Antonio Lauletta, Luca Bosco, Gioia Merlonghi, Yuri Matteo Falzone, Marta Cheli, Roberta Piera Bencivenga, Dario Zoppi, Marco Ceccanti, Felix Kleefeld, Sarah Léonard-Louis, Werner Stenzel, Olivier Benveniste, Lorenzo Maggi, Stefano Carlo Previtali, Matteo Garibaldi
{"title":"炎症性肌病的线粒体病理：临床结果较差的标志。","authors":"Antonio Lauletta, Luca Bosco, Gioia Merlonghi, Yuri Matteo Falzone, Marta Cheli, Roberta Piera Bencivenga, Dario Zoppi, Marco Ceccanti, Felix Kleefeld, Sarah Léonard-Louis, Werner Stenzel, Olivier Benveniste, Lorenzo Maggi, Stefano Carlo Previtali, Matteo Garibaldi","doi":"10.1007/s00415-025-13192-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.</p><p><strong>Methods: </strong>Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.</p><p><strong>Results: </strong>Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.</p><p><strong>Conclusions: </strong>Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 7","pages":"480"},"PeriodicalIF":4.8000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondrial pathology in inflammatory myopathies: a marker of worse clinical outcome.\",\"authors\":\"Antonio Lauletta, Luca Bosco, Gioia Merlonghi, Yuri Matteo Falzone, Marta Cheli, Roberta Piera Bencivenga, Dario Zoppi, Marco Ceccanti, Felix Kleefeld, Sarah Léonard-Louis, Werner Stenzel, Olivier Benveniste, Lorenzo Maggi, Stefano Carlo Previtali, Matteo Garibaldi\",\"doi\":\"10.1007/s00415-025-13192-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.</p><p><strong>Methods: </strong>Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.</p><p><strong>Results: </strong>Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.</p><p><strong>Conclusions: </strong>Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.</p>\",\"PeriodicalId\":16558,\"journal\":{\"name\":\"Journal of Neurology\",\"volume\":\"272 7\",\"pages\":\"480\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-06-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00415-025-13192-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-025-13192-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Mitochondrial pathology in inflammatory myopathies: a marker of worse clinical outcome.
Objectives: Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.
Methods: Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.
Results: Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.
Conclusions: Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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