{"paper_id":"28c831b4-0f50-47c6-b6b2-7aba070c511a","body_text":"Review began\n 03/27/2024 \nReview ended\n 04/13/2024 \nPublished\n 04/29/2024\n© Copyright \n2024\nChi et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nAdenomyosis Accompanied by Multiple\nHemorrhagic Cerebral Infarction: A Case Report\nBin Chi \n, \nMeiyan Liu \n, \nPengwei Hou \n, \nJianwu Wu \n, \nShousen Wang \n1.\n Neurosurgery, Fuzhou 900th Hospital, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, CHN \n2.\nGastroenterology, Fuzhou 900th Hospital, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, CHN\nCorresponding author: \nShousen Wang, \nwshsen1965@126.com\nAbstract\nThis study aims to present a case of uterine adenomyosis accompanied by multiple hemorrhagic cerebral\ninfarctions (CIs), summarize therapeutic experiences based on the literature review, and improve the clinical\ndiagnosis and treatment of multiple hemorrhagic CIs. This paper describes a 46-year-old female with a four-\nyear history of uterine adenomyosis complicated by multiple hemorrhagic CIs. During treatment, elevated\nlevels of D-dimer, CA-125, and severe anemia were observed. Following internal medicine treatment\ntargeting uterine adenomyosis and hemorrhagic CIs, the cerebral hemorrhage gradually resolved. Women\npresenting with multiple CIs, particularly hemorrhagic ones, should be evaluated for the presence of\ngynecological diseases. Treating gynecological conditions may aid in the management of multiple CIs.\nCategories:\n Neurosurgery, Obstetrics/Gynecology\nKeywords:\n women and health, hemorrhagic transformation, cerebral hemorrhage, cerebral infarction, adenomyosis\nIntroduction\nUterine adenomyosis is a benign gynecological condition characterized by the infiltration of endometrial\ntissue into the uterine myometrium, with the endometrial tissue composed of glands and stroma \n[1-3]\n.\nAdenomyosis commonly occurs in women of childbearing age and is often associated with symptoms such\nas dysmenorrhea, menorrhagia, and heavy menstrual bleeding (HMB); although approximately 30% of\nwomen with adenomyosis are asymptomatic, the prevalence of adenomyosis diagnosed by imaging is\nestimated to be 20-30% \n[3,4]\n.\nIn some patients, adenomyosis may progress to cerebral infarctions (CIs), particularly in middle-aged\nwomen with severe anemia and elevated levels of D-dimer and CA-125. Reports suggest that women with\nadenomyosis who have elevated levels of glycoprotein CA-125 and D-dimer, especially during menstruation,\nare at higher risk of acute CI \n[5]\n. However, to our knowledge, there have been few reports of adenomyosis\ncomplicating multiple hemorrhagic CIs. This study aims to improve the clinical diagnosis and treatment of\nmultiple hemorrhagic CIs by presenting a case of adenomyosis accompanied by multiple hemorrhagic CIs\nand summarizing treatment experiences based on a literature review.\nCase Presentation\nA 46-year-old woman was admitted to the neurosurgery department due to a one-day history of headaches\nand recurrent seizures with altered consciousness for one hour. She experienced persistent headaches one\nday prior to admission and subsequently developed altered consciousness, generalized muscle stiffness, limb\nconvulsions, and foaming at the mouth one hour before admission, with her eyes deviating to the right. Her\nlast menstrual period occurred on June 27, 2023, and headaches developed after menstruation. She had a\nhistory of increased menstrual bleeding for 10 years and was diagnosed with uterine fibroids five years ago.