Neuromuscular Disorders最新文献

{"title":"282nd ENMC international workshop - standards of diagnosis and care for the sarcoglycanopathies. 8-10 November 2024, Amsterdam, Netherlands","authors":"M.A. Iammarino ,&nbsp;J. Alonso-Pérez ,&nbsp;T. Stojkovic ,&nbsp;E. Pegoraro ,&nbsp;L. Lowes ,&nbsp;J. Díaz-Manera ,&nbsp;282nd workshop study group","doi":"10.1016/j.nmd.2025.106212","DOIUrl":"10.1016/j.nmd.2025.106212","url":null,"abstract":"<div><div>Sarcoglycanopathies are rare autosomal recessive limb-girdle muscular dystrophies (LGMD R3–R6) caused by pathogenic variants in SGCA, SGCB, SGCG, or SGCD genes. They present predominantly in childhood with progressive proximal muscle weakness, frequently leading to loss of ambulation in adolescence or early adulthood, and may involve cardiac and respiratory complications. Despite their severity and multisystem impact, no internationally agreed standards of care (SoC) currently exist, contributing to diagnostic delays, inconsistent management, and inequitable access to multidisciplinary expertise. The 282nd ENMC International Workshop (Amsterdam, November 2024) convened 29 global stakeholders including clinicians, researchers, industry, and patient representatives to harmonize literature evidence with international clinical experience. Key outputs included: consensus on the clinical spectrum and diagnostic algorithm (with and without genetic testing); recommendations for multidisciplinary management covering neurology, cardiology, respiratory care, rehabilitation, and psychosocial support; and identification of outcome measures for clinical monitoring and trials. Natural history data were reviewed to define prognostic factors, and emerging therapeutic avenues including gene therapy, small-molecule correctors, and antifibrotic strategies were discussed. The workshop concluded with a mandate to develop and disseminate comprehensive, accessible SoC guidelines tailored to sarcoglycanopathies to improve care delivery and readiness for forthcoming disease-modifying therapies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"54 ","pages":"Article 106212"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118448","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":"30PMalignancy characteristics among idiopathic inflammatory myopathies: a retrospective study at Dr Cipto Mangunkusumo hospital","authors":"L. Indrawati ,&nbsp;M. Putri ,&nbsp;W. Isaac ,&nbsp;N. Shafitha ,&nbsp;S. Simatupang ,&nbsp;A. Safri ,&nbsp;N. Fadli ,&nbsp;A. Harsono ,&nbsp;W. Wiratman ,&nbsp;A. Budikayanti ,&nbsp;F. Octaviana ,&nbsp;M. Hakim","doi":"10.1016/j.nmd.2025.105493","DOIUrl":"10.1016/j.nmd.2025.105493","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) can be associated with malignancy, therefore concomitant malignancy management will improve the response of IIM to immunosuppressive agents. This study aimed to study the characteristics of malignancy among IIM patients at Dr. Cipto Mangunkusumo Hospital. We identified 106 patients diagnosed with IIM between 2018 and April 2025, collected data on malignancy risk stratification using International Myositis Assessment and Clinical Studied (IMACS) 2023 criteria, malignancy occurrence (proven or suspected), and myositis-specific antibodies (MSA). The patients were predominantly female (75; 70.7%) with (57; 53%) aged over 40 years. Dermatomyositis (DM) was the most common subtype (48; 45.3%), followed by Polymyositis (PM) (25; 23.6%), Immune-mediated necrotizing myopathy (IMNM) (19; 17.9%), ASSD (3; 2.8%), and Overlap myositis (OM) (24; 22.64%). According to IMACS, 34 (32.7%) and 30 (28.3%) patients were at high risk and moderate risk for malignancy, respectively. Malignancy was confirmed in 16 patients (14.9%), including cases of Hepatocellular carcinoma, Ovarian and Gastrointestinal adenocarcinoma, Acute myeloid leukemia, Lymphoma, Lung, Thyroid, and Nasopharyngeal cancers. DM was the most frequently associated subtype (13/16,81.25%); within this group, one patient was juvenile-onset DM. Two malignancies occurred in overlap myositis (OM) patients with HCC and Thyroid cancer. Most cancers (13 out of 16) were detected within three years after IIM onset. TIF1-γ was the most commonly detected MSA in malignancy cases. Additionally, 12 patients (11.32%) underwent evaluation