Cerebral venous thrombosis with myelodysplastic syndrome: a rare case report

Cerebral venous thrombosis with myelodysplastic syndrome: a rare case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Cerebral venous thrombosis with myelodysplastic syndrome: a rare case report Jia Zhang, Tianfang Jiang, Xu Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4417154/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Cerebral venous thrombosis (CVT) is an important cause of stroke in young adults caused by complete or partial occlusion of the cerebral major venous sinuses or smaller feeding cortical veins. Myelodysplastic syndrome (MDS) represents a heterogeneous group of myeloid neoplasms that are characterized by ineffective hematopoiesis, variable cytopenias, and a risk of progression to acute myeloid leukemia. However, CVT is rarely reported in patients with MDS. Case presentation: A 45-year-old woman with recurrent chronic headache for three months. Later, the headache symptoms gradually worsened, accompanied by disturbance of consciousness and cerebral hemorrhage. Multiple thromboses of the intracranial venous sinus were confirmed by cranial magnetic resonance venography (MRV). After treatment with heparin anticoagulation and mannitol dehydration, the symptoms gradually improved, and the hematoma was absorbed before discharge. Bone marrow biopsy revealed morbid hematopoiesis in the erythroid system and 10% of the circular iron granulocyte erythrocytes. Whole-exon detection revealed U2AF1 c.101C>T, CEBPA c.283G>A, and KMT2D c.468T>G gene mutations, which confirmed the diagnosis of MDS. Conclusions: MDS complicated with venous sinus thrombosis is rare. A highindex of suspicion is needed for a correct diagnosis of CVT presenting with ICH or chronic headache in female patients. Cerebral venous thrombosis Myelodysplastic syndromes Intracerebral hemorrhage Anticoagulation Magnetic resonance venography Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Cerebral venous thrombosis (CVT) is an infrequent but potentially life-threatening cerebrovascular disease that accounts for 0.5–1% of all strokes.[ 1 ] Its incidence in adults is estimated at 1.3 per 100,000 person-years, with a higher rate among women and middle-aged patients.[ 2 ] The symptoms of CVT range from minor to life-threatening depending on the sinuses and veins involved, the extent of brain parenchymal injury, the chronicity, and the effect on intracranial pressure.[ 3 ] The etiology of CVT is a complex and multifactorial process, including genetic or acquired factors such as prothrombotic conditions, oral contraceptives, pregnancy and puerperium, infection, and malignancy.[ 4 ] Any of three changes in blood composition, hemodynamics, or vascular endothelium may lead to CVT. Myelodysplastic syndrome (MDS) is a myeloid neoplasm characterized by clonal proliferation of hematopoietic stem cells, recurrent genetic abnormalities, myelodysplasia, ineffective hematopoiesis, peripheral blood cytopenia, and a high risk of progression to acute myeloid leukemia (AML).[ 5 ] The incidence rate of MDS in the general population is 4.5 per 100,000 people per year; the incidence is greater in males than in females (6.2 vs. 3.3 per 100,000 people per year) and substantially increases with age.[ 6 ] CVT is rarely reported in patients with MDS.[ 7 , 8 ] Approximately one-third of CVT patients develop intracerebral hemorrhage (ICH). The presentation of cerebral hemorrhage may be challenging and a common pitfall in diagnosing CVT.[ 9 ] Here, we describe a patient with MDS who presented with ICH and was diagnosed with CVT. We describe the brain computed tomography (CT) and MR findings as well as the bone marrow aspiration results and the clinical course of the patient, which all support a diagnosis of MDS with CVT. The patient was successfully managed with anticoagulation therapy. Patients and methods A 41-year-old female patient was admitted to the hospital complaining of headache for more than 3 months and disturbance of consciousness for 1 day. Three months ago, the patient developed dizziness and headache without obvious inducement, accompanied by blurred vision in the right eye, ignoring object rotation and no nausea or vomiting. No obvious abnormalities were found in the plain CT scan of the head at the local hospital. She was given glycerin fructose, dexamethasone and flunarizine capsules, and her symptoms were relieved. One month prior, she was admitted to the hospital for treatment because her headache reappeared. No obvious abnormalities were found on MR (Fig. 1 . A, B) and MRV (Fig. 1 . C, D) of the head. During hospitalization, the white blood cell count, hemoglobin level and platelet count were significantly lower (WBC, 1.27*10^9/L; Hb, 94 g/L; and PTL, 98*10^9/L). Eperisone and flunarizine were given to improve the headache. Her headache symptoms slightly improved, and she was discharged 17 days later with no significant findings for the cause of her headache. After that, the patient still had recurrent headache. Eight days prior, she experienced transient numbness of her left limb, which lasted for 2–3 minutes and was relieved by herself. One day prior, the patient's headache symptoms worsened again, accompanied by dizziness and vomiting. The cranial CT (Fig. 1 . E, F) Multiple intracerebral hemorrhages. After admission, the patient was given alternating dehydration consisting of albumin, mannitol and glycerol fructose. Four days later, cranial MR (Fig. 1 . G, H) Multiple intracerebral hemorrhages in the left temporal occipital lobe and the right frontal lobe. No obvious abnormalities were found in the cranial MRA (Fig. 2 . A, B), cranial MRV enhancement (Fig. 2 . C-F) Multiple filling defects of the intracranial venous sinus and internal jugular venous sinus, suggesting thrombosis, especially on the right. After that, she was treated with low-molecular-weight heparin fraxiparine anticoagulant and levetiracetam tablets to prevent epilepsy. The patient’s white blood cells were low, and she was treated with a subdermal injection of oprelvekin. On day 23, the head MRV (Fig. 2 . G, H) was rechecked, and the degree of venous sinus thrombosis was less than before. Her symptoms of head pain improved gradually, and she was discharged on day 32. Follow-up The patient had a history of a decrease in the three blood systems for 10 years. The hematology department consulted and considered the possibility of blood diseases. During hospitalization, the platelet count was low, and a bone puncture examination was not yet performed. Two months later, routine blood tests revealed a WBC of 1.12*10^9/L, Hb of 108 g/L, and PTL of 111*10^9/L. Bone marrow puncture blood smears revealed that the proliferation of bone marrow nucleated cells was within the normal range, the granulocyte-to-red ratio was inverted (0.22:1), morbid hematopoiesis could be observed in the erythroid system, morbid erythrocytes accounted for 4% of nuclear erythrocytes, the morphology and size of mature erythrocytes were different, and ring iron pellet erythrocytes accounted for 10% (Fig. 3A-D). Karyotype analysis of bone marrow cells revealed an abnormal number of chromosome 8 and an abnormal structure of chromosome 5. Karyotype: 46~47, XX,? del5 (q11.2), +?8, inc[cp3] (Fig. 4). The flow cytometry results of bone marrow puncture showed that no obvious immunophenotypes related to acute leukemia, NHL or high-risk MDS were detected (Fig. 5). Whole-exon detection of MDS-related gene mutations via bone marrow puncture revealed that U2AF1 c.101C>T (p. S34F), CEBPA c.283G>A (p. V95M), KMT2D c.468T>G (p. V1561G) gene mutation (Table 1), which confirmed the diagnosis of MDS. Discussion Here, we report a young woman with recurrent chronic headache as the main complaint. She had a history of abnormal blood system results. Later, the headache symptoms gradually worsened, accompanied by disturbance of consciousness and cerebral hemorrhage. Multiple thromboses of the intracranial venous sinus were confirmed by cranial MRV. After treatment with heparin anticoagulation and mannitol dehydration, the symptoms gradually improved, and the hematoma was absorbed before discharge. After discharge, bone marrow biopsy revealed morbid hematopoiesis in the erythroid system and 10% of the circular iron granulocyte erythrocytes. Whole-exon detection revealed U2AF1 c.101C > T, CEBPA c.283G > A, and KMT2D c.468T > G gene mutations, which proved that the patient had myelodysplastic syndrome (MDS). MDS complicated with venous sinus thrombosis is rare. After treatment, the patient improved and was discharged from the hospital, suggesting that patients with recurrent headache need to undergo dynamic MRI of the head to eliminate venous sinus thrombosis. Cerebral venous thrombosis (CVT) is an important cause of stroke in young adults caused by complete or partial occlusion of the cerebral major venous sinuses or smaller feeding cortical veins. Diagnosis and management can be difficult because of the diversity of underlying risk factors, variation in clinical presentation, and the absence of a uniform treatment approach.[ 10 ] Generally, CVT has a favorable outcome, with complete functional recovery reported in approximately 75% of patients.[ 11 ] Among patients with CVT, the incidence of cerebral hemorrhage is 35–39%, and CVT is usually associated with poorer outcomes.[ 9 ] Through definite diagnosis and treatment, our patient achieved a good outcome. CVT is not a common complication of MDS. A 46-year-old man with myelodysplastic syndrome died of complications from cerebral sagittal sinus thrombosis in 1997.[ 7 ] Headache is usually a manifestation of elevated intracranial pressure and is the most common symptom of CVT. The clinical manifestations also depend on the location of thrombosis. A delay in diagnosis is common, and approximately 56% of patients present with subacute (> 48 h to 30 days) onset of symptoms.[ 3 ] Headache, mental status disorder, confusion and loss of consciousness are commonly found in hemorrhagic CVT,[ 9 ] which is consistent with our patient’s manifestations. Patients with suspected CVT require urgent neuroimaging to confirm the diagnosis, using either CT or MR to visualize the thrombus directly, showing impaired venous flow or both.[ 10 ] Our patient had no obvious abnormalities in cranial MRV two months after headache onset, but intracranial venous sinus thrombosis occurred three months after onset, indicating that venous sinus thrombosis is a chronic process, and the absence of abnormalities in cranial MRV cannot exclude the possibility of CVT. Anticoagulation therapy in CVT helps to prevent thrombus growth, facilitates recanalization, and prevents deep vein thrombosis or pulmonary embolism. Anticoagulation remains the first-line treatment of choice for CVT in the acute setting, even when there is concurrent intracranial hemorrhage (ICH).[ 1 ] European guidelines provide a weak recommendation for low-molecular weight heparin (LMWH) over unfractionated heparin (UFH) in terms of the incidence of bleeding.