Neuromuscular Disorders最新文献

{"title":"Management of presymptomatic juvenile patients with late-onset Pompe disease (LOPD)","authors":"M. Porcino ,&nbsp;O. Musumeci ,&nbsp;C. Usbergo ,&nbsp;A. Pugliese ,&nbsp;I.G. Arena ,&nbsp;C. Rodolico ,&nbsp;B. Schoser ,&nbsp;A. Toscano","doi":"10.1016/j.nmd.2025.105277","DOIUrl":"10.1016/j.nmd.2025.105277","url":null,"abstract":"<div><div>Late-onset Pompe disease (LOPD) includes patients from 1 year of age to adulthood. The vast heterogeneity in clinical manifestations and disease progression is not fully explained; however, a short disease duration and a young age seem to be good predictors of a better response to treatment. For this purpose, we investigated and followed up a cohort of 13 juvenile patients with LOPD from the clinical and therapeutic point of view, mainly pointing out the transition from presymptomatic to symptomatic status.</div><div>We retrospectively collected clinical, morphological, biochemical and molecular data from 13 juvenile LOPD patients. Motor and respiratory functional data, obtained during annual follow-up visits, were analyzed. The data included serial evaluations of the Medical Research Council (MRC) scale, the 6-Minute Walking Test (6MWT), the Gait, Stairs, Gower, and Chair (GSGC) score, and seated and supine Forced Vital Capacity (FVC). Muscle Magnetic Resonance Imaging (MRI) was also included, although it was not performed in all cases.</div><div>Currently, patients mean age is 18 years. All patients but one were diagnosed because of an isolated hyperCKemia: the mean age at diagnosis was 6.8 years (range 1–18). The onset of symptoms occurred from 6 months to 12 years after the diagnosis. The mean clinical follow-up duration was 9 years (range 2–18). From the genetic point of view, the most shared mutation was c.32–13T&gt;<em>G</em>, found in twelve patients as compound heterozygosis. Seven patients underwent muscle biopsy, which showed vacuolar myopathy with glycogen accumulation in four of them with unspecific changes in the other three cases. Five patients developed proximal muscle weakness during the follow-up with a mild waddling gait and a positive Gowers manoeuver. Muscle MRI revealed mild hypotrophy of the thighs at the development of symptoms in four out of five cases. Four patients started alglucosidase alfa, and one avalglucosidase alfa. These five patients on Enzyme Replacement Therapy (ERT) showed motor and respiratory stability in the following years.</div><div>Timely identification of emerging clinical manifestations in presymptomatic LOPD patients, as a result of careful follow-up, is essential to start prompt treatment to modify the disease natural course.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105277"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WMS General Information","authors":"","doi":"10.1016/j.nmd.2025.105307","DOIUrl":"10.1016/j.nmd.2025.105307","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105307"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle imaging in facioscapulohumeral muscular dystrophy research: A scoping review and expert recommendations","authors":"Sanne C․C․ Vincenten ,&nbsp;Sjan Teeselink ,&nbsp;Karlien Mul ,&nbsp;Linda Heskamp ,&nbsp;Hermien E․ Kan ,&nbsp;Arend Heerschap ,&nbsp;Donnie Cameron ,&nbsp;Giorgio Tasca ,&nbsp;Doris G․ Leung ,&nbsp;Nicol C․ Voermans ,&nbsp;Baziel G․M․ van Engelen ,&nbsp;Nens van Alfen","doi":"10.1016/j.nmd.2025.105274","DOIUrl":"10.1016/j.nmd.2025.105274","url":null,"abstract":"<div><div>Clinical trial readiness is an important topic in the field of facioscapulohumeral muscular dystrophy (FSHD). As FSHD is a slowly progressive and clinically heterogeneous disease, imaging biomarkers have been proposed to complement clinical outcome measures. Muscle magnetic resonance imaging (MRI), ultrasound and dual energy X-ray absorptiometry (DEXA) have been used to measure disease severity, activity and progression. We conducted a scoping review of the literature on these imaging modalities to assess gaps in knowledge and subsequently collaborated with a panel of neuromuscular imaging experts to generate recommendations on the road ahead. We systematically searched PubMed, EMBASE and Cochrane Library databases. Three-hundred and twenty-eight studies were screened and one hundred and five studies were included. MRI indices related to