for suspected neoplasm, with DM being the most common associated subtype (41.67%). Similar to overall population studies, DM was the most prevalent IIM subtype linked to malignancy, with TIF1-γ as the primary MSA. Prompt cancer screening is essential, especially in high-risk IMACS patients, as even those with OM and SLE may have an increased risk of malignancy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105493"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204098","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":"09PCase series of immune checkpoint inhibitor-induced overlap syndrome: myasthenia, myositis, and miocarditis in a tertiary center","authors":"F. Gomez Fernandez ,&nbsp;M. Cabrera Serrano ,&nbsp;I. Rojas-Marcos ,&nbsp;I. Lopera Rodriguez ,&nbsp;E. Rivas Infante ,&nbsp;E. Montes Latorre ,&nbsp;C. Paradas López","doi":"10.1016/j.nmd.2025.105473","DOIUrl":"10.1016/j.nmd.2025.105473","url":null,"abstract":"<div><div>Case Series of Immune checkpoint inhibitor-induced overlap syndrome: myasthenia, myositis, and miocarditis in a tertiary center. Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatments and expectations but are associated with several immune-related adverse events, including severe neuromuscular and cardiac toxicities. The myasthenia-myositis-miocarditis overlap syndrome (IM3OS) is particularly life-threatening and under-recognized. We retrospectively reviewed 10 patients who developed neuromuscular symptoms following treatment with ICIs and were referred for neurological evaluation. Demographic data, oncologic diagnosis, ICI type, clinical features, laboratory results, neurophysiological and muscle biopsy findings, treatment strategies, and clinical outcomes were collected. The mean age was 68.5 years. The most frequent underlying malignancies were lung adenocarcinoma and renal cell carcinoma. Four patients were treated with pembrolizumab and three with nivolumab. The median baseline modified Rankin Scale (mRS) score was 1. Symptoms appeared a mean of 25.6 days after ICI initiation; the mean time to neurological consultation was 42.3 days after ICI initiation. Neuromuscular adverse events prompted hospitalization in 9 patients, with 2 requiring intensive care. Five patients (50%) had concurrent thyroid dysfunction. Eight patients (80%) tested positive for anti-AChR antibodies. Elevated troponin levels were noted in 7 patients (mean initial value 1760 ng/L), and creatine kinase (CK) was elevated in most cases (mean 2357 U/L). EMG findings showed decremental response in one patient and spontaneous activity in seven of them. Six patients underwent muscle biopsy; four demonstrated typical patchy necrotizing myositis with macrophage infiltration. Treatment included corticosteroids in all cases, with additional use of intravenous immunoglobulin (IVIG), plasma exchange, tacrolimus, and pyridostigmine. Despite aggressive immunosuppression, the overall mortality rate was 50%. ICI-induced overlap syndrome is a threatening-life condition with high morbidity and mortality. Early recognition through clinical suspicion, serology, neurophysiological tests, and biopsy is essential. Fast and intensive multimodal immunosuppressive therapy may improve outcomes, but prognosis remains poor in many cases. Increased awareness and interdisciplinary collaboration are mandatory in managing these complex presentations.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105473"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204189","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":"28PAmyloid myopathy: hypertrophic subtype correlates with higher muscular amyloid deposition","authors":"F. Authier ,&nbsp;B. Periou ,&nbsp;M. Araujo ,&nbsp;K. Hankiewicz ,&nbsp;C. Heyraut-Blanchet ,&nbsp;V. Plante-Bordeneuve ,&nbsp;C. Lefeuvre ,&nbsp;A. Zaroui ,&nbsp;T. Damy ,&nbsp;G. Severa ,&nbsp;E. Malfatti ,&nbsp;S. Souvannanorath","doi":"10.1016/j.nmd.2025.105491","DOIUrl":"10.1016/j.nmd.2025.105491","url":null,"abstract":"<div><div>Muscle involvement is a rare complication of systemic amyloidosis resulting from monoclonal dysglobulinemia (AL amyloidosis) or from a mutation in the gene encoding the transthyretin (TTR) transport protein. We retrospectively studied 20 patients (13M- 7F; mean age: 67 years) with biopsy-proven