{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:01Z","timestamp":1792806421269,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Findings<\/jats:title>\n                <jats:p>We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage.<\/jats:p>\n                <jats:p>We identified 77 cases of CVT after COVID-19 vaccination. Patients\u2019 age was below 60\u2009years in 74\/77 (95.8%) cases and 61\/68 (89.7%) were women. Headache was described in 38\/77 (49.4%) cases, and in 35\/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19\/77 (24.7%) cases, intracranial hemorrhage in 33\/77 (42.9%) cases and 19\/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0\u20139.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7\u201320.8, <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.001), but not with death (OR: 0.51, 95% CI: 0.18\u20131.47, <jats:italic>p<\/jats:italic>\u00a0=\u20090.213).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-021-01324-5","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T10:03:29Z","timestamp":1631873009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis"],"prefix":"10.1186","volume":"22","author":[{"given":"David","family":"Garc\u00eda-Azor\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thien Phu","family":"Do","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas R.","family":"Gantenbein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob M\u00f8ller","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcio Nattan P.","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Obermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Pohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph J.","family":"Schankin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Winther","family":"Schytz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guus G.","family":"Schoonman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-5424","authenticated-orcid":false,"given":"Espen Saxhaug","family":"Kristoffersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"issue":"10240","key":"1324_CR1","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1016\/S0140-6736(20)31208-3","volume":"395","author":"FC Zhu","year":"2020","unstructured":"Zhu FC, Li YH, Guan XH, Hou LH, Wang WJ, Li JX, Wu SP, Wang BS, Wang Z, Wang L, Jia SY, Jiang HD, Wang L, Jiang T, Hu Y, Gou JB, Xu SB, Xu JJ, Wang XW, Wang W, Chen W (2020) Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 395(10240):1845\u20131854. https:\/\/doi.org\/10.1016\/S0140-6736(20)31208-3","journal-title":"Lancet"},{"key":"1324_CR2","unstructured":"Vaccine Adverse Event Reporting System (VAERS). VAERS Data Sets. Available on: https:\/\/vaers.hhs.gov\/data.html Accessed on May 10, 2021"},{"key":"1324_CR3","unstructured":"European Medicines Agency. Signal assessment report on embolic and thrombotic events (SMQ) with COVID-19 Vaccine (ChAdOx1-S [recombinant]) \u2013 Vaxzevria (previously COVID-19 Vaccine AstraZeneca) (Other viral vaccines). Published on 08 April 2021. Available on: https:\/\/www.ema.europa.eu\/en\/documents\/prac-recommendation\/signal-assessment-report-embolic-thrombotic-events-smq-covid-19-vaccine-chadox1-s-recombinant_en.pdf"},{"key":"1324_CR4","doi-asserted-by":"publisher","unstructured":"Krzywicka K, Heldner MR, S\u00e1nchez van Kammen M, van Haaps T, Hiltunen S, Silvis SM, Levi M, Kremer Hovinga JA, Jood K, Lindgren E, Tatlisumak T, Putaala J, Aguiar de Sousa D, Middeldorp S, Arnold M, Coutinho JM, Ferro JM (2021) Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European medicines agency. Eur J Neurol (Epub ahead of print). https:\/\/doi.org\/10.1111\/ene.15029","DOI":"10.1111\/ene.15029"},{"key":"1324_CR5","doi-asserted-by":"publisher","unstructured":"Schulz JB, Berlit P, Diener HC, Gerloff C, Greinacher A, Klein C, Petzold GC, Piccininni M, Poli S, R\u00f6hrig R, Steinmetz H, Thiele T, Kurth T, the German Society of Neurology