[ 12 ] Hence, fraxiparine was chosen for our patient. Two weeks after subcutaneous injection, the fraxiparine was changed to rivaroxaban for oral anticoagulation. The mechanism responsible for CVT in MDS remains speculative. The etiology seems to be multifactorial, including factors attributable to hematological conditions, such as increased thrombin generation, the synthesis of procoagulant molecules and inflammatory cytokines by malignant cells and their interaction with vascular endothelial cells, promoting a hypercoagulable state.[ 8 ] In MDS patients, the burden of thrombotic events does not seem to be much greater than that in the general population, but the effect of some treatments on increasing thrombotic risk is under investigation.[ 13 ] Through genetic testing, we found that the patient had mutations in the U2AF1, CEBPA and KMT2D genes, while the thrombophilia gene detection panel was negative. U2AF1 gene mutation, which is detected in 21.7% of MDSs, results in the downregulation of many genes, including those encoding splicing and RNA recognition motifs (RRMs), following alterations of two amino acid residues, such as S34 in the zinc finger 1 domain or Q157 in the zinc finger 2 domain[ 14 , 15 ]. In addition, previous studies have demonstrated that U2AF1 mutants are prone to anemia, thrombocytopenia, and poor survival in both lower-risk and higher-risk MDS patients[ 16 ]. The CEBPA gene, which is located at 19q13.11 and has no introns, encodes a transcription factor involved in hematopoiesis, as it controls the proliferation and differentiation of myeloid progenitor cells[ 17 ]. The inheritance of a germline CEBPA mutation predisposes patients to the development of AML with autosomal dominant inheritance[ 18 ]. In our patient, NM_004364.5 (CEBPA):c.283G > A (p.Val95Met) has already been reported in dbSNP, which means that she tended to be predisposed to AML. Histone-lysine N-methyltransferase 2D (KMT2D), which belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases, plays critical roles in regulating development, differentiation, metabolism, and tumor suppression. It is frequently mutated in developmental diseases, such as Kabuki syndrome and congenital heart disease, and various forms of cancer.[ 19 ] In our patient, KMT2D c.468T > G (p. V1561G) mutation has not been reported in dbSNP, and she may have had a tendency to develop cancer. In conclusion, MDS is a rare cause of CVT. A high index of suspicion is needed for a correct diagnosis of CVT presenting with ICH or chronic headache in female patients. Identification of these patients is important due to significant treatment implications. Abbreviations CVT: Cerebral venous thrombosis; MDS: Myelodysplastic syndrome; MRV: Magnetic resonance venography; ICH: Intracerebral hemorrhage. Declarations Acknowledgments We thank Dr. Dongqin Yang and Dr. Yumei Zhang for tissue sample collection and interpretation of the pathological results. Disclosure The authors have no conflicts of interest related to this work. No funding was received. The authors obtained written consent from the patient. Authors’ contributions JZ and JTF contributed to the conception, drafting, and reporting of the case. XC contributed to the revision of the manuscript. All authors have read and approved the final manuscript. Funding No funding was received for this work. Availability of data and materials The datasets generated during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Shanghai Eighth People's Hospital. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Competing interests The authors report no competing interests. References Alimohammadi A, Kim DJ, Field TS. Updates in Cerebral Venous Thrombosis. Curr Cardiol Rep. 2022;24 1:43-50; doi: 10.1007/s11886-021-01622-z. Ruuskanen JO, Kyt V, Posti JP, Rautava P, Sipil J. Cerebral Venous Thrombosis – Finnish Nationwide Trends. Stroke. 2020;52. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation. 2011;42 4:1158. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. The Lancet Neurology. 2007;6 2:162-70; doi: 10.1016/s1474-4422(07)70029-7. Cazzola M. Myelodysplastic Syndromes. N Engl J Med. 2020;383 14:1358-74; doi: 10.1056/NEJMra1904794. Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35 8:2182-98; doi: 10.1038/s41375-021-01265-7. Finelli PF, Harrison RB, Uphoff DF. Myelodysplastic syndrome and sagittal sinus thrombosis. Journal of Stroke and Cerebrovascular Diseases. 1998;7 3:211-2. Pinto MJ, Medeiros PB, Principe F, Carvalho M. Cerebral Venous Thrombosis in Hematological Malignancy: Balancing the Risks. J Stroke Cerebrovasc Dis. 2020;29 4:104683; doi: 10.1016/j.jstrokecerebrovasdis.2020.104683. Pongmoragot J, Saposnik G. Intracerebral hemorrhage from cerebral venous thrombosis. Current atherosclerosis reports. 2012;14 4:382-9; doi: 10.1007/s11883-012-0260-1. Ulivi L, Squitieri M, Cohen H, Cowley P, Werring DJ. Cerebral venous thrombosis: a practical guide. Pract Neurol. 2020;20 5:356-67; doi: 10.1136/practneurol-2019-002415. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35 3:664-70; doi: 10.1161/01.Str.0000117571.76197.26. Ferro JM, Bousser MG, Canhão P, Coutinho JM, Crassard I, Dentali F, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. European journal of neurology. 2017;24 10:1203-13; doi: 10.1111/ene.13381. Alkharabsheh OA, Saadeh SS, Zblewski DL, Gangat N, Begna KH, Elliott MA, et al. Frequency of venous thrombotic events in patients with myelodysplastic syndrome and 5q deletion syndrome during lenalidomide therapy. Annals of hematology. 2019;98 2:331-7; doi: 10.1007/s00277-018-3509-0. Wang H, Guo Y, Dong Z, Li T, Xie X, Wan D, et al. Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome. Scientific reports. 2020;10 1:18622; doi: 10.1038/s41598-020-74744-z. Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood. 2012;119 14:3203-10; doi: 10.1182/blood-2011-12-399774. Li B, Liu J, Jia Y, Wang J, Xu Z, Qin T, et al. Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes. Genes, chromosomes & cancer. 2018;57 2:80-8; doi: 10.1002/gcc.22510. Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004;351 23:2403-7; doi: 10.1056/NEJMoa041331. Gao J, Gong S, Chen YH. Myeloid Neoplasm With Germline Predisposition: A 2016 Update for Pathologists. Archives of pathology & laboratory medicine. 2019;143 1:13-22; doi: 10.5858/arpa.2017-0194-RA. Froimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D. Gene. 2017;627:337-42; doi: 10.1016/j.gene.2017.06.056. Table Table 1. Whole exon detection of MDS related gene mutation in bone marrow puncture Gene Mutant named exons Mutation frequency (sequencing depth) U2AF1 NM_006758: c.101C>T(p.S34F) exon2 41.6%(2348X) CEBPA NM_004364: c.283G>A(p.V95M) exon1 50%(4087X) KMT2D NM_003482: c.468T>G(p.V1561G) exon17 50.2%(3626X) No variation was detected in the following genes ANKRD11,ASXL1,BCOR,CALR,CBL,CSF3R,CUX1,DDX41,DHX9,DICER,DNMT3A,ETNK1,ETV6,EZH2,FLT3,GATA2,IDH1,IDH2,IKZF1,ITIH3,JAK2,KIF20B,KIT, KRAS,MPL,NF1,NPM1,NRAS,PDGFRA,PDGFRB,PHF6,PTPN11,PTPRD,ROBO1,ROBO2,RUNX1,SETBP1,SF3B1,SRSF2,STAG2,STAT3,TET2,TP53,UPF3A,UTX,WT1,ZRSR2 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4417154","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":304697874,"identity":"0e422f75-2063-42d6-9178-e1ab38acf5a6","order_by":0,"name":"Jia Zhang","email":"","orcid":"","institution":"Shanghai Eighth People Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Zhang","suffix":""},{"id":304697875,"identity":"7de68a63-5e02-4c18-939d-5b5bebf64786","order_by":1,"name":"Tianfang Jiang","email":"","orcid":"","institution":"Shanghai Eighth People Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tianfang","middleName":"","lastName":"Jiang","suffix":""},{"id":304697876,"identity":"5f4c2084-e7de-4f41-a620-995e6c41ec7c","order_by":2,"name":"Xu Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYLCCj39sePj5G0jQwTizIU1GcsYBErQwczYctjFoSCBSOf+MHLPHjDvO8xgwHGD88DGHCC0SZ86YGxeeuc1jztzALDlzGxFaDNh7t0nPYLvNY9lwgI2ZlygtQGXSPGzneAwOJBCrBWQLb9sBErRInDn/3XDGmWQeyRkHm4nzC/+MtLQHHyrs7Pn5mw9++EiMFiBgg9KMDcSpR9IyCkbBKBgFowAHAAA3fTUu45sr9gAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Eighth People Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xu","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-05-14 07:16:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4417154/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4417154/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57444279,"identity":"4e8d08bc-6092-4384-9964-167a108d37c7","added_by":"auto","created_at":"2024-05-30 18:53:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103337,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCranial imaging date before and after admission. \u003c/strong\u003eOne month before admission, there was no obvious abnormality in the head MR axial T1 (A,B) and MRV (C,D).\u003cstrong\u003e \u003c/strong\u003eOne day before admission, head CT showed multiple intracerebral hemorrhage in left temporal occipital lobe and right frontal lobe (E,F). On day 4, head MR axial T1 showed multiple intracerebral hemorrhage in left temporal occipital lobe and right frontal lobe (G,H).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/19dfe0d018dabfd7f527a950.jpg"},{"id":57444277,"identity":"58351144-c581-48e2-8cde-b4d9bf11a0a3","added_by":"auto","created_at":"2024-05-30 18:53:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":76232,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMagnetic resonance angiography and venography of the brain after admission. \u003c/strong\u003eOn day 4, no obvious abnormality was found in the cranial MRA (A,B). The enhancement of cranial MRV suggested that multiple cord like filling defects could be seen in the superior lossy sinus, sinus confluence (C,D), right transverse sinus, sigmoid sinus and internal jugular vein (E,F). On day 23, reexamination of cranial MRV showed that the intracranial venous sinus thrombosis was partially alleviated than before (G,H).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/9c699b99ba8a35d7c5de2766.jpg"},{"id":57444278,"identity":"40f437d0-34d6-4ac5-9d7c-9a95768a0525","added_by":"auto","created_at":"2024-05-30 18:53:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":53245,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMorphological examination of bone marrow cells. \u003c/strong\u003eTwo months after discharge, the blood smear examination of bone marrow puncture showed that the proliferation of bone marrow nucleated cells was within the normal range, and the granulocyte/erythrocyte ratio was inverted (0.22:1). Morbid hematopoiesis could be seen in the erythroid system. Morbid erythrocytes accounted for 4% of the nucleated erythrocytes, the morphology and size of mature erythrocytes were different, and the circular iron granulocyte erythrocytes accounted for 10%.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/c69ad389f1737a6164f32236.jpg"},{"id":57444281,"identity":"25ae427e-6917-4a5d-b041-a1d4e201f660","added_by":"auto","created_at":"2024-05-30 18:53:34","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":13405,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaryotype analysis of bone marrow cells.\u003c/strong\u003e Karyotype analysis showed abnormal number of chromosome 8 and abnormal structure of chromosome 5. Karyotype: 46~47, XX, ? del5 (q11.2), +?8, inc[cp3].