{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T04:37:49Z","timestamp":1769920669343,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is a motor neuron disorder, although extra\u2010motor degeneration is well recognized, especially in frontotemporal regions manifested as ALS with frontotemporal dementia (ALS\u2010FTD). Previous neuroimaging studies of the brains of ALS\u2010FTD patients have measured abnormalities of either grey matter (GM) or white matter (WM) structures but not of both together. Therefore, the aim was to evaluate both GM and WM in the same ALS\u2010FTD patient using functional and structural neuroimaging. By doing so, insights could be gained into whether neurodegeneration in ALS\u2010FTD is primarily a neuronopathy or axonopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After high\u2010resolution brain 2\u2010deoxy\u20102\u2010[<jats:sup>18<\/jats:sup>F]fluoro\u2010D\u2010glucose (<jats:sup>18<\/jats:sup>F\u2010FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) scans were obtained in ALS\u2010FTD patients and in age\u2010 and sex\u2010matched neurological controls, changes in metabolic rate, cortical thickness (CT) and WM network analysis using graph theory were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant reductions in <jats:sup>18<\/jats:sup>F\u2010FDG PET metabolism, CT and WM connections were observed in motor and extra\u2010motor brain regions of ALS\u2010FTD patients compared to controls. Both CT and underlying WM networks were abnormal in frontal, temporal, parietal and occipital lobes of ALS\u2010FTD patients with 86 of 90 brain regions showing reductions of CT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Abnormalities in significantly fewer WM networks underlying the affected cortical regions suggest that neurodegeneration in brains of ALS\u2010FTD patients is primarily a \u2018neuronopathy\u2019 rather than an \u2018axonopathy.\u2019<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14332","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T18:10:09Z","timestamp":1589998209000},"page":"1904-1912","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["2\u2010Deoxy\u20102\u2010[<sup>18<\/sup>F]fluoro\u2010<scp>d<\/scp>\u2010glucose positron emission tomography, cortical thickness and white matter graph network abnormalities in brains of patients with amyotrophic lateral sclerosis and frontotemporal dementia suggest early neuronopathy rather than axonopathy"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9040-0785","authenticated-orcid":false,"given":"V.","family":"Rajagopalan","sequence":"first","affiliation":[{"name":"Department of Electrical and Electronics Engineering Birla Institute of Technology and Science Pilani Hyderabad Campus Hyderabad India"},{"name":"Department of Biomedical Engineering Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-6065","authenticated-orcid":false,"given":"E. P.","family":"Pioro","sequence":"additional","affiliation":[{"name":"Neuromuscular Center Department of Neurology Neurological Institute, Cleveland Clinic Cleveland OH USA"},{"name":"Department of Neurosciences Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.6.2105"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000167602.38643.29"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.02.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7012-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.02.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.07.020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308239"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199105000-00008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200504250-00001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2018162967"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002242"},{"key":"e_1_2_9_13_1","first-page":"306","article-title":"Brain FDG\u2010PET changes in ALS and ALS\u2010FTD","volume":"111","author":"Renard D","year":"2011","journal-title":"Acta Neurol Belg"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00234"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1332077"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482968.2011.593036"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073614"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043993"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23452"},{"key":"e_1_2_9_20_1","first-page":"1238","article-title":"A diagnostic approach in Alzheimer's disease using three\u2010dimensional stereotactic surface projections of fluorine\u201018\u2010FDG PET","volume":"36","author":"Minoshima S","year":"1995","journal-title":"J Nucl Med"},{"key":"e_1_2_9_21_1","first-page":"1528","article-title":"Anatomical standardization: linear scaling and nonlinear warping of functional brain images","volume":"35","author":"Minoshima S","year":"1994","journal-title":"J Nucl Med"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200033797"},{"key":"e_1_2_9_23_1","unstructured":"LeemansAJ JeurissenB SijbersJ JonesDK.ExploreDTI: a graphical toolbox for processing analyzing and visualizing diffusion MR data. In Proc Intl Soc Mag Reson Med 2009 Apr 18;2009: Vol.17 p.3537."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040709"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608200300079536"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01063"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70014-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.9.1708"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024239"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.7551\/mitpress\/8476.001.0001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn102"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107904108"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105632"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0646-x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829a33f8"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22481"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820510038538"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134108"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d9edde"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1407795"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.14332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.14332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.14332","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.14332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:28:16Z","timestamp":1693355296000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.14332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,27]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/ene.14332"],"URL":"https:\/\/doi.org\/10.1111\/ene.14332","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,27]]},"assertion":[{"value":"2020-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}