====== Polycythemia vera ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1nESb63TAKHyQUGe2gbxY8U0dyxgFVWxa0K509rIB5DyZbXsFB/?limit=15&utm_campaign=pubmed-2&fc=20230426054117}} ---- [[Myeloproliferative neoplasm]]s (MPN) are a group of clonal haematological malignancies first described by Dameshek in 1957. [[Philadelphia-negative myeloproliferative neoplasm]] are [[polycythemia vera]] (PV), essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF). ---- Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by somatic mutations in [[JAK2]], leading to increased [[red blood cell]] (RBC) production uncoupled from mechanisms that regulate physiological [[erythropoiesis]]. [[Polycythemia]] vera (PV) is a clonal proliferative disorder of the [[bone marrow]] characterized by autonomous [[hematopoiesis]], which results in a panmyelosis in the peripheral blood. It is typically characterized by an acquired [[mutation]] in [[JAK2 V617F]]. Progression to [[myelofibrosis]] (MF), characterized by worsening cytopenias and the development of constitutional symptoms, is seen in up to 10% of cases. [[Extramedullary hematopoiesis]] (EMH) in the [[spleen]] is a common finding in myelofibrotic transformation, but elsewhere in the body, it is extremely unusual. Randhawa et al. reported the case of a 69-year-old male whose PV progressed to secondary MF and who presented with compression of the [[thoracic spinal cord]] directly as a result of EMH. Cytogenetic and molecular findings in the bone marrow were in keeping with evolving myeloid disease. He was managed by surgical [[laminectomy]] with an excellent outcome. Extramedullary hematopoiesis may be seen in both PV and on transformation to MF. This very rare complication should be borne in mind when managing patients with [[myeloproliferative disorder]]s. ((Randhawa MS, Harrison L, Walkden J, Watson H. Spinal cord compression secondary to extramedullary haematopoiesis in transformed polycythaemia rubra vera. J R Coll Physicians Edinb. 2022 Mar;52(1):24-26. doi: 10.1177/14782715221088912. PMID: 36146966.)). ---- Sporadic reports of hemorrhage within the central nervous system in the setting of PV exist and are attributed to microvascular thrombotic events with hemorrhagic conversion. Though rare, spontaneous central nervous system hemorrhage in the absence of vascular malformation or an inciting event such as trauma can occur in the setting of myeloproliferative disorders like [[Polycythemia Vera]] ((Entezami P, Raval MP, Sanders LN, Adepoju A, Yamamoto J. Spontaneous Subdural Hematoma in Patient with Polycythemia Vera. World Neurosurg. 2019 May;125:354-356. doi: 10.1016/j.wneu.2019.01.258. Epub 2019 Feb 16. PMID: 30780039.)) ((Rana I, Tripathy LN, Basu S. Polycythemia Vera Presenting as Subdural Hematoma. Neurol India. 2022 Jul-Aug;70(4):1717-1719. doi: 10.4103/0028-3886.355135. PMID: 36076704.)) ---- Gautham et al. reported the anesthetic management of a patient with PV who underwent neurosurgical intervention for vestibular schwannoma excision ((Gautham NS, Arulvelan A, Manikandan S. Anesthetic management of a patient with polycythemia vera for neurosurgery. J Anesth. 2016 Oct;30(5):907-10. doi: 10.1007/s00540-016-2206-1. Epub 2016 Jun 22. PMID: 27334391.)). ---- Diffuse large B-cell lymphoma (DLBCL) represent the most frequently non-Hodgkin's lymphoma (NHL) (over 30%), especially in developing countries. Many associations of NHL with another neoplasia were described following chemotherapy or radiotherapy regimens. The coexistence of DLBCL with [[myeloproliferative neoplasms]] (MPNs) JAK2V617F positive at the onset was very rare reported in the literature. We describe a clinical case of a 52-year-old man who presented both diagnoses at the onset - DLBCL and MPN - polycythemia vera (PV) type. The patient was treated with two CHOP cycles (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone) followed by six R-CHOP (Rituximab-CHOP) cycles, together with a platelet-reducing agent, achieving remission for 20 months, followed by a relapse which is under treatment. The clonally expansion of an abnormal pluripotent hematopoetic stem cell could be responsible for both, PV and DLBCL. However, recent reports suggested the possible involvement of two different clones. The clinical significance and the role of JAK2 mutation in the evolution of patients with NHLs, including DLBCL are still unknown. Further genetic and clinical studies have to point out common gene mutations for the two diseases and their connection with the diseases behavior under the treatment ((Popov VM, Dobrea CM, Popescu M, Pleşea IE, Grigorean VT, Sinescu RD, Strâmbu VD. Diffuse large B-cell lymphoma and polycythemia vera discovered at the onset - a rare association and its possible importance in lymphoma prognosis. Rom J Morphol Embryol. 2016;57(1):313-8. PMID: 27151728.)). ---- 6: Choi KS, Kim JM, Ryu JI, Oh YH. Concurrent Ruptured Pseudoaneurysm of the Internal Carotid Artery and Cerebral Infarction as an Initial Manifestation of Polycythemia Vera. J Korean Neurosurg Soc. 2015 Aug;58(2):137-40. doi: 10.3340/jkns.2015.58.2.137. Epub 2015 Aug 28. PMID: 26361530; PMCID: PMC4564746. 7: Sami MT, Bohnstedt BN, Hattab EM, Markham R, Cohen-Gadol AA. Cerebral arteriovenous malformation presenting with polycythemia vera: A case report and literature review. Int J Surg Case Rep. 2013;4(10):813-7. doi: 10.1016/j.ijscr.2013.06.019. Epub 2013 Jul 20. PMID: 23959406; PMCID: PMC3785924. 8: Akins PT, Axelrod YK, Ji C, Ciporen JN, Arshad ST, Hawk MW, Guppy KH. Cerebral venous sinus thrombosis complicated by subdural hematomas: Case series and literature review. Surg Neurol Int. 2013 Jun 19;4:85. doi: 10.4103/2152-7806.113651. PMID: 23869285; PMCID: PMC3709281. 9: Mattei TA, Higgins M, Joseph F, Mendel E. Ectopic extramedullary hematopoiesis: evaluation and treatment of a rare and benign paraspinal/epidural tumor. J Neurosurg Spine. 2013 Mar;18(3):236-42. doi: 10.3171/2012.12.SPINE12720. Epub 2013 Jan 18. PMID: 23330877. 10: Kremer M, Horn T, Koch I, Dechow T, Gattenloehner S, Pfeiffer W, Quintanilla-Martínez L, Fend F. Quantitation of the JAK2V617F mutation in microdissected bone marrow trephines: equal mutational load in myeloid lineages and rare involvement of lymphoid cells. Am J Surg Pathol. 2008 Jun;32(6):928-35. doi: 10.1097/pas.0b013e31815d6305. PMID: 18551750. 11: Baehring JM. Cord compression caused by extramedullary hematopoiesis within the epidural space. J Neurooncol. 2008 Jan;86(2):173-4. doi: 10.1007/s11060-007-9453-9. Epub 2007 Jul 17. PMID: 17634741. 12: Rutherfoord GS, Lamprecht D, Hewlett RH. October 2001: 40-year-old Xhosa male with back pain and leg weakness. Brain Pathol. 2002 Apr;12(2):263-4, 269. doi: 10.1111/j.1750-3639.2002.tb01092.x. PMID: 11958381; PMCID: PMC8096019. 13: Ohta Y, Shichinohe H, Nagashima K. Spinal cord compression due to extramedullary hematopoiesis associated with polycythemia vera--case report. Neurol Med Chir (Tokyo). 2002 Jan;42(1):40-3. doi: 10.2176/nmc.42.40. PMID: 11902077. 14: Navone R, Azzoni L, Valente G. Immunohistochemical assessment of ferritin in bone marrow trephine biopsies: correlation with marrow hemosiderin. Acta Haematol. 1988;80(4):194-8. doi: 10.1159/000205636. PMID: 2464264. 15: Brown JA, Gomez-Leon G. Subdural hemorrhage secondary to extramedullary hematopoiesis in postpolycythemic myeloid metaplasia. Neurosurgery. 1984 May;14(5):588-91. doi: 10.1227/00006123-198405000-00013. PMID: 6728168. 16: Gillespie G. Peripheral gangrene as the presentation of myeloproliferative disorders. Br J Surg. 1973 May;60(5):377-80. doi: 10.1002/bjs.1800600516. PMID: 4706484. 