1.Cerebral Venous Thrombosis in a Mexican Multicenter Registry of Acute Cerebrovascular Disease: The RENAMEVASC Study Jos L. Ruiz-Sandoval, MD,* Erwin Chiquete, MD, PhD,* e ~ L. Jacqueline Banuelos-Becerra, MD, Carolina Torres-Anguiano, MD, Christian Gonzlez-Padilla, MD, Antonio Arauz, MD,x aCarolina Leon-Jimnez, MD,k Luis M. Murillo-Bonilla, MD, MSc,** e Jorge Villarreal-Careaga, MD, Fernando Barinagarrementer MD, a, Carlos Cant -Brito, MD, PhD xx and the RENAMEVASC investigatorskk uBackground: Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that is usually not mentioned in multicenter registries on all-type acute stroke. We aimed to describe the experience on hospitalized patients with CVT in a Mexican multicenter registry on acute cerebrovascular disease. Methods: CVT patients were selected from the RENAMEVASC registry, which was conducted between 2002 and 2004 in 25 Mexican hospitals. Risk factors, neuroimaging, and 30-day outcome as assessed by the modied Rankin scale (mRS) were analyzed. Results: Among 2000 all-type acute stroke patients, 59 (3%; 95% CI, 2.3-3.8%) had CVT (50 women; female:male ratio, 5:1; median age, 31 years). Puerperium (42%), contraceptive use (18%), and pregnancy (12%) were the main risk factors in women. In 67% of men, CVT was registered as idiopathic, but thrombophilia assessment was suboptimal. Longitudinal superior sinus was the most frequent thrombosis location (78%). Extensive (.5 cm) venous infarction occurred in 36% of patients. Only 81% of patients received anticoagulation since the acute phase, and 3% needed decompressive craniectomy. Mechanical ventilation (13.6%), pneumonia (10.2%) and systemic thromboembolism (8.5%) were the main in-hospital complications. The 30-day case fatality rate was 3% (2 patients; 95% CI, 0.23-12.2%). In a Cox proportional hazards model, only age ,40 years was associated with a mRS score of 0 to 2 (functional independence; rate ratio, 3.46; 95% CI, 1.34-8.92). Conclusions: The relative frequency of CVT and the associated in-hospital complications were higher than in other registries. Thrombophilia assessment and acute treatment was suboptimal. Young age is the main determinant of a good short-term outcome. Key Words: Cerebral veins cerebral venous thrombosiscerebrovascular diseasecranial sinusesoutcome stroke. 2012 by National Stroke AssociationFrom the *Department of Neurology, Hospital Civil de Guadalajara Fray Antonio Alcalde,, Department of Neurosciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Department of Internal Medicine, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico, xStroke Clinic, Instituto Nacional de Neurolog y Neurociruga, Mexico City, Mexico, a kDepartment of Neurology, Hospital Valentn Gmez Far Zapo o as, pan, Mexico, **Endovascular Therapy, Instituto Panvascular de Occidente and Universidad Autnoma de Guadalajara, Guadalajara, o Mexico, Department of Neurology, Hospital General de Culiacn, aCuliacn, Hospital Angeles Quertaro, Quertaro, xxInstituto Naa e e cional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico e o aCity, Mexico; and kkRENAMEVASC investigators are listed in the Appendix. Received May 2, 2010; revision received December 23, 2010; accepted January 13, 2011. Address correspondence to Jos L. Ruiz-Sandoval, MD, Servicio de e Neurologa y Neurocirug Hospital Civil Fray Antonio Alcalde, a, Hospital 278, 44280 Guadalajara, Jalisco, Mexico. E-mail: jorulej-1nj@prodigy.net.mx. 1052-3057/$ - see front matter 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.01.001Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 5 (July), 2012: pp 395-400395

