{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:29:55Z","timestamp":1765776595212,"version":"3.48.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fabry disease (FD) is a lysosomal storage disorder that causes glycosphingolipid deposition in the vascular endothelium. Early neurovascular involvement is difficult to detect because conventional magnetic resonance imaging (MRI) findings overlap with age-related small- and large-vessel changes. We hypothesized that integrating microvascular and macrovascular MRI markers could improve the detection of FD-related vasculopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospective case\u2013control study, 26 genetically confirmed FD patients and 26 age- and sex-matched healthy controls underwent three-Tesla MRI (3\u202fT MRI), including high-resolution vessel wall imaging. The macrovascular metrics included the basilar artery (BA) diameter, BA tortuosity index (BATI), and a composite BA degeneration index (BADI). The microvascular markers included the perivascular space (PVS) burden (Potter scale), white matter lesion severity (modified Fazekas scale), and global cerebral atrophy. Associations with FD were assessed using multivariable logistic regression, adjusting for age, sex, and vascular risk factors. Correlations between microvascular and macrovascular markers and age-stratified analyses were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with FD exhibited a larger BA diameter, higher PVS burden in the basal ganglia and centrum semiovale, and greater cerebral atrophy than controls, while Fazekas scores were similar. Both PVS burden and BA diameter were independently associated with FD after adjustment, and the PVS burden remained significant after controlling for vascular risk factors. In patients with FD, but not in controls, the PVS burden correlated positively with the BADI, indicating coupled microvascular and macrovascular remodeling. Age-stratified analyses revealed steeper increases in BA metrics and PVS burden with advancing age in patients with FD, suggesting accelerated vascular degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining the PVS burden with posterior circulation remodeling indices (BA diameter\/BADI) reveals the disease-specific coupling of microvascular and macrovascular degeneration in FD. This quantitative MRI approach may enable earlier diagnosis, more precise risk stratification, and monitoring of therapeutic responses in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1689057","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:25:15Z","timestamp":1765776315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Perivascular spaces and basilar artery remodeling in Fabry disease\u2014a dual vascular pathology"],"prefix":"10.3389","volume":"16","author":[{"given":"Jieun","family":"Roh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong Kun","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Yong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Kug","family":"Baik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Gyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Pil","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Ho","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1016\/S0140-6736(08)61589-5","article-title":"Fabry's disease","volume":"372","author":"Zarate","year":"2008","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ymgme.2009.10.004","article-title":"Vasculopathy in patients with Fabry disease: current controversies and research directions","volume":"99","author":"Rombach","year":"2010","journal-title":"Mol Genet Metab"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.15171\/jnp.2017.22","article-title":"Fabry disease; early diagnosis improves prognosis but diagnosis is often delayed","volume":"6","author":"Jamboti","year":"2017","journal-title":"J. Nephropathol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"569","DOI":"10.2215\/CJN.09480819","article-title":"The changing landscape of Fabry disease","volume":"15","author":"Svarstad","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol Genet Metab"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1024\/0301-1526\/a000017","article-title":"Fabry disease - vascular manifestations","volume":"39","author":"Karetov\u00e1","year":"2010","journal-title":"VASA Zeitschrift f\u00fcr Gef\u00e4sskrankheiten"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1161\/HYPERTENSIONAHA.112.195685","article-title":"Vascular aspects of Fabry disease in relation to clinical manifestations and elevations in plasma Globotriaosylsphingosine","volume":"60","author":"Rombach","year":"2012","journal-title":"Hypertension"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.amjms.2020.07.011","article-title":"When and how to diagnose Fabry disease in clinical Pratice","volume":"360","author":"Michaud","year":"2020","journal-title":"Am J Med Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/cge.13546","article-title":"Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients","volume":"96","author":"Germain","year":"2019","journal-title":"Clin Genet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.mri.2015.06.006","article-title":"High resolution three dimensional intracranial arterial wall imaging at 3 T using T1 weighted SPACE","volume":"33","author":"Zhang","year":"2015","journal-title":"Magn Reson Imaging"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/CIRCULATIONAHA.110.990549","article-title":"Increased vertebral artery tortuosity index is associated with adverse outcomes in children and young adults with connective tissue disorders","volume":"124","author":"Morris","year":"2011","journal-title":"Circulation"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1159\/000375153","article-title":"Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability","volume":"39","author":"Potter","year":"2015","journal-title":"Cerebrovasc Dis"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging","volume":"149","author":"Fazekas","year":"1987","journal-title":"AJR Am J