Ischemic stroke in young women: risk of recurrence during subsequent pregnancies. French Study Group on Stroke in Pregnancy

OBJECTIVE: To assess whether subsequent pregnancies increase the risk of recurrent stroke and whether the occurrence of an ischemic stroke affects reproductive history. METHODS: The authors identified 489 consecutive women aged 15 to 40 years with a first-ever arterial ischemic stroke or cerebral venous thrombosis from the record system of nine French neurologic centers. Information on stroke recurrence and reproductive history was obtained by means of chart review, written questionnaire, and telephone interview. RESULTS: Data were analyzed from 441 women (373 with arterial ischemic stroke and 68 with cerebral venous thrombosis). During a mean follow-up of 5 years, 13 arterial recurrent ischemic strokes occurred. There were no cases of recurrent cerebral venous thrombosis. The overall risk of recurrence was 1% within 1 year and 2.3% within 5 years. The risk of recurrence was significantly higher in patients with stroke of definite cause. Eleven recurrent strokes occurred outside pregnancy (absolute risk of recurrence = 0.5%; 95% CI 0.3, 0.95) and two during pregnancy or the puerperium (absolute risk of recurrence = 1. 8%; 95% CI 0.5, 7.5). The relative risk of recurrence was significantly higher during the postpartum period (risk ratio = 9.7; 95% CI 1.2, 78.9) than during pregnancy (risk ratio = 2.2; 95% CI 0. 3, 17.5) itself. The outcome of the 187 subsequent pregnancies was similar to that expected from the general population. Thirty-four percent of women indicated that they would have desired more pregnancies after their initial stroke. The main reasons for not considering pregnancy were concern of a recurrent stroke, medical advice against pregnancy, and residual handicap. CONCLUSION: Young women with a history of ischemic stroke have a low risk of recurrence during subsequent pregnancies. The postpartum period, not the pregnancy itself, is associated with an increased risk of recurrent stroke. The outcome of pregnancies in these women appears to be similar to that expected in the general population. A previous ischemic stroke is not a contraindication to a subsequent pregnancy.     

Hormonal contraceptives as a risk factor for cerebral venous and sinus thrombosis

This review will focus on recent developments in our understanding of cerebral venous and sinus thrombosis (CVST), as a side effect of combined oral contraceptives (COCs) use. Case-control studies have shown an increased risk of CVST in women who use COCs, especially third-generation contraceptives that contain gestodene or desogestrel. Several studies have indicated that the combination of COCs and thrombophilia greatly increased the risk of CVST, particularly in women with hyperhomocysteinaemia, factor V Leiden and the prothrombin-gene mutation. Women with thrombophilia who developed CVST while taking oral contraceptives should be definitively advised to stop using COCs. These patients should be considered for preventive therapy with low doses of heparin in prothrombotic situations such as bed rest or pregnancy, and the duration of anticoagulation should be considered on a case-by-case basis. Patients may be considered candidates for chronic treatment with antiplatelet agents. The best and most cost-effective screening method for thrombophilia in women who are planning to conceive is selective screening based on the presence of previous personal or family history of either prior extracerebral or cerebral venous thromboembolism events.     

Cerebral venous sinus thrombosis with cerebral hemorrhage during early pregnancy

Cerebral venous sinus thrombosis (CVST) rarely induces cerebral hemorrhage, and CVST with cerebral hemorrhage during early pregnancy is extremely rare. Upon literature review, we are able to find only one case of CVST with cerebral hemorrhage in early pregnancy. In this paper, we report another case of a 27-year-old patient who developed CVST with cerebral hemorrhage in her fifth week of pregnancy. Although the optimal treatment for this infrequent condition remains controversial, we adopted anticoagulation as the first choice of treatment and obtained favorable results.Cerebral venous sinus thrombosis (CVST) accounts for 0.5-1.0% of all strokes.1 During late pregnancy and puerperium, CVST is an uncommon but important cause of stroke.2 Hemorrhagic infarction can occur in the acute stage of CVST. However, CVST with cerebral hemorrhage is extremely rare in early pregnancy. Upon literature review, we are able to find only one case of CVST resulting in cerebral hemorrhage in early pregnancy.3 Here, we present another case of CVST with cerebral hemorrhage in early pregnancy, the patient received a favorable outcome by use of anticoagulation therapy. Our objective in presenting this particular case is to discuss its diagnosis, and treatment, and review the related literature.     