2. J.L. RUIZ-SANDOV AL ET AL.396Cerebral venous thrombosis (CVT) is the least common form of acute cerebrovascular disease,1 accounting for about 0.5% among all types of strokes.2 Depending on the population and methodology, the estimated annual incidence ranges from 1 to 12 cases per million adults per year,3-6 and about 7 cases per million children (especially neonates) per year.7 Although generally considered a condition with a very good outcome in developed countries, the case fatality rate during the hospitalization period may surpass 15% in low-income nations, especially associated with a delay in diagnosis and with low anticoagulation practice.6,8-10 In Mexico, information regarding CVT has mainly derived from single-center reports, with a relative frequency among all forms of acute cerebrovascular disease ranging from 0.43% to 8%.11-13 There is a paucity of international epidemiologic data on incidence, prevalence, or relative frequency among hospitalized stroke patients, and hospital registers on all-type acute stroke cases rarely refer specically to CVT.14,15 The National Mexican Registry of Cerebral Vascular Disease (RENAMEVASC) was a multicenter stroke surveillance system that included 2000 consecutive patients with all types of acute cerebrovascular disease,16,17 of whom 59 were identied with CVT. The aim of this report on CVT is to describe the risk factors, neuroimaging features, acute management, in-hospital complications, and the 30-day outcomes of CVT patients hospitalized in Mexico.Methods Patients This prospective, hospital-based multicenter registry was conducted between November 2002 and October 2004 in 25 referral centers from 14 states of Mexico. All investigators were neurologists trained in cerebrovascular disease. The complete methodology of the RENAMEVASC study has been reported elsewhere.16,17 Briey, consecutive patients were registered if a suspected acute cerebrovascular disease was conrmed and accurately classied by computed tomographic (CT) or magnetic resonance imaging (MRI) scanning in all patients. A standardized case report form was used to collect clinical data from the patient or primary guardian. The patients functional status was classied by the modied Rankin scale (mRS). For the purpose of this report, patients with CVT conrmed by MRI, MRI venography, or four-vessel angiography were included. The coordinating ofce performed the case ascertainments. The internal committee of ethics of every participating center approved the present study. Informed consent was obtained from the patient or the legal proxy.Data Analysis For the main relative frequencies reported, 95% condence intervals (CIs) were calculated using the adjustedWald method. Pearson Chi-square or Fisher exact tests were used to assess proportions in nominal variables for bivariate analyses. To compare quantitative variables between 2 groups, the Student t and MannWhitney U tests were performed in distributions of parametric and nonparametric variables, respectively. A Cox proportional hazards model was constructed to nd independent predictors of 30-day functional independence (mRS, 0-2). Competing variables were chosen with a P set at , .1 in the bivariate selection process. Adjusted rate ratios (RRs) with the respective 95% CIs are provided. A KaplanMeier actuarial analysis was performed to evaluate the association of the independent predictors with a good functional outcome (mRS, 0-2) during the follow-up. P values are 2-sided and considered signicant when P , .05. SPSS for Windows (version 17.0; SPSS, Chicago, IL) was used in all calculations.Results The RENAMEVASC registry included 2000 hospitalized patients with all types of acute cerebrovascular disease. In all, 59 (2.97%; 95% CI, 2.3-3.8%) had CVT. There were 50 (85%) women and 9 (15%) men (female:male ratio, 5:1), with a median age of 31 years (interquartile range, 22-39 years). A total of 45 (76%) patients were younger than 40 years of age. The median time from