卵圆孔未闭与隐源性卒中的研究进展

隐源性卒中约占所有缺血性卒中的40%,其病因、诊断和治疗一直是临床工作者的研究热 点。近年来发现,卵圆孔未闭与隐源性卒中的发病密切相关,是隐源性卒中的重要危险因素。在临床 中常用经食管超声心动图、经胸壁超声心动图、经颅多普勒发泡试验和心脏MRI等方法来检测卵圆孔 未闭。反常栓塞是卵圆孔未闭导致隐源性卒中的主要发病机制。在头部影像学检查中,绝大多数卵圆 孔未闭相关隐源性卒中患者为多血管分布区的多发散在小梗死。在药物治疗方面,抗血小板药物相 对于抗凝药物,可能更适合大多数卵圆孔未闭合并隐源性卒中的患者。此外,近期多项临床随机对照 研究均表明,卵圆孔未闭封堵术对于预防卵圆孔未闭合并隐源性卒中患者卒中再发的疗效明显优于 药物治疗。     

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     

Prevalence of atrial septal abnormalities in older patients with cryptogenic ischemic stroke or transient ischemic attack

OBJECTIVE: To evaluate the association of atrial septal abnormalities - patent foramen ovale (PFO), atrial septal aneurysm (ASA), or the combination of both (PFO+ASA) - with cryptogenic stroke or transient ischemic attack (TIA) in older patients. METHODS: We examined the prevalences of PFO, ASA, and PFO+ASA in 132 consecutive patients aged 55 years or more who underwent transesophageal echocardiography (TEE) for evaluation of ischemic stroke or TIA. We compared patients with cryptogenic stroke/TIA and those with stroke/TIA of known cause. RESULTS: PFO+ASA was more common in patients with cryptogenic stroke/TIA than in patients with stroke/TIA of known cause (12/62 or 19% vs. 2/70 or 3%; adjusted odds ratio, 7.4; 95% CI, 1.4-38.2). Differences between groups for isolated PFO, and isolated ASA were not significant. The association of PFO+ASA with cryptogenic stroke/TIA was confirmed in the subgroup of patients aged 75 years or more (odds ratio, 15.0; 95% CI, 1.5-146.7). CONCLUSION: This study indicates a significant association of PFO+ASA with cryptogenic stroke or TIA in older patients.     

Sleep apnea syndrome and patent foramen ovale: a dangerous association in ischemic stroke?

BackgroundThe coexistence of patent foramen ovale (PFO) and sleep apnea syndrome (SAS) might be related to the pathogenesis of cryptogenic stroke (CS). We aimed to determine the prevalence of SAS in patients with cryptogenic stroke and PFO.MethodsThis is a prospective case-control study in which we included ischemic stroke patients consecutively admitted to our hospital's Acute Stroke Unit. Contrast transcranial Doppler (c-TCD) and sleep polygraphy within the first 72 h after stroke onset were performed to detect PFO and SAS. Demographic and clinical characteristics, time of stroke onset, score in the National Institute of Health Stroke Scale (NIHSS), and stroke subtype were registered.ResultsA total of 97 patients were studied. Overall, 76% were men, with a mean ± SD age of 61 ± 13 years, and an NIHSS of 5 ± 5. Subtype of stroke was cryptogenic (CS) in 28 (29%) and non-CS in 69 (71%) of patients. PFO was more frequent among patients with CS (64% vs 29%, p = 0.002) and without SAS (60% vs 32%, p = 0.013). SAS was diagnosed in 74% of the whole group, with a higher prevalence in patients with known stroke etiology (83% vs 53%, p = 0.003). Finally, the prevalence of SAS and PFO coexistence was similar in patients with or without cryptogenic stroke (25% vs 22%, p = 1), and when comparing the group of patients with cryptogenic wake-up stroke to the other stroke patients (43% vs 21%, p = 0.35).ConclusionsAccording to our results, there is no evidence of an association of PFO and SAS in the pathogenesis of cryptogenic stroke.     

Patent foramen ovale. What is it and what does it indicate?

Cryptogenic stroke accounts for up to 40 % of all ischemic strokes and is even more frequent in young patients. The patent foramen ovale (PFO) is found in almost 60% of these young patients and has been suggested as a potential cause of cryptogenic stroke in this age group. However, the pathological relevance of PFO in cryptogenic stroke and the most appropriate therapeutic handling of it have not been established. In this review, the current state of therapeutic handling and ongoing controversies are discussed and the most interesting results in this field, including recent metaanalyses, are presented.     

