{"paper_id":"dc1c3ea1-f373-46a3-9f51-74cea784a86c","body_text":"Abstract\nIntroduction\nUterine adenomyosis is a benign disorder in which endometrial glands and stroma are present within the myometrium. There have been several case reports of cerebral infarction associated with adenomyosis, but their clinical characteristics, optimal treatment, and prognosis have not been systematically reviewed.\nMethods\nA case of cerebral infarction with adenomyosis is reported, and a comprehensive systematic literature search using the PubMed database was conducted.\nResults\nA 42-year-old woman, previously diagnosed with adenomyosis, developed multiple cerebral infarctions during menstruation. Her CA125 level was 293 U/mL, and treatment with edoxaban 30 mg was started. Seven days after hospital discharge, she had her subsequent menstrual period and then developed a recurrent stroke. Her CA125 level was 743 U/mL on readmission. A hysterectomy was performed, and the patient has had no further stroke recurrence. A systematic review identified 19 cases with cerebral infarction associated with adenomyosis, including the present case. The patients’ clinical characteristics included young age (44.7 ± 6.2 years), stroke development during menstruation (85%), multiple infarctions affecting ≥ 3 vessel territories (39%), and high levels of CA125 and D-dimer (810.6 ± 888.4 U/mL, and 10.3 ± 18.6 μg/mL, respectively). Antithrombotic therapy was given to 14 patients, but recurrent stroke occurred in 5 (36%) patients. Hysterectomy was conducted in 5 and 4 patients with initial and recurrent stokes, respectively, and there were no further recurrences thereafter.\nConclusion\nCerebral infarction associated with adenomyosis has specific clinical characteristics. Antithrombotic therapy was insufficient, and hysterectomy should particularly be considered in cases of recurrent stroke.\nSimilar content being viewed by others\nReferences\nHong EY, Lin HZ, Fong YF (2020) Venous Thromboembolism and Adenomyosis: A Retrospective Review. Gynecol Minim Invasive Ther 9(2):64–68. https://doi.org/10.4103/GMIT.GMIT_77_19\nYin X, Wu J, Song S, Zhang B, Chen Y (2018) Cerebral infarcts associated with adenomyosis: a rare risk factor for stroke in middle-aged women: a case series. BMC Neurol 18(1):213. https://doi.org/10.1186/s12883-018-1213-2\nYasuda M, Yamanaka Y, Kano H, Araki N, Ishikawa H, Ikeda JI, Kuwabara S (2022) Recurrent Cerebral Infarcts Associated with Uterine Adenomyosis: Successful Prevention by Surgical Removal. Intern Med 61(5):735–738. https://doi.org/10.2169/internalmedicine.7320-21\nAso Y, Chikazawa R, Kimura Y, Kimura N, Matsubara E (2018) Recurrent multiple cerebral infarctions related to the progression of adenomyosis: a case report. BMC Neurol 18(1):119. https://doi.org/10.1186/s12883-018-1117-1\nYamashiro K, Tanaka R, Nishioka K, Ueno Y, Shimura H, Okuma Y, Hattori N, Urabe T (2012) Cerebral infarcts associated with adenomyosis among middle-aged women. J Stroke Cerebrovasc Dis 21 (8):910 e911–915. https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.10.017\nOkazaki K, Oka F, Ishihara H, Suzuki M (2018) Cerebral infarction associated with benign mucin-producing adenomyosis: report of two cases. BMC Neurol 18(1):166. https://doi.org/10.1186/s12883-018-1169-2\nArai N, Yachi K, Ishihara R, Fukushima T (2022) Adenomyosis-associated recurrent acute cerebral infarction mimicking Trousseau’s syndrome: A case study and review of literature. Surg Neurol Int 13:179. https://doi.org/10.25259/SNI_252_2022\nZhao Y, Zhang Y, Yang Y (2020) Acute cerebral infarction with adenomyosis in a patient with fever: a case report. BMC Neurol 20(1):210. https://doi.org/10.1186/s12883-020-01787-0\nKim B, Kim SH, Kim T (2018) Cerebral Infarcts by Nonbacterial Thrombotic Endocarditis Associated with Adenomyosis: A Case Report. J Stroke Cerebrovasc Dis 27(3):e50–e53. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.10.005\nAiura R, Nakayama S, Yamaga H, Kato Y, Fujishima H (2021) Systemic thromboembolism including multiple cerebral infarctions with middle cerebral artery occlusion caused by the progression of adenomyosis with benign gynecological tumor: a case report. BMC Neurol 21(1):14. https://doi.org/10.1186/s12883-021-02045-7\nZhang S, Zhao LM, Xue BQ, Liang H, Guo GC, Liu Y, Wu RY, Li CY (2022) Acute recurrent cerebral infarction caused by moyamoya disease complicated with adenomyosis: A case report. World J Clin Cases 10(14):4617–4624. https://doi.org/10.12998/wjcc.v10.i14.4617\nHijikata N, Sakamoto Y, Nito C, Matsumoto N, Abe A, Nogami A, Sato T, Hokama H, Okubo S, Kimura K (2016) Multiple Cerebral Infarctions in a Patient with Adenomyosis on Hormone Replacement Therapy: A Case Report. J Stroke Cerebrovasc Dis 25(10):e183-184. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.024\nUchino K, Shimizu T, Mizukami H, Isahaya K, Ogura H, Shinohara K, Hasegawa Y (2018) Nonbacterial Thrombotic Endocarditis Complicated by Cerebral Infarction in a Patient with Adenomyosis with High Serum CA125 Level; A Case Report. J Stroke Cerebrovasc Dis 27(3):e42–e45. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.09.064\nHirsh J, Anand SS, Halperin JL, Fuster V (2001) Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 21(7):1094–1096. https://doi.org/10.1161/hq0701.093686\nEdaravone Acute Infarction Study G (2003) Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 15 (3):222–229. https://doi.org/10.1159/000069318\nMiyamoto S, Ogasawara K, Kuroda S, Itabashi R, Toyoda K, Itoh Y, Iguchi Y, Shiokawa Y, Takagi Y, Ohtsuki T, Kinouchi H, Okada Y, Takahashi JC, Nakase H, Kakuda W, Committee for Stroke Guideline tJSS, (2022) Japan Stroke Society Guideline 2021 for the Treatment of Stroke. Int J Stroke 17(9):1039–1049. https://doi.org/10.1177/17474930221090347\nGiugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, Investigators EA-T (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093–2104. https://doi.org/10.1056/NEJMoa1310907\nNouh AM, Staff I, Finelli PF (2019) Three Territory Sign: An MRI marker of malignancy-related ischemic stroke (Trousseau syndrome). Neurol Clin Pract 9(2):124–128. https://doi.org/10.1212/CPJ.0000000000000603\nMorassutto C, Monasta L, Ricci G, Barbone F, Ronfani L (2016) Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study. PLoS One 11 (4):e0154227. https://doi.org/10.1371/journal.pone.0154227\nUpson K, Missmer SA (2020) Epidemiology of Adenomyosis. Semin Reprod Med 38(2–03):89–107. https://doi.org/10.1055/s-0040-1718920\nFukamatsu Y, Tsukahara Y, Fukuta T (1984) A clinicopathologic study on adenomyosis uteri. Nihon Sanka Fujinka Gakkai Zasshi 36(3):431–436\nVarki A (2007) Trousseau’s syndrome: multiple definitions and multiple mechanisms. Blood 110(6):1723–1729. https://doi.org/10.1182/blood-2006-10-053736\nKan YY, Yeh SH, Ng HT, Lou CM (1992) Effect of menstruation on serum CA125 levels. Asia Oceania J Obstet Gynaecol 18(4):339–343. https://doi.org/10.1111/j.1447-0756.1992.tb00329.x\nLevgur M (2007) Therapeutic options for adenomyosis: a review. Arch Gynecol Obstet 276(1):1–15. https://doi.org/10.1007/s00404-006-0299-8\nFujishita A, Masuzaki H, Khan KN, Kitajima M, Ishimaru T (2004) Modified reduction surgery for adenomyosis. A preliminary report of the transverse H incision technique. Gynecol Obstet Invest 57 (3):132–138. https://doi.org/10.1159/000075830\nNishioka K, Tanaka R, Tsutsumi S, Yamashiro K, Nakahara M, Shimura H, Hattori N, Urabe T (2014) Cerebral dural sinus thrombosis associated with adenomyosis: a case report. J Stroke Cerebrovasc Dis 23(7):1985–1987. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.027\nFunding\nThis work was partly supported by JSPS KAKENHI (Grant Number JP20K07909).\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflicts of interest\nYU received lecture fees from OHARA Pharmaceutical Co., Ltd., and research funds from Bristol-Myers Squibb. The other authors declare no potential conflicts of interest.\nEthical approval\nNot applicable.\nInformed consent\nWritten, informed consent was obtained from the patient included in the study.\nAdditional information\nPublisher's note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nMorishima, Y., Ueno, Y., Satake, A. et al. Recurrent embolic stroke associated with adenomyosis: A single case report and literature review. Neurol Sci 44, 2421–2429 (2023). https://doi.org/10.1007/s10072-023-06701-3\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s10072-023-06701-3","source_license":"CC0","license_restricted":false}