neurologic symptoms to hospital presentation was 48 hours (interquartile range, 15-96 hrs). Only 1 case of CVT was identied during hospital stay for another cause. Table 1 shows the main risk factors and clinical presentation associated with CVT, stratied by gender and age. Puerperium and oral contraceptives use were the most frequent risk factors (in the female gender separately, 42% and 18%, respectively). Only 1 of 21 (4.7%) women in puerperium had severe concomitant anemia (hemoglobin concentration ,7 g/dl), and only one patient (a 57year-old woman) had this factor as the unique etiology of CVT. As expected, puerperium was more frequent among young women than their older counterparts (51.2% v 0%); however, no differences on contraceptive use were observed when comparing women aged ,40 years of age with older females (17.1% v 22.2%; P 5 .66). CVT was associated with pregnancy in 6 (14.5%) women. Among all patients, a previous major surgery in the last 15 days was more frequently observed in people $40 years of age than in younger patients (P 5.009). No cases associated with malignancy were identied. There were no assessments for hereditary thrombophilia in this cohort. At hospital arrival, 33 (56%) patients were alert, 21 (36%) drowsy, 3 (5%) stuporous, and 2 (3%) in coma. The mean Glasgow coma score at hospital presentation was 13.5 points (range, 3-15 points; median, 14; interquartile range, 13-15 points). Headache and nausea/vomiting were more frequent in women than in men, whereas motor decit was more common in the male gender (Table 1). 3. CEREBRAL VENOUS THROMBOSIS IN MEXICO397Table 1. Analysis of risk factors and clinical presentation of cerebral venous thrombosis Gender, n (%)Age, n (%)All patients (n 5 59)Variables Risk factors,* n (%) Puerperium Oral contraceptives Major surgery in the last 15 days Pregnancy Current smoking Severe anemia Migraine Clinical presentation, n (%) Headache Seizures Nausea/vomiting Altered mental status Focal motor decit Impaired speechMale (n 5 9)Female (n 5 50)Py,40 y (n 5 45)$40 y (n 5 14)Pz21 (35.6) 9 (15.3) 6 (10.2) 6 (10.2) 5 (8.5) 4 (6.9) 2 (3.4)0 0 2 (22.2) 0 1 (11.1) 1 (11.1) 021 (42.0) 9 (18.0) 4 (8.0) 6 (12.0) 4 (8.0) 3 (6.1) 2 (4.0).01 .17 .20 .27 .76 .50 .9921 (46.7) 7 (15.6) 2 (4.4) 6 (13.3) 3 (6.7) 2 (4.5) 2 (4.4)0 2 (14.3) 4 (28.6) 0 2 (14.3) 2 (14.3) 0.001 .90 .009 .15 .37 .21 .9954 (91.5) 12 (20.3) 34 (57.6) 28 (47.5) 10 (16.9) 12 (20.3)6 (66.7) 0 1 (11.1) 4 (44.4) 4 (44.4) 048 (96.0) 12 (24.0) 33 (66.0) 24 (48.0) 6 (12.0) 12 (24.0).02 .18 .003 .99 .04 .1843 (95.6) 10 (22.2) 27 (60.0) 20 (44.4) 7 (15.6) 1 (2.2)11 (78.6) 2 (14.3) 7 (50.0) 8 (57.9) 3 (21.4) 3 (21.4).08 .71 .51 .41 .69 .04*No risk factors were identied in 6 (66.7%) male patients. yP value for differences between men and women; Chi-square or Fisher exact test as appropriate. zP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.Brain imaging studies showed extensive venous infarction (length .5 cm) or edema in 21 (36%) patients and bihemispheric infarction in 13 (22%; Table 2). Longitudinal superior sinus was the most frequent location of CVT (78% of patients), followed by the lateral sinus in 9 (15%) cases. No differences were observed according to gender or age groups with respect to CVT location, extension, or in-hospital complications. Mean in-hospital stay was 16.8 days (range, 3-57 days); being signicantly higher among older patients than in younger individuals (24.1 v 14.6 days, respectively; P 5 .005). Mechanical ventilation and hospital-acquired pneumonia were more frequent in patients $40 years of age than in younger individuals (Table 3). It is noteworthythat systemic thromboembolism occurred during hospital stay in 8% of cases (1 case resulting in death) without differences between genders or age groups. A total