{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:06:37Z","timestamp":1790705197327,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/07559\u20103"],"award-info":[{"award-number":["2013\/07559\u20103"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Spinal cord has been considered the main target of damage in hereditary spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected. Despite this, little is known about the brain signature of HSPs, in particular regarding stratification for specific genetic subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to characterize cerebral and cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29 SPG11) and to uncover the clinical and gene expression correlates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained high\u2010resolution brain T1 and diffusion tensor image (DTI) datasets in this cross\u2010sectional case\u2013control study (n\u00a0=\u00a084). The MRICloud, FreeSurfer, and CERES\u2010SUIT pipelines were employed to assess cerebral gray (GM) and white matter (WM) as well as the cerebellum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain abnormalities were found in all but one HSP group (SPG3A), but the patterns were gene\u2010specific: basal ganglia, thalamic, and posterior WM involvement in SPG4; diffuse WM and cerebellar involvement in SPG7; cortical thinning at the motor cortices and pallidal atrophy in SPG8; and widespread GM, WM, and deep cerebellar nuclei damage in SPG11. Abnormal regions in SPG4 and SPG8 matched those with higher <jats:italic>SPAST<\/jats:italic> and <jats:italic>WASHC5<\/jats:italic> expression, whereas in SPG7 and SPG11 this concordance was only noticed in the cerebellum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Brain damage is a conspicuous feature of HSPs (even for pure subtypes), but the pattern of abnormalities is genotype\u2010specific. Correlation between brain structural damage and gene expression maps is different for autosomal dominant and recessive HSPs, pointing to distinct pathophysiological mechanisms underlying brain damage in these subgroups of the disease. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28519","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T23:36:37Z","timestamp":1613259397000},"page":"1644-1653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes"],"prefix":"10.1002","volume":"36","author":[{"given":"Katiane R.","family":"Servelhere","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Junqueira Ribeiro","family":"Rezende","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-6032","authenticated-orcid":false,"given":"Fabr\u00edcio Diniz","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Rabelo","family":"de Brito","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan Fl\u00e1vio","family":"de Fran\u00e7a Nunes","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medical Sciences University 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