Surgical Treatment of Space Occupying Edema and Hemorrhage due to Cerebral Venous Thrombosis During Pregnancy

Background  

During late pregnancy and the puerperium cerebral venous and sinus thrombosis (CVST) is a rare but important cause of stroke. Despite adequate anticoagulation some patients deteriorate, which may warrant the use of more aggressive treatment modalities.     

产褥期颅内静脉系统血栓形成临床分析

目的 探讨产褥期颅内静脉血栓形成的发病机制、临床表现及治疗对策。方法 回顾性分析2000年1月～2011年12月收治的46例产后颅内静脉血栓形成患者的临床资料,并进行归纳总结。结果 产后颅内静脉血栓形成患者以高颅内压及局灶性脑损伤为主要临床表现,经低分子肝素抗凝及对症治疗,患者症状均有改善。结论 对于存在静脉血栓形成风险的产褥期女性,应尽快完成相关检查,早诊断、早治疗,以期改善患者预后。     

Cerebral venous and sinus thrombosis

Abstract. Cerebral venous and sinus thrombosis (CVST) can present with a variety of clinical symptoms ranging from isolated headache to deep coma. Prognosis is better than previously thought and prospective studies have reported an independent survival of more than 80% of patients. Although it may be difficult to predict recovery in an individual patient, clinical presentation on hospital admission and the results of neuroimaging investigations are—apart from the underlying condition—the most important prognostic factors. Comatose patients with intracranial haemorrhage (ICH) on admission brain scan carry the highest risk of a fatal outcome. Available treatment data from controlled trials favour the use of anticoagulation (AC) as the first-line therapy of CVST because it may reduce the risk of a fatal outcome and severe disability and does not promote ICH. A few patients deteriorate despise adequate AC which may warrant the use of more aggressive treatment modalities such as local thrombolysis. The risk of recurrence is low (< 10%) and most relapses occur within the first 12 months. Analogous to patients with extracerebral venous thrombosis, oral AC is usually continued for 3 months after idiopathic CVST and for 6–12 months in patients with inherited or acquired thrombophilia but controlled data proving the benefit of long-term AC in patients with CVST are not available.Abbreviations CVST cerebral venous and sinus thrombosis - aPTT activated partial thromboplastin time - IU international units - INR international normalized ratio - AED antiepileptic drug - ICP intracranial pressure - mOsm/kg milliosmole per kilogram     

脑静脉窦血栓形成的临床与治疗

目的:探讨脑静脉窦血栓形成(cerebral venous sinus thrombosis,CVST)的临床特征、影像特点及治疗。方法:分析34例脑静脉窦血栓形成病因、临床表现、影像特征及治疗。结果:本组病因依次为产褥期(58.8%)、感染(23.5%)、脱水(2.9%)、血液病(2.9%)、外伤(2.9%);头痛、恶心、呕吐为首发症状,查体视乳头水肿89.4%,癫痫发作44.1%,脑膜刺激征阳性35.3%,意识障碍26.5%,轻偏瘫5.9%,眼球突出伴活动障碍5.9%;头MRI、MRV均显示脑静脉窦血栓形成,2例行DSA检查发现双侧横窦血栓形成;本组在应用降颅压、抗感染等药物的同时,应用低分子肝素5000u,12小时一次,疗效显著,治愈25例(73.5%),好转3例,死亡6例。结论:产褥期、感染、脱水是CVST常见原因; CVST患者主要表现为高颅压症状;头MRI和MRV能清楚显示血栓形成部位;抗凝治疗是脑静脉窦血栓形成痊愈的关键。     

