Outcome of patients with cryptogenic stroke and patent foramen ovale

OBJECTIVES: The aim was to estimate the recurrence rate and to define subgroups at increased risk for recurrent cerebral ischaemia in patients with patent foramen ovale (PFO) and so called cryptogenic stroke due to paradoxical embolism. METHODS: Patent foramen ovale was diagnosed in 318 patients with otherwise unexplained ischaemic stroke or transient ischaemic attack (TIA). One hundred and fifty nine were treated medically (oral anticoagulation 79, platelet inhibitors 80) and represent the study population. The remaining 159 patients underwent endovascular or surgical closure of the PFO and are not part of this study. RESULTS: Mean age was 50.7 (SD 13.5) years. The event leading to the diagnosis of PFO was a TIA in 38 patients (23.9%), an ischaemic stroke in 119 (74.8%), and an amaurosis fugax in two patients (1.3%). Forty four patients (27.7%) had experienced multiple cerebrovascular ischaemic events before the diagnosis of the PFO. During mean follow up of 29 (SD 23) months 21 patients (13.4%) had a recurrent cerebrovascular event (seven strokes and 14 TIAs). The average annual rate of recurrent strokes was 1.8% and that of recurrent strokes or TIAs was 5.5%. When patients with PFO with multiple cerebrovascular events before the diagnosis of the PFO were analyzed separately, the average annual rates of recurrent cerebral ischaemia were 3.6% for recurrent strokes and 9.9% for recurrent strokes or TIAs. These rates were significantly higher than in patients with first ever stroke or TIA (p=0.02). CONCLUSIONS: The study confirms a risk of stroke recurrence that is similar to the rates of previously published series of patients with PFO and cryptogenic strokes. Patients with more than one previous event were at increased risk of recurrent cerebral ischaemia.     

Recurrent stroke/TIA in cryptogenic stroke patients with patent foramen ovale

BACKGROUND: Patent foramen ovale (PFO) is present in 40% of patients with cryptogenic stroke and may be associated with paradoxical emboli to the brain. Therapeutic options include antiplatelet agents, anticoagulation, percutaneous device and surgical closure. We assessed the hypothesis that there are differences in rates of recurrent TIA or stroke between patients in the four treatment groups. METHODS: Patients presenting from January 1997 with cryptogenic stroke or TIA and PFO were followed prospectively until June 2003. Treatment choice was made on an individual case basis. The primary outcome was recurrent stroke. The secondary outcome was a composite of stroke, TIA, and vascular death. RESULTS: Baseline. Our cohort consisted of 121 patients; 64 (53%) were men. Median age was 43 years. Sixty-nine percent presented with stroke and 31% with TIA. One or more vascular risk factor was present in 40%. Atrial septal aneurysm (ASA) was present in 24%. Treatment consisted of antiplatelet agents (34%), anticoagulation (17%), device (39%) and surgical closure (11%). Follow-up. Recurrent events occurred in 16 patients (9 antiplatelet, 3 anticoagulation, 4 device closure); 7 were strokes, 9 were TIA. Comparing individual treatments there was a trend toward more strokes in the antiplatelet arm (p = 0.072); a significant difference was seen for the composite endpoint (p = 0.012). Comparing closure versus combined medical therapy groups, a significant difference was seen for primary (p = 0.014) and secondary (p = 0.008) outcomes, favoring closure. Age and pre-study event predicted outcome. CONCLUSION: Patent foramen ovale closure was associated with fewer recurrent events. Complications of surgical and device closure were self-limited.     

