weekly rozanolixizumab in adult patients with gMG. Open-label extension studies demonstrated consistent symptom improvement over additional treatment cycles.</p><p><strong>Objective: </strong>To present findings from pooled analyses on the long-term safety of repeated cycles of rozanolixizumab.</p><p><strong>Methods: </strong>Data from the Phase 3 randomized MycarinG study (NCT03971422) and the ongoing open-label extension study MG0007 (NCT04650854) were pooled to assess safety outcomes during cyclical treatment, including incidence of any treatment-emergent adverse events (TEAEs), severe TEAEs, serious TEAEs and TEAEs leading to discontinuations. Additional analyses were performed for TEAEs, including headache, infections, and hypersensitivity reactions.</p><p><strong>Results: </strong>At data cutoff (July 8, 2022), a total of 188 patients in MycarinG and MG0007 had received ≥1 treatment cycle with rozanolixizumab; total time in studies was 174.71 patient-years. Overall, 169/188 (89.9%) patients experienced any TEAE: 89/188 (47.3%) experienced any headache (including migraine, migraine with aura); 85/188 (45.2%) experienced an infection; 25/188 (13.3%) experienced a hypersensitivity reaction. One patient experienced an event of aseptic meningitis. The majority of AEs were mild-to-moderate in intensity, and incidence did not increase with repeated cyclic treatment. A total of 50/188 (26.6%) patients experienced severe TEAEs, the most common of which were MG worsening in 4/133 (3.0%) and 7/131 (5.3%) patients in the rozanolixizumab 7 mg/kg and rozanolixizumab 10 mg/kg groups, respectively, MG crisis in 0 and 4/131 (3.1%) patients, and headache in 1/133 (0.8%) and 7/131 (5.3%) patients.</p><p><strong>Conclusions: </strong>These pooled results, representing 174.71 patient-years in the studies, demonstrate that treatment with rozanolixizumab in patients with gMG was well tolerated, and TEAEs were consistent and did not increase in incidence over repeated cycles in this patient population.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"231-243"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542418","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":"Genetic landscape of Charcot-Marie-Tooth disease in Vietnam: A prospective multicenter study.","authors":"Hoang Tien Trong Nghia, Thirugnanam Umapathi, Nguyen Minh Duc, Nguyen Le Trung Hieu, Mai Phuong Thao","doi":"10.1177/22143602251313722","DOIUrl":"10.1177/22143602251313722","url":null,"abstract":"<p><strong>Background: </strong>In many developing regions, genetic data on Charcot-Marie-Tooth disease (CMT) remains scarce.</p><p><strong>Objective: </strong>This study aimed to investigate the genetic landscape of CMT in Vietnam to guide the development of cost-effective diagnostic algorithms for patients with suspected genetic neuropathies.</p><p><strong>Methods: </strong>We recruited 44 patients with a diagnosis of CMT from three tertiary centers between March 2021 and December 2023 and recorded their clinical and electrophysiological characteristics. All patients were analyzed for duplications or deletions of <i>PMP22</i>, <i>GJB1</i>, <i>MPZ</i>, and <i>MFN2</i> via multiplex ligation-dependent probe amplification (MLPA) and for 94 genes via targeted next-generation sequencing (NGS). The identified variants were classified per the American College of Medical Genetics and Genomics 2015 guidelines using VarSome, a bioinformatics engine.</p><p><strong>Results: </strong>Among 44 patients, 24 carried a total of 26 variants. Of these 26 variants, 15 were (57.7%) pathogenic, 6 (23.1%) were likely pathogenic, and 5 (19.2%) were variants of uncertain significance (VUS). Excluding the VUS, the diagnostic yield of the targeted sequencing was 43.2% (19/44). Through MLPA, <i>PMP22</i> duplications were identified in 10 patients with the demyelinating type of CMT and 1 patient with the unclassified CMT type. The combined yield of MLPA and gene panels was 68.2% (30/44). We detected three novel pathogenic/likely pathogenic variants in <i>GJB1</i>, <i>INF2</i>, and <i>IGHMBP2</i>, as well as three novel VUS in <i>MPZ</i>, <i>PMP22</i>, and <i>INF2</i>. <i>IGHMBP2</i> may represent the most prevalent autosomal recessive gene associated with CMT in Vietnam.