孕产妇脑静脉窦及静脉血栓形成的早期诊断及误诊分析

脑静脉窦及静脉血栓形成(cerebral venous and sinus thrombosis,CVST)是缺血性脑血管病的特殊类型,好发于妊娠期和产褥期的孕产妇。发病率低,起病隐匿,临床表现错综复杂,易于误诊、漏诊,死亡率、致残率高,但早期诊断和干预则预后良好。本文重点就孕产妇CVST的早期诊断及误诊相关研究做一综述,以促进临床医师及早识别危险预警,避免误诊,早期诊断,及时干预。     

Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women

BACKGROUND: Pregnancy is a known risk factor for stroke, but relatively few studies have been conducted in Asian populations to document the risk. This study aimed to analyze the incidence and etiologies of stroke occurring during pregnancy and puerperium in Taiwanese women. METHODS: From 1984 to 2002, female patients 15 through 40 years of age with first-ever stroke during pregnancy or within 6 weeks of delivery were recruited. Stroke was classified as ischemic stroke (IS), cerebral venous thrombosis (CVT), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). The incidence, time of stroke onset (1st through 3rd trimester or puerperium), and etiologies of different stroke subtypes were analyzed. RESULTS: Of 402 young female stroke patients, 49 had stroke during pregnancy and puerperium, including 16 with IS, 11 with CVT, 19 with ICH and 3 with SAH. After excluding referral patients, the incidences of pregnancy-related stroke were 46.2 (95% CI 30.7-69.5) per 100,000 pregnancies. 67% developed stroke in the 3rd trimester and puerperium, and 73% of CVT occurred in the puerperium period. Etiologies were well defined in 78% of patients. Eclampsia (37%) and arteriovenous malformation (26%) were the most important etiologies of ICH. For IS and CVT, rheumatic heart disease (44%) and coagulopathy (64%) were the major etiologies respectively. CONCLUSIONS: The incidence of stroke occurrence during pregnancy and puerperium in Taiwanese women is higher than that of Caucasian populations; the majority of strokes occurred in the 3rd trimester and puerperium, particularly CVT.     

Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium

Venous thromboembolism is a rare but threatening complication of pregnancy. Little conclusive information is available on the actual risk of venous thromboembolism during pregnancy or puerperium in women with inherited thrombophilia, particularly in carriers of factor V Leiden and of the G20210A prothrombin gene mutation. To determine the pregnancy-related and puerperium-related risk of venous thromboembolism in women with inherited thrombophilia, we performed a case-control study on 119 women who had a first episode of deep vein thrombosis and/or pulmonary embolism during pregnancy or puerperium and 232 healthy women who had at least one pregnancy without thrombosis. Inherited thrombophilia was diagnosed in 47 patients (39.5%) and 15 controls (6.5%). The relative risk of venous thromboembolism was 10.6 (95% CI, 5.6-20.4) for heterozygous carriers of factor V Leiden, 2.9 (95% CI, 1.0-8.6) for heterozygous carriers of the prothrombin mutation and 13.1 (95% CI, 5.0-34.2) for those with antithrombin, protein C or protein S deficiency taken together. Sixty-eight of the 119 women (57%) had thrombosis after delivery, confirming the puerperium as a particularly high-risk period. When women were divided into two groups of those with antenatal or postnatal thrombosis. the relative risks associated with each type of inherited thrombophilia were of similar magnitude. In conclusion, women with inherited thrombophilia have an increased risk of venous thromboembolism during pregnancy. Among thrombophilic abnormalities, the prothrombin mutation was the weakest risk factor. Thrombosis occurred more frequently in puerperium than in pregnancy, whether or not thrombophilia was diagnosed.     

Cerebral venous thrombosis associated with oligodendroglioma and pregnancy

Until now, cerebral venous sinus thrombosis (CVST) was principally an autopsy diagnosis; however, with the introduction of MRI and angiography, as well as enhanced clinical attentiveness, it is now reliably diagnosed during life. Herein, we describe a case of CVST accompanied by oligodendroglioma and pregnancy. In our patient, the following factors contributed to the formation of CVST: First, the pregnancy state, which is a known risk factor for developing venous thrombosis; and secondly, the oligodendroglioma could have changed the architecture of adjacent sinus (right lateral sinus) and provocation of the development of clot in the sinus.     

