{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:07:41Z","timestamp":1790654861912,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100031307","name":"Johannes Kepler University Linz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031307","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12\u00a0months to detect thrombus resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45\u2009\u00b1\u200916\u00a0years and 78% were female. In patients with CSVT, mean baseline D-dimer (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and sPECAM-1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994;\u2009&lt;\u20090.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (&gt;\u2009198\u00a0ng\/ml) on admission were associated with delayed venous thrombus resolution at 3\u00a0months (AUC\u2009=\u20090.83).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-024-12225-3","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:02:07Z","timestamp":1712304127000},"page":"4095-4104","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Endothelial receptor proteins in acute venous thrombosis and delayed thrombus resolution in cerebral sinus vein thrombosis"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-5657","authenticated-orcid":false,"given":"Lukas","family":"Kellermair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"H\u00f6fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W. G.","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Kubasta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Bandke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Kellermair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Forstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimund","family":"Helbok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan R.","family":"Vosko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"issue":"9","key":"12225_CR1","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1161\/STROKEAHA.116.013617","volume":"47","author":"S Devasagayam","year":"2016","unstructured":"Devasagayam S, Wyatt B, Leyden J, Kleinig T (2016) Cerebral venous sinus thrombosis incidence is higher than previously thought: a retrospective population-based study. Stroke 47(9):2180\u20132182","journal-title":"Stroke"},{"issue":"9","key":"12225_CR2","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/nrneurol.2017.104","volume":"13","author":"SM Silvis","year":"2017","unstructured":"Silvis SM, de Sousa DA, Ferro JM, Coutinho JM (2017) Cerebral venous thrombosis. Nat Rev Neurol 13(9):555\u2013565","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"12225_CR3","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(07)70029-7","volume":"6","author":"MG Bousser","year":"2007","unstructured":"Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6(2):162\u2013170","journal-title":"Lancet Neurol"},{"issue":"9","key":"12225_CR4","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s11886-014-0523-2","volume":"16","author":"JM Ferro","year":"2014","unstructured":"Ferro JM, Canhao P (2014) Cerebral venous sinus thrombosis: update on diagnosis and management. Curr Cardiol Rep 16(9):523","journal-title":"Curr Cardiol Rep"},{"issue":"1","key":"12225_CR5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.7861\/clinmedicine.18-1-75","volume":"18","author":"R Behrouzi","year":"2018","unstructured":"Behrouzi R, Punter M (2018) Diagnosis and management of cerebral venous thrombosis. Clin Med (Lond) 18(1):75\u201379","journal-title":"Clin Med (Lond)"},{"issue":"4","key":"12225_CR6","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1161\/STR.0b013e31820a8364","volume":"42","author":"G Saposnik","year":"2011","unstructured":"Saposnik G, Barinagarrementeria F, Brown RD Jr et al (2011) Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American heart association\/American stroke association. Stroke 42(4):1158\u20131192","journal-title":"Stroke"},{"issue":"3","key":"12225_CR7","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1161\/01.CIR.0000135582.53444.87","volume":"110","author":"EA Varga","year":"2004","unstructured":"Varga EA, Moll S (2004) Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation). Circulation 110(3):e15-18","journal-title":"Circulation"},{"issue":"4","key":"12225_CR8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/00063198-199707000-00007","volume":"3","author":"AY Lee","year":"1997","unstructured":"Lee AY, Ginsberg JS (1997) The role of D-dimer in the diagnosis of venous thromboembolism. Curr Opin Pulm Med 3(4):275\u2013279","journal-title":"Curr Opin Pulm Med"},{"issue":"4","key":"12225_CR9","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/j.1538-7836.2012.04637.x","volume":"10","author":"F Dentali","year":"2012","unstructured":"Dentali F, Squizzato A, Marchesi C, Bonzini M, Ferro JM, Ageno W (2012) D-dimer testing in the diagnosis of cerebral vein thrombosis: a systematic review and a meta-analysis of the literature. J Thromb Haemost 10(4):582\u2013589","journal-title":"J Thromb Haemost"},{"key":"12225_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1471-2377-11-69","volume":"11","author":"C