Transcatheter closure of patent foramen ovale in patients after cryptogenic stroke

Paradoxical embolism through a patent foramen (PFO) is a possible mechanism of ischaemic stroke in patients with cryptogenic stroke. Occlusion of PFO in such patients is considered by some authors as most effective in stroke prevention. We present our initial experience with transcatheter closure of PFO with the new self-expanding device--the Amplatzer PFO occluder in three young patients (age < 50 years). Each of them experienced at least one ischaemic stroke episode, without a left heart or carotid source and each had an interatrial communication with right-to-left shunting during Valsalva manoeuvre on echocardiography. The PFO's were closed completely without complications, under transoesophageal echo guidance in general anaesthesia. Complete closure was confirmed at one-month follow-up echocardiogram in each patient. No repeat cerebral accidents occurred at that time. The procedures were relatively easy and the clear presentation of the implant on TEE and fluoroscopy, made implantation fully controlled. The unique feature of the device is, that until release it can easily be retrieved, repositioned or removed. Transcatheter closure of PFO with the Amplatzer PFO occluder may become the new therapeutic option for patients with cryptogenic stroke and presumed paradoxical embolism.     

与卵圆孔未闭相关的不明原因脑卒中的研究进展

卵圆孔未闭(PFO)是一种先天性心脏病,在普通人群中发病率达25%,在青年不明原因脑卒中(CS)患者中高达46%。PFO与多种疾病相关,其中最重要的是脑卒中,与PFO相关的脑卒中大多归属于CS,目前认为PFO造成的反常栓塞是其最常见的致病机制。与PFO相关的CS的特点、诊断与治疗已经越来越受到重视。本文现围绕近年来相关的研究进展进行综述,以期为PFO相关的CS的诊治提供临床依据。     

伴有卵圆孔未闭的隐源性脑梗死的临床特点

目的探讨伴有卵圆孔未闭(PFO)的隐源性脑梗死的临床特点。方法回顾性分析8例伴有PFO的隐源性脑梗死患者的临床资料。结果 8例患者年龄15~55岁,平均39.75岁,均急性起病。主要临床表现为肢体无力5例,言语障碍2例,行走不稳、双下肢无力、癫痫发作、偏身针刺觉减退各1例。超声心动图检查示患者均有PFO。头颅MRI表现为额叶、顶叶、颞叶、枕叶、岛叶皮质、脑室体旁、内囊后肢、基底节、小脑半球T1低信号,T2高信号;单侧受累4例,双侧受累4例;6例为多发病灶,2例为单一病灶;累及前循环系统4例,后循环系统1例,前后循环均累及3例。8例患者治疗后未再复发。结论伴有PFO的隐源性脑梗死患者发病年龄相对偏小。头颅MRI多发病灶多见,可累及双侧,前后循环系统均可受累。伴有PFO的隐源性脑梗死预后较好。     

Patent foramen ovale closure versus medical therapy in cases with cryptogenic stroke,meta-analysis of randomized controlled trials

Background

PFO is more common in cases with cryptogenic stroke compared to cases with no stroke or stroke of identified etiology. Several randomized controlled trials (RCTs) comparing PFO closure with medical therapy have been published with controversial findings.

Methods

PubMed, Embase and Cochrane library databases were searched for RCT comparing PFO closure with medical therapy including antiplatelet therapy (aspirin or clopidogrel or combination) or anticoagulation. We identified 5 trials, including 3627 cases. The mean duration of follow-up was 4 years. Relative risk (RR) and 95% confidence intervals (CI) were calculated using fixed and random-effects models.

Results

There was a significant reduction in the incidence of stroke among the PFO closure group compared to medical therapy group, 2.0 versus 4.2%, RR 0.48; 95% CI (0.3, 0.7), p < 0.001. The incidence of AF was higher in the PFO closure group compared to medical therapy group, 4.2 versus 0.7%, respectively, RR 5.9, 95% CI (3, 11), p < 0.001. After exclusion of oral anticoagulants cases (19%), analysis showed a lower incidence of stroke in the PFO closure group (2%) compared to antiplatelet therapy (5.2%), RR 0.4; 95% CI (0.3, 0.6), p < 0.001. There was no significant difference between both groups in the incidence of transient ischemic attacks or all-cause deaths.

