{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:40Z","timestamp":1792047820451,"version":"4.4.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Friedreich\u2019s Ataxia Research Alliance"},{"name":"CureFA Foundation"},{"name":"Bob Allison Ataxia Research Center"},{"name":"the Friedreich\u2019s Ataxia Research Alliance"},{"name":"The Center for Magnetic Resonance Research"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P41EB027061"],"award-info":[{"award-number":["P41EB027061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30NS076408"],"award-info":[{"award-number":["P30NS076408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1S10OD017974"],"award-info":[{"award-number":["1S10OD017974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Friedreich ataxia is the most common hereditary ataxia. Atrophy of the spinal cord is one of the hallmarks of the disease. MRI and magnetic resonance spectroscopy are powerful and non-invasive tools to investigate pathological changes in the spinal cord. A handful of studies have reported cross-sectional alterations in Friedreich ataxia using MRI and diffusion MRI. However, to our knowledge no longitudinal MRI, diffusion MRI or MRS results have been reported in the spinal cord. Here, we investigated early-stage cross-sectional alterations and longitudinal changes in the cervical spinal cord in Friedreich ataxia, using a multimodal magnetic resonance protocol comprising morphometric (anatomical MRI), microstructural (diffusion MRI), and neurochemical (1H-MRS) assessments.We enrolled 28 early-stage individuals with Friedreich ataxia and 20 age- and gender-matched controls (cross-sectional study). Disease duration at baseline was 5.5 \u00b1 4.0 years and Friedreich Ataxia Rating Scale total neurological score at baseline was 42.7 \u00b1 13.6. Twenty-one Friedreich ataxia participants returned for 1-year follow-up, and 19 of those for 2-year follow-up (cohort study). Each visit consisted in clinical assessments and magnetic resonance scans. Controls were scanned at baseline only. At baseline, individuals with Friedreich ataxia had significantly lower spinal cord cross-sectional area (\u221231%, P = 8 \u00d7 10\u221217), higher eccentricity (+10%, P = 5 \u00d7 10\u22127), lower total N-acetyl-aspartate (tNAA) (\u221236%, P = 6 \u00d7 10\u22129) and higher myo-inositol (mIns) (+37%, P = 2 \u00d7 10\u22126) corresponding to a lower ratio tNAA\/mIns (\u221252%, P = 2 \u00d7 10\u221213), lower fractional anisotropy (\u221224%, P = 10\u22129), as well as higher radial diffusivity (+56%, P = 2 \u00d7 10\u22129), mean diffusivity (+35%, P = 10\u22128) and axial diffusivity (+17%, P = 4 \u00d7 10\u22125) relative to controls. Longitudinally, spinal cord cross-sectional area decreased by 2.4% per year relative to baseline (P = 4 \u00d7 10\u22124), the ratio tNAA\/mIns decreased by 5.8% per year (P = 0.03), and fractional anisotropy showed a trend to decrease (\u22123.2% per year, P = 0.08). Spinal cord cross-sectional area correlated strongly with clinical measures, with the strongest correlation coefficients found between cross-sectional area and Scale for the Assessment and Rating of Ataxia (R = \u22120.55, P = 7 \u00d7 10\u22126) and between cross-sectional area and Friedreich ataxia Rating Scale total neurological score (R = \u22120.60, P = 4 \u00d7 10\u22127). Less strong but still significant correlations were found for fractional anisotropy and tNAA\/mIns. We report here the first quantitative longitudinal magnetic resonance results in the spinal cord in Friedreich ataxia. The largest longitudinal effect size was found for spinal cord cross-sectional area, followed by tNAA\/mIns and fractional anisotropy. Our results provide direct evidence that abnormalities in the spinal cord result not solely from hypoplasia, but also from neurodegeneration, and show that disease progression can be monitored non-invasively in the spinal cord.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac246","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T17:03:04Z","timestamp":1663952584000},"source":"Crossref","is-referenced-by-count":21,"title":["Spinal cord magnetic resonance imaging and spectroscopy detect early-stage alterations and disease progression in Friedreich ataxia"],"prefix":"10.1093","volume":"4","author":[{"given":"James M","family":"Joers","sequence":"first","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac M","family":"Adanyeguh","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh K","family":"Deelchand","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane H","family":"Hutter","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn E","family":"Eberly","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Iltis","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalaf O","family":"Bushara","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Lenglet","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Gilles","family":"Henry","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"issue":"1","key":"2022102811450186000_fcac246-B1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/bmb\/ldx034","article-title":"Friedreich's ataxia: Clinical features, pathogenesis and management","volume":"124","author":"Cook","year":"2017","journal-title":"Br Med Bull"},{"issue":"Suppl 1","key":"2022102811450186000_fcac246-B2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jnc.12215","article-title":"Prevalence gradients of friedreich's ataxia and R1b haplotype in Europe co-localize, suggesting a common palaeolithic origin in the franco-Cantabrian ice age refuge","volume":"126","author":"Vankan","year":"2013","journal-title":"J Neurochem"},{"issue":"5254","key":"2022102811450186000_fcac246-B3","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"issue":"16","key":"2022102811450186000_fcac246-B4","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and genetic abnormalities in patients with friedreich's ataxia","volume":"335","author":"Durr","year":"1996","journal-title":"N Engl J Med"},{"issue":"10","key":"2022102811450186000_fcac246-B5","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1001\/archneur.65.10.1296","article-title":"Friedreich ataxia","volume":"65","author":"Pandolfo","year":"2008","journal-title":"Arch 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