of 48 (81%) patients received anticoagulation in the acute stage, with intravenous heparin being the most frequent method (46%) followed by low-molecular-weight heparin (LMWH; 31%) and oral coumarins (5%). Two (3%) patients underwent craniectomy (Table 2). In all, 37 (63%) patients attained functional independence (mRS, 0-2) at hospital discharge, 20 (34%) were dependent, and 2 (3%; 95% CI, 0.23-12.2%) died (Table 4). Of the 2 fatalities registered, 1 was attributed to a neurologic etiology (a women in puerperium with longitudinal sinus thrombosis, severe hemorrhagic venous infarction,Table 2. Radiologic features of patients with cerebral venous thrombosis Gender, n (%)Age, n (%)VariablesAll patients (n 5 59)Male (n 5 9)Female (n 5 50)P*,40 y (n 5 45)$40 y (n 5 14)PyRadiologic features, n (%) Extensive venous infarction (.5 cm) Bihemispheric venous infarction Longitudinal superior Lateral Straight sinus Cortical veins21 (35.6) 13 (22.0) 46 (78.0) 9 (15.3) 2 (3.4) 2 (3.4)3 (33.3) 2 (22.2) 6 (66.7) 3 (33.3) 0 2 (4.0)18 (36.0) 11 (22.0) 40 (80.0) 6 (12.0) 2 (4.0) 0.88 .99 .37 .10 .99 .9916 (35.6) 10 (22.2) 34 (75.6) 8 (17.8) 2 (4.4) 1 (2.2)5 (35.7) 3 (21.4) 12 (85.7) 1 (7.1) 0 1 (7.1).99 .95 .42 .33 .99 .42*P value for differences between men and women; Chi-square or Fisher exact test as appropriate. yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate. 4. J.L. RUIZ-SANDOV AL ET AL.398Table 3. In-hospital management and complications in patients with cerebral venous thrombosis Gender, n (%)Age, n (%)VariablesAll patients (n 5 59)Male (n 5 9)Female (n 5 50)P*,40 y (n 5 45)$40 y (n 5 14)PyComplications, n (%) Mechanical ventilation Hospital-acquired pneumonia DVT/pulmonary embolism Urinary tract infections Acute management, n (%) Intravenous heparin LMWH at therapeutic dosage LMWH at prophylactic dosage Oral anticoagulant therapy Antiplatelets Steroids Craniectomy8 (13.6) 6 (10.2) 5 (8.5) 2 (3.4) 57 (96.6) 27 (45.8) 11 (18.6) 7 (11.9) 3 (5.1) 7 (11.9) 1 (1.7) 2 (3.4)2 (22.2) 2 (22.2) 1 (11.1) 0 8 (88.9) 3 (33.3) 2 (22.2) 1 (11.1) 0 2 (22.2) 0 06 (12.0) 4 (8.0) 4 (8.0) 2 (4.0) 49 (98.0) 24 (48.0) 9 (18.0) 6 (12.0) 3 (6.0) 5 (10.0) 1 (2.0) 2 (4.0).41 .19 .76 1 .28 .42 .76 .94 .99 .29 .99 .993 (6.7) 1 (2.2) 4 (8.9) 1 (2.2) 45 (100) 24 (53.3) 7 (15.6) 5 (11.1) 2 (4.4) 6 (13.3) 0 1 (2.2)5 (35.7) 5 (35.7) 1 (7.1) 1 (7.1) 12 (85.7) 3 (21.4) 4 (28.6) 2 (14.3) 1 (7.1) 1 (7.1) 1 (7.1) 1 (7.1).006 .001 .84 .42 .05 .04 .27 .74 .56 .99 .24 .42Abbreviations: DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin. *P value for differences between men and women; Chi-square or Fisher exact test as appropriate. yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate.and coma at hospital presentation) and the other as of systemic cause (a women with hypothyroidism who develop massive pulmonary thromboembolism, is spite of anticoagulation with LMWH). At 30 days of follow-up, 43 (73%) patients were independent and 14 (24%) remained functionally dependent for activities of daily living. No further deaths were registered at 30 days (Table 4). In a Cox proportional hazards model adjusted for gender, Glasgow coma scale at admission, in-hospital pneumonia, and systemic thromboembolism, only age , 40 years was independently associated with a good 30-day outcome (RR, 3.46; 95% CI, 1.34-8.92; Fig 1). Time from CVT onset to hospital presentation was not independently associated with a good or adverse outcome.Discussion The RENAMEVASC study is the rst collaborative, nongovernmental, nonindustry sponsored registry on patients hospitalized with all-type acute cerebrovascular disease. In this registry, we observed 3% of cases with CVT among all stroke types. In other countries, the relative frequency ranges from 0.5% to 2%.2,5,9,10 However, in autopsy studies, CVT has