muscular AL (16/20) and hereditary TTR amyloidosis (4/20; Ile107Val n=2; Val142Ile n=1; Ile88Leu n=1) with muscle involvement. Three patients had isolated hyperCKemia (HCK), 3 muscle hypertrophy (HPT), and 14 muscle weakness and atrophy (MYOP). CK levels ranged from N to 20xN. In AL amyloidosis, biopsy showed vascular deposits of amyloidosis in all patients, isolated in 4/16, and associated with necrotizing (11/16) and/or inflammatory (6/15) myopathy. In TTR amyloidosis, biopsy showed interstitial (4/4), vascular (1/4), and perivascular (1/4) deposits, with a myonecrotic appearance (4/4). Muscle hypertrophy was present only in patients with AL amyloidosis, and only amyloid deposits in the vessels and/or interstitium were visible. In contrast, muscle weakness was associated with signs of myonecrosis (except one) or inflammation, regardless of the type of amyloidosis. Morphometrical analysis of myofibre size and microvasculature (density, diameter) did not show difference between AL and TTR cases, or between clinical subtypes. In contrast the quantification of muscular congophilic area through home-made macro script for Fiji-ImageJ (cryosection, fluorescence, 555nm) showed that HPT subtype associated with higher amyloid deposition compared to HCK and MYOP (4.7% vs 1.2% and 0.7%, p=0.03 and p=0.003, respectively). In conclusion, amyloid myopathies presented either as muscle hypertrophy (AL) or as necrotizing ± inflammatory myopathy (AL and TTR). Morphometrical analysis indicated that hypertrophic subtype associates with higher muscular amyloid deposition compared to other subtypes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105491"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204190","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":"03PA study of muscle biopsy cases positive for anti-cytosolic 5′-nucleotidase 1A antibodies","authors":"M. Ishida ,&nbsp;T. Kurashige ,&nbsp;T. Murao ,&nbsp;H. Maruyama ,&nbsp;T. Ohshita","doi":"10.1016/j.nmd.2025.105467","DOIUrl":"10.1016/j.nmd.2025.105467","url":null,"abstract":"<div><div>Anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) antibodies are known to be related with inclusion body myositis (IBM). However, there are atypical patients whose clinical symptoms and pathological findings are different from typical cases of IBM. In addition, anti-cN1A antibodies are sometimes detected in serum of amyotrophic lateral sclerosis (ALS). Recently, autoantibodies associated with myositis, including anti-cN1A antibodies, can be detected by the Autoantibody Array Assay. In this study, we evaluated the characteristics of muscle biopsy cases positive for anti-cN1A antibodies. We evaluated clinicopathological characteristics of 32 patients from January 2023 to December 2024. They were examined by muscle biopsy and serological test by the Autoantibody Array Assay. Anti-cN1A antibodies were detected in 12 patients; 5 of the 12 patients were diagnosed with IBM. Antibody titers were 397.9±268.7 in the IBM group and 81.4±41.7 in the non-IBM group (p=0.011). Two patients in the non-IBM group had myositis-specific antibodies (anti-SRP or anti-HMGCR antibodies) and anti-SS-A antibodies detected simultaneously and were diagnosed as immune–mediated necrotizing myopathy (IMNM) clinicopathologically. Among 12 patients with anti-cN1A antibodies, five patients were positive for anti-cN1A antibodies alone, and two were diagnosed with IBM, two with seronegative IMNM complicated by malignancy, and one with ALS. Anti-cN1A antibodies are useful in the diagnosis of IBM, but anti-cN1A antibodies themselves have little pathological significance, and antibody levels may be elevated in correlation with the presence or absence of pathology.