Patent foramen ovale and migraine

Recent epidemiological data suggest a bidirectional link between patent foramen ovale (PFO) and migraine with aura (MA) with a relative risk of 2 for PFO in subjects with MA and for MA in subjects with PFO. There is no evidence for a link between PFO and migraine without aura. This link is not systematic and applies only to subsets of PFO, mostly large ones, and to subsets of patients with MA. Although comorbidity cannot be ruled out, it may be that this link is partly causal and that some large PFOs may favor MA attacks in genetically predisposed subjects, by allowing vasoactive substances, platelet emboli or paradoxical emboli to bypass the lung filter and trigger the cortical spreading depression of the aura. The first double blind randomised trial of PFO closure in refractory MA, "MIST", has failed to show a benefit on the primary efficacy end point: cessation of attacks during the analysis period included between 3 and 6 months after the procedure. There is thus at present no scientific reason to look for PFO or to close PFO in migraine patients.     

The persistent foramen ovale and migraine

There is association between migraine, particularly migraine with aura, and large persistent foramen ovale (PFO) and other right-to-left shunts. Migraine is often improved by closure of a PFO in patients who have a large shunt. Inheritance of migraine is linked to the inheritance of large atrial shunts in some families. The data indicate that in some patients PFOs play a causal role in migraine with aura. These observations may also improve understanding of the etiology of migraine in patients who do not have a shunt.     

Quantitation of Contrast TCD in Patients With and Without Atrial Septal Aneurysm

BACKGROUND AND PURPOSE: Patients with a combination of atrial septal aneurysm (ASA) and patent foramen ovale (PFO) have a substantially higher rate of recurrent ischemic events as compared to PFO alone. One possible explanation is a greater degree of right-to-left shunting with the combination. METHODS: Retrospective study using contrast transcranial Doppler ultrasonography (c-TCD) to study the degree of shunting in 46 patients with PFO with either transient ischemic attack or cryptogenic ischemic stroke. Eight patients with PFO+ASA identified on transesophageal echocardiogram were compared to 38 patients with PFO but without ASA. RESULTS: The number of embolic counts was no different with or without an ASA. Valsalva maneuver increased number of emboli, especially in patients with large PFOs. CONCLUSIONS: Patients with ASA in addition to PFO do not appear to have an increased risk of right-to-left shunting as measured by c-TCD as compared to PFO alone.     

Management of patients with stroke and a patent foramen ovale

Observational studies have established a strong association between the presence of patent foramen ovale (PFO) and increased risk of ischemic stroke. The mechanism involved is presumed to be a paradoxical embolism from a venous thrombus that travels via the PFO to the systemic circulation. The best treatment modality to prevent recurrent stroke in patients with PFO remains undefined. There are four major choices: 1) medical therapy with anticoagulants, 2) medical therapy with antiplatelet agents, 3) surgical closure, and 4) percutaneous device closure. The Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated that antiplatelet and anticoagulant therapies are of equal benefit in preventing recurrent neurologic events in stroke patients with a PFO. Medical therapy should remain as the initial choice of secondary prophylactic therapy. PFO closure, either surgical or percutaneous, may further reduce event rates; however, this remains to be demonstrated because no randomized trial to date has compared PFO closure with medical therapy.     

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.     

Risk of recurrent ischemic stroke in patients with patent foramen ovale: The role of D-dimer

BackgroundParadoxical embolism under elevated thromboembolic conditions is known to be the primary mechanism of patent foramen ovale (PFO)-related stroke. We hypothesized that higher levels of D-dimer, a marker of thromboembolism, could increase the risk of stroke recurrence in patients with PFO.MethodsWe conducted a retrospective analysis of data from 1226 consecutive patients with acute ischemic cryptogenic stroke (CS) who underwent transesophageal echocardiography (TEE). D-dimer was assessed during admission. We used a multivariate Cox proportional hazards model to evaluate the association of long-term outcomes between the presence of PFO and levels of D-dimer.ResultsOf the 1226 patients, the study included 461 who underwent TEE. Among them, 242 (52.5%) had PFOs. Among PFO patients, those with a D-dimer level >1.0 mg/L had a significantly higher risk of stroke recurrence compared to those with <0.5mg/L (adjusted hazard ratio (aHR) 4.04, 95% confidence interval [CI] 1.63–10.02). A pattern of increased risk of event with increasing D-dimer levels was observed (P_trend=0.008). However, there was no significant difference in the risk of stroke recurrence at any D-dimer level compared to D-dimer level <0.5 mg/L among patients without PFO. In these patients, there was little evidence of increased risk with increasing D-dimer levels (P_trend=0.570).ConclusionsThis study demonstrated that the elevated D-dimer level increased the recurrence of stroke in CS patients with PFO, particularly showing a dose-dependent relationship between D-dimer levels and recurrence. However, no such effect was observed in patients without PFO. These findings provide valuable insights into the potential benefits of anticoagulation for strokes related to PFO.     