\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/1f2d442614ee06714b581f2b.jpg"},{"id":57444679,"identity":"fafb3965-6777-44f9-b179-d0dfbf6408bb","added_by":"auto","created_at":"2024-05-30 19:01:34","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":50163,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBone marrow puncture flow cytometry analysis. \u003c/strong\u003eThe results of bone marrow puncture flow cytometry showed that CD34 + primitive/immature cells accounted for about 0.8% of the samples, and their immunophenotypes were not significantly abnormal; Erythrocytosis accounted for about 45%, and no obvious abnormality was found.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/74b5f77b7378f68e4de62a1e.jpg"},{"id":79846145,"identity":"96d8d547-dcc0-4913-8909-cdd9110b0f4c","added_by":"auto","created_at":"2025-04-03 13:46:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":819528,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4417154/v1/617fcd1b-94c7-41c4-8b16-795936844e3b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebral venous thrombosis with myelodysplastic syndrome: a rare case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCerebral venous thrombosis (CVT) is an infrequent but potentially life-threatening cerebrovascular disease that accounts for 0.5\u0026ndash;1% of all strokes.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Its incidence in adults is estimated at 1.3 per 100,000 person-years, with a higher rate among women and middle-aged patients.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] The symptoms of CVT range from minor to life-threatening depending on the sinuses and veins involved, the extent of brain parenchymal injury, the chronicity, and the effect on intracranial pressure.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The etiology of CVT is a complex and multifactorial process, including genetic or acquired factors such as prothrombotic conditions, oral contraceptives, pregnancy and puerperium, infection, and malignancy.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Any of three changes in blood composition, hemodynamics, or vascular endothelium may lead to CVT.\u003c/p\u003e \u003cp\u003eMyelodysplastic syndrome (MDS) is a myeloid neoplasm characterized by clonal proliferation of hematopoietic stem cells, recurrent genetic abnormalities, myelodysplasia, ineffective hematopoiesis, peripheral blood cytopenia, and a high risk of progression to acute myeloid leukemia (AML).[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] The incidence rate of MDS in the general population is 4.5 per 100,000 people per year; the incidence is greater in males than in females (6.2 vs. 3.3 per 100,000 people per year) and substantially increases with age.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eCVT is rarely reported in patients with MDS.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Approximately one-third of CVT patients develop intracerebral hemorrhage (ICH). The presentation of cerebral hemorrhage may be challenging and a common pitfall in diagnosing CVT.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Here, we describe a patient with MDS who presented with ICH and was diagnosed with CVT. We describe the brain computed tomography (CT) and MR findings as well as the bone marrow aspiration results and the clinical course of the patient, which all support a diagnosis of MDS with CVT. The patient was successfully managed with anticoagulation therapy.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eA 41-year-old female patient was admitted to the hospital complaining of headache for more than 3 months and disturbance of consciousness for 1 day. Three months ago, the patient developed dizziness and headache without obvious inducement, accompanied by blurred vision in the right eye, ignoring object rotation and no nausea or vomiting. No obvious abnormalities were found in the plain CT scan of the head at the local hospital. She was given glycerin fructose, dexamethasone and flunarizine capsules, and her symptoms were relieved.\u003c/p\u003e \u003cp\u003eOne month prior, she was admitted to the hospital for treatment because her headache reappeared. No obvious abnormalities were found on MR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A, B) and MRV (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. C, D) of the head. During hospitalization, the white blood cell count, hemoglobin level and platelet count were significantly lower (WBC, 1.27*10^9/L; Hb, 94 g/L; and PTL, 98*10^9/L). Eperisone and flunarizine were given to improve the headache. Her headache symptoms slightly improved, and she was discharged 17 days later with no significant findings for the cause of her headache. After that, the patient still had recurrent headache.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEight days prior, she experienced transient numbness of her left limb, which lasted for 2\u0026ndash;3 minutes and was relieved by herself. One day prior, the patient's headache symptoms worsened again, accompanied by dizziness and vomiting. The cranial CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. E, F) Multiple intracerebral hemorrhages.\u003c/p\u003e \u003cp\u003eAfter admission, the patient was given alternating dehydration consisting of albumin, mannitol and glycerol fructose. Four days later, cranial MR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. G, H) Multiple intracerebral hemorrhages in the left temporal occipital lobe and the right frontal lobe. No obvious abnormalities were found in the cranial MRA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A, B), cranial MRV enhancement (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. C-F) Multiple filling defects of the intracranial venous sinus and internal jugular venous sinus, suggesting thrombosis, especially on the right. After that, she was treated with low-molecular-weight heparin fraxiparine anticoagulant and levetiracetam tablets to prevent epilepsy. The patient\u0026rsquo;s white blood cells were low, and she was treated with a subdermal injection of oprelvekin. On day 23, the head MRV (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. G, H) was rechecked, and the degree of venous sinus thrombosis was less than before. Her symptoms of head pain improved gradually, and she was discharged on day 32.