\nThere was no history of hypertension, diabetes, heart disease, hyperlipidemia, or family history of\ncerebrovascular diseases. Additionally, she had not taken contraceptives or hormone medications. A cranial\nCT scan revealed hemorrhagic CI in the right occipital lobe, multiple hemorrhages in the right frontal lobe,\nleft basal ganglia, left thalamus, and left lateral ventricle, along with subarachnoid hemorrhage (Figure \n1A\n).\n1\n2\n1\n1\n1\n \nOpen Access Case\nReport\n \nDOI:\n 10.7759/cureus.59280\nHow to cite this article\nChi B, Liu M, Hou P, et al. (April 29, 2024) Adenomyosis Accompanied by Multiple Hemorrhagic Cerebral Infarction: A Case Report. Cureus 16(4):\ne59280. \nDOI 10.7759/cureus.59280\n\nFIGURE\n 1: The basal ganglia level images of cranial CT scans before\nand after the onset of the illness\nA shows the cranial CT upon admission to the neurosurgery department (yellow arrow indicating subarachnoid\nhemorrhage and the white arrow indicating hemorrhagic focus); B depicts the cranial CT image on the first day of\nadmission (green arrow indicating hemorrhage from the thalamus into the ventricle and the white arrow indicating\naggravation of the hemorrhagic focus); C displays the cranial CT scan performed on the seventh day after\nadmission (white arrow indicating slight absorption of the hemorrhagic focus compared to previous images);\nD presents the cranial CT scan taken two weeks after admission (white arrow indicating old hemorrhagic focus);\nE exhibits the cranial CT scan during the patient's orthopedic hospitalization.\nOne day later, there was a progression of intracranial hemorrhage, with the appearance of hemorrhagic foci\naround the infarcted area (Figure \n1B\n). The lumbar puncture revealed red-colored cerebrospinal fluid with a\npressure of 320 mmH\n2\nO. Hemoglobin (Hb) levels were normal (Figure \n2A\n), while D-dimer levels were\nelevated (Figure \n2C\n)\n, and serum CA-125 levels were elevated (\n253 U/mL\n).\nFIGURE\n 2: Line chart of some laboratory indexes of patients regularly\nreviewed during hospitalization\nA, B, and C show numerical line plots of red blood cells, Hb, and D-dimer, respectively.\nHb, hemoglobin\nThree months prior to admission, the patient sustained a tibial fracture due to a fall and underwent open\nreduction and internal fixation of the tibial fracture at our orthopedic department. Significant decreases in\nHb levels and elevated D-dimer levels were noted before the surgery (\nFigures \n2B\n, \n2C\n)\n. After receiving\nsymptomatic treatments such as blood transfusion and anticoagulation, orthopedic surgery was\nperformed. \nColor Doppler ultrasound revealed a thrombus in the left posterior tibial vein (14x4.5 mm), and\ngynecological ultrasonography showed uterine enlargement (78x73x64 mm, Figure \n3A\n). The muscular layer\nof the anterior wall was thicker than that of the posterior wall, about 42.1 mm (yellow crosshair 1) and 29.3\nmm (yellow crosshair 2), and the echo of the muscular layer was uneven (Figure \n3B\n). \nSubsequently,\nanticoagulant therapy with nadroparin calcium (1 mL - 9500 IU) was administered at a dose of 4250 IU, 85\nIU/kg (0.1 mL/kg) subcutaneously daily, along with a transfusion of suspended red blood cells to improve Hb\nlevels (\nFigure \n2\n).\n2024 Chi et al. Cureus 16(4): e59280. DOI 10.7759/cureus.59280\n2\n of \n6\n\nFIGURE\n 3: Ultrasound images of the uterus\nA shows the uterine ultrasonography; the uterus appears uniformly enlarged and symmetrical (68.8×64.3×55.7\nmm) with a thickened muscle layer and heterogeneous echo, and the endometrium is centrally located with\nunclear demarcation from the muscle layer. B - The muscular layer of the anterior wall was thicker than that of the\nposterior wall, about 42.1 mm (yellow crosshair 1) and 29.3 mm (yellow crosshair 2)\nEN, endometrium; BL, bladder\nDuring April 2023\n, while hospitalized in the orthopedic ward, the patient experienced three episodes of\ngrand mal seizures, characterized by generalized muscle stiffness, upper limb convulsions, frothing at the\nmouth, and transient loss of consciousness. \nA comprehensive cranial MRI scan revealed multiple infarct\nlesions in the bilateral parietal and occipital lobes, as well as the right caudate nucleus (Figure \n4A\n). \nSo we\nconsidered at that time that the patient had secondary epilepsy due to multiple intracranial infarctions.