been observed in a relative frequency of as much as 10%,19 which suggests that CVT is often clinically overlooked. Here we observed a very high female:male ratio, possibly because of selection bias and to a high proportion of genderspecic risk factors. For comparison, in the ISCVTTable 4. Outcome at hospital discharge and at 30-day follow-up in patients with cerebral venous thrombosis Gender, n (%)Variables mRS at discharge, n (%) 0-2 3-5 6 mRS at 30-day follow-up 0-2 3-5 6Age, n (%)All patients (n 5 59)Male (n 5 9)Female (n 5 50)P*,40 y (n 5 45)$40 y (n 5 14)Py37 (62.7) 20 (33.9) 2 (3.4)3 (33.3) 6 (66.7) 034 (68.0) 14 (28.0) 2 (4.0).05 .02 .9934 (75.6) 10 (22.2) 1 (2.2)3 (21.4) 10 (71.4) 1 (7.1),.001 .001 .4243 (72.9) 14 (23.7) 2 (3.4)6 (66.7) 3 (33.3) 037 (74.0) 11 (22.0) 2 (4.0).65 .46 .9938 (84.4) 6 (13.3) 1 (2.2)5 (35.7) 8 (57.1) 1 (7.1),.001 .001 .42Abbreviation: mRs, modied Rankin score. *P value for differences between men and women; Chi-square or Fisher exact test as appropriate. yP value for differences between persons $40 years of age or younger; Chi-square or Fisher exact test as appropriate. 5. CEREBRAL VENOUS THROMBOSIS IN MEXICOFigure 1. KaplanMeier actuarial analyses on the probability of achieving a modied Rankin scale score of 0 to 2 (functional independence) during the follow-up period, as a function of age , 40 years (n 5 45) or older (n 5 14).registry, roughly 75% of patients were women (a 3:1 female:male ratio).20 In most international studies, the main risk factors for CVT are thrombophilia, oral contraceptive use, infections, pregnancy, puerperium, and malignancy.9,10,18,20-24 In our study, gender-specic risk factors explained the majority of cases. This differs greatly from registries conducted in developed countries,20,23 where a systematic search for thrombophilia and an active seeking of patients from the oncology and hematology wards is performed. CVT is a consequence of multiple factors, and the identication of one of them should not prevent the intentional search for coexisting causes1 that may potentially increase the probability of recurrence.25-27 In the ISCVTregistry, 44% of the patients had .1 risk factor, and congenital or genetic thrombophilia was present in 22% of patients.20 A gender-specic risk factor was present in 65% women.20 A case fatality rate of 3% was observed in our registry, considerably lower than other studies that report rates from about 6% to as high as 27% in elderly patients.8-10,20,28,29 Indeed, this could represent a survival bias of our study; nevertheless, this low case fatality rate occurred at expense of a relatively high frequency of cases with severe disabilities and numerous short-term (mainly in-hospital) complications. In-hospital systemic thromboembolism was observed in 8% of our cases. An early literature review (1942-1990) performed by Diaz et al.30 revealed that 11% of CVT cases were associated with pulmonary embolism, and among these patients, the overall mortality rate was 96%. In a recent report on the ISCVT cohort, 6% of cases had systemic thromboembolism.31 This discrepancy between ours and the ISCVT registry with respect to systemic venous thromboembolism parallels the different frequency of full anticoagulation in the acute phase of management (64% v 83% in the RENAMEVASC and ISCVT registries, respectively).20399This important nding emphasizes the need for anticoagulation at therapeutic doses as soon as CVT is identied.1,32 The main limitation of this report is the small sample size, which prevents an accurate detection of small, but clinically meaningful differences, especially in outcome analyses. Long-term follow-up was not registered, and as a consequence, other important complications, such as neuropsychological impairment and CVT recurrence, could not be