{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:59:13Z","timestamp":1791496753071,"version":"4.3.4"},"reference-count":170,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"initiatives Alle-Lieben-Schmidt e.V., Alzheimer Forschung e.V","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"initiatives Alle-Lieben-Schmidt e.V., Alzheimer Forschung e.V","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]},{"name":"the intramural BONFOR program of the University Hospital Bonn","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"the intramural BONFOR program of the University Hospital Bonn","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]},{"name":"Clinician Scientist Program of the University Medical Center Rostock","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Clinician Scientist Program of the University Medical Center Rostock","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness of all voluntary muscles and eventual respiratory failure. Non-motor symptoms, such as cognitive and behavioral changes, frequently occur over the course of the disease. Considering its poor prognosis with a median survival time of 2 to 4 years and limited causal treatment options, an early diagnosis of ALS plays an essential role. In the past, diagnosis has primarily been determined by clinical findings supported by electrophysiological and laboratory measurements. To increase diagnostic accuracy, reduce diagnostic delay, optimize stratification in clinical trials and provide quantitative monitoring of disease progression and treatment responsivity, research on disease-specific and feasible fluid biomarkers, such as neurofilaments, has been intensely pursued. Advances in imaging techniques have additionally yielded diagnostic benefits. Growing perception and greater availability of genetic testing facilitate early identification of pathogenic ALS-related gene mutations, predictive testing and access to novel therapeutic agents in clinical trials addressing disease-modified therapies before the advent of the first clinical symptoms. Lately, personalized survival prediction models have been proposed to offer a more detailed disclosure of the prognosis for the patient. In this review, the established procedures and future directions in the diagnostics of ALS are summarized to serve as a practical guideline and to improve the diagnostic pathway of this burdensome disease.<\/jats:p>","DOI":"10.3390\/cells12050736","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T04:05:40Z","timestamp":1677470740000},"page":"736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Current State and Future Directions in the Diagnosis of Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1453-1681","authenticated-orcid":false,"given":"Maximilian","family":"Vidovic","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-3270","authenticated-orcid":false,"given":"Lars Hendrik","family":"M\u00fcschen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Brakemeier","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Translational Neuro and Behavioral Sciences (C-TNBS), University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8955-5306","authenticated-orcid":false,"given":"Gerrit","family":"Machetanz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Naumann","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology, University Medical Center, University of Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-474X","authenticated-orcid":false,"given":"Sergio","family":"Castro-Gomez","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease and Geriatric Psychiatry\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"},{"name":"Department of Neuroimmunology, Institute of Innate Immunity, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. 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