Countable and non-countable microembolic signals by TCD in first-ever stroke or TIA patients with PFO

BACKGROUND: There are data in the literature indicating that the number of microembolic signals (MES) in patients with patent foramen ovale (PFO) is directly related to stroke incidence and recurrence. We thus hypothesized that the amount of artificially induced microembolic signals monitored by contrast transcranial Doppler (cTCD) would be greater in younger patients with PFO and stroke (when cryptogenic strokes related to the PFO are frequent). PATIENTS AND METHODS: The final analysis included 109 patients with first-ever ischemic stroke or TIA with PFO, as detected by Transesophageal Echocardiography (TEE), and MES, as measured by cTCD. Thirty-seven patients (aged 19-45 years) were defined as the "younger" group, and the other 72 patients (aged 46-77 years) were defined as the "older" group. Eighty-six patients (78.9%) suffered from stroke, including 28 in the younger group and 58 in the older group. The pattern of microembolization was defined as "countable" when the observers were able to calculate the number of MES. In the case of a "shower" of MES on TCD examination, the pattern of monitoring was defined as "non-countable." RESULTS: Ischemic heart disease, and hyperlipidemia were found to be significantly more frequent in the group of older patients. Twenty-three patients (62.2%) in the younger group had cryptogenic stroke or TIA (no risk factors found), as compared to 26 patients (36.1%) in the older group (p=0.009). There were 23 patients with a non-countable pattern of MES in the older group, as compared with 5 such patients in the younger group (p=0.04). There was no difference found in the number of MES between the groups in those patients with a countable pattern of MES (13.3+/-11.8 in the younger group vs. 13.7+/-11.7 in the older group). CONCLUSIONS: In stroke and TIA patients above 45 years of age, PFOs producing a large amount of MES on TCD examination are frequent. Thus, there is no correlation between a large amount of MES and stroke or TIA in young patients.     

Dye dilution and oximetry for detection of patent foramen ovale

Objectives - Patent foramen ovale (PFO) is a risk factor for stroke of undetermined (cryptogenic) origin. Low cost and non-invasive bedside tests for detection of PFO are needed as alternatives to contrast transesophageal echocardiography. We investigated whether dye dilution curves and oximeter recordings are useful for detecting PFO and what is the prevalence of PFO in patients with cryptogenic stroke determined with these bedside methods. We also studied whether stroke risk factors, number of brain lesions, and stroke recurrence rates were different in patients with an unexplained stroke with and without PFO. Material and methods - Dye dilution curves and oximeter recordings with non-invasive earpiece apparatus were obtained in 59 patients aged under 50 years who had had a cryptogenic brain infarction. The number of ischemic lesions in the brain was counted by MRI. Results - PFO was found in 24 (41%) of 59 patients. There was a 100% concordance in results obtained by dye dilution and by oximetry. Risk factors for stroke were similar in subjects with PFO and those without PFO. No significant association was found between PFO and Valsalva-like activity at stroke onset. Those with PFO did not have more ischemic lesions detected by MRI nor did they have more recurrent ischemic episodes. Conclusion - Dye dilution and oximetry are cheap and useful methods for detection of PFO and could be used for screening of the risk of paradoxical embolism. Because these 2 methods were not compared with the golden standard, transesophageal echocardiography, the specificity and sensitivity of the tests remain unsettled.     

Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause

BACKGROUND AND PURPOSE: Atrial septal abnormalities have been associated with cryptogenic ischemic stroke in young patients, but the causal link has not yet been established. Paradoxical embolism is considered the most likely mechanism but is rarely proven. It can be hypothesized that, in those patients, paroxysmal atrial arrhythmias, potentially favored by the anatomic abnormalities, can be another cause of thrombus formation and subsequent embolism to the brain. In this study we assessed the relationship between atrial vulnerability, reflecting arrhythmogenic properties of the atria, and atrial septal abnormalities in young patients with cryptogenic ischemic stroke. METHODS: We enrolled 62 consecutive patients aged <55 years who had ischemic stroke of unknown cause and transesophageal echocardiography to assess atrial septal aneurysm (ASA) or patent foramen ovale (PFO) (ie, atrial septal abnormalities). These patients underwent electrophysiological study to measure atrial refractoriness and conduction time defining a vulnerability index (ie, latent atrial vulnerability) and to assess the inducibility of sustained (lasting >60 seconds) atrial fibrillation with the use of programmed atrial stimulation. Actual atrial vulnerability was defined by the presence of both latent vulnerability and inducibility of sustained atrial fibrillation lasting >60 seconds. RESULTS: We found atrial vulnerability in 58% of patients with atrial septal abnormalities and in 25% of patients without (odds ratio=4.1 [95% CI, 1.3 to 12.7; P<0.02]). The difference between patients with and without PFO or between patients with both PFO and ASA and those without were also significant. Patients with inducible sustained atrial fibrillation had more frequent past history of palpitations and syncope than patients without (P<0.02). CONCLUSIONS: Atrial vulnerability is associated with atrial septal abnormalities in patients with cryptogenic stroke. This result raises the question of the potential role of transient atrial arrhythmias in thrombus formation in the presence of PFO or ASA.     

