{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:04:01Z","timestamp":1792047841157,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1106533"],"award-info":[{"award-number":["1106533"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1184403"],"award-info":[{"award-number":["1184403"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 EB020403"],"award-info":[{"award-number":["U54 EB020403"]}],"id":[{"id":"10.13039\/100000002","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":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole\u2010brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen\n                      <jats:italic>d<\/jats:italic>\n                      \u00a0=\u20091.5\u20132.6). Cerebellar gray matter alterations were most pronounced in lobules I\u2013VI (\n                      <jats:italic>d<\/jats:italic>\n                      \u00a0=\u20090.8), whereas cerebral differences occurred most prominently in precentral gyri (\n                      <jats:italic>d<\/jats:italic>\n                      \u00a0=\u20090.6) and corticospinal tracts (\n                      <jats:italic>d<\/jats:italic>\n                      \u00a0=\u20091.4). Earlier onset age predicted less volume in the motor cerebellum (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      \u00a0=\u20090.35) and peduncles (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      \u00a0=\u20090.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior\/inferior cerebellar peduncles (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      \u00a0=\u2009\u22120.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>FRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570\u2013583<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26200","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T07:49:14Z","timestamp":1629964154000},"page":"570-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Brain Structure and Degeneration Staging in Friedreich Ataxia:\n                    <scp>Magnetic Resonance Imaging<\/scp>\n                    Volumetrics from the\n                    <scp>ENIGMA\u2010Ataxia<\/scp>\n                    Working Group"],"prefix":"10.1002","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6843-9592","authenticated-orcid":false,"given":"Ian H.","family":"Harding","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne VIC Australia"},{"name":"Monash Biomedical Imaging Monash University  Clayton VIC 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II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-5160","authenticated-orcid":false,"given":"Sirio","family":"Cocozza","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Corben","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences, Turner Institute for Brain and Mental Health Monash University  Clayton VIC Australia"},{"name":"Bruce Lefroy Centre Murdoch Children's Research Institute  Parkville VIC Australia"},{"name":"University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2427-1302","authenticated-orcid":false,"given":"Andreas","family":"Deistung","sequence":"additional","affiliation":[{"name":"University Clinic and Outpatient 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