重症脑静脉窦血栓形成的血管内溶栓抗凝治疗

目的探讨重症脑静脉窦血栓形成血管内溶栓抗凝治疗的效果与安全性。方法选择传统治疗方法无效的重症脑静脉窦血栓形成病例2例,采用在数字减影血管造影(DSA)下静脉窦接触性溶栓抗凝与颈内动脉抗凝溶栓联合治疗。结果2例病人临床症状全部缓解,闭塞静脉窦开通,无严重并发症发生。结论血管内介入溶栓抗凝治疗可能是治疗重症脑静脉窦血栓形成的一种安全有效的方法。     

脑静脉窦血栓形成并发癫痫的常见临床表现及其发病的预测因素

目的调查脑静脉窦血栓形成(CVST)后癫痫的发病率、临床表现形式和预测因素。方法2010年1月到2015年1月本院神经科住院CVST的患者90例。按有无继发癫痫,将90例CVST患者分为两组,通过病例报道表收集患者的人口学信息,症状和体征,以及辅助检查结果脑电图(EEG)、磁共振(MRI)和全脑血管造影(DSA)和诊断治疗方法,对是否并发癫痫进行单因素分析和多因素分析。应用受试者工作曲线(ROC)的曲线下面积(AUC)评价多因素模型,并和CVST预后量表的预测价值相比较。结果 CVST继发癫痫的发病率为34.4%,单因素分析显示,孕妇或产褥期(χ~2=5.517,P=0.019)、视物模糊(χ~2=6.103,P=0.013)、意识障碍(χ~2=32.505,P0.001)、脑出血(χ~2=4.822,P=0.028)、上矢状窦血栓形成(χ~2=5.908,P=0.015),以及横窦血栓形成(χ~2=6.669,P=0.010),在是否并发癫痫两组中比较差异有统计学意义。多因素分析显示,孕妇或产褥期(OR=3.64,95%CI 1.65~8.53)、脑出血(OR=3.02,95%CI 1.43~6.18),以及上矢状窦血栓形成(OR=1.98,95%CI 1.23~4.36)是CVST继发癫痫的独立危险因素。本研究预测模型的预测准确性AUC为0.73(95%CI 0.63~0.81,P0.05),CVST预后量表AUC为0.78(95%CI 0.65~0.86,P0.05),两模型的预测价值差异无统计学意义(P0.05)。结论癫痫是CVST患者的常见临床表现,孕妇或产褥期,脑出血和上矢状窦血栓形成是CVST并发癫痫的独立危险因素。本研究预测模型和CVST预后量表能较好的预测是否继发癫痫。     

脑静脉窦血栓形成的诊断

目的探讨诊断脑静脉窦血栓形成(CVST)的方法。方法对54例CVST患者的发病诱因、起病形式、临床表现、影像学特征以及血液和脑脊液检查等资料进行回顾性分析。结果 54例CVST患者平均年龄(33.33±12.20)岁,其中45岁以下45例。在妊娠和产褥期(31.5%)、脱水(22.2%)、上呼吸道感染(18.5%)、乳突炎(9.3%)等诱因下急性或亚急性起病,首发出现头痛(87.0%)、恶心(50.0%)、性发作(7.4%)、意识障碍(5.5%)以及肢体无力(3.7%)等症状,同时有D-二聚体水平增高,影像学表现为静脉窦闭塞及脑组织水肿或梗死,伴有出血性病变。多数脑脊液压力增高、白细胞数正常。结论在妊娠、产褥、脱水、感染等诱因下,出现头痛、恶心、意识障碍、性发作等症状的青年患者,要高度怀疑CVST,应及时行头颅CT或MRI检查;D-二聚体增高的情况下,脑静脉造影和脑脊液检查有助于进一步确诊。     