Management of right-to-left shunt in cryptogenic cerebrovascular disease: results from the observational Austrian paradoxical cerebral embolism trial (TACET) registry

Paradoxical embolism due to a patent foramen ovale (PFO) is a possible cause of ischemic stroke, particularly in young cryptogenic stroke patients. In most cases, however, it is difficult to establish a firm etiological association and the debate about management is ongoing. The Austrian Paradoxical Cerebral Embolism Trial was designed as a prospective, national, multi-center, non-randomized registry to add further data on this topic before the completion of randomized controlled trials. Over 27 months 188 cryptogenic stroke/TIA patients ≤55 years were entered by 15 Austrian stroke units. Contrast transesophageal echocardiography demonstrated a cardiac right-to-left shunt (RLS) in 176 patients; a pulmonary RLS was assumed in 10, and 2 showed both. Ninety-seven (55 %) patients with cardiac RLS underwent interventional treatment, and this was more likely for patients with stroke as index event, a symptomatic infarction on MRI and a large size of PFO. Over 2 years, recurrences occurred at a rate of approximately 1.3 % for stroke and 4.3 % for TIA, and were especially frequent in patients with pulmonary RLS. When comparing outcomes in patients with cardiac RLS there was a trend for fewer recurrences with interventional management (closure: four TIA in four patients vs. medical: three strokes and seven TIA in nine patients; p = 0.066 for events, p = 0.085 for patients). The complication rate was 13.4, and 5.7 % had residual shunting. The possible causes for paradoxical embolism in young patients with cryptogenic stroke appear more variable than usually considered, and other causes than PFO should not be neglected. Interventional treatment of a cardiac RLS may offer a small benefit, but has to be weighed against possible complications and the problem of establishing causality.     

Closure of Patent Foramen Ovale and Cryptogenic Stroke: Unresolved Issues

Purpose of Review

This review summarises the results of randomised trials comparing closure of patent foramen ovale (PFO) with antithrombotic therapy in patients with cryptogenic stroke.

Recent Findings

Initially, three randomised trials failed to show superiority of PFO closure over antithrombotic therapy in patients with cryptogenic stroke. Three recently performed trials and the prolongation of an earlier trial provided evidence that PFO closure in patients with cryptogenic stroke and an age range of 18–60 years is superior to stroke prevention with antiplatelet therapy. PFO closure was not superior to anticoagulation. Anticoagulation, however, has a higher long-term bleeding risk. PFO closure could result in atrial fibrillation (AF) in a small number of patients. In most patients, AF was transient in duration. Optimal patient selection requires future research.

Summary

In patients with cryptogenic stroke aged &lt;?60 years, PFO closure is superior to antiplatelet therapy in the prevention of recurrent stroke.

     

Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies

OBJECTIVE: To examine the association between patent foramen ovale (PFO) and atrial septal aneurysm (ASA) and stroke. METHOD: Data from case-control studies that examined the relative frequency of PFO, ASA, or both, in all patients with ischemic stroke, cryptogenic stroke, and known stroke cause as well as control subjects were included. Trials were categorized by age, clinical comparison, and abnormality. Combined OR were calculated using fixed effect (FE) and random effect (RE) methods. RESULTS: Comparing patients with ischemic stroke with control subjects using RE, OR for all ages was 1.83 (95% CI, 1.25 to 2.66) for PFO (15 studies), 2.35 (95% CI, 1.46 to 3.77) for ASA (nine studies), and 4.96 (95% CI, 2.37 to 10.39) for PFO plus ASA (four studies). Homogeneous results were found within the group younger than age 55: using FE, OR was 3.10 (95% CI, 2.29 to 4.21) for PFO, 6.14 (95% CI, 2.47 to 15.22) for ASA, and 15.59 (95% CI, 2.83 to 85.87) for PFO plus ASA. For patients older than age 55, using FE, OR was 1.27 (95% CI, 0.80 to 2.01) for PFO, 3.43 (95% CI, 1.89 to 6.22) for ASA, and 5.09 (95% CI, 1.25 to 20.74) for PFO plus ASA. Comparing cryptogenic stroke with known stroke cause, heterogeneous results were derived from total group examination using RE: OR was 3.16 (95% CI, 2.30 to 4.35) for PFO (22 studies), 3.65 (95% CI, 1.34 to 9.97) for ASA (five studies), and 23.26 (95% CI, 5.24 to 103.20) for PFO plus ASA (two studies). In patients younger than age 55, using FE the OR was 6.00 (95% CI, 3.72 to 9.68) for PFO; only one study examined ASA or PFO plus ASA. In patients aged 55 years or older, three studies produced heterogeneous results for PFO: using RE, OR was 2.26 (95% CI, 0.96 to 5.31); no data were available on ASA prevalence. CONCLUSIONS: PFO and ASA are significantly associated with ischemic stroke in patients younger than 55 years. Further studies are needed to establish whether an association exists between PFO and ischemic stroke in those older than 55.     

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。     

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。     

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.     

From cryptogenic to ESUS: Toward precision medicine?

Cryptogenic infarctions are infarctions without a defined cause, despite a complete work-up. They differ from infarctions of undetermined causes, which may involve overlapping causes or an incomplete investigation. It is also different from uncommon heritable and non-heritable causes. The term embolic stroke of undetermined source (ESUS) proposed in 2014 is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. The major advantage of this definition compared to cryptogenic definition is the proposition of a specific work-up. In a general population, frequent potential sources of embolism in patients with ESUS have been suggested since a long time and include: patent foramen ovale (PFO), covert atrial fibrillation (AF), complex aortic arch atheroma, large vessel atheroma with stenosis < 50%, carotid web, atrial cardiomyopathy, thrombophilia associated with cancer. It took almost 30 years to show, in patients under 60 with a cryptogenic stroke and a PFO, that PFO occlusion was superior to medical treatment alone for recurrent stroke. PFO under 60 is therefore no longer a cryptogenic cause of infarction. The concept of cryptogenic stroke and its refinement in ESUS have been fruitful for the identification of PFO associated as a cause. Covert AF can be detected by different techniques but its risk significance for recurrent stroke might be different from the simple electrocardiographic detection of AF. With the development of direct oral anticoagulants (DOAs), randomized studies in patients with ESUS, were run for stroke prevention but no difference was observed between patients treated by DOA compared to aspirin. These studies showed however the heterogeneity of ESUS patients. Further ESUS classification should be considered as a tool to identify homogeneous groups. We propose to further split the ESUS group into different subgroups: ESU-PFO > 60-year-old, ESUS-ATH with stenosis < 50%, ESUS-AF (covert AF & atrial cardiomyopathy), ESUS-cancer and others. Precision medicine is the ability to make targeted healthcare decisions based on the specific risks of individual patients. One preliminary stage is therefore to identify homogeneous groups suitable in the future for new therapeutic trials and, at the end, for new specific treatments.     

Cryptogenic stroke

In about a quarter of ischaemic strokes the cause is undetermined, because the investigation is incomplete or delayed, because there are multiple causes or because the stroke is truly cryptogenic. Cryptogenic stroke can be further classified as non‐embolic or embolic. Embolic stroke of undetermined source can be due to paroxysmal atrial fibrillation, minor emboligenic cardiac conditions, atheroembolism, cancer associated and paradoxical embolism through a patent foramen ovale (PFO) or less often a pulmonary fistula. Currently, risk factor control, statins and antiplatelets are the main therapeutic measures to prevent recurrent stroke. There is no evidence to implement routine closure of PFO in patients with cryptogenic stroke. Direct anticoagulants are being evaluated in randomized controlled trials including embolic stroke of undetermined source patients. Advances in high resolution ultrasound or magnetic resonance imaging of extracranial and intracranial vessels and of the heart and prolonged heart rhythm monitoring will be instrumental techniques to identify arterial and cardiac hidden causes of stroke.     

