{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T07:20:02Z","timestamp":1771226402021,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>FMR1<\/jats:italic>\n                      premutation carriers (55\u2013200 CGG repeats) are at risk of developing fragile X-associated tremor\/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. The inferior cerebellar peduncles (ICP) contain fibers related to proprioception and vestibular functions (such as the rostral and posterior spinocerebellar tracts and the juxta restiform body), which are clinically associated with cerebellar gait ataxia, a major clinical criterion for FXTAS diagnosis. However, the ICP hyperintensity has yet to be studied in FXTAS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated 588 MRI scans (mean 2.05 visits\/participant) from 202 male premutation carriers (164 with FXTAS and 38 without FXTAS at last visits) and 85 controls. Two radiologists, independently, rated as absent or present the signal of the right and left ICP in T2-Fluid-attenuated inversion recovery (FLAIR) scans. Mixed-effects models were used for statistical analysis adjusting for age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Only carriers with FXTAS revealed ICP hyperintensities at last visits. Furthermore, ICP hyperintensity was associated with brain atrophy, increased white matter disease, the MCP sign, FXTAS stage, abnormal gait, lower cognitive functioning and faster age-related increase in anxiety and depression scores. Finally, carriers with ICP hyperintensities had significantly higher CGG repeat length than carriers without ICP hyperintensities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study describes ICP hyperintensity as a new potential radiological finding in FXTAS, suggests involvement of the vestibulo-cerebellar, rostral, and posterior spinocerebellar tracts, and the vestibular system in FXTAS physiopathology, and reinforces the association of CGG expansion in the range of brain changes seen in FXTAS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1720370","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:38:49Z","timestamp":1771223929000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["T2-FLAIR hyperintensities in the inferior cerebellar peduncles and their association with clinical symptoms, molecular and MRI markers in male FMR1 premutation carriers"],"prefix":"10.3389","volume":"19","author":[{"given":"Andrea","family":"Elias-Mas","sequence":"first","affiliation":[{"name":"Department of Radiology, Hospital Universitari M\u00fatua de Terrassa, (HUMT)","place":["Terrassa, Spain"]},{"name":"Institute for Research and Innovation Parc Taul\u00ed (I3PT)","place":["Sabadell, Spain"]},{"name":"Genetics Doctorate Program, Universitat de Barcelona (UB)","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Paracuellos-Ayala","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital Universitari M\u00fatua de Terrassa, (HUMT)","place":["Terrassa, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Mind and Brain, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, School of Medicine, University of California, Davis","place":["Sacramento, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis","place":["Sacramento, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Schneider","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Department of Pediatrics, University of California Davis Medical Center","place":["Sacramento, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hessl","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis","place":["Sacramento, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Center for Mind and Brain, University of California, Davis","place":["Davis, CA, United States"]},{"name":"MIND Institute, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Department of Psychology, University of Maryland","place":["College Park, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randi J.","family":"Hagerman","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Department of Pediatrics, University of California Davis Medical Center","place":["Sacramento, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1212\/01.wnl.0000269781.10417.7b","article-title":"Volumetric brain changes in females with fragile X-associated tremor\/ataxia syndrome (FXTAS).","volume":"69","author":"Adams","year":"2007","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/WAD.0b013e3182163b62","article-title":"Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease.","volume":"26","author":"Apostolova","year":"2012","journal-title":"Alzheimer Dis. 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