脑静脉/静脉窦血栓形成伴颅内出血患者的临床特点及相关因素

目的探讨脑静脉/静脉窦血栓形成(Cerebral venous sinus thrombosis CVST)伴颅内出血患者的临床特点及相关因素。方法回顾性分析80例CVST患者,将其分为出血及未出血两组,分析比较两组患者的一般资料、既往病史、潜在病因、临床表现及血栓部位。结果入组80例CVST患者中,出血患者35例(43.75%)。其临床表现以癫痫发作(P0.001)、感觉及运动障碍(P=0.001)、失语(P=0.033)、意识障碍(P0.001)更常见,视力下降患者(P=0.012)较少。单因素分析显示,与未出血组相比,出血组患者发病年龄较大(P=0.023),自症状出现至首次就诊时间较短(P0.001),妊娠/产褥期(P=0.037)更多,直窦/深静脉更易受累(P=0.037)。出血组与未出血组患者的CVST评分差异无统计学意义。多因素分析发现,年龄偏大、急性期入院及直窦/深静脉受累与CVST伴出血的独立相关。结论年龄较大、妊娠/产褥期和直窦受累的CVST患者更易发生颅内出血。合并出血患者局灶性神经功能障碍、癫痫和意识障碍发生率高。     

Thrombophilia, thrombosis and pregnancy

The risk of venous thromboembolism (VTE) in pregnancy is 0.05-1.8%, six times greater than in the non-pregnant state, and pulmonary embolism remains the most common cause of maternal death. Maternal age, previous history of VTE, Caesarean section and the presence of thrombophilia, significantly increase the risk of VTE. Acquired or hereditary thrombophilia occur in almost two-thirds of women presenting with recurrent miscarriages, pre-eclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth, which are associated with microvascular thrombosis in placental blood vessels. Women with VTE during pregnancy and especially those with thrombophilia require individualized management, based on the type of defect, the family history and the presence of additional risk factors. These factors are important in determining the dose and duration of antithrombotic therapy during pregnancy and the puerperium, and the thromboprophylactic strategy for future pregnancies. Oral anticoagulants are now seldom used during pregnancy because of their significant side effects. Low-molecular-weight heparins (LMWHs) are increasingly replacing unfractionated heparin in the prevention and treatment of VTE during pregnancy. LMWHs have also been shown to be effective in improving the outcome of pregnancy in women with previous obstetric complications.     

Effect of hemostatic risk factors on the individual probability of thrombosis during pregnancy and the puerperium

In a retrospective study of 190 women with a first history of venous thromboembolism during pregnancy and the puerperium and 190 age-matched women with at least one prior pregnancy and no history of venous thromboembolism, the individual probability of thrombosis was determined. Assuming an overall risk of 1 in 1500 pregnancies, the probability of pregnancy-related thrombosis in carriers of homozygous factor V Leiden was 1 in 80 (odds ratio 20.6, p=0.005) and among carriers of combined heterozygous factor V Leiden and heterozygous G20210A mutation in the prothrombin gene 1 in 20 (odds ratio 88, p<0.001). The probability of thrombosis per pregnancy among women with elevated levels of factor VIII:C (>172 % activity) was 1 in 385 (odds ratio 4.5, p<0.001) and among those with increased levels of von Willebrand factor antigen (>190 %) 1 in 435 (odds ratio 4.0, p=0.002), independent of elevated factor VIII:C levels. The high prevalence of combined and homozygous defects of hemostatic components (21.6%) in patients as compared with normal women (0.86%) supports the concept that venous thromboembolism is a multicausal disorder.     