Transesophageal echocardiography in patients less than 60 years of age without obvious cardiac source of embolism

Abstract

Minor potential cardioembolic sources of stroke such as atrial septal aneurysms (ASA) or patent foramen ovale (PFO) are important risk factors for cryptogenic stroke. We aim to determine the prevalence of these abnormalities through an exhaustive etiological workup including transesophageal echocardiography and cervical arteries assessment in stroke patients younger than 60 years of age who had no evidence of a significant source of embolism. We classified 118 stroke patients into four groups according to transesophageal echocardiography (TEE) and cervical arteries assessment findings. Group A, consisted of 30 (25.4%) patients who had an arteriopathy likely related to stroke without any cardiac abnormality; Group B, 49 (41%) patients who had only a potential cardiac source; Group C, 9 (7.6%) patients who had an obvious arterial source of stroke and incidental cardiac abnormalities, and Group D, 30 (25.4%) patients who had neither cardiac nor arterial source. Data were analysed with X2 test for the comparison of risk factors between groups. Variance analysis was used to compare age between groups. Significance was assessed as p <0.05. ASA represented 56.8% of the cardiac abnormalities and was diagnosed in 35.4% of the 79 patients who had an unexplained stroke (B and D). A PFO was found in 34.1% of the patients who had a cryptogenic stroke (B and D). According to Fisher's exact test, ASA was significantly associated to PFO (p"0.001). According to this selection one fourth of the patients might have a truly cryptogenic stroke as the etiological workup failed to demonstrate any source of stroke. Comparison between groups showed that the patients in whom an arterial source was detected also had a potential cardioembolic source in 23% of the cases (G), versus 62% in patients who had no arterial source (B and D) (p = 0.0007). Our study confirmed the strong association between ASA, PFO and stroke. Although there was a lower incidence of minor potential cardioembolic sources in patients who had a cervical artery disease, we suggest a systematic TEE screening in all patients with stroke without major cardiac source, in order to ensure a better prevention. [Neurol Res 1995; 17: 368-372]     

Patent foramen ovale closure. Pro and cons

Because patent foramen ovale (PFO) represents a lesion which may be repaired a number of expert clinicians believe that mechanical closure should be the primary treatment modality for patients with PFO after cryptogenic stroke; interest has grown on percutaneous devices and in the last years there has been great technological advancement of percutaneous techniques for PFO closure. However, we should not close a PFO before establishing the evidence-based indications. At the same time, efforts to develop safer and more effective closure devices are under way. These devices include those with little or no metal component and those with biodegradable discs. Ideally, we should be able to identify at-risk patients before they sustain a stroke and to prevent stroke by closing the PFO with a device that should result in complete closure, be made of material that conforms to both sides of the septum, and have no risk of erosion, infection, arrhythmia, or thrombogenicity. Randomised trials comparing medical and percutaneous closure approaches are underway, but large patient enrollment is necessary because of the low event rate in the younger patients. Meanwhile, as the complication rate from device implantation decreases and simpler devices are developed with reliability further demonstrated, the threshold for percutaneous closure is likely to decline.     

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.     

Mutations in the NKX2-5 gene in patients with stroke and patent foramen ovale

Objective

Patent foramen ovale (PFO) has been related to stroke but its existence has not been explained to date. NKX2-5 is the most implicated gene in fetal atrial septation. We studied NKX2-5 with respect to the presence or absence of PFO in stroke patients.

Methods

A prospective analysis of NKX2-5 regarding age, gender, PFO, right-to-left shunt (RLS) size and atrial septal aneurysm (ASA) was performed in consecutive stroke patients and in 50 controls. The entire coding region and intron–exon boundaries of NKX2-5 gene were analyzed by PCR and sequencing of DNA from peripheral lymphocytes.

Results

One hundred patients participated in the study (mean age 56.5 ± 12.4 years, 58% males) and PFO was diagnosed in 34% of them by transesophageal echocardiography. RLS was small (12%), moderate (2%) and large (20%). ASA was present in four patients. DNA revealed a novel c.2357G>A change in one PFO patient with cryptogenic stroke. Furthermore, c.182C>T, a mutation previously described in patients with cardiac defects, was detected in two non-PFO women with cryptogenic stroke. None of these changes were detected in our controls. The c.172A>G polymorphism was found in 21% of controls. It appeared more frequently in ASA patients (p = 0.084), in cryptogenic PFO stroke patients (p = 0.097) and in patients with known causes of stroke (p = 0.037). The c.2850C>A polymorphism was also detected in our series with no differences in PFO, RLS size or ASA.

Conclusion

Despite the fact that the NKX2-5 could account for the persistence of PFO, mutations of this gene in peripheral blood DNA were barely detected in our study.