\n The\ndynamic electrocardiogram did not reveal paroxysmal atrial fibrillation. Additionally, no significant\nabnormalities were observed in the dynamic electroencephalogram or the cranial CT scan (Figure \n1E\n). After\ndischarge from the orthopedic ward, the patient was prescribed oral sodium valproate (\n500 mg bid\n) to control\nepilepsy. \nDuring the neurosurgery inpatient period in July 2023, \nfollowing conservative treatments such as\nlumbar puncture to release hemorrhagic cerebrospinal fluid and mannitol to reduce intracranial pressure,\nthe patient experienced improvement in symptoms such as headache and altered consciousness. Subsequent\nimaging on the seventh and 14th days showed gradual absorption of the hematoma (as depicted in Figures\n1C\n, \n1D\n, \n4B\n, and 4C). \nRegarding the treatment for adenomyosis, due to the patient's refusal of definitive\nhysterectomy, she opted for standardized therapy with gonadotropin-releasing hormone agonists (GnRH-\nα\n)\n(\nGnRH-\nα\n injection, leuprorelin acetate, 3.75 mg, subcutaneous injection, every 1/4 week, administered a\ntotal of three times \non 2023-5-16, 2023-6-22, 2023-7-10)\n.\n \nFIGURE\n 4: The MRI T2 flair images and cervical CTV obtained during the\ncourse of the illness\nA shows the MRI image taken during the first seizure episode while hospitalized in the orthopedic department\n(white arrows indicate ischemic lesions in the right caudate nucleus head and left occipital lobe). B displays the\nMRI findings two weeks after the hemorrhage (white arrows indicate ischemic lesions with necrosis in the right\nfrontal lobe, occipital lobe, and left thalamus). C presents the follow-up cranial MRI conducted one month later\n(white arrows indicate old hemorrhagic lesions). D exhibits the three-dimensional reconstruction image of the\ncervical CTA (white arrows indicate two filling defects in the right transverse sinus).\nCTV, CT venogram\nThe patient was discharged three weeks later, maintaining regular oral administration of sodium valproate\n(\n500 mg bid\n) \nto control seizures. Additionally, she received standardized treatment for adenomyosis with\nGnRh-\nα\n at the gynecology outpatient clinic. A follow-up examination after one month revealed a right\ntransverse sinus thrombosis on the neck CT \nvenogram (CTV)\n (Figure \n4D\n). During the follow-up period, there\nwere no reported symptoms of headache or seizures, and levels of Hb and D-dimer remained within the\nnormal range (Figure \n2C\n).\n2024 Chi et al. Cureus 16(4): e59280. DOI 10.7759/cureus.59280\n3\n of \n6\n\nDiscussion\nWe report a case of a 46-year-old female with adenomyosis and multiple hemorrhagic CIs, who presented\nwith elevated D-dimer, CA-125, and severe anemia during hospitalization. According to the literature, the\nmechanisms underlying adenomyosis-induced multiple CIs may be associated with factors such as elevated\nD-dimer, elevated CA-125, severe anemia, and menstrual periods, leading to hypercoagulability, hormone\nreplacement therapy, and increased tissue factor (TF) levels \n[1]\n. To the best of our knowledge, this is the first\nreport of adenomyosis complicated by multiple hemorrhagic CIs.