SARS\u2010CoV\u20102 Vaccination Study Group, Alonso A, Bartsch T, Baumsteiger C, Bode F, Cang\u00fcr H, Daffertshofer M, Dafotakis M, Dieterich M, Fabian F, Fousse M, Godau J, Grond M, G\u00fcnther A, Gutschalk A, Hagemann G, Hartmann C, Hilker-Roggendorf R, H\u00f6glinger G, Ikenberg B, Ismail FS, Jesse S, Kallm\u00fcnzer B, Kern R, Klietz M, Knau\u00df S, Knier B, Limmroth V, Mengel A, Meyne J, Morgenthaler M, M\u00fcller M, Nagel S, Niels RD, Onur OA, Pelz J, Plenge J, Poli S, Roth C, R\u00f6ther J, Sa\u00df C, Sch\u00f6nenberger S, Schubert R, Simon O, Agaplesion IS, Sperfeld A, Spreer A, Steinbrecher A, Steiner J, Stetefeld H, Trendelenburg G, Vatankhah NB, Wahl CM, Wartenberg K, Witt K, Wittstock M, Wolf B, Wolf J, Zimmermann J (2021) COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Ann Neurol (Epub ahead of print). https:\/\/doi.org\/10.1002\/ana.26172","DOI":"10.1002\/ana.26172"},{"issue":"24","key":"1324_CR6","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1001\/jama.2021.7517","volume":"325","author":"I See","year":"2021","unstructured":"See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, Streiff MB, Rao AK, Wheeler AP, Beavers SF, Durbin AP, Edwards K, Miller E, Harrington TA, Mba-Jonas A, Nair N, Nguyen DT, Talaat KR, Urrutia VC, Walker SC, Creech CB, Clark TA, DeStefano F, Broder KR (2021) US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, march 2 to April 21, 2021. JAMA 325(24):2448\u20132456. https:\/\/doi.org\/10.1001\/jama.2021.7517","journal-title":"JAMA"},{"issue":"22","key":"1324_CR7","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","volume":"84","author":"A Greinacher","year":"2021","unstructured":"Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S (2021) Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 84(22):2092\u20132101. https:\/\/doi.org\/10.1056\/NEJMoa2104840","journal-title":"N Engl J Med"},{"key":"1324_CR8","doi-asserted-by":"publisher","first-page":"n1114","DOI":"10.1136\/bmj.n1114","volume":"373","author":"A Potteg\u00e5rd","year":"2021","unstructured":"Potteg\u00e5rd A, Lund LC, Karlstad \u00d8 et al (2021) Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ 373:n1114","journal-title":"BMJ"},{"issue":"10","key":"1324_CR9","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1161\/STROKEAHA.120.030800","volume":"51","author":"ES Kristoffersen","year":"2020","unstructured":"Kristoffersen ES, Harper CE, Vetvik KG, Zarnovicky S, Hansen JM, Faiz KW (2020) Incidence and mortality of cerebral venous thrombosis in a Norwegian population. Stroke 51(10):3023\u20133029. https:\/\/doi.org\/10.1161\/STROKEAHA.120.030800","journal-title":"Stroke"},{"issue":"9","key":"1324_CR10","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. https:\/\/doi.org\/10.1038\/nrneurol.2017.104","journal-title":"Nat Rev Neurol"},{"issue":"29","key":"1324_CR11","doi-asserted-by":"publisher","first-page":"e20900","DOI":"10.1097\/MD.0000000000020900","volume":"99","author":"D Garc\u00eda-Azor\u00edn","year":"2020","unstructured":"Garc\u00eda-Azor\u00edn D, Monje MHG, Gonz\u00e1lez-Garc\u00eda N, Guerrero \u00c1L, Porta-Etessam J (2020) Presence of red flags in patients with cerebral venous sinus thrombosis admitted to the emergency department because of headache: a STROBE compliant cohort-study. Medicine (Baltimore) 99(29):e20900. https:\/\/doi.org\/10.1097\/MD.0000000000020900","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"1324_CR12","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1212\/WNL.0000000000006697","volume":"92","author":"TP Do","year":"2019","unstructured":"Do TP, Remmers A, Schytz HW, Schankin C, Nelson SE, Obermann M, Hansen JM, Sinclair AJ, Gantenbein AR, Schoonman GG (2019) Red and orange flags for secondary headaches in clinical practice: SNNOOP10 list. Neurology 92(3):134\u2013144. https:\/\/doi.org\/10.1212\/WNL.0000000000006697","journal-title":"Neurology"},{"key":"1324_CR13","doi-asserted-by":"publisher","unstructured":"FACME