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105467"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204243","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":"03OCognitive development in children with 5q-SMA identified by neonatal screening - 4 years follow-up","authors":"H. Kölbel ,&nbsp;M. Kopka ,&nbsp;S. Pum ,&nbsp;S. Alina ,&nbsp;A. Blaschek ,&nbsp;U. Schara-Schmidt ,&nbsp;W. Müller-Felber ,&nbsp;O. Schwartz ,&nbsp;K. Vill","doi":"10.1016/j.nmd.2025.105461","DOIUrl":"10.1016/j.nmd.2025.105461","url":null,"abstract":"<div><div>The impaired cognitive development of children with 5q-SMA and two SMN2 copies, despite early initiation of therapy, which was detected during neonatal screening, underlines the crucial role of the SMN protein in the early stages of brain development. Long-term data on the cognitive development of these children are lacking to further elucidate the situation. A total of 46 families with 47 children identified in newborn screening were invited to have their children tested with the WISC-IV and the CBCL after the age of four. Twenty-two children with a mean age of 59.09 months (SD = 8.85) were included, 13 girls and 9 boys, 12 patients with two, 5 patients with three, and 5 patients with 4 SMN2 copies. The total IQ score on the WPPSI-IV was in the normal range (M = 87.53; SD = 15.96). The non-verbal index (M = 80.42; SD = 20.51), the general ability index (M = 79.13; SD = 20.71), and the cognitive performance index (M = 77.86; SD = 22.08) were all below average. The mean scores for the WPPSI-IV subtest areas of language comprehension (M = 83.35; SD = 16.67) and processing speed (M = 83.64; SD = 15.19) were below average. The mean scores for the subtest areas of visual-spatial processing (M = 94.45; SD = 23.21), fluid reasoning (M = 89.91; SD = 19.42) and working memory (M = 89.09; SD = 23.63) subtest areas were average. All CBCL scales were rated as average by the parents. In the regression analysis, the Bayley Cognitive Scale scores from our initial study were significantly associated with current IQ scores using the WPPSI-IV (β = 0.80, p = 0.002, R² = 0.64) and with nonverbal IQ scores (β = 0.83, p = 0.006, R ² = 0.68). Our preliminary data of the long-term follow-up of patients confirm that cognitive development can be impaired in children with SMA despite early treatment. Findings have to be confirmed in a larger group. Fearing negative consequences of diagnosis of cognitive impairment hinders some parents to agree to cognitive testing.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105461"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204244","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":"04PNovel mouse model for inclusion body myositis: transgenic upregulation of lymphotoxin together with impaired autophagy induces inflammation and protein accumulation in skeletal muscle","authors":"J. Bremer ,&nbsp;J. Nagel ,&nbsp;J. Zschüntzsch ,&nbsp;K. Zajt ,&nbsp;T. Palaz ,&nbsp;T. Blank ,&nbsp;A. Ikis ,&nbsp;L. Fischer ,&nbsp;C. Einer ,&nbsp;A. Eck ,&nbsp;V. Kana ,&nbsp;A. Aguzzi ,&nbsp;M. Prinz ,&nbsp;D. Liebetanz ,&nbsp;F. Odoardi ,&nbsp;C. Kuo ,&nbsp;J. Weis ,&nbsp;F. Kraft ,&nbsp;J. Schmidt ,&nbsp;M. Heikenwälder","doi":"10.1016/j.nmd.2025.105468","DOIUrl":"10.1016/j.nmd.2025.105468","url":null,"abstract":"<div><div>Inclusion body myositis (IBM) is a progressive muscle disorder characterized by inflammation and degeneration with altered proteostasis. To better understand the interrelationship between these two features, we aimed at establishing a novel preclinical IBM model. First, we used quantitative PCR to determine expression of pro-inflammatory chemo- and cytokines including lymphotoxin (LT)-signaling pathway components in human skeletal muscle tissue diagnosed with myositis. Based on these results we generated a mouse model that we analyzed at the histological, ultrastructural, transcriptional, biochemical, and behavioural level. Lastly, we subjected this model to anti-inflammatory treatments. After confirming and extending previous data on activation of lymphotoxin (LT)-signaling in human myositis, we generated a transgenic mouse line co-expressing LTalpha and -beta in skeletal muscle fibers. Transgenic mice displayed chronic myositis accompanied by dysregulated proteostasis, including an altered autophagolysosomal pathway. Related genes were temporarily up- and later downregulated, possibly in a compensatory manner. Therefore, we genetically impaired autophagy in skeletal muscle cells. Autophagy impairment alone induced a pro-inflammatory transcriptional state, but no obvious cellular inflammation. However, the combination of LT-driven myositis with autophagy impairment induced the full spectrum of characteristic molecular and pathological features of IBM in skeletal muscle, including protein aggregates with typical ultrastructural