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Machine learning (ML) has the potential to improve diagnosis by detecting subtle physiological patterns and distinguishing between CDH subtypes. This review systematically explores current ML applications in CDH, assesses their limitations, and suggests future directions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, MEDLINE, Embase, PsycINFO, IEEE Xplore, CINAHL, Web of Science, and Google Scholar (up to June 2025) were searched for studies using ML to classify or characterize CDH in adults. ML methods, data types, and diagnostic outcomes were extracted and analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Out of 3274 studies, 41 met the inclusion criteria (37 peer\u2010reviewed articles and 4 preprints). Data sources included neuroimaging (fMRI, PET), sleep assessments (MSLT, polysomnography), demographics, and standardized questionnaires. Supervised ML reliably identified known features, including early REM onset, hypocretin deficiency, and spectral EEG changes, showing strong performance for NT1 but limited generalizability across other CDH subtypes. Although many studies reported high accuracy, clinical relevance was often limited by rigid diagnostic labels that may not reflect the true complexity of CDH. Unsupervised learning uncovered heterogeneous phenotypes and exposed limitations in existing diagnostic labels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ML has the potential to improve CDH diagnosis. Deep learning models are promising for feature extraction; however, their black\u2010box nature and high data requirements hinder clinical application. Future advancements depend on large, diverse datasets, multimodal and longitudinal data, and close collaboration between clinicians and data scientists.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70661","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:46:38Z","timestamp":1780559198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning for Diagnosis and Differentiation of Central Disorders of Hypersomnolence: A Systematic Review"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1221-7581","authenticated-orcid":false,"given":"Annina","family":"Helmy","sequence":"first","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Center for Experimental Neurology, Sleep Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-0961","authenticated-orcid":false,"given":"Livia G.","family":"Fregolente","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Graduate School for Health Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-5226","authenticated-orcid":false,"given":"Marc","family":"von Gernler","sequence":"additional","affiliation":[{"name":"Medical Library, University Library of Bern University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-7898","authenticated-orcid":false,"given":"Rafael","family":"Morand","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Center for Experimental Neurology, Sleep Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences University of Bern  Bern Switzerland"},{"name":"ARTORG Center for Biomedical Engineering Research University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1913-5146","authenticated-orcid":false,"given":"Julia","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-1318","authenticated-orcid":false,"given":"Markus","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Center for Experimental Neurology, Sleep Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-9982","authenticated-orcid":false,"given":"Stavroula","family":"Mougiakakou","sequence":"additional","affiliation":[{"name":"ARTORG Center for Biomedical Engineering Research University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-1418","authenticated-orcid":false,"given":"Athina","family":"Tzovara","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurology, Sleep Wake Epilepsy Center, NeuroTec, Department of Neurology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"},{"name":"Institute of Computer Science University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-0245","authenticated-orcid":false,"given":"Claudio L. 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