multidisciplinary working group on the management of cerebral venous sinus thrombosis associated with COVID-19 vaccination. Diagnostic and treatment recommendations from the FACME ad-hoc expert working group on the management of cerebral venous sinus thrombosis associated with COVID-19 vaccination. Neurologia (Engl Ed) Jul-Aug 2021 36(6):451\u2013461. Doi: https:\/\/doi.org\/10.1016\/j.nrleng.2021.05.001","DOI":"10.1016\/j.nrleng.2021.05.001"},{"key":"1324_CR14","unstructured":"World Health Organization. Guidance document for clinical case management of thrombosis with thrombocytopenia syndrome (TTS) following coronavirus disease (COVID-19) vaccination. Interim guidance 1 July 2021. Available on: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/342999\/WHO-2019-nCoV-TTS-2021.1-eng.pdf"},{"issue":"22","key":"1324_CR15","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","volume":"384","author":"NH Schultz","year":"2021","unstructured":"Schultz NH, S\u00f8rvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, Wiedmann M, Aamodt AH, Skatt\u00f8r TH, Tj\u00f8nnfjord GE, Holme PA (2021) Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med 384(22):2124\u20132130. https:\/\/doi.org\/10.1056\/NEJMoa2104882","journal-title":"N Engl J Med"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01324-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-021-01324-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01324-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T10:03:38Z","timestamp":1631873018000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejournalofheadacheandpain.biomedcentral.com\/articles\/10.1186\/s10194-021-01324-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1324"],"URL":"https:\/\/doi.org\/10.1186\/s10194-021-01324-5","relation":{},"ISSN":["1129-2369","1129-2377"],"issn-type":[{"value":"1129-2369","type":"print"},{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,17]]},"assertion":[{"value":"16 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with Helsinki Declaration as revised in 2013. According to local IRB no ethical approval or informed patient consent was necessary because no new individually collected patient data were used in this study. For this type of study formal consent is not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"David Garc\u00eda-Azor\u00edn received scientific support and received honoraria from the Brain Health Unit of the World Health Organization as scientific advisor for the COVID-19 Global Forum.Thien Phu Do reports no conflicts of interest.Andreas R. Gantenbein reports no conflicts of interest.Jakob M\u00f8ller Hansen reports no conflicts of interest.Marcio Nattan Souza received speaker fees from Novartis, TEVA, Lilly, Allergan, Sanofi, Libbs and Lundbeck.Mark Obermann received scientific support, travel support and\/or honoraria from Biogen Idec, Novartis, Sanofi\/Genzyme, Pfizer, Teva, Lilly, Schwarz and Heel. He received research grants from Allergan, Electrocore, Heel, and the German Ministry for Education and Research (BMBF).Heiko Pohl was funded by the Werner Dessauer Stiftung and received speaker fees from TEVA Pharmaceuticals and honoraria from Eli Lilly.Christoph J. Schankin received scientific support, travel support and\/or honoraria from Novartis, Eli Lilly, TEVA Pharmaceuticals, Allergan, Almirall, Amgen, MindMed, Gr\u00fcnenthal. He received research grants from German Migraine and Headache Society, Eye on Vision Foundation, and Baasch Medicus Foundation. He is part-time employee at Zynnon.Henrik Winther Schytz has received honoraria from Novartis, TEVA, Lilly and has received a research grant from Novartis.Alexandra Sinclair has received speaker fees and Honoraria from Novartis and Allergan.Guus Schoonman reports no conflict of interest.Espen Saxhaug Kristoffersen reports no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"108"}}