</p><p><strong>Conclusions: </strong>We propose a sequential genetic testing approach for CMT in resource-limited settings, with the initial testing via MLPA for demyelinating CMT, followed by NGS for those who test negative. Our findings broaden the CMT genotype-phenotype profile of the Vietnamese population by identifying six novel candidate variants.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"12 1","pages":"22143602251313722"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458380","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":"In response to Gulcin Akinci's and Haluk Topaloglu's letter regarding our article \"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":"10.1177/22143602241312519","DOIUrl":"https://doi.org/10.1177/22143602241312519","url":null,"abstract":"","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"12 1","pages":"22143602241312519"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515870","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":"Characterization of swallowing biomechanics and function in untreated infants with spinal muscular atrophy: A natural history dataset.","authors":"Katlyn Elizabeth McGrattan, Robert J Graham, Alicia Hofelich Mohr, Anna Miles, Jacqui Allen, Juliet Ochura, Kayla Hernandez, Katie Walsh, Vamshi Rao, Melanie Stevens, Lindsay Alfano, Mackenzi Coker, Carmen Leon-Astudillo, Leann Schow Smith, John Brandsema, Hiba Farah, Julia Welc, Deborah Salle Levy, Miranda Clements, Whitney J Tang, Tina Duong, Carolina Tesi Rocha, Graham Schenck, Heather McGhee, Keeley Nichols, Ashley Brown, Allison Brown, Diana Castro, Basil T Darras","doi":"10.1177/22143602241308762","DOIUrl":"10.1177/22143602241308762","url":null,"abstract":"<p><strong>Background: </strong>Spinal Muscular Atrophy (SMA) is a progressive neuromuscular disorder that in its most severe form, causes profound swallowing deficits. There remains a paucity of research systematically elucidating the biomechanical and functional correlates. This void limits the ability to evaluate the effects of disease-modifying treatments on swallowing.</p><p><strong>Objective: </strong>Elucidate characteristics of swallowing biomechanics and function among untreated patients with SMA.</p><p><strong>Methods: </strong>Infants with SMA who had not received disease modifying therapy when they underwent a videofluoroscopic swallow study (VFSS) were retrospectively identified from 13 international children's hospitals. Infants were eligible if they exhibited symptoms by six months old, or in cases where they detected prior to symptom onset, if they had two copies of SMN2. Eligible infants underwent medical record review to gather oral intake status and need for suctioning for secretion management. Digital files of VFSS' were extracted and analyzed using BabyVFSSImP™. Non-parametric t-tests were used to compare swallowing biomechanics based on viscosity and the presence of dysphagia symptoms.</p><p><strong>Results: </strong>62 infants were included in this investigation with average age at initial VFSS 4.4 ± 3.11 months. A high proportion of infants exhibited profound deficits in swallowing biomechanics that impeded extraction of the bolus from the nipple, clearance of the bolus from the pharynx, and prevention of the bolus from entering the airway. Deficits were significantly more prevalent in infants referred for VFSS due to dysphagia symptoms than asymptomatic infants referred as part of high-risk referral (t ≤ 2.5, p ≤ 0.03). A high proportion of infants relied on suctioning for secretion management (34%; N = 21) and alternative nutrition (39%; N = 24), with those relying on these supports exhibiting significantly worse swallowing biomechanics than those who did not (t ≤ 2.8, p ≤ 0.01).</p><p><strong>Conclusions: </strong>Profound deficits in swallowing biomechanics and function are common in infants with SMA. Though clinical symptoms may aid in identifying infants with the most profound swallowing deficits, their absence in cases of more mild deficits inhibits the ability to use these clinical markers as a valid metric of swallowing integrity.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"12 1","pages":"22143602241308762"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458321","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}