Tanislav","year":"2011","unstructured":"Tanislav C, Siekmann R, Sieweke N et al (2011) Cerebral vein thrombosis: clinical manifestation and diagnosis. BMC Neurol 11:69","journal-title":"BMC Neurol"},{"key":"12225_CR11","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12883-015-0389-y","volume":"15","author":"IM Alons","year":"2015","unstructured":"Alons IM, Jellema K, Wermer MJ, Algra A (2015) D-dimer for the exclusion of cerebral venous thrombosis: a meta-analysis of low risk patients with isolated headache. BMC Neurol 15:118","journal-title":"BMC Neurol"},{"issue":"8","key":"12225_CR12","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1212\/01.WNL.0000090562.66120.1F","volume":"61","author":"PH Lalive","year":"2003","unstructured":"Lalive PH, de Moerloose P, Lovblad K, Sarasin FP, Mermillod B, Sztajzel R (2003) Is measurement of D-dimer useful in the diagnosis of cerebral venous thrombosis? Neurology 61(8):1057\u20131060","journal-title":"Neurology"},{"issue":"19","key":"12225_CR13","doi-asserted-by":"publisher","first-page":"3376","DOI":"10.1182\/blood-2013-04-499558","volume":"122","author":"J Kellermair","year":"2013","unstructured":"Kellermair J, Redwan B, Alias S et al (2013) Platelet endothelial cell adhesion molecule 1 deficiency misguides venous thrombus resolution. Blood 122(19):3376\u20133384","journal-title":"Blood"},{"key":"12225_CR14","doi-asserted-by":"publisher","first-page":"711","DOI":"10.3389\/fimmu.2019.00711","volume":"10","author":"I Wimmer","year":"2019","unstructured":"Wimmer I, Tietz S, Nishihara H et al (2019) PECAM-1 stabilizes blood-brain barrier integrity and favors paracellular T-cell diapedesis across the blood-brain barrier during neuroinflammation. Front Immunol 10:711","journal-title":"Front Immunol"},{"issue":"2","key":"12225_CR15","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1160\/TH16-03-0218","volume":"117","author":"AT Obi","year":"2017","unstructured":"Obi AT, Andraska E, Kanthi Y et al (2017) Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia. Thromb Haemost 117(2):339\u2013348","journal-title":"Thromb Haemost"},{"issue":"3","key":"12225_CR16","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/jth.12814","volume":"13","author":"A Rabinovich","year":"2015","unstructured":"Rabinovich A, Cohen JM, Cushman M et al (2015) Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome. J Thromb Haemost 13(3):398\u2013408","journal-title":"J Thromb Haemost"},{"issue":"10","key":"12225_CR17","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1172\/JCI13005","volume":"107","author":"K Ley","year":"2001","unstructured":"Ley K, Huo Y (2001) VCAM-1 is critical in atherosclerosis. J Clin Invest 107(10):1209\u20131210","journal-title":"J Clin Invest"},{"issue":"3","key":"12225_CR18","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1080\/10623320213631","volume":"9","author":"GA Koning","year":"2002","unstructured":"Koning GA, Schiffelers RM, Storm G (2002) Endothelial cells at inflammatory sites as target for therapeutic intervention. Endothelium 9(3):161\u2013171","journal-title":"Endothelium"},{"issue":"2","key":"12225_CR19","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1007\/s11239-020-02087-7","volume":"50","author":"J Kellermair","year":"2020","unstructured":"Kellermair J, Fellner A, Bittinger A et al (2020) Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT). J Thromb Thrombolysis 50(2):380\u2013385","journal-title":"J Thromb Thrombolysis"},{"issue":"9","key":"12225_CR20","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","volume":"33","author":"Headache Classification Committee of the International Headache S","year":"2013","unstructured":"Headache Classification Committee of the International Headache S (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33(9):629\u2013808","journal-title":"Cephalalgia"},{"issue":"2","key":"12225_CR21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1001\/jama.295.2.172","volume":"295","author":"A van Belle","year":"2006","unstructured":"van Belle A, Buller HR, Huisman MV et al (2006) Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA 295(2):172\u2013179","journal-title":"JAMA"},{"issue":"17","key":"12225_CR22","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1056\/NEJMoa042905","volume":"352","author":"A Perrier","year":"2005","unstructured":"Perrier A, Roy PM, Sanchez O et al (2005) Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 352(17):1760\u20131768","journal-title":"N Engl J Med"},{"key":"12225_CR23","unstructured":"Weimar C, Kurth T et al (2018) Zerebrale Venen- und Sinusthrombose, S2k-Leitlinie, 2018. Deutsche Gesellschaft f\u00fcr Neurologie (Hrsg.), Leitlinien f\u00fcr Diagnostik und Therapie in der Neurologie. Online: www.dgn.org\/leitlinien. Published 2018. Accessed 01 June 2018"},{"issue":"Suppl 1","key":"12225_CR24","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/ijlh.12665","volume":"39","author":"LA Linkins","year":"2017","unstructured":"Linkins LA, Takach LS (2017) Review of D-dimer testing: good, bad, and