analyzed. Nevertheless, this study may provide important information for comparative epidemiology that may potentially improve deliver of care in Mexico. In conclusion, this multicenter registry showed that the relative frequency of CVT in hospitalized cerebrovascular patients in Mexico is higher than expected. Acute case fatality rate is relatively low, but numerous in-hospital short-term complications occurred. Acute management with therapeutic anticoagulation was suboptimal and may potentially account for the high rate of systemic thromboembolism observed in this registry.References 1. Einhupl K, Stam J, Bousser MG, et al. EFNS guideline on a the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol 2010;17:1229-1235. 2. Filippidis A, Kapsalaki E, Patramani G, et al. Cerebral venous sinus thrombosis: Review of the demographics, pathophysiology, current diagnosis, and treatment. Neurosurg Focus 2009;27:E3. 3. Saadatnia M, Mousavi SA, Haghighi S, et al. Cerebral vein and sinus thrombosis in Isfahan-Iran: A changing prole. Can J Neurol Sci 2004;31:474-477. 4. Janghorbani M, Zare M, Saadatnia M, et al. Cerebral vein and dural sinus thrombosis in adults in Isfahan, Iran: Frequency and seasonal variation. Acta Neurol Scand 2008;117:117-121. 5. Siddiqui FM, Kamal AK. Incidence and epidemiology of cerebral venous thrombosis. J Pak Med Assoc 2006; 56:485-487. 6. Ferro JM, Correia M, Pontes C, et al. Cerebral vein and dural sinus thrombosis in Portugal: 1980-1998. Cerebrovasc Dis 2001;11:177-182. 7. deVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001;345: 417-423. 8. Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: A systematic review. Blood 2006;108:1129-1134. 9. Daif A, Awada A, al-Rajeh S, et al. Cerebral venous thrombosis in adults. A study of 40 cases from Saudi Arabia. Stroke 1995;26:1193-1195. 10. Khealani BA, Wasay M, Saadah M, et al. Cerebral venous thrombosis: A descriptive multicenter study of patients in Pakistan and Middle East. Stroke 2008;39:2707-2711. 11. Nieto de-Pascual RH, G izar-Berm dez C, Ort u u z-Trejo JF. Epidemiolog de la enfermedad vascular cerebral en el a Hospital General de Mxico [in Spanish]. Rev Med e Hosp Gen Mex 2003;66:7-12. 12. Rodr guez-Rubio LR, Medina-Crdova LL, Andradeo Ramos MA, et al. Trombosis venosa cerebral en el Hospital Civil de Guadalajara Fray Antonio Alcalde [in Spanish]. Rev Mex Neuroci 2009;10:177-183. 6. 400 13. Ruiz-Sandoval JL, Chiquete E, Navarro-Bonnet J, et al. Isolated vein thrombosis of the posterior fossa presenting as localized cerebellar venous infarctions or hemorrhages. Stroke 2010;41:2358-2361. 14. Lavados PM, Sacks C, Prina L, et al. Incidence, 30-day case-fatality rate, and prognosis of stroke in Iquique, Chile: A 2-year community-based prospective study (PISCIS project). Lancet 2005;365:2206-2215. 15. Cantu-Brito C, Majersik JJ, Snchez BN, et al. Hospitala ized stroke surveillance in the community of Durango, Mexico: The brain attack surveillance in Durango study. Stroke 2010;41:878-884. 16. Ruiz-Sandoval JL, Cant C, Chiquete E, et al. Aneurysu mal subarachnoid hemorrhage in a Mexican multicenter registry of cerebrovascular disease: The RENAMEVASC study. J Stroke Cerebrovasc Dis 2009;18:48-55. 17. Arauz A, Cantu C, Ruiz-Sandoval JL, et al. Short-term prognosis of transient ischemic attacks: Mexican multicenter stroke registry. Rev Invest Clin 2006;58:530-539. 18. Bousser MG, Ferro JM. Cerebral venous thrombosis: An update. Lancet Neurol 2007;6:162-170. 19. Banerjee AK, Varma M, Vasista RK, et al. Cerebrovascular disease in north-west India: A study of necropsy material. J Neurol Neurosurg Psychiatry 1989;52:512-515. 20. Ferro JM, Canh~o P, Stam J, et al. Prognosis of cerebral a vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670. 