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This narrative review aims to provide an overview on the pathophysiology of fatigue at a biochemical and molecular level with regard to muscular dystrophies, metabolic myopathies, and primary mitochondrial disorders with a focus on mitochondrial myopathies and spinal muscular atrophy, which, although fulfilling the definition of rare diseases, as a group represent a representative ensemble of neuromuscular disorders that the neurologist may encounter in clinical practice. The current use of clinical and instrumental tools for fatigue assessment, and their significance, is discussed. A summary of therapeutic approaches to address fatigue, encompassing pharmacological treatment and physical exercise, is also overviewed.<\/jats:p>","DOI":"10.3390\/ijms24055005","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"5005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Pathophysiology and Management of Fatigue in Neuromuscular Diseases"],"prefix":"10.3390","volume":"24","author":[{"given":"Francesca","family":"Torri","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-3129","authenticated-orcid":false,"given":"Piervito","family":"Lopriore","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Montano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-8562","authenticated-orcid":false,"given":"Michelangelo","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/mds.27461","article-title":"Fatigue in Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"33","author":"Siciliano","year":"2018","journal-title":"Mov. 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