intramuscular fat content, STIR positivity and T2_water are used as diagnostic as well as prognostic and monitoring biomarkers. Ultrasound echogenicity can be used as a diagnostic and potentially as a prognostic and monitoring biomarker. DEXA lean muscle mass may be used as an additional monitoring biomarker. Each imaging modality has its own benefits but also challenges. Based on our expert opinions, we propose a roadmap to address these challenges, ensuring the optimal use of each modality in multi-center clinical trials in FSHD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105274"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic resonance imaging in idiopathic inflammatory myopathies: deciphering the pattern of muscle involvement","authors":"S Sridhar ,&nbsp;Saraswati Nashi ,&nbsp;Karthik Kulanthaivelu ,&nbsp;Seena Vengalil ,&nbsp;Dipti Baskar ,&nbsp;Kiran Polavarapu ,&nbsp;Veeramani Preethish-Kumar ,&nbsp;Hansashree Padmanabha ,&nbsp;Mainak Bardhan ,&nbsp;Gopikrishnan Unnikrishnan ,&nbsp;Akshata Huddar ,&nbsp;Deepak Menon ,&nbsp;Vidya Nittur ,&nbsp;Manoj Rajanna ,&nbsp;Nandeesh Bevinahalli ,&nbsp;Aneesha Thomas ,&nbsp;Muddasu Suhasini Keerthipriya ,&nbsp;Yashwanth Gangadhar ,&nbsp;P V Pratyusha ,&nbsp;Jitender Saini ,&nbsp;Atchayaram Nalini","doi":"10.1016/j.nmd.2024.105257","DOIUrl":"10.1016/j.nmd.2024.105257","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) constitute a group of immune-mediated disorders, affecting muscles. Our study aims to investigate the specific patterns of muscle involvement in subgroups of IIM. An ambispective and observational study was conducted. The evaluation encompassed clinical characterization, scales of MMT8, MDAAT, assessment of severity of edema/ fatty replacement using Modified Stramare (grades 1-5) &amp; Modified Goutallier-Lamminen-Mercuri (GLM) scores, respectively on the muscle MRI of 125 patients with IIM. A total of 125 patients were categorized into four subgroups: dermatomyositis (DM), immune- mediated necrotizing myopathy (IMNM), overlap myositis (OM), &amp; seronegative groups. Median age at presentation was 35 years. Median duration of illness was 8 months. In DM, 53.12% of patients showed grade 3 to grade 5 edema in adductor group. In the leg, 46.8% showed grade 3-5 edema in the deep flexors of leg &amp; peronei, and 65.6% had significant fasciitis. In IMNM, 52.1% displayed grade 4-5 edema in rectus femoris &amp; semimembranosus. Interestingly, in the leg, 78.2% of IMNM patients lacked edema in peroneii. For OM subgroup, there was no specific pattern of involvement. In seronegative subset, vastus lateralis showed grade 4-5 edema, while in the leg, deep posterior compartment and peroneal muscle group exhibited subtle to no edema. The involvement of peroneus muscles in leg emerged as a characteristic feature of DM, they were conspicuously spared in other subgroups. Mild muscle fatty replacement was observed in all groups except for IMNM, where it was more pronounced. The research broadens the imaging spectrum of inflammatory myositis &amp; introduces innovative concepts of selective involvement of muscles.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105257"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932450","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":"Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double–blind, placebo–controlled, phase 3 trial (TAMDMD Group B)","authors":"Bettina C. Henzi ,&nbsp;Niveditha Putananickal ,&nbsp;Simone Schmidt ,&nbsp;Sara Nagy ,&nbsp;Daniela Rubino–Nacht ,&nbsp;Sabine Schaedelin ,&nbsp;Helge Amthor ,&nbsp;Anne–Marie Childs ,&nbsp;Nicolas Deconinck ,&nbsp;Iain Horrocks ,&nbsp;Saskia Houwen–van Opstal ,&nbsp;Vincent Laugel ,&nbsp;Mercedes Lopez Lobato ,&nbsp;Andrés Nascimento Osorio ,&nbsp;Ulrike Schara–Schmidt ,&nbsp;Stefan Spinty ,&nbsp;Arpad von Moers ,&nbsp;Fiona Lawrence ,&nbsp;Patricia Hafner ,&nbsp;Olivier M. Dorchies ,&nbsp;Dirk Fischer","doi":"10.1016/j.nmd.2025.105275","DOIUrl":"10.1016/j.nmd.2025.105275","url":null,"abstract":"<div><div>Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model. Our objective was to assess the safety and efficacy of tamoxifen over 48 weeks in non-ambulant DMD patients. In this multicentre, randomised, double–blind, placebo–controlled, phase 3 trial at six European centres boys aged 10–16 years with genetically diagnosed