17: Meier-Ewert K, Reischle W, Glötzner F. Subthalamotomier verhindert das Auftreten von urämischen "flaping tremor" [Subthalamotomy inhibiting the appearance of uremic "flapping tremor"]. Nervenarzt. 1970 Mar;41(3):148-50. German. PMID: 4915109. 18: Mirand EA. Extra-renal and renal control of erythropoietin production. Ann N Y Acad Sci. 1968 Mar 29;149(1):94-106. doi: 10.1111/j.1749-6632.1968.tb15141.x. PMID: 4297617. 19: BRUNNER HE, REGLI F, KRAYENBUEHL H. SEKUNDAERE ERYTHROZYTHAEMIE BEI EINEM ANGIORETIKULOM DES KLEINHIRNS. UNTERSUCHUNG DER FERRO- UND ERYTHROZYTENKINETIK MIT RADIOAKTIVEM EISEN (59FE) UND CHROM (51CR) [SECONDARY ERYTHROCYTHEMIA ASSOCIATED WITH CEREBELLAR ANGIORETICULOMA. EXAMINATION OF IRON AND ERYTHROCYTE KINETICS WITH RADIOACTIVE IRON (FE59) AND CHROMIUM (CR51)]. Dtsch Med Wochenschr. 1965 Apr 9;90:633-6. German. doi: 10.1055/s-0028-1111391. PMID: 14259369. 20: REIXACH GRANES R, BECKER PF. S'INDROMO DE OBLITERAC AO DOS TRONCOS SUPRA-A'ORTICOS. (APRESENTAC AO DE UM CASO DE MOL'ESTIA DE TAKAYASHU, ASSOCIADO COM POLICITEMIA "VERA") [SYNDROME OF OBLITERATION OF THE SUPRA-AORTIC TRUNKS. (PRESENTATION OF A CASE OF TAKAYASHU'S DISEASE ASSOCIATED WITH POLYCYTHEMIA "VERA")]. Hospital (Rio J). 1964 Nov;66:977-1005. Portuguese. PMID: 14229930. 21: WASSERMAN LR, GILBERT HS. SURGERY IN POLYCYTHEMIA VERA. N Engl J Med. 1963 Dec 5;269:1226-30. doi: 10.1056/NEJM196312052692302. PMID: 14060567. 22: STEEL GC. Intermittent claudication in a case of polycythemia vera treated by sympathetic nerve block. Postgrad Med J. 1954 Apr;30(342):196-8. doi: 10.1136/pgmj.30.342.196. PMID: 13155263; PMCID: PMC2500803. 23: MEREDITH JM, KELL J Jr. Reduction in hemoglobin concentration and in red blood cell count following thoracolumbar sympathectomy for hypertension, with suggestions for the possible use of this operation in polycythemia vera. Am Surg. 1952 Mar;18(3):307-312. PMID: 14903545. ===== Epidemiology ===== It is estimated to affect more than 100,000 people in the USA ((Mehta J, Wang H, Iqbal SU, Mesa R. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma. 2014 Mar;55(3):595-600. doi: 10.3109/10428194.2013.813500. Epub 2013 Jul 29. PMID: 23768070.)). ===== Clinical features ===== Patients with PV have burdensome signs and symptoms including [[pruritus]], [[fatigue]], night sweats, [[concentration problem]]s, and [[splenomegaly]] ===== Diagnosis ===== Radiographic manifestations are varied and non-specific and can affect a number of systems, including: [[splenomegaly]] organ infarcts e.g. splenic infarcts features of extramedullary [[hematopoiesis]] Increased radiographic attenuation of cerebral arteries, veins and dural sinuses (may mimic cerebral vein thrombosis). ===== Phenotypic Characterization ===== A total of 111 patients with MPN suffering from polycythemia vera, essential thrombocythemia, or primary myelofibrosis (PMF) were examined. In almost all patients tested, CD34+ /CD38- stem cells expressed CD33, CD44, CD47, CD52, CD97, CD99, CD105, CD117, CD123, CD133, CD184, CD243, and CD274 (PD-L1). In patients with PMF, MPN stem cells often expressed CD25 and sometimes also CD26 in an aberrant manner. MPN stem cells did not exhibit substantial amounts of CD90, CD273 (PD-L2), CD279 (PD-1), CD366 (TIM-3), CD371 (CLL-1), or IL-1RAP. The phenotype of CD34+ /CD38- stem cells did not change profoundly during the progression from MPN to sAML. The disease-initiating capacity of putative MPN stem cells was confirmed in NSGS mice. Whereas CD34+ /CD38- MPN cells were engrafted in NSGS mice, no substantial engraftment was produced by CD34+ /CD38+ or CD34- cells. The [[JAK2]]-targeting drug [[fedratinib]] and the BRD4 degrader [[dBET6]] induced [[apoptosis]] and suppressed proliferation in Myeloproliferative Neoplasm stem cells. Together, MPN stem cells display a unique [[phenotype]], including [[cytokine receptor]]s, immune checkpoint molecules, and another