卵圆孔未闭并隐源性卒中的临床及影像学分析

目的探讨卵圆孔未闭(patent foramen ovale,PFO)并隐源性卒中(cryptogenic stroke,CS)的临床及影像学特征。方法连续性纳入2015年3月~2015年12月入住郑州大学附属洛阳中心医院神经内科的年龄≤65岁的急性缺血性脑卒中患者,对其进行脑血管病危险因素筛查,并行TOAST分型。对所有入组患者通过经胸超声心动图声学造影(c TTE)联合经颅多普勒声学造影(c TCD)(即发泡试验)行PFO筛查,两者均为阳性视为存在PFO。分析PFO在急性缺血性卒中中检出率,及PFO并CS的分流量、影像学分布特征及部分封堵术后疗效观察。结果共纳入141例符合标准的急性缺血性卒中患者。隐源性卒中48例(34.0%),非隐源性卒中93例(66.0%)。PFO阳性率在缺血性卒中组、CS组、非CS组中分别为31.2%(44/141)、47.9%(23/48)、22.6%(21/93)。PFO阳性组中,隐源性卒中较非隐源性卒中存在较大的分流量,且差异有统计学意义(P=0.007)。而PFO相关性隐源性卒中与非PFO相关性隐源性卒中患者在其病灶分布的部位、数量之间的差异无统计学意义。PFO封堵术后6月随访未见复发,但尚缺乏对照性研究。结论 PFO及其分流量与CS密切相关,但PFO并CS患者无特异性影像学表现,应加强对此类患者的筛查与管理。     

Cerebral embolism with interventional closure of symptomatic patent foramen ovale: An MRI-based study using diffusion-weighted imaging

Paradoxical embolism via patent foramen ovale (PFO) is an important cause of stroke, especially in younger patients. Transcatheter PFO closure is considered to bear a low risk and to be technically feasable with a high primary success rate. There are no data for the rate of procedure-associated silent embolic events. The present study sought to analyze the total number of cerebral ischemic complications with interventional PFO closure. Thirty-five symptomatic PFO patients (15 male, 26–71 years) with cerebral infarctions proven by magnetic resonance imaging (MRI) were examined by diffusion-weighted imaging (DWI) before and after PFO closure. In the MRI examinations following the intervention, new microembolic lesions were found in three of 35 (8.6%) patients. The lesions were located in the right and left thalamus and the left frontoparietal white matter respectively. Two of three infarcts were clinically inapparent, whereas the third patient suffered from a transient right-sided hemihypaesthesia for 12 h. If the prevention of recurrent cerebrovascular events associated with the presence of PFO is necessary, a low frequency of closure associated silent cerebral embolisms was documented after interventional PFO closure. The rate of microembolic events with neurological deficit was 1/35 (∼ 2.8%).     

Prognosis after percutaneous closure of patent foramen ovale for paradoxical embolism

The long-term risk and risk factors for recurrent embolism after percutaneous closure of patent foramen ovale (PFO) were investigated in 152 consecutive patients with presumed paradoxical embolism. During follow-up, the actuarial freedom from recurrent embolism was 95.1% at 1 year, and 90.6% at 2 and 6 years. A residual shunt after percutaneous PFO closure was a predictor for recurrence (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02). Randomized trials comparing medical treatment with percutaneous PFO closure in the prevention of recurrent embolism are in progress.     

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.

     

Neurosonological examinations]

Neurosonological examinations play an important role in the diagnosis of cerebrovascular disease. The target used to be limited to the extracranial carotid artery but is now extended to the intracranial arteries. Carotid artery ultrasound can evaluate not only the degree of stenosis but also the vulnerability of plaque. Transcranial Doppler can detect the micro-embolus in the intracranial artery. Transesophagial echocardiography and cruralvein ultrasound are indispensable to detect embolic source. Transesophagial echocardiography is able to detect thrombus, tumor and vegitation in the heart, patent foramen ovale (PFO) and atheroma of aorta. Because PFO is found rather commonly in healthy subjects, the detection of deep vein thrombosis (DVT) is essential for the diagnosis of paradoxical embolism. In stroke patients with PFO, RI venography can rarely detect DVT, while cruralvein ultrasound commonly detect DVT in small vein. The demand of neurosonological examinations is considered to increase more and more because of their non-invasiveness and convenience.     

Migraine and Patent Foramen Ovale

Migraine is a widespread disorder with a large impact on society. Patent foramen ovale (PFO) is a common occurrence, affecting about 25 % of the population. Observational studies report PFO to be more prevalent in patients with migraine with aura, and patients with migraine with aura have a higher incidence of PFO. The only population-based study does not support this link. It is possible that an association exists between large-sized PFO and migraine. This association may explain how migraine with aura can be triggered. Numerous studies have reported improved migraine with PFO closure, but the only prospective placebo-controlled trial aimed at closure of PFO in patients with migraine with aura did not support this. At this time, evidence does not support the routine detection and closure of PFO in patients with migraine.     

Prevention of stroke recurrence with presumed paradoxical embolism

Paradoxical cerebral embolism (PCE) through a patent foramen ovale (PFO) should be considered as a cause of ischemic stroke, particularly in young patients without an altenative cause for stroke. PCE is even more important that it is potentially treatable. However, PCE remains often presumed because it rests upon the rarely demonstrated findings of a deep venous thrombosis and a thrombus lodged in the PFO. Recent studies have shown a rather low stroke recurrence rate in patients with PFO and stroke but suggest that some subgroups of patients with a higher stroke recurrence risk exist according clinical, echocardiographical and radiological characteristics. For these subgroups, it seems that a more invasive treatment should be required. There are four therapeutic options; antiaggregants, anticoagulation, transcatheter closure of PFO, and surgical closure of PFO. However, these treatments have yet to be evaluated in clinical trials. Received: 12 September 1996 Accepted: 1 October 1996     

Prevalence of patent foramen ovale in ischemic stroke in Italy: the SISIFO study

Patent foramen ovale (PFO) is a common congenital anatomical defect in the general population with a mean prevalence of 20 %. Transcranial Doppler sonography and echocardiography, both with infusion of agitated saline as an echo contrast, have been introduced for the diagnosis of PFO. Transesophageal echocardiography is considered the gold standard. Several studies have suggested an association between cryptogenetic stroke and PFO, but the role of this condition as a risk factor for stroke is still debated. The aims of this prospective multicentre study are the evaluