{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:23:20Z","timestamp":1791296600738,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            White matter (WM) hyperintensities on MRI or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in postmortem tissue from the temporal pole to reveal the cause of CADASIL-specific WM hyperintensities.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index, WM myelination as the myelin index, and damage within the WM as accumulated degraded myelin basic protein in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischemic vascular dementia cases, and 5 similarly aged (young) and 5 older controls. Luxol fast blue-stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Luxol fast blue sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The myelin index was severely reduced in CADASIL in relation to the subcortical ischemic vascular dementia and control sample that was consistent with increased immunoreactivity of degraded myelin basic protein, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5-fold greater number of basophilic (hyalinized) vessels and a 57% increase in the sclerotic index values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinized vessels and sclerotic index values was also apparent (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Our findings suggest that MRI hyperintensities in the temporal pole of CADASIL patients are explained by enlarged PVS and degeneration of myelin accompanied by lack of drainage of the interstitial fluid rather than lacunar infarcts. Consistent with the lack of MR hypersignals in the temporal pole of older subcortical ischemic vascular dementia subjects, our observations imply greater progression of pathological changes in CADASIL patients.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.108.528299","type":"journal-article","created":{"date-parts":[[2009,4,10]],"date-time":"2009-04-10T02:14:31Z","timestamp":1239329671000},"page":"2004-2011","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":134,"title":["Neuropathological Correlates of Temporal Pole White Matter Hyperintensities in CADASIL"],"prefix":"10.1161","volume":"40","author":[{"given":"Yumi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ihara","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Tham","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger W.C.","family":"Low","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet Y.","family":"Slade","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Moss","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur E.","family":"Oakley","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo","family":"Polvikoski","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"From Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/383707a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91557-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.1998.00087.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.32.1.17"},{"key":"e_1_3_2_5_2","first-page":"1729","volume":"26","year":"1995","unstructured":"Chabriat H, Bousser MG, Pappata S. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a positron emission tomography study in two affected family members. Stroke. 1995; 26: 1729\u20131730.","journal-title":"Stroke"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000124124.69842.2d"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.2.452"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.5.628"},{"key":"e_1_3_2_9_2","first-page":"350","volume":"12","year":"2002","unstructured":"Kalimo H, Ruchoux M-M, Viitanen M, Kalaria RN. CADASIL: a common form of hereditary arteriopathy causing brain infarcts. Brain Pathology. 2002; 12: 350\u2013359.","journal-title":"Brain Pathology"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.8.1134"},{"key":"e_1_3_2_11_2","first-page":"2481","volume":"26","year":"2005","unstructured":"Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal leukoencephalopathy and their relationships to age and clinical features. AJNR Am J Neuroradiol. 2005; 26: 2481\u20132487.","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2006.01113.x"},{"key":"e_1_3_2_13_2","first-page":"298","volume":"26","year":"2005","unstructured":"Salzman KL, Osborn AG, House P, Jinkins JR, Ditchfield A, Cooper JA, Weller RO. Giant tumefactive perivascular spaces. AJNR Am J Neuroradiol. 2005; 26: 298\u2013305.","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-2-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1997.19130337.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000089923.29724.ce"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.2.250"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000237236.88823.47"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl360"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.28.11.2222"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000236838.84150.c2"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199712010-00014"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.17.6.3810705"},{"key":"e_1_3_2_24_2","unstructured":"Salamon G. Atlas de la vascularisation arterielle du cerveau chez l'homme. Sandoz Editions Paris; 1971."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000184480.07394.fb"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00133.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.12.2637"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000041681.25514.22"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00571504"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199709000-00001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00078.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00401-002-0530-z","volume":"104","year":"2002","unstructured":"Brulin P, Godfraind C, Leteurtre E, Ruchoux M-M. Morphometric analysis of ultrastructural vascular changes in CADASIL: Analysis of 50 skin biopsy specimens and pathogenic implications. Acta Neuropathologica. 2002; 104: 241\u2013248.","journal-title":"Acta Neuropathologica"},{"key":"e_1_3_2_33_2","first-page":"1268","volume":"22","year":"2001","unstructured":"Bruening R, Dichgans M, Berchtenbreiter C, Yousry T, Seelos KC, Wu RH, Mayer M, Brix G, Reiser M. Cerebral autosomal dominant arteriopathy with subcortical Infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance. Am J Neuroradiol. 2001; 22: 1268\u20131274.","journal-title":"Am J Neuroradiol"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.31.8.1904"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2363041454"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/09638280410001704331"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/135245850000600106"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7474"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)00875-2"},{"key":"e_1_3_2_40_2","first-page":"1512","volume":"26","year":"2005","unstructured":"Patankar TF, Mitra D, Varma A, Snowden J, Neary D, Jackson A. Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. AJNR Am J Neuroradiol. 2005; 26: 1512\u20131520.","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1159\/000047722"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2003.030858"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.7.1091"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh282"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.108.528299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:53:32Z","timestamp":1715604812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.108.528299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1161\/STROKEAHA.108.528299"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.108.528299","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]},"assertion":[{"value":"2008-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-01-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}