Conclusion

PFO closure results in a significant reduction in the recurrence of ischemic stroke compared to medical therapy alone, primarily antiplatelet, among cases with PFO and cryptogenic stroke.

     

Coagulation abnormalities in adults with cryptogenic stroke and patent foramen ovale

A patent foramen ovale (PFO) is found by transesophageal echocardiography in one half of patients with cryptogenic stroke (CS). Coagulation abnormalities may promote paradoxical emboli in these patients. Seventeen patients were identified with PFO and CS. Thirty-one percent of patients had hematologic risk factors for venous thrombosis. These included abnormal activated protein C resistance and increased anticardiolipin antibodies. Patients with coagulation abnormalities and a PFO were three times as likely to be treated with warfarin compared to aspirin (P<0.05). Prothrombotic states are common in patients with PFO and CS and identifying these conditions may impact the choice of antithrombotic therapy.     

伴卵圆孔未闭的隐源性脑卒中的临床表现及影像学特征

目的 探讨伴卵圆孔未闭(Patent foramen oval,PFO)的隐源性脑卒中(Cryptogenic stroke, CS)的临床表现及影像学特征。方法 收集2014年11月-2019年6月在华中科技大学同济医院神经内科住院确诊为PFO的患者,筛选出122例存在隐源性脑卒中患者,根据头颈血管影像学检查表现将其分为主动脉弓斑块(Aortic arch atheroma, AAA)合并PFO组、轻度动脉硬化(Mild atherosclerosis, MSA)合并PFO组及单纯PFO组,比较3组的一般临床资料及影像学特点。结果 与AAA合并PFO组及MSA合并PFO比较,单纯PFO组患者年龄更小,吸烟史、高血压病史及既往脑卒中病史比例更低,反常性风险栓塞评分量表(Risk of paradoxical embolism, RoPE)数值更高(P<0.05)。影像学上AAA合并PFO组患者与MAS合并PFO组及单纯PFO组比较,其梗死灶数量更多,小病灶及累及两根以上血管和同时累及前后循环的比例更高,而MAS合并PFO组及单纯PFO组中梗死灶数量更少,大病灶及累及单根血管的比例更高(P<0.05); 单纯PFO组病灶分布于后循环的比例高于AAA合并PFO组(χ²=4.854,P=0.028); MAS合并PFO组及单纯PFO组中梗死灶数量、大小、累及的血管情况无明显差异(P>0.05)。结论 PFO引起的反常栓塞及主动脉斑块脱落栓塞可能是引起CS的重要病因,CS患者的梗死灶影像学特点能作为寻找隐源性脑卒中发病机制的线索     

Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale

Background Among patients with a patent foramen ovale and cryptogenic ischemic stroke, the long-term prognosis is unclear. Aims This study aims to estimate the recurrence rate in young cryptogenic stroke patients with and without patent foramen ovale. Patients and methods One hundred eighty-six cryptogenic stroke patients (aged 18-45 years) were prospectively followed for up to five-years. They were divided into two groups according to the echocardiographic presence of patent foramen ovale. All patients received aspirin (100?mg/day) for secondary prevention. Results Mean age was 32·3 (standard deviation 7·9) years. During the mean follow-up of 66 months five patients with patent foramen ovale had recurrent strokes compared with 11 patients without patent foramen ovale. The average annual rate of recurrent cerebral ischemia was 1·1% and 1·6% for patients with and without patent foramen ovale, respectively. The recurrence rate did not increase with the presence of patent foramen ovale, atrial septal aneurysm or other variables. More than 60% of the reported cases achieved a good functional outcome. Conclusions Young patients with cryptogenic ischemic stroke with and without patent foramen ovale have a low recurrence rate in a long-term follow-up and most present a favorable outcome. Patent foramen ovale with or without atrial septal aneurysm did not increase the risk of recurrence.     