clinically relevant target [[antigen]]s. Phenotypic characterization of neoplastic stem cells in MPN and sAML should facilitate their enrichment and the development of better, stem cell-eradicating (curative), therapies ((Ivanov D, Milosevic Feenstra JD, Sadovnik I, Herrmann H, Peter B, Willmann M, Greiner G, Slavnitsch K, Hadzijusufovic E, Rülicke T, Dahlhoff M, Hoermann G, Machherndl-Spandl S, Eisenwort G, Fillitz M, Sliwa T, Krauth MT, Bettelheim P, Sperr WR, Koller E, Pfeilstöcker M, Gisslinger H, Keil F, Kralovics R, Valent P. Phenotypic Characterization of Disease-Initiating Stem Cells in JAK2- or CALR-mutated Myeloproliferative Neoplasms. Am J Hematol. 2023 Feb 22. doi: 10.1002/ajh.26889. Epub ahead of print. PMID: 36814396.)). ===== Treatment ===== [[Polycythemia vera treatment]]. ===== Outcome ===== [[Patient-reported outcomes]] Patients with PV presenting with neurological diseases that require surgical intervention are at an increased risk due to various factors, such as immobility, prolonged surgical time, hypothermia and dehydration. Gautham et al., report anesthetic management of a patient with PV who underwent neurosurgical intervention for vestibular schwannoma excision ((Gautham NS, Arulvelan A, Manikandan S. Anesthetic management of a patient with polycythemia vera for neurosurgery. J Anesth. 2016 Oct;30(5):907-10. doi: 10.1007/s00540-016-2206-1. Epub 2016 Jun 22. PubMed PMID: 27334391. )). ===== Complications ===== Increased risks of [[thrombosis]], [[mortality]], and disease transformation to [[myelofibrosis]] or [[acute myeloid leukemia]] [[Thromboembolism]] is the most common complication of PV, which has significant effects on the [[quality of life]] and survival of patients. To standardize the diagnosis, treatment, and prevention strategies of thromboembolism associated with PV, the Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) Association affiliated to Chinese Medicine Education Association has reached the following consensus based on available proofs from evidence-based medicine after repeated considerations. The consensus covers risk stratification, diagnosis and treatment of PV, multidisciplinary management of PV thromboembolism, and patient follow-up, thereby providing the reference for the standardized diagnosis, treatment, and management of thromboembolism for Chinese PV patients ((Myelodysplastic Syndrome/Myeloproliferative Neoplasms Association Affiliated to Chinese Medicine Education Association. [Chinese expert consensus on the comprehensive management of thromboembolism in polycythemia vera]. Zhonghua Yi Xue Za Zhi. 2023 Feb 7;103(5):319-328. Chinese. doi: 10.3760/cma.j.cn112137-20220708-01508. PMID: 36740389.)). ===== Case series ===== The aim of this study was to determine the frequency and characteristics of [[peripheral neuropathy]] associated with polycythemia vera. A prospective clinical and electrophysiological study was performed on 28 patients with polycythemia vera. Other causes of neuropathy were excluded. Eleven patients experienced paresthesia, which was usually mild. In 13 (46%) patients, clinical examination revealed features suggesting polyneuropathy. Nerve conduction indexes were abnormal in 20 (71%) patients, suggesting the presence of predominantly sensory axonal polyneuropathy. In the somatosensory evoked potentials a delay of the P40 wave was seen in 17 patients, while 11 exhibited a delay of the N20 wave. Three of these patients also showed bilateral increases in the I-III, I-V, and III-V intervals of brainstem evoked potentials. In most cases, the delay was moderate and symmetrical. No differences in sex, age, duration of disease, hematocrit values, or platelet counts were found between patients with or without clinical or electrophysiological polyneuropathy. A high percentage of patients with polycythemia vera present clinical or electrophysiological signs of predominantly sensory axonal polyneuropathy which is probably secondary to ischemia, due to increased blood viscosity and platelet dysfunction ((Poza JJ, Cobo AM, Martí-Massó JF. Peripheral neuropathy associated with polycythemia vera. Neurologia. 