DMD, non-ambulant and off corticosteroid treatment for ≥6 months, randomly assigned (1:1) to either 20 mg/day tamoxifen orally or placebo were included. The primary outcome was change in D2 motor function measure from baseline to week 48. Of 15 non-ambulant male patients with DMD screened, 14 were enrolled from January 24th, 2019, to January 6th, 2021. Eight patients were randomised to the treatment and six to the placebo group. The primary efficacy outcome did not differ significantly between tamoxifen and placebo (7.8 percentage points, 95 % CI, –26.82 to 11.22, <em>p</em> <em>=</em> <em>0.359</em>) with a trend not favouring tamoxifen. No deaths or life-threatening serious AEs occurred. Tamoxifen was safe but due to insufficient clinical evidence, it cannot be recommended as a treatment option for DMD. Trial registration: ClinicalTrials.gov (NCT03354039).</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105275"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Natural history of skeletal muscle laminopathies: a 2-year prospective study”","authors":"Luca Spiro Santovito ,&nbsp;Silvia Bonanno ,&nbsp;Maria Barbara Pasanisi ,&nbsp;Annamaria Gallone ,&nbsp;Federica Ricci ,&nbsp;Irene Tramacere ,&nbsp;Riccardo Zanin ,&nbsp;Stefano Carlo Previtali ,&nbsp;Lorenzo Maggi","doi":"10.1016/j.nmd.2024.105256","DOIUrl":"10.1016/j.nmd.2024.105256","url":null,"abstract":"<div><div>Skeletal muscle laminopathies (SMLs) are rare disorders characterized by skeletal muscle involvement caused by mutations in <em>LMNA</em> gene. To date, the natural history of SMLs has not been clearly elucidated. Through a 2-year prospective study, we aimed to describe the natural history of SMLs. We enrolled 26 SMLs patients, assessed with: North Star Ambulatory Assessment scale (NSAA), timed tests, manual muscle testing, joint range of motion, six-minutes walking test (6MWT); respiratory evaluation including forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1); individualized neuromuscular quality of life (INQoL). Muscular performance with the aforementioned tools significantly correlated with phenotypes at the baseline, showing the worse outcome in those with autosomal dominant Emery-Dreifuss muscular dystrophy as compared to limb girdle phenotype. NSAA score significantly (<em>p</em> = 0.0005) worsened during the 2-year follow-up. Moreover, the respiratory function through FVC and FEV1 significantly (<em>p</em> = 0.0086 and <em>p</em> = 0.0290, respectively) deteriorated over the follow-up period. 6MWT, INQoL and timed tests did not significantly change, as well as ankle, knee, and elbow contractures. This study showed a slow progression of motor and respiratory function in SMLs patients over a period of 2 years.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105256"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807081","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":"Investigating phenotypic variability patterns in myotonic dystrophy type 2 in a neuromuscular referral center retrospective cohort","authors":"Vincent Picher-Martel ,&nbsp;Joseph J Locascio ,&nbsp;Kathy Chuang ,&nbsp;William S David ,&nbsp;Anthony A Amato ,&nbsp;Paloma Gonzalez-Perez","doi":"10.1016/j.nmd.2024.105255","DOIUrl":"10.1016/j.nmd.2024.105255","url":null,"abstract":"<div><div>We aimed at investigating the presence of patterns that account for the phenotypic variability in a myotonic dystrophy type 2 (DM2) retrospective cohort at the Mass General Brigham Neuromuscular Centers. We collected the presence or absence of 23 clinical variables at symptom onset and diagnosis (<em>n</em> = 67 patients) and follow-up (<em>n</em> = 37 patients). We first identified set/s of variables (factors or cluster/s) representative of the large research data pool at onset by performing factor analyses, then assigned each patient to the cluster for which they had the highest computed total factor score. Twelve variables grouped into two distinct clusters that, based on their variable content, we named as proximal myotonic myopathy (PROMM)-DM2 or non-PROMM-DM2. Patients assigned to non-PROMM-DM2 more frequently had clinical myotonia and positive family history, and less frequently multiorgan involvement. Most patients (67.2 %) remained assigned to same cluster during disease course and 11 non-PROMM eventually transitioned to PROMM-DM2. Dyslipidemia and