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Follow-up","content":"\u003cp\u003eThe patient had a history of\u0026nbsp;a decrease in\u0026nbsp;the three blood systems for 10 years. The hematology department consulted and considered the possibility of blood diseases. During hospitalization, the platelet\u0026nbsp;count\u0026nbsp;was low, and\u0026nbsp;a\u0026nbsp;bone puncture examination was not yet\u0026nbsp;performed. Two months later,\u0026nbsp;routine\u0026nbsp;blood\u0026nbsp;tests revealed a WBC of\u0026nbsp;1.12*10^9/L, Hb\u0026nbsp;of 108 g/L,\u0026nbsp;and\u0026nbsp;PTL\u0026nbsp;of\u0026nbsp;111*10^9/L.\u0026nbsp;Bone\u0026nbsp;marrow puncture blood\u0026nbsp;smears revealed\u0026nbsp;that the proliferation of bone marrow nucleated cells was within the normal range, the granulocyte-to-red ratio was inverted (0.22:1), morbid hematopoiesis could be\u0026nbsp;observed\u0026nbsp;in the erythroid system, morbid erythrocytes accounted for 4% of nuclear erythrocytes, the morphology and size of mature erythrocytes were different,\u0026nbsp;and\u0026nbsp;ring iron pellet\u0026nbsp;erythrocytes accounted\u0026nbsp;for 10% (Fig.\u0026nbsp;3A-D).\u003c/p\u003e\n\u003cp\u003eKaryotype analysis of bone marrow cells revealed an abnormal number of chromosome 8 and an abnormal structure of chromosome 5. Karyotype: 46~47, XX,? del5 (q11.2), +?8, inc[cp3] (Fig. 4). The flow cytometry results of bone marrow puncture showed that no obvious immunophenotypes related to acute leukemia, NHL or high-risk MDS were detected (Fig. 5). Whole-exon detection of MDS-related gene mutations via bone marrow puncture revealed that U2AF1 c.101C\u0026gt;T (p. S34F), CEBPA c.283G\u0026gt;A (p. V95M), KMT2D c.468T\u0026gt;G (p. V1561G) gene mutation (Table 1), which confirmed the diagnosis of MDS.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHere, we report a young woman with recurrent chronic headache as the main complaint. She had a history of abnormal blood system results. Later, the headache symptoms gradually worsened, accompanied by disturbance of consciousness and cerebral hemorrhage. Multiple thromboses of the intracranial venous sinus were confirmed by cranial MRV. After treatment with heparin anticoagulation and mannitol dehydration, the symptoms gradually improved, and the hematoma was absorbed before discharge. After discharge, bone marrow biopsy revealed morbid hematopoiesis in the erythroid system and 10% of the circular iron granulocyte erythrocytes. Whole-exon detection revealed U2AF1 c.101C\u0026thinsp;\u0026gt;\u0026thinsp;T, CEBPA c.283G\u0026thinsp;\u0026gt;\u0026thinsp;A, and KMT2D c.468T\u0026thinsp;\u0026gt;\u0026thinsp;G gene mutations, which proved that the patient had myelodysplastic syndrome (MDS). MDS complicated with venous sinus thrombosis is rare. After treatment, the patient improved and was discharged from the hospital, suggesting that patients with recurrent headache need to undergo dynamic MRI of the head to eliminate venous sinus thrombosis.\u003c/p\u003e \u003cp\u003eCerebral venous thrombosis (CVT) is an important cause of stroke in young adults caused by complete or partial occlusion of the cerebral major venous sinuses or smaller feeding cortical veins. Diagnosis and management can be difficult because of the diversity of underlying risk factors, variation in clinical presentation, and the absence of a uniform treatment approach.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Generally, CVT has a favorable outcome, with complete functional recovery reported in approximately 75% of patients.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Among patients with CVT, the incidence of cerebral hemorrhage is 35\u0026ndash;39%, and CVT is usually associated with poorer outcomes.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Through definite diagnosis and treatment, our patient achieved a good outcome.\u003c/p\u003e \u003cp\u003eCVT is not a common complication of MDS. A 46-year-old man with myelodysplastic syndrome died of complications from cerebral sagittal sinus thrombosis in 1997.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Headache is usually a manifestation of elevated intracranial pressure and is the most common symptom of CVT. The clinical manifestations also depend on the location of thrombosis. A delay in diagnosis is common, and approximately 56% of patients present with subacute (\u0026gt;\u0026thinsp;48 h to 30 days) onset of symptoms.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Headache, mental status disorder, confusion and loss of consciousness are commonly found in hemorrhagic CVT,[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] which is consistent with our patient\u0026rsquo;s manifestations.\u003c/p\u003e \u003cp\u003ePatients with suspected CVT require urgent neuroimaging to confirm the diagnosis, using either CT or MR to visualize the thrombus directly, showing impaired venous flow or both.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Our patient had no obvious abnormalities in cranial MRV two months after headache onset, but intracranial venous sinus thrombosis occurred three months after onset, indicating that venous sinus thrombosis is a chronic process, and the absence of abnormalities in cranial MRV cannot exclude the possibility of CVT.