\nAlthough reports of adenomyosis complicated by multiple CIs are rare, similar cases have been documented.\nThese occurrences may be associated with the following factors: (1) elevated D-dimer is a reliable predictor\nof ischemic stroke, as its elevation signifies thrombin formation and fibrinolysis \n[2]\n. Ohara indicated that D-\ndimer can be utilized for etiological classification and diagnosis of ischemic stroke, while Kim et al. similarly\nsuggested that admission D-dimer >1.0 mg/L is an independent predictor of recurrent ischemic stroke \n[3,4]\n.\n(2) Elevated CA-125 levels may increase the risk of ischemic stroke. Previous studies have reported that\nelevated CA-125 is associated with a higher risk of ischemic stroke \n[5]\n. CA-125 is a biomarker used for\nmonitoring epithelial ovarian cancer and for distinguishing pelvic masses. Previous reports have also\ndocumented elevated CA-125 levels in patients with adenomyosis who experienced concurrent stroke \n[5]\n.\nThis cancer antigen, CA-125, induces systemic thromboembolism by activating platelets and neutrophils,\nleading to clot formation throughout the body \n[6]\n. Therefore, elevated CA-125 levels are believed to be\nassociated with a hypercoagulable state. (3) In patients with adenomyosis, the elevated immunoreactive\nexpression of TF in the endometrial tissue plays a significant role in the coagulation cascade \n[7,8]\n. (4)\nAnemia may also be a risk factor for thrombus formation. (5) Iron deficiency is a common cause of anemia,\nand iron deficiency anemia has been linked to thrombotic events in cancer patients \n[9,10]\n. (6) Hemostatic\ndysfunction resulting from menstrual bleeding during the menstrual period is also considered a potential\nrisk factor for CI \n[11]\n. In this case, the patient also presented with elevated D-dimer and CA-125 levels, and\nthe lowest Hb level reached 23g/L. Despite intermittent blood transfusions and conservative medical\ntreatment, the patient still had mild to moderate anemia. Therefore, the CIs observed in this patient were\nlikely related to the aforementioned two factors.\nIn this case, the woman was admitted to the neurosurgery department due to intracerebral hemorrhage\nrather than CI. We speculate that this may be related to hemorrhagic transformation (HT). It has been\nreported that approximately 10% of stroke patients experience HT \n[12]\n. According to the time of occurrence,\nHT can be classified into two types: early HT occurs within several days (within five days) after acute CI,\nwhile delayed HT occurs in the subacute phase (approximately one week to one month) \n[13]\n. On one hand,\nthe mechanism of HT after CI is related to the loss of basal membrane components of brain microvessels and\ndecreased vascular wall integrity following infarction \n[13,14]\n. On the other hand, HT is also significantly\nassociated with petechiae near the damaged vessels and the development of bleeding \n[15]\n. Risk factors for\nHT after CI include advanced age, greater stroke severity, elevated blood glucose, atrial fibrillation, INR >1.7,\ncongestive heart failure, renal impairment, and dual antiplatelet therapy \n[15,16]\n. Dual antiplatelet therapy\nalso increases the risk of HT \n[17]\n. The reason for HT in this case could be the worsening severity of the stroke.