经颅多普勒超声在不明原因缺血性脑卒中的应用研究

目的探讨经颅多普勒超声(transcranial Doppler,TCD)技术结合生理盐水发泡试验在不明原因缺血性脑卒中患者卵圆孔未闭(PFO)筛查中的应用价值。方法收集51例55岁以下不明原因缺血性脑卒中患者,行TCD结合生理盐水发泡试验和经胸超声心动图(TTE)检查。结果 51例患者中,23例患者TCD检查栓子信号阳性,其中18例患者TTE检查发现PFO,而在28例TCD检查栓子信号阴性的患者中未发现PFO;TCD检查阳性患者中偏头痛发病率、合并下肢深静脉血栓比例以及房间隔瘤比例较阴性者高(P<0.05)。结论 TCD结合生理盐水发泡试验是筛查PFO的有效手段,可以作为不明原因缺血性脑卒中病因筛查的手段。     

心脏卵圆孔未闭对不同年龄人群隐源性卒中的影响

目的 探讨心脏卵圆孔未闭(patent foramen ovale,PFO)与不同年龄人群隐源性脑卒中(cryptogenic stroke,CS)的关系.方法 从238例中青年(＜55岁)和373例老年(≥55岁)急性脑梗死患者中筛查出181例隐源性卒中患者,为隐源性卒中组,根据年龄分为两亚组:中青年CS组(＜55岁)和老年CS组(≥55岁),并分别设立同年龄段的非卒中患者为对照组.隐源性卒中组及对照组均进行发泡实验明确是否存在PFO.多因素Logistic回归分析用来检验PFO和隐源性卒中间的关系.结果 PFO在中青年CS患者及老年CS患者中都明显高于其对照组相,差异都具有统计学意义(P值分别为0.005和0.023);校正年龄等因素后,多因素Logistic回归分析显示无论中青年(P＜0.01)还是老年(P＜0.05),PFO都是隐源性卒中的独立危险因素;PFO在CS两亚组间差异不明显(P＞0.05),没有统计学意义.结论 无论中青年及老年,PFO都是CS的独立危险因素,年龄不是影响PFO与CS关系的主要因素.     

Ischaemic stroke in patients with patent foramen ovale

Patent foramen ovale (PFO) is one of the most common defects of the atrial septum. PFO can be linked to several brain disorders including stroke. PFO is more prevalent in young patients with cryptogenic stroke than in the general stroke population. Data from the literature do not indicate the role of PFO and/or atrial septal aneurysm in pathogenesis of first-ever and recurrent stroke. Antithrombotics seem to decrease the risk of stroke recurrence, but oral anticoagulants also increase the risk of haemorrhagic complications. Results of studies on percutaneous or surgical closure of PFO are insufficient to make clinical therapeutic decisions. Both the role of PFO in recurrent stroke as well as the most efficacious therapeutic approach in preventing recurrent strokes remain to be elucidated in further studies.     

Closure of a patent foramen ovale: effective therapy of migraine and occipital stroke

Whether stroke in a patient with migraine and patent foramen ovale (PFO) is due to PFO or migraine is difficult to decide. In a 33-year-old woman with migraine with aura, a visual field defect developed acutely. Neurological investigation revealed double vision when looking to the left and exaggerated patella tendon reflexes. Since then the patient complained about permanent visual impairment. CT- and MRI-scans of the brain showed a right occipital ischemic stroke. Intensive search for risk factors revealed cigarette smoking and chronic hypovolemia On transesophageal echocardiography an inter-atrial hypermobile septum and a PFO were detected. The patient underwent closure of the PFO by means of an Amplatzer PFO occluder nine weeks after the stroke. Since then she did not experience a further cerebrovascular event or migraine attack. This case shows that in a patient with PFO and migraine with aura, stroke may be attributable to migraine rather than to PFO. Occlusion of the PFO may reduce the frequency and intensity of migraine attacks.