morphology and mild mitochondrial pathology. Our attempts to treat the pathology by subjecting these mice to corticosteroids or anti-Thy1.2 antibodies mirrored recent treatment failures in humans, i.e., none of these treatments resulted in significant clinical improvement of motor performance or the transcriptional profile of muscle pathology. In summary, these data provide evidence that inflammation and autophagy disruption play a synergistic role in the development of IBM-like muscular pathology. Furthermore, once established, IBM-like pathology in these mice, as in human IBM patients cannot be reverted or prevented from progression by conventional means of immunosuppression. We expect that this novel mouse model will help to identify future treatment modalities for IBM.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105468"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204260","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":"06PPersistent exanthema mainly on the trunk with pathologically dermal interstitial mucin as anti-HMGCR myopathy-associated skin rash: case series","authors":"W. Zhu ,&nbsp;N. Cheng ,&nbsp;Z. Liu ,&nbsp;S. Zheng ,&nbsp;L. Chen","doi":"10.1016/j.nmd.2025.105470","DOIUrl":"10.1016/j.nmd.2025.105470","url":null,"abstract":"<div><div>Antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) form a newly identified distinct serological marker for immune-mediated necrotizing myopathy (IMNM), whose skin involvement has been reported but its characteristics only vaguely described. We retrospectively examined the clinical and dermatologic histological features of non-dermatomyositis-like persistent exanthema in five anti-HMGCR myopathy patients followed up in the neurology and dermatology clinic of Huashan Hospital between December 2020 and September 2024. The exanthema presented as persistent violaceous or erythematous plaques, asymptomatic or itching, mainly distributed on the trunk, whereas dermatomyositis-specific lesions such as Gottron's sign and papules, heliotrope rash, V or shawl signs, and nailfold telangiectasia were all absent. Skin rash in 80% of patients (4/5) appeared earlier than muscle symptoms such as fatigue, proximal limb weakness, and hyperCKemia, with the median advanced time of 3 years (8 months to 7 years). Biopsies revealed scant interface dermatitis, interstitial mucin, and perivascular lymphocytic infiltrate with occasionally plasma cells and/or neutrophils. Notably, the exanthema showed no response to topical or even systemic corticosteroid but relieved after systemic immunosuppressive therapy for myopathy, in accordance with the improvement of muscle symptoms and hyperCKemia. Persistent exanthema mainly on the trunk with pathologically dermal interstitial mucin can be onset sign in anti-HMGCR myopathy. Neurologists and dermatologists should be aware of this rare entity of “pseudo-dermatomyositis”, carefully evaluate muscle syndromes and carry out further investigations, including muscle biopsy and serum anti-HMGCR antibodies assays if present.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105470"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204291","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":"23PMyopathology and immune profile of granulomatous myositis in sarcoid myopathy","authors":"M. Holzer ,&nbsp;N. Ruffer ,&nbsp;I. Pinal-Fernandez ,&nbsp;F. Kleefeld ,&nbsp;H. Goebel ,&nbsp;A. Schänzer ,&nbsp;M. Casal-Dominguez ,&nbsp;I. Kötter ,&nbsp;N. Görl ,&nbsp;R. Alten ,&nbsp;E. Braasch ,&nbsp;T. Lempert ,&nbsp;A. Krause ,&nbsp;T. Huber ,&nbsp;T. Liewluck ,&nbsp;A. Mammen ,&nbsp;W. Stenzel ,&nbsp;C. Preuße ,&nbsp;U. Schneider ,&nbsp;M. Krusche","doi":"10.1016/j.nmd.2025.105486","DOIUrl":"10.1016/j.nmd.2025.105486","url":null,"abstract":"<div><div>Sarcoid myopathy (SaM) is characterized by granulomatous myositis and can overlap with inclusion body myositis (IBM), a late-onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. Systematic studies assessing the myopathologic features of SaM are scarce and the immunopathogenesis of muscle inflammation in SaM is poorly understood. In this context, we performed a multidimensional characterization of muscle biopsy specimens from patients with ‘pure SaM’, SaM with concomitant IBM (SaM-IBM) and ‘pure IBM’ including