{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:56:08Z","timestamp":1785329768875,"version":"3.55.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81\u00a0years) and 9 controls (2 men, 7 women; mean age, 90\u00a0years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T\u2010cell marker); (3) CD19 (a B\u2010cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease (\n              <jats:italic>P<\/jats:italic>\n              =0.015) and gliosis (\n              <jats:italic>P<\/jats:italic>\n              =0.003). T cells were increased in RLS compared with controls (\n              <jats:italic>P<\/jats:italic>\n              =0.009) and tended to colocalize with microvascular disease (\n              <jats:italic>P<\/jats:italic>\n              =0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T\u2010cell invasion may be a secondary phenomenon.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019627","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T09:22:06Z","timestamp":1621070526000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-7817","authenticated-orcid":false,"given":"Arthur S.","family":"Walters","sequence":"first","affiliation":[{"name":"Sleep Division Department of Neurology Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paisit","family":"Paueksakon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1045-2743","authenticated-orcid":false,"given":"Charles H.","family":"Adler","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic College of Medicine Scottsdale AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Moussouttas","sequence":"additional","affiliation":[{"name":"Cerebrovascular Division Department of Neurology Rutgers Medical School New Brunswick NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6484-1691","authenticated-orcid":false,"given":"Leonard B.","family":"Weinstock","sequence":"additional","affiliation":[{"name":"Specialists in Gastroenterology and Washington University Saint Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2914-9074","authenticated-orcid":false,"given":"Karen","family":"Spruyt","sequence":"additional","affiliation":[{"name":"INSERM Neurocampus Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanika","family":"Bagai","sequence":"additional","affiliation":[{"name":"Sleep Division Department of Neurology Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.5.589"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7065-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsw080"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5966"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2011.09.003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0943-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20992"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2011.03.007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.8216"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2015.03.018"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12189"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1389-9457(02)00258-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2017.1360272"},{"key":"e_1_3_2_15_2","first-page":"203","article-title":"Delayed and remote effects of focal cortical infarctions: secondary damage and reactive plasticity","volume":"73","author":"Wite OW","year":"1997","unstructured":"Wite OW, Stoll G. Delayed and remote effects of focal cortical infarctions: secondary damage and reactive plasticity. Adv Neurol. 1997;73:203\u2013207.","journal-title":"Adv Neurol"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0483-x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.021474"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8050437"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.534503"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.128"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018674"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.120.019627","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:21:35Z","timestamp":1715599295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.120.019627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1161\/JAHA.120.019627"],"URL":"https:\/\/doi.org\/10.1161\/jaha.120.019627","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"2020-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e019627"}}