21. Ferro JM, Canh~o P, Stam J, et al. Delay in the diagnosis of a cerebral vein and dural sinus thrombosis: Inuence on outcome. Stroke 2009;40:3133-3138. 22. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-1798. 23. Wasay M, Bakshi R, Bobustuc G, et al. Cerebral venous thrombosis: Analysis of a multicenter cohort from the United States. J Stroke Cerebrovasc Dis 2008;17:49-54. 24. Cant C, Barinagarrementeria F. Cerebral venous thromu bosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 1993;24:1880-1884. 25. Maqueda VM, Thijs V. Risk of thromboembolism after cerebral venous thrombosis. Eur J Neurol 2006;13:302-305. 26. Jukic I, Titlic M, Tonkic A, et al. Cerebral venous sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy: How long should we treat these patients with warfarin? J Thromb Thrombolysis 2007;24:77-80. 27. Chen CM, Lee-Chen GJ, Wu YR, et al. Recurrent cerebral venous thrombosis: An Arg359X mutation in the antithrombin gene in a Taiwanese family. Thromb Res 2006; 118:235-240. 28. Ferro JM, Canh~o P, Bousser MG, et al. Cerebral vein and a dural sinus thrombosis in elderly patients. Stroke 2005; 36:1927-1932. 29. Koopman K, Uyttenboogaart M, Vroomen PC, et al. Long-term sequelae after cerebral venous thrombosis in functionally independent patients. J Stroke Cerebrovasc Dis 2009;18:198-202. 30. Diaz JM, Schiffman JS, Urban ES, et al. Superior sagittal sinus thrombosis and pulmonary embolism: AJ.L. RUIZ-SANDOV AL ET AL. syndrome rediscovered. Acta Neurol Scand 1992;86: 390-396. 31. Miranda B, Ferro JM, Canh~o P, et al. Venous thromboema bolic events after cerebral vein thrombosis. Stroke 2010; 41:1901-1906. 32. Bousser MG. Cerebral venous thrombosis: Nothing, heparin, or local thrombolysis? Stroke 1999;30:481-483.AppendixThe RENAMEVASC Investigators Steering committee: C. Cant -Brito, A. Arauz-Gngora, J.L. u o Ruiz-Sandoval, J. Villarreal-Careaga, L. Murillo-Bonilla, R. Rangel-Guerra, and F. Barinagarrementeria. Coordinating ofce: C. Cant -Brito and L. Murillo-Bonilla. u Participants: The following centers and investigators participated in the RENAMEVASC study: C. Cant -Brito u (Instituto Nacional de Ciencias Mdicas y Nutricin Salvae o dor Zubirn, Ciudad de Mxico); A. Arauz-Gngora, a e o L. Murillo-Bonilla, and L. Hoyos (Instituto Nacional de Neurolog y Neurocirug Ciudad de Mxico). J.L. a a, e Ruiz-Sandoval and E. Chiquete (Hospital Civil de Guadalajara, Jalisco); J. Villarreal-Careaga and F. Guzmn-Reyes a (Hospital General de Culiacn, Sinaloa); F. Barinagarrea menteria (Hospital Angeles de Quertaro, Quertaro); e e J.A. Fernndez (Hospital Jurez, Ciudad de Mxico); a a e B. Torres (Hospital General de Len, Guanajuato); o C. Len-Jimnez (Hospital General ISSSTE, Zapopan, o e Jalisco); I. Rodr guez-Leyva (Hospital General de San Luis Potos San Luis Potosi): R. Rangel-Guerra (Hospital , Universitario de Nuevo Len, Monterrey, Nuevo Len); o o M. Ba~ os (Hospital General de Balbuena, Ciudad de n Mxico); L. Espinosa and M. de la Maza, Hospital San e Jos de Monterrey, Nuevo Len); H. Colorado (Hospital e o General ISSSTE, Veracruz, Veracruz); M.C. Loy-Gerala (Hospital General de Puebla, Puebla); J. Huebe-Rafool (Hospital General de Pachuca, Hidalgo); G. Aguayo Leytte (Hospital General de Aguascalientes, Aguascalientes); G. Tavera-Guittings (Hospital General ISSSTE, Campeche, Campeche); V. Garcia-Talavera (Hospital IMSS La Raza, Ciudad de Mxico); O. Ibarra and M. Segura (Hospital e General de Morelia, Morelia); J.L. Sosa (Hospital General de Villahermosa, Tabasco); O. Talams-Murra (Hospital a General ISSSTE, Torren, Coahuila); M. Alanis-Quirga o o (Hospital Universitario de Torren, Coahuila); J.M. Escao milla (Hospital de la Marina Nacional, Ciudad de Mxico); e M.A. Alegr (Hospital Central Militar, Ciudad de a Mxico); and J.C. Angulo (Hospital General, Veracruz, e Veracruz).