histopathologic and ultrastructural analysis in addition to molecular profiling. Myopathologic analysis revealed a prototypical appearance of SaM that is characterized by endomysial and perimysial granulomatous inflammation frequently extending to the fascia, endomysial fibrosis, muscle fibre atrophy, variations of muscle fibre size and capillary thickening. Findings from immunohistochemical studies established Chitinase 1 as a pure giant cell marker in SaM. In addition, SaM is characterized by disease-specific immune dysregulation that involves macrophage function and maturation. Finally, SaM-IBM represents a noteworthy overlap syndrome that shares multiple dysregulated immune pathways with ‘pure SaM’.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105486"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204300","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":"20PRituximab in treatment-refractory childhood-onset immune-mediated necrotizing myopathy: a case series","authors":"H. Dang,&nbsp;S. Le","doi":"10.1016/j.nmd.2025.105484","DOIUrl":"10.1016/j.nmd.2025.105484","url":null,"abstract":"&lt;div&gt;&lt;div&gt;IMNM is a rare and severe autoimmune myopathy, recognized as one of the most disabling forms of inflammatory muscle disease. Several case reports have described a slowly progressive clinical course, occasionally mimicking muscular dystrophy. The ENMC has recommended rituximab (RTX) as a second-line therapeutic option for IMNM. However, this recommendation is based on limited evidence derived from a single case series involving eight patients. In this report, we describe two pediatric-onset, treatment-refractory cases of IMNM in which rituximab was initiated following inadequate response to prolonged immunosuppressive therapy. A 17-year-old girl presented with tetraplegia. Her symptoms began at age 7 with difficulty climbing stairs, frequent falls, and inability to rise from a seated position. She was misdiagnosed with muscular dystrophy for many years before being referred to our hospital. Her weakness had progressed to the point where she could no longer walk independently. She had no dysphagia or skin rash. On examination, she showed prominent proximal muscle weakness (MRC 3/5), neck flexors weaker than extensors, and no sensory deficits. Her mRS score was 3. Anti-HMGCR antibodies were positive; anti-SRP was negative. Muscle biopsy revealed features consistent with IMNM with some fatty replacement. MRI showed symmetrical muscle edema in both upper and lower limbs. She was diagnosed with childhood-onset IMNM mimicking muscular dystrophy. Initial treatment with corticosteroids (1 mg/kg) and mycophenolate mofetil led to reduced but persistently elevated CPK levels and no significant clinical improvement after one year. RTX was then initiated (1 cycle of 1000 mg, two weeks apart). Following treatment, she regained the ability to walk independently, though she remained unable to climb stairs, and CPK levels remained stable. An 18-year-old female presented with progressive limb weakness. She reported mild lower limb weakness beginning five years prior, which gradually worsened. In the past 6–8 months, the weakness progressed more rapidly, particularly affecting her ability to climb stairs. She had no joint pain, skin changes, dysphagia, or family history of neuromuscular disease. Neurological examination revealed proximal muscle weakness (MRC 3/5), with neck flexors weaker than extensors, and no sensory deficits or cranial nerve involvement. Her mRS score was 3. Autoantibody testing was negative for anti-HMGCR and anti-SRP, but anti-Mi-2α was strongly positive. Due to this antibody profile being atypical for the clinical presentation, a muscle biopsy was performed, confirming a diagnosis of IMNM. MRI showed a diffuse, symmetric muscle edema with fatty replacement of the posterior thigh. Initial treatment with corticosteroids and azathioprine failed to halt disease progression, and serum CPK remained elevated. RTX was given as in Case 1. Following treatment, while the mRS score remained unchanged, disease progression stabilized, CPK levels d","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105484"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204344","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}