26例脑静脉窦血栓形成临床分析

目的分析脑静脉窦血栓形成(CVST)的病因、临床特点,提高对脑静脉窦血栓形成的诊断和治疗水平。方法回顾性分析2008-01-2016-01我院经头CT、MRV及脑血管造影(DSA)确诊的26例CVST患者,分析其病因、临床症状、腰椎穿刺结果、影像学特点及预后。结果病因有产褥期、妊娠期、长期服避孕药、重度脱水、肺癌、血液病、肥胖、自身免疫性疾病,另有病因不明者。首发症状表现为头痛、视乳头水肿、恶心呕吐、意识障碍、癫痫、偏瘫、发热及复视、视力下降。脑脊液检查示颅压增高、蛋白轻度增高,头CT示弥漫性脑水肿、蛛网膜下腔出血、空三角症、静脉性梗死致出血及未见异常。结论 CVST的临床症状多样化,确诊需影像学检查,积极治疗预后好,以综合治疗为主,包括脱水降颅压、降纤、抗凝及原发病的治疗和血管介入治疗。     

Stroke in pregnancy and the puerperium

Recent studies suggest that the risk of cerebral infarction is increased during the puerperium but not during pregnancy itself. Most of the known causes of ischaemic stroke in the young have been reported during pregnancy. In most of these conditions, it is uncertain whether pregnancy is coincidental or plays a role in the occurrence of stroke. Eclampsia is the main pregnancy-specific cause, which may be associated with focal neurological deficits of sudden onset, consistent with a clinical diagnosis of stroke. However, the precise pathogenesis of these stroke-like focal deficits remains poorly understood. The two other pregnancy-specific conditions (choriocarcinoma and amniotic fluid embolism) are rarely responsible for focal cerebral ischaemia. In a significant number of patients, the cause of the stroke remains undetermined, despite an extensive aetiological investigation. Whether a hypercoagulable state and vessel wall changes associated with pregnancy may play a role in the occurrence of these otherwise unexplained ischaemic strokes remains unknown. The occurrence of cerebral venous thrombosis is clearly linked to the puerperal state, suggesting a direct role of the latter. However, cerebral venous thrombosis during pregnancy or the puerperium has been related to various aetiologies, stressing the need for an aetiological study, particularly when the thrombosis occurs during pregnancy. Pregnancy may increase the risk of subarachnoid haemorrhage, The most common cause is rupture of an arterial aneurysm. Although this is a controversial issue, the increased tendency of an aneurysm to bleed with advancing gestational age suggests that haemodynamic, hormonal or other physiological changes of pregnancy may play a role in aneurysmal rupture. The classic notion that rupture of an arterial aneurysm occurs more frequently during labour has not been confirmed. Most authors agree that surgical management after subarachnoid haemorrhage in pregnancy should be the same as that in the non-pregnant state. Data specifically devoted to intraparenchymal haemorrhage in pregnancy are scarce. Pregnancy and in particular the puerperium seem to be associated with an increased risk of intracerebral haemorrhage. The most common causes are eclampsia and ruptured vascular malformations. Whether pregnancy increases the risk of rupture of an arteriovenous malformation is controversial. Received: 30 September: 1997 Accepted: 27 October 1997     

Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study

BACKGROUND: Smoking and obesity are associated with adverse pregnancy outcomes. The aim of the present study was to examine the association between smoking, obesity (BMI>30), and risk for venous thromboembolism (VTE) during pregnancy and the puerperium. MATERIALS AND METHODS: In a population-based case-control study nested within a Danish cohort of 71,729 women, we identified 129 cases with VTE in pregnancy or the puerperium, and 258 pregnant non-VTE controls. We obtained data from medical records regarding current smoking status, BMI, and other covariates, and computed the odds ratios (OR) for VTE as a measure of relative risk. RESULTS: Smoking and obesity were associated with increased risk of VTE during pregnancy and the puerperium (adjusted OR 2.7 (95% CI: 1.5, 4.9) and 5.3 (95% CI: 2.1, 13.5), respectively). Obesity appeared to be associated with a higher risk of pulmonary embolism (adjusted OR: 14.9 (95% CI: 3.0, 74.8) than of deep venous thrombosis (adjusted OR: 4.4, 95% CI: 1.6, 11.9). CONCLUSION: Smoking and obesity are risk factors for VTE in pregnancy and the puerperium.