\nHowever, there might also be other factors yet to be discovered, as the patient was not on dual antiplatelet\ntherapy and did not have any other aforementioned risk factors. Small hemorrhages have minimal impact\non clinical symptoms and prognosis, while large hemorrhages can affect thrombolytic and anticoagulant\ntherapy, with severe cases potentially leading to impaired consciousness or death. Surgical treatment is not\nroutine for HT, and in this patient with multiple bleeding sites, conservative treatment was chosen. After the\ndisappearance of neurological symptoms through rehabilitative exercises, the patient was discharged. Upon\nfollow-up, a CTV revealed thrombosis in the right transverse sinus, but as the patient did not exhibit\nsignificant clinical symptoms, and to prevent further bleeding, continued anticoagulant therapy was not\ninitiated.\nAccording to literature reports, the treatment of adenomyosis plays a crucial role in cases of adenomyosis\ncombined with multiple CIs \n[18]\n. Surgical treatment for adenomyosis, such as hysterectomy, may be an\neffective method for preventing recurrent CIs \n[1]\n. However, in this case, the patient declined surgical\ntreatment and opted for GnRH-\nα\n therapy for adenomyosis. Based on the follow-up CTV results showing\nthrombosis in the right transverse sinus, we consider that GnRH-\nα\n therapy alone still carries a risk of\nrecurrent CIs, which aligns with the viewpoint of Zhao \n[19]\n. To prevent the patient from experiencing further\nstroke risks, it is recommended that the patient seek proper treatment for adenomyosis from the gynecology\ndepartment, including surgical intervention such as hysterectomy.\nConclusions\nThis study reports a case of a 46-year-old woman with adenomyosis complicated by multiple hemorrhagic\nCIs. The diagnostic and treatment process of this case suggests that women with multiple hemorrhagic CIs\naccompanied by elevated D-dimer, CA-125, and anemia should be assessed for concurrent gynecological\ndiseases. This includes not only malignant tumors such as ovarian cancer but also benign conditions such as\nadenomyosis. Furthermore, early treatment of gynecological diseases after hemorrhage stabilization is\ncrucial to prevent stroke recurrence. Surgical treatment for adenomyosis may be a preferable preventive\nmeasure.\n2024 Chi et al. Cureus 16(4): e59280. DOI 10.7759/cureus.59280\n4\n of \n6\n\nAdditional Information\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nAcquisition, analysis, or interpretation of data:\n  \nPengwei Hou, Bin Chi, Meiyan Liu, Jianwu Wu\nDrafting of the manuscript:\n  \nPengwei Hou, Bin Chi, Meiyan Liu\nConcept and design:\n  \nBin Chi, Meiyan Liu, Shousen Wang\nCritical review of the manuscript for important intellectual content:\n  \nBin Chi, Meiyan Liu, Jianwu Wu,\nShousen Wang\nSupervision:\n  \nShousen Wang\nDisclosures\nHuman subjects:\n Consent was obtained or waived by all participants in this study. \nConflicts of interest:\n In\ncompliance with the ICMJE uniform disclosure form, all authors declare the following: \nPayment/services\ninfo:\n \nThis research was funded by the Fujian Provincial Science and Technology Plan Key Project (Grant\nNumber: 2019Y9045) and the Fujian Medical University Sailing Fund Project (Grant Number: 2019QH2043).\nFinancial relationships:\n All authors have declared that they have no financial relationships at present or\nwithin the previous three years with any organizations that might have an interest in the submitted work.\nOther relationships:\n All authors have declared that there are no other relationships or activities that could\nappear to have influenced the submitted work.\nReferences\n1\n. \nAso Y, Chikazawa R, Kimura Y, Kimura N, Matsubara E: \n\"Recurrent multiple cerebral infarctions related to\nthe progression of adenomyosis: a case report\"\n. BMC Neurol. 2018, 18:119. \n10.1186/s12883-018-1117-1\n2\n. \nLiu X, Nie J, Guo SW: \nElevated immunoreactivity to tissue factor and its association with dysmenorrhea\nseverity and the amount of menses in adenomyosis\n. Hum Reprod. 