ugly. Int J Lab Hematol 39(Suppl 1):98\u2013103","journal-title":"Int J Lab Hematol"},{"issue":"9","key":"12225_CR25","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1503\/cmaj.060366","volume":"175","author":"D Scarvelis","year":"2006","unstructured":"Scarvelis D, Wells PS (2006) Diagnosis and treatment of deep-vein thrombosis. CMAJ 175(9):1087\u20131092","journal-title":"CMAJ"},{"issue":"3","key":"12225_CR26","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1056\/NEJMra0907731","volume":"363","author":"G Agnelli","year":"2010","unstructured":"Agnelli G, Becattini C (2010) Acute pulmonary embolism. N Engl J Med 363(3):266\u2013274","journal-title":"N Engl J Med"},{"issue":"10","key":"12225_CR27","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.ejim.2015.10.024","volume":"26","author":"M Schwameis","year":"2015","unstructured":"Schwameis M, Steiner MM, Schoergenhofer C et al (2015) D-dimer and histamine in early stage bacteremia: a prospective controlled cohort study. Eur J Intern Med 26(10):782\u2013786","journal-title":"Eur J Intern Med"},{"issue":"9","key":"12225_CR28","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1016\/j.ajem.2012.04.033","volume":"30","author":"JR Rodelo","year":"2012","unstructured":"Rodelo JR, De la Rosa G, Valencia ML et al (2012) D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med 30(9):1991\u20131999","journal-title":"Am J Emerg Med"},{"issue":"6","key":"12225_CR29","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00381-012-1744-6","volume":"28","author":"N Adeeb","year":"2012","unstructured":"Adeeb N, Mortazavi MM, Tubbs RS, Cohen-Gadol AA (2012) The cranial dura mater: a review of its history, embryology, and anatomy. Childs Nerv Syst 28(6):827\u2013837","journal-title":"Childs Nerv Syst"},{"key":"12225_CR30","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1159\/000111256","volume":"23","author":"T Kilic","year":"2008","unstructured":"Kilic T, Akakin A (2008) Anatomy of cerebral veins and sinuses. Front Neurol Neurosci 23:4\u201315","journal-title":"Front Neurol Neurosci"},{"issue":"4","key":"12225_CR31","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/jth.13954","volume":"16","author":"E Rezoagli","year":"2018","unstructured":"Rezoagli E, Martinelli I, Poli D et al (2018) The effect of recanalization on long-term neurological outcome after cerebral venous thrombosis. J Thromb Haemost 16(4):718\u2013724","journal-title":"J Thromb Haemost"},{"issue":"7","key":"12225_CR32","first-page":"970","volume":"12","author":"L Kellermair","year":"2022","unstructured":"Kellermair L, Zeller MWG, Kulyk C, Tomasits J, von Oertzen TJ, Vosko MR (2022) Dabigatran in cerebral sinus vein thrombosis and thrombophilia. Life (Basel). 12(7):970","journal-title":"Life (Basel)."},{"issue":"5","key":"12225_CR33","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/S0741-5214(97)70101-0","volume":"26","author":"LA Killewich","year":"1997","unstructured":"Killewich LA, Macko RF, Cox K et al (1997) Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement. J Vasc Surg 26(5):861\u2013868","journal-title":"J Vasc Surg"},{"issue":"1","key":"12225_CR34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0741-5214(89)90223-1","volume":"9","author":"LA Killewich","year":"1989","unstructured":"Killewich LA, Bedford GR, Beach KW, Strandness DE Jr (1989) Spontaneous lysis of deep venous thrombi: rate and outcome. J Vasc Surg 9(1):89\u201397","journal-title":"J Vasc Surg"},{"issue":"2","key":"12225_CR35","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1161\/01.CIR.86.2.414","volume":"86","author":"B van Ramshorst","year":"1992","unstructured":"van Ramshorst B, van Bemmelen PS, Hoeneveld H, Faber JA, Eikelboom BC (1992) Thrombus regression in deep venous thrombosis. Quantification of spontaneous thrombolysis with duplex scanning. Circulation 86(2):414\u2013419","journal-title":"Circulation"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12225-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-024-12225-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12225-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T06:25:40Z","timestamp":1720506340000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-024-12225-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":35,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["12225"],"URL":"https:\/\/doi.org\/10.1007\/s00415-024-12225-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.06.23297882","asserted-by":"object"}]},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,5]]},"assertion":[{"value":"14 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Lukas Kellermair has nothing to declare Christoph H\u00f6fer has nothing to declare Matthias W.G. Zeller: has nothing to declare Christa Kubasta: has nothing to declare; Bandke, Dave: has nothing to declare Serge Weis: has nothing to declare; J\u00f6rg Kellermair: has nothing to declare; Thomas Forstner: has nothing to declare Raimund Helbok: has nothing to declare Milan R. Vosko: has nothing to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}