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Herein, we present two patients with CML and long\u2010term nilotinib treatment, who developed severe carotid atherosclerotic stenoses, both extra\u2010 and intracranial, resulting in ischemic stroke. The clinical and radiological findings as well as the possible pathophysiological mechanisms of these clinically significant complications are discussed. It seems that new\u2010generation TKIs such as nilotinib, ponatinib, and, to a far lesser extent, bosutinib increase the incidence of vascular occlusive events compared to imatinib, in a dose\u2010 and duration\u2010dependent manner. The mechanisms leading to vasculopathy are various and comprise promoting a prothrombotic platelet state, the dysregulation of glucose and lipid metabolism, increase of inflammatory cytokines, and affecting vessel wall endothelial cells. Regarding the outcome of cerebrovascular events, it seems that the discontinuation of TKIs alone or switching to a safer one is insufficient to resolve the stenoses of the cerebral arteries, even under dual antiplatelet treatment, anticoagulation, or high\u2010potency statin therapy. Thus, revascularization strategies such as extracranial to intracranial bypass surgery or stenting should be considered, especially when there is no improvement with medical treatment. These observations expand our knowledge on the association between TKIs and cerebral vascular disease, as well as provide more insights into the underlying pathogenesis. TKIs should not only be selected based on disease\u2010related variables but also based on patient\u2010related factors such as cardiovascular comorbidities.<\/jats:p>","DOI":"10.1155\/crnm\/1871606","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T10:03:27Z","timestamp":1766225007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tyrosine Kinase Inhibitors as Risk Factors for Cerebral Vascular Disease: Report of Two Cases and Literature Review"],"prefix":"10.1155","volume":"2025","author":[{"given":"Evangelos","family":"Papatolis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4541-5384","authenticated-orcid":false,"given":"Stefania","family":"Kalampokini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Liouta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-7881","authenticated-orcid":false,"given":"Stefanos","family":"Foinitsis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evdoxia","family":"Hatjiharissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kourti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tegos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianthi","family":"Arnaoutoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-3019","authenticated-orcid":false,"given":"Vasilios K.","family":"Kimiskidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00603"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.04.016"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-018-3412-8"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1624566"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23442"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.69"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2225-1"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyae061"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-739086"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-020-09926-y"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000501927"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35384"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-024-04006-2"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.04.005"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2018-013777"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrleng.2015.11.011"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-021-05043-3"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105883"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/1591019917710810"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.2176\/jns-nmc.2022-0298"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.72952"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2018.1780"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2019.116577"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.3337-23"},{"key":"e_1_2_11_25_2","first-page":"113","article-title":"Cerebrovascular Events During Nilotinib Treatment","volume":"72","author":"Jager N. 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