Roentgenol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1159\/000117270","article-title":"Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts","volume":"36","author":"Pasquier","year":"1996","journal-title":"Eur Neurol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/ana.20423","article-title":"Intracranial arterial dolichoectasia and small-vessel disease in stroke patients","volume":"22","author":"Pico","year":"2005","journal-title":"Ann Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1161\/01.STR.0000259708.05806.76","article-title":"Association of Small-Vessel Disease with Dilatative Arteriopathy of the brain: Neuropathologic evidence","volume":"38","author":"Pico","year":"2007","journal-title":"Stroke"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1212\/WNL.50.6.1746","article-title":"Quantitative analysis of cerebral vasculopathy in patients with Fabry disease","volume":"50","author":"Crutchfield","year":"1998","journal-title":"Neurology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1161\/STROKEAHA.114.006283","article-title":"Cerebrovascular involvement in Fabry disease: current status of knowledge","volume":"46","author":"Kolodny","year":"2015","journal-title":"Stroke"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ana.410400105","article-title":"Cerebrovascular complications of Fabry's disease","volume":"40","author":"Mitsias","year":"1996","journal-title":"Ann Neurol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e87054","DOI":"10.1371\/journal.pone.0087054","article-title":"Increased arterial diameters in the posterior cerebral circulation in men with Fabry disease","volume":"9","author":"U\u00e7eyler","year":"2014","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3174\/ajnr.A5069","article-title":"Basilar artery changes in Fabry disease","volume":"38","author":"Manara","year":"2017","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jns.2018.10.009","article-title":"Brain MRI findings in children and adolescents with Fabry disease","volume":"395","author":"Marchesoni","year":"2018","journal-title":"J Neurol Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1212\/01.wnl.0000173030.70057.eb","article-title":"White matter lesion severity in male and female patients with Fabry disease","volume":"65","author":"Fellgiebel","year":"2005","journal-title":"Neurology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1161\/hs0202.102601","article-title":"Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement","volume":"33","author":"Moore","year":"2002","journal-title":"Stroke"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s00415-004-0364-9","article-title":"Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease","volume":"251","author":"Hilz","year":"2004","journal-title":"J Neurol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1161\/STROKEAHA.114.008548","article-title":"Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event","volume":"46","author":"Fazekas","year":"2015","journal-title":"Stroke"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41582-020-0312-z","article-title":"Perivascular spaces in the brain: anatomy, physiology and pathology","volume":"16","author":"Wardlaw","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1177\/1747493019830321","article-title":"Perivascular spaces and their associations with risk factors, clinical disorders and neuroimaging features: a systematic review and meta-analysis","volume":"14","author":"Francis","year":"2019","journal-title":"Int J Stroke"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1002\/ana.26734","article-title":"Dilated Juxtacortical perivascular spaces and venous cerebral microbleeds in cerebral amyloid Angiopathy-related inflammation","volume":"94","author":"Wang","year":"2023","journal-title":"Ann Neurol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1177\/0271678X211002279","article-title":"Deep white matter hyperintensity is associated with the dilation of perivascular space","volume":"41","author":"Huang","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e744","DOI":"10.1161\/STROKEAHA.121.036077","article-title":"Association between enlarged perivascular spaces and white matter microstructure","volume":"52","author":"Liu","year":"2021","journal-title":"Stroke"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1161\/STROKEAHA.119.025528","article-title":"Magnetic resonance imaging findings related to stroke risk in Japanese patients with Fabry disease","volume":"50","author":"Yagita","year":"2019","journal-title":"Stroke"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1161\/01.STR.32.7.1559","article-title":"Enhanced endothelium-dependent vasodilation in Fabry disease","volume":"32","author":"Altarescu","year":"2001","journal-title":"Stroke"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1161\/STROKEAHA.112.663708","article-title":"Acute cerebrovascular disease in the young: the stroke in young Fabry patients study","volume":"44","author":"Rolfs","year":"2013","journal-title":"Stroke"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1002\/jimd.12271","article-title":"Cognitive functioning and depressive symptoms in Fabry disease: a follow-up study","volume":"43","author":"K\u00f6rver","year":"2020","journal-title":"J Inherit Metab Dis"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/ana.26134","article-title":"Blood\u2013brain barrier breakdown in relationship to Alzheimer and vascular disease","volume":"90","author":"Lin","year":"2021","journal-title":"Ann Neurol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1093\/brain\/awaa282","article-title":"White matter integrity correlates with cognition and disease severity in Fabry disease","volume":"143","author":"Ulivi","year":"2020","journal-title":"Brain J Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1689057\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:25:16Z","timestamp":1765776316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1689057\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":40,"alternative-id":["10.3389\/fneur.2025.1689057"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1689057","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]},"article-number":"1689057"}}