{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:48:17Z","timestamp":1789861697075,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR4328.2\u20101"],"award-info":[{"award-number":["BR4328.2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease\u2010modifying therapies. X\u2010linked dystonia\u2010parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult\u2010onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long\u2010lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X\u2010linked dystonia\u2010parkinsonism, structural and iron\u2010sensitive magnetic resonance imaging (MRI) was performed in 10 non\u2010manifesting carriers and 24 healthy controls in a double\u2010blind fashion. Seventeen patients with X\u2010linked dystonia\u2010parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non\u2010manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single\u2010nucleotide polymorphisms associated with age at onset. Voxel\u2010based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non\u2010manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non\u2010manifesting carriers. Susceptibility\u2010weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non\u2010manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X\u2010linked dystonia\u2010parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X\u2010linked dystonia\u2010parkinsonism. 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