1996 Oct;11(8):276-9. PMID: 8950863.)) ===== Case reports ===== A 74-year-old Japanese woman was referred for [[leukocytosis]] that occurred for the past one year. Oral [[iron]] supplementation was started as iron deficiency anemia (IDA), but three months later, physical examination revealed flushing of the skin on her hands. Finally polycythemia vera (PV) with IDA was diagnosed. There have been reports of PV combined with IDA, which can mask diagnosis and delay treatment because of the lack of symptoms and the anemic presentation. Several possibilities for the pathogenesis of IDA associated with PV have been proposed, including the presence of [[Helicobacter pylori]] ((Hotta K, Shikino K, Niwa R. Masked polycythemia vera due to iron deficiency anemia. Clin Case Rep. 2023 Mar 30;11(4):e7157. doi: 10.1002/ccr3.7157. PMID: 37006850; PMCID: PMC10062308.)) ---- A 70-year-old male with a known case of beta-thalassemia trait and was on yearly follow-up was found to have a [[hemoglobin]] of 14.8 g/dL, [[hematocrit]] of 47.7%, and RBC count of 6.0 × 1012/L. Total [[leukocyte]] count (TLC) was 5 × 109/L and [[platelet]] count was 4 × 109/L. Secondary causes of polycythemia were ruled out (e.g., renal or cardiac disease and smoking). He did not have symptoms of hyperviscosity syndrome. The abdominal ultrasound showed no abnormalities. On further investigation, a JAK-2 (Exon 14) mutation was detected in this patient confirming the diagnosis of polycythemia vera (PV) ((Khan AA, Rathod SG, Geelani SA, Roshan R, Bhatt JR. Polycythemia vera in patients of beta-thalassemia trait and stress erythropoiesis. J Family Med Prim Care. 2023 Feb;12(2):403-405. doi: 10.4103/jfmpc.jfmpc_1473_22. Epub 2023 Feb 28. PMID: 37091000; PMCID: PMC10114569.)). ---- A case of a fertile-age woman with menometrorrhagia, whose blood loss and consequent iron depletion worked as a limiting factor for Hb and Htc increase, delaying the proper diagnosis. Splenomegaly, iron deficiency markers, and low erythropoietin supported PV investigation. The correction of iron depletion led to the unveiling of covert erythrocytosis. Concomitant hemoglobinopathies and secondary causes for erythrocytosis were excluded. The diagnosis was confirmed with polymerase chain reaction (PCR) for V617F-JAK2 mutation and bone marrow biopsy. As this case highlights, despite not meeting diagnostic criteria at presentation, masked PV exhibited clinical, laboratory, and imaging features of active symptomatic disease. For that, a higher level of suspicion must be held for fertile-age women who present with normal Hb and Htc levels and significant iron depletion, in the presence of low serum erythropoietin or splenomegaly ((Almeida LR, Faustino D, Gameiro R, Salvado V, Dias L. Masked Polycythemia Vera and Iron Deficiency in a Fertile-Age Woman. Cureus. 2023 Jan 9;15(1):e33545. doi: 10.7759/cureus.33545. PMID: 36779103; PMCID: PMC9907734.)). ==== 2022 ==== A 46-year-old man who had an isolated cerebellar infarct with high hematocrit and hemoglobin levels and low serum erythropoietin levels is described. Further investigations eventually led to the unmasking of a JAK2 mutation-negative polycythemia vera ((Krishnan P. Isolated cerebellar infarction in a case of JAK 2 mutation-negative polycythemia vera: A case report. Brain Circ. 2022 Dec 6;8(4):225-227. doi: 10.4103/bc.bc_37_22. PMID: 37181843; PMCID: PMC10167854.)). ==== 2019 ==== Spontaneous hemorrhage/bleeding in PV patients is seldom reported in Neurosurgical literature. Entezami et al., report the case of a 76 