early cataracts (both in PROMM-DM2 cluster) were the earliest extramuscular manifestations that occurred during disease course and they accounted for the conversion of up to 8 out of 11 non-PROMM to PROMM converters. Identification of phenotypically homogeneous patient subgroups may help investigating DM2 prognosis and disease biomarkers in future prospective studies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105255"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CMT2 and distal hereditary motor neuropathy associated with VRK1 variants: Case series","authors":"Sasha A. Živković ,&nbsp;Richard J. Nowak ,&nbsp;Daniel DiCapua","doi":"10.1016/j.nmd.2024.105254","DOIUrl":"10.1016/j.nmd.2024.105254","url":null,"abstract":"<div><div>Axonal Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN) are associated with a heterogeneous group of genes encoding proteins that are involved in axonal transport, control of RNA metabolism, mitochondrial dynamics and DNA repair. VRK1 (vaccinia-related kinase 1) is a serine/threonine kinase which is widely expressed in human tissue and plays a role in RNA maturation and processing and in DNA damage response. Variants of <em>VRK1</em> have been associated with neurodevelopmental and neuromuscular disorders including pontocerebellar hypoplasia, motor neuron disorders and distal hereditary motor neuropathy. We present 3 cases of <em>VRK1</em>-associated neuromuscular disorders without neurodevelopmental abnormalities including CMT2 associated with homozygous variant of <em>VRK1</em> at Arg387His and dHMN with combination of heterozygous variants at Arg133His and Asp243Asn. While our case series expands the clinical spectrum of <em>VRK1</em>-associated neuromuscular disorders, additional studies are needed to elucidate pathophysiology of neuromuscular disorders associated with <em>VRK1</em> variants.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105254"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854712","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":"Vienna WMS 2025","authors":"","doi":"10.1016/j.nmd.2025.105306","DOIUrl":"10.1016/j.nmd.2025.105306","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105306"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor function testing rates and outcomes in Duchenne muscular dystrophy with comorbid autism and attention-deficit/hyperactivity disorder","authors":"Dennis Keselman ,&nbsp;Allan Glanzman ,&nbsp;Michael Y. Thelen ,&nbsp;Laura A. Prosser ,&nbsp;Jennifer McGuire ,&nbsp;Susan E. Matesanz","doi":"10.1016/j.nmd.2025.105281","DOIUrl":"10.1016/j.nmd.2025.105281","url":null,"abstract":"<div><div>Patients with Duchenne muscular dystrophy have a higher incidence of neurodevelopmental disorders, particularly autism spectrum and attention-deficit/hyperactivity disorders, than the general population. However, the clinical outcome assessments used in the evaluation of patients with Duchenne and as endpoints in clinical trials require significant patient cooperation, which can be challenging in those with severe behavioral issues and leads to their exclusion. With ongoing expansion of the therapeutic arsenal, we aimed to explore differences in motor function test completion and measurements between Duchenne patients with and without autism spectrum disorder or attention-deficit/hyperactivity disorder in a large tertiary care hospital's pediatric neuromuscular clinic. We identified significantly lower rates of motor function testing and motor function test scores among Duchenne patients with autism or attention-deficit/hyperactivity disorder. These findings underscore the need for adequate opportunity to complete motor function testing in those patients. Alternatively, the Duchenne community could consider validating more patient-reported outcomes and wearable device outcome measures in trials that families of children with neurodevelopmental disorders could more easily use. These interventions would improve equitable access to new therapies for patients with severe behavioral issues and allow researchers to track broader clinical outcomes among all patients as the Duchenne treatment landscape expands.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"48 ","pages":"Article 105281"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394091","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}