{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:06:51Z","timestamp":1784678811750,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Dopa\u2010responsive dystonia is caused by pathogenic variants in the\n                      <jats:italic>GCH1<\/jats:italic>\n                      gene. Although its clinical features and reduced penetrance are known, in vivo metabolic and structural alterations in symptomatic (sMC) and asymptomatic mutation carriers (aMC) remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The aims were to characterize the volumetric and neurometabolic brain changes in\n                      <jats:italic>GCH1<\/jats:italic>\n                      mutation carriers (MC) and explore their relationship with clinical severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied 20 sMCs, 5 aMCs, and 25 mutation\u2010free healthy controls (HC) using volumetric magnetic resonance imaging (MRI) combined with\n                      <jats:sup>31<\/jats:sup>\n                      phosphorus magnetic resonance spectroscopy imaging (\n                      <jats:sup>31<\/jats:sup>\n                      P\u2010MRSI) of the basal ganglia and cerebellum. Analysis of covariance (ANCOVA) was used for group comparisons, and correlations were assessed using clinical symptom severity rating scales.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Volumetric analyses revealed enlarged globus pallidus (16.6%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0010) and putamen (7.2%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0310) volumes in sMCs and increased cerebellar gray matter in aMCs (8.0%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0500). Nicotinamide adenine dinucleotide (NAD) levels were significantly reduced in the basal ganglia of carriers (NAD\/Pi [inorganic phosphate]: \u221214.7%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0460; NAD\/ATP\u2010\u03b1: \u221215.5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0180). In the cerebellum, aMCs demonstrated elevated high\u2010energy phosphate ratios ([ATP\u2010\u03b1\u2009+\u2009PCr]\/Pi: 23.7%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0170; ATP\u2010\u03b1\/Pi: 21.3%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0460; PCr [phosphocreatine]\/Pi: 25.2%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009= 0.0090) compared with sMCs and HCs. Smaller cerebellar volumes correlated with greater dystonia severity (Burke\u2010Fahn\u2010Marsden Dystonia Rating Scale, \u03c1\u2009= \u22120.557,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0133), whereas lower basal ganglia NAD ratios correlated with higher Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale, Part III (\u03c1\u2009=\u2009\u22120.527,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0204), and Toronto Western Spasmodic Torticollis Rating Scale scores (\u03c1\u2009=\u2009\u22120.475,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0398).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Volumetric MRI and\n                      <jats:sup>31<\/jats:sup>\n                      P\u2010MRSI reveal region\u2010 and subgroup\u2010specific metabolic and structural alterations in\n                      <jats:italic>GCH1<\/jats:italic>\n                      MCs, linking basal ganglia vulnerability and cerebellar adaptation to clinical severity. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70332","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T02:29:24Z","timestamp":1777256964000},"page":"1716-1726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic and Volumetric Alterations in the Basal Ganglia and the Cerebellum in Dopa\u2010Responsive Dystonia in Symptomatic and Asymptomatic\n                    <scp>\n                      <i>GCH1<\/i>\n                    <\/scp>\n                    Mutation Carriers"],"prefix":"10.1002","volume":"41","author":[{"given":"Jannik","family":"Prasuhn","sequence":"first","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"van Well","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3211-9149","authenticated-orcid":false,"given":"Marta M.","family":"Pokotylo","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-2776","authenticated-orcid":false,"given":"Feline","family":"Hamami","sequence":"additional","affiliation":[{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Systems Motor Science, Center for Rare Diseases University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke\u2010Lina","family":"A\u00dfmann","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian G.","family":"K\u00f6dderitzsch\u2010Mertins","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Henkel","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Uter","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-2284","authenticated-orcid":false,"given":"Alexander","family":"M\u00fcnchau","sequence":"additional","affiliation":[{"name":"Institute of Systems Motor Science, Center for Rare Diseases University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center of Rare Diseases, University\u2010Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Weissbach","sequence":"additional","affiliation":[{"name":"Center for Brain, Behavior and Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Systems Motor Science, Center for Rare Diseases University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center of Rare Diseases, University\u2010Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Section of Movement Disorders, Department of Neurology, University Medical Center Schleswig\u2010Holstein (UKSH) Campus L\u00fcbeck  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