year-old male with PV who developed a [[spontaneous subdural hematoma]] requiring surgical evacuation. He improved significantly after the resolution of brain compression and mass effect caused by the hematoma. Sporadic reports of hemorrhage within the central nervous system (CNS) in the setting of PV exist, and are attributed to microvascular thrombotic events with hemorrhagic conversion. Though rare, spontaneous CNS hemorrhage in the absence of vascular malformation or an inciting event such as trauma can occur in the setting of myeloproliferative disorders such as PV ((Entezami P, Sanders LN, Raval MP, Adepoju A, Yamamoto J. Spontaneous Subdural Hematoma in a Patient with Polycythemia Vera. World Neurosurg. 2019 Feb 16. pii: S1878-8750(19)30377-8. doi: 10.1016/j.wneu.2019.01.258. [Epub ahead of print] PubMed PMID: 30780039. )). ---- A clinical case of a 52-year-old man who presented both diagnoses at the onset - DLBCL and MPN - polycythemia vera (PV) type. The patient was treated with two CHOP cycles (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone) followed by six R-CHOP ([[Rituximab]]-CHOP) cycles, together with a platelet-reducing agent, achieving remission for 20 months, followed by a relapse which is under treatment. The clonally expansion of an abnormal pluripotent hematopoetic stem cell could be responsible for both, PV and DLBCL. However, recent reports suggested the possible involvement of two different clones. The clinical significance and the role of JAK2 mutation in the evolution of patients with NHLs, including DLBCL are still unknown. Further genetic and clinical studies have to point out common gene mutations for the two diseases and their connection with the diseases behavior under the treatment. The coexistence of NHLs and especially DLBCLs and MPNs JAK2 positive is very rare. Although DLBCL alone has good prognosis, other prognostic factors should be checked when it is associated with PV. The presence of JAK2V617F seems to be a candidate but whose role in DLBCL evolution, natural or under treatment has to be cleared up ((Popov VM, Dobrea CM, Popescu M, Pleşea IE, Grigorean VT, Sinescu RD, Strâmbu VD. Diffuse large B-cell lymphoma and polycythemia vera discovered at the onset - a rare association and its possible importance in lymphoma prognosis. Rom J Morphol Embryol. 2016;57(1):313-8. PubMed PMID: 27151728. )). ---- The most common neurologic manifestations of polycythemia vera (PV) are cerebral infarction and transient ischemic attacks, while cerebral hemorrhage or intracranial dissection has been rarely associated with PV. Here we report the first case of a 59-year-old patient with intracranial supraclinoid internal carotid artery (ICA) dissection causing cerebral infarction and concomitant subarachnoid hemorrhage due to pseudoaneurysm rupture as clinical onset of PV. This case report discusses the possible mechanism and treatment of this extremely rare condition ((Choi KS, Kim JM, Ryu JI, Oh YH. Concurrent Ruptured Pseudoaneurysm of the Internal Carotid Artery and Cerebral Infarction as an Initial Manifestation of Polycythemia Vera. J Korean Neurosurg Soc. 2015 Aug;58(2):137-40. doi: 10.3340/jkns.2015.58.2.137. Epub 2015 Aug 28. PMID: 26361530; PMCID: PMC4564746.)). ---- A 68-year-old woman presented with an acute SDH requiring craniotomy and a thrombosed cortical vein was noted intraoperatively. Computed tomography venography showed thrombosis of the superior sagittal sinus. She had polycythemia vera with the V617 Jak2 gene mutation and was managed with aspirin and hydroxyurea ((Akins PT, Axelrod YK, Ji C, Ciporen JN, Arshad ST, Hawk MW, Guppy KH. Cerebral venous sinus thrombosis complicated by subdural hematomas: Case series and literature review. Surg Neurol Int. 2013 Jun 19;4:85. doi: 10.4103/2152-7806.113651. PMID: 23869285; PMCID: PMC3709281.)).