2011, 26:337-45. \n10.1093/humrep/deq311\n3\n. \nOhara T, Farhoudi M, Bang OY, Koga M, Demchuk AM: \nThe emerging value of serum D-dimer measurement\nin the work-up and management of ischemic stroke\n. Int J Stroke. 2020, 15:122-31.\n10.1177/1747493019876538\n4\n. \nKim YD, Song D, Nam HS, et al.: \nD-dimer for prediction of long-term outcome in cryptogenic stroke\npatients with patent foramen ovale\n. Thromb Haemost. 2015, 114:614-22. \n10.1160/TH14-12-1040\n5\n. \nJovin TG, Boosupalli V, Zivkovic SA, Wechsler LR, Gebel JM: \nHigh titers of CA-125 may be associated with\nrecurrent ischemic strokes in patients with cancer\n. Neurology. 2005, 14:1944-5. \n10.1212/01\n6\n. \nShao B, Wahrenbrock MG, Yao L, et al.: \nCarcinoma mucins trigger reciprocal activation of platelets and\nneutrophils in a murine model of Trousseau syndrome\n. Blood. 2011, 118:4015-23. \n10.1182/blood-2011-07-\n368514\n7\n. \nvan Es N, Bleker S, Sturk A, Nieuwland R: \nClinical significance of tissue factor-exposing microparticles in\narterial and venous thrombosis\n. Semin Thromb Hemost. 2015, 41:718-27. \n10.1055/s-0035-1556047\n8\n. \nGrover SP, Mackman N: \nTissue factor: an essential mediator of hemostasis and trigger of thrombosis\n.\nArterioscler Thromb Vasc Biol. 2018, 38:709-25. \n10.1161/ATVBAHA.117.309846\n9\n. \nHung SH, Lin HC, Chung SD: \nAssociation between venous thromboembolism and iron-deficiency anemia: a\npopulation-based study\n. Blood Coagul Fibrinolysis. 2015, 26:368-72. \n10.1097/MBC.0000000000000249\n10\n. \nTsai CF, Yip PK, Chen CC, Yeh SJ, Chung ST, Jeng JS: \nCerebral infarction in acute anemia\n. J Neurol. 2010,\n257:2044-51. \n10.1007/s00415-010-5657-6\n11\n. \nNakamura Y, Kawamura N, Ishiko O, Ogita S: \nAcute disseminated intravascular coagulation developed\nduring menstruation in an adenomyosis patient\n. Arch Gynecol Obstet. 2002, 267:110-2.\n10.1007/s004040100243\n12\n. \nTerruso V, D'Amelio M, Di Benedetto N, et al.: \nFrequency and determinants for hemorrhagic transformation\nof cerebral infarction\n. Neuroepidemiology. 2009, 33:261-5. \n10.1159/000229781\n13\n. \nHornig CR, Dorndorf W, Agnoli AL: \nHemorrhagic cerebral infarction--a prospective study\n. Stroke. 1986,\n17:179-85. \n10.1161/01.str.17.2.179\n14\n. \nHamann GF, del Zoppo GJ, von Kummer R: \n[Mechanisms for the development of intracranial hemorrhage.\nPossible implications for thrombolysis in cerebral infarct]\n. Nervenarzt. 1999, 70:1116-20.\n10.1007/s001150050549\n15\n. \nJiao Y, Li G, Xing Y, Nie D, Liu X: \nInfluencing factors of hemorrhagic transformation in non-thrombolysis\npatients with cerebral infarction\n. Clin Neurol Neurosurg. 2019, 181:68-72. \n10.1016/j.clineuro.2019.04.018\n16\n. \nJickling GC, Liu D, Stamova B, Ander BP, Zhan X, Lu A, Sharp FR: \nHemorrhagic transformation after\nischemic stroke in animals and humans\n. J Cereb Blood Flow Metab. 2014, 34:185-99. \n10.1038/jcbfm.2013.203\n17\n. \nHankey GJ: \nDual antiplatelet therapy in acute transient ischemic attack and minor stroke\n. N Engl J Med.\n2013, 369:82-3. \n10.1056/NEJMe1305127\n18\n. \nAiura R, Nakayama S, Yamaga H, Kato Y, Fujishima H: \nSystemic thromboembolism including multiple\ncerebral infarctions with middle cerebral artery occlusion caused by the progression of adenomyosis with\nbenign gynecological tumor: a case report\n. BMC Neurol. 2021, 21:14. \n10.1186/s12883-021-02045-7\n2024 Chi et al. Cureus 16(4): e59280. DOI 10.7759/cureus.59280\n5\n of \n6\n\n19\n. \nZhao Y, Zhang Y, Yang Y: \nAcute cerebral infarction with adenomyosis in a patient with fever: a case report\n.\nBMC Neurol. 2020, 20:210. \n10.1186/s12883-020-01787-0\n2024 Chi et al. Cureus 16(4): e59280. DOI 10.7759/cureus.59280\n6\n of \n6","source_license":"CC0","license_restricted":false}