\u003c/p\u003e \u003cp\u003eAnticoagulation therapy in CVT helps to prevent thrombus growth, facilitates recanalization, and prevents deep vein thrombosis or pulmonary embolism. Anticoagulation remains the first-line treatment of choice for CVT in the acute setting, even when there is concurrent intracranial hemorrhage (ICH).[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] European guidelines provide a weak recommendation for low-molecular weight heparin (LMWH) over unfractionated heparin (UFH) in terms of the incidence of bleeding.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Hence, fraxiparine was chosen for our patient. Two weeks after subcutaneous injection, the fraxiparine was changed to rivaroxaban for oral anticoagulation.\u003c/p\u003e \u003cp\u003eThe mechanism responsible for CVT in MDS remains speculative. The etiology seems to be multifactorial, including factors attributable to hematological conditions, such as increased thrombin generation, the synthesis of procoagulant molecules and inflammatory cytokines by malignant cells and their interaction with vascular endothelial cells, promoting a hypercoagulable state.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] In MDS patients, the burden of thrombotic events does not seem to be much greater than that in the general population, but the effect of some treatments on increasing thrombotic risk is under investigation.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThrough genetic testing, we found that the patient had mutations in the U2AF1, CEBPA and KMT2D genes, while the thrombophilia gene detection panel was negative. U2AF1 gene mutation, which is detected in 21.7% of MDSs, results in the downregulation of many genes, including those encoding splicing and RNA recognition motifs (RRMs), following alterations of two amino acid residues, such as S34 in the zinc finger 1 domain or Q157 in the zinc finger 2 domain[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition, previous studies have demonstrated that U2AF1 mutants are prone to anemia, thrombocytopenia, and poor survival in both lower-risk and higher-risk MDS patients[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The CEBPA gene, which is located at 19q13.11 and has no introns, encodes a transcription factor involved in hematopoiesis, as it controls the proliferation and differentiation of myeloid progenitor cells[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The inheritance of a germline CEBPA mutation predisposes patients to the development of AML with autosomal dominant inheritance[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our patient, NM_004364.5 (CEBPA):c.283G\u0026thinsp;\u0026gt;\u0026thinsp;A (p.Val95Met) has already been reported in dbSNP, which means that she tended to be predisposed to AML. Histone-lysine N-methyltransferase 2D (KMT2D), which belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases, plays critical roles in regulating development, differentiation, metabolism, and tumor suppression. It is frequently mutated in developmental diseases, such as Kabuki syndrome and congenital heart disease, and various forms of cancer.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In our patient, KMT2D c.468T\u0026thinsp;\u0026gt;\u0026thinsp;G (p. V1561G) mutation has not been reported in dbSNP, and she may have had a tendency to develop cancer.\u003c/p\u003e \u003cp\u003eIn conclusion, MDS is a rare cause of CVT. A high index of suspicion is needed for a correct diagnosis of CVT presenting with ICH or chronic headache in female patients. Identification of these patients is important due to significant treatment implications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCVT: Cerebral venous thrombosis; MDS: Myelodysplastic syndrome; MRV: Magnetic resonance venography; ICH: Intracerebral hemorrhage.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch1\u003eAcknowledgments\u003c/h1\u003e\n\u003cp\u003eWe thank Dr.\u0026nbsp;Dongqin Yang and\u0026nbsp;Dr.\u0026nbsp;Yumei Zhang for tissue sample collection and\u0026nbsp;interpretation of the\u0026nbsp;pathological results.\u0026nbsp;\u003c/p\u003e\n\u003ch1\u003eDisclosure\u003c/h1\u003e\n\u003cp\u003eThe authors have no conflicts of interest related to this work. No funding was received. The authors obtained written consent from the patient.\u003c/p\u003e\n\u003ch1\u003eAuthors\u0026rsquo; contributions\u003c/h1\u003e\n\u003cp\u003eJZ and JTF contributed to the conception, drafting, and reporting of the case. XC contributed to the revision of the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003ch1\u003eFunding\u003c/h1\u003e\n\u003cp\u003eNo funding was received\u0026nbsp;for\u0026nbsp;this work.\u003c/p\u003e\n\u003ch1\u003eAvailability of data and materials\u003c/h1\u003e\n\u003cp\u003eThe datasets generated during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003ch1\u003eEthics approval and consent to participate\u003c/h1\u003e\n\u003cp\u003eThis study was approved by the Medical Ethics Committee of Shanghai Eighth People\u0026apos;s Hospital.\u003c/p\u003e\n\u003ch1\u003eConsent for publication\u003c/h1\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003ch1\u003eCompeting interests\u003c/h1\u003e\n\u003cp\u003eThe authors report no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlimohammadi A, Kim DJ, Field TS. 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Annals of hematology. 2019;98 2:331-7; doi: 10.1007/s00277-018-3509-0.\u003c/li\u003e\n\u003cli\u003eWang H, Guo Y, Dong Z, Li T, Xie X, Wan D, et al. Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome. Scientific reports. 2020;10 1:18622; doi: 10.1038/s41598-020-74744-z.\u003c/li\u003e\n\u003cli\u003eMakishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood. 2012;119 14:3203-10; doi: 10.1182/blood-2011-12-399774.\u003c/li\u003e\n\u003cli\u003eLi B, Liu J, Jia Y, Wang J, Xu Z, Qin T, et al. Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes. Genes, chromosomes \u0026amp; cancer. 2018;57 2:80-8; doi: 10.1002/gcc.22510.\u003c/li\u003e\n\u003cli\u003eSmith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004;351 23:2403-7; doi: 10.1056/NEJMoa041331.\u003c/li\u003e\n\u003cli\u003eGao J, Gong S, Chen YH. Myeloid Neoplasm With Germline Predisposition: A 2016 Update for Pathologists. Archives of pathology \u0026amp; laboratory medicine. 2019;143 1:13-22; doi: 10.5858/arpa.2017-0194-RA.\u003c/li\u003e\n\u003cli\u003eFroimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D. Gene. 2017;627:337-42; doi: 10.1016/j.gene.2017.06.056.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eWhole exon detection of MDS related gene mutation in bone marrow puncture\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"574\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.43804537521815%\" valign=\"top\"\u003e\n \u003cp\u003eGene\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.33682373472949%\" valign=\"top\"\u003e\n \u003cp\u003eMutant named \u0026nbsp;exons\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.225130890052355%\" valign=\"top\"\u003e\n \u003cp\u003eMutation frequency (sequencing depth)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.43804537521815%\" valign=\"top\"\u003e\n \u003cp\u003eU2AF1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.33682373472949%\" valign=\"top\"\u003e\n \u003cp\u003eNM_006758:\u0026nbsp;c.101C\u0026gt;T(p.S34F) exon2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.225130890052355%\" valign=\"top\"\u003e\n \u003cp\u003e41.6%(2348X)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.43804537521815%\" valign=\"top\"\u003e\n \u003cp\u003eCEBPA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.33682373472949%\" valign=\"top\"\u003e\n \u003cp\u003eNM_004364:\u0026nbsp;c.283G\u0026gt;A(p.V95M) exon1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.225130890052355%\" valign=\"top\"\u003e\n \u003cp\u003e50%(4087X)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.43804537521815%\" valign=\"top\"\u003e\n \u003cp\u003eKMT2D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.33682373472949%\" valign=\"top\"\u003e\n \u003cp\u003eNM_003482:\u0026nbsp;c.468T\u0026gt;G(p.V1561G) exon17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.225130890052355%\" valign=\"top\"\u003e\n \u003cp\u003e50.2%(3626X)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eNo variation was detected in the following genes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eANKRD11,ASXL1,BCOR,CALR,CBL,CSF3R,CUX1,DDX41,DHX9,DICER,DNMT3A,ETNK1,ETV6,EZH2,FLT3,GATA2,IDH1,IDH2,IKZF1,ITIH3,JAK2,KIF20B,KIT,\u003cbr/\u003eKRAS,MPL,NF1,NPM1,NRAS,PDGFRA,PDGFRB,PHF6,PTPN11,PTPRD,ROBO1,ROBO2,RUNX1,SETBP1,SF3B1,SRSF2,STAG2,STAT3,TET2,TP53,UPF3A,UTX,WT1,ZRSR2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cerebral venous thrombosis, Myelodysplastic syndromes, Intracerebral hemorrhage, Anticoagulation, Magnetic resonance venography","lastPublishedDoi":"10.21203/rs.3.rs-4417154/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4417154/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCerebral venous thrombosis (CVT) is an important cause of stroke in young adults caused by complete or partial occlusion of the cerebral major venous sinuses or smaller feeding cortical veins. Myelodysplastic syndrome (MDS) represents a heterogeneous group of myeloid neoplasms that are characterized by ineffective hematopoiesis, variable cytopenias, and a risk of progression to acute myeloid leukemia. However, CVT is rarely reported in patients with MDS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 45-year-old woman with recurrent chronic headache for three months. Later, the headache symptoms gradually worsened, accompanied by disturbance of consciousness and cerebral hemorrhage. Multiple thromboses of the intracranial venous sinus were confirmed by cranial magnetic resonance venography (MRV). After treatment with heparin anticoagulation and mannitol dehydration, the symptoms gradually improved, and the hematoma was absorbed before discharge. Bone marrow biopsy revealed morbid hematopoiesis in the erythroid system and 10% of the circular iron granulocyte erythrocytes. Whole-exon detection revealed U2AF1 c.101C\u0026gt;T, CEBPA c.283G\u0026gt;A, and KMT2D c.468T\u0026gt;G gene mutations, which confirmed the diagnosis of MDS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eMDS complicated with venous sinus thrombosis is rare. A highindex of suspicion is needed for a correct diagnosis of CVT presenting with ICH or chronic headache in female patients.\u003c/p\u003e","manuscriptTitle":"Cerebral venous thrombosis with myelodysplastic syndrome: a rare case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-30 18:53:29","doi":"10.21203/rs.3.rs-4417154/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3badc22a-41ad-4997-b4e5-d30e15801d9a","owner":[],"postedDate":"May 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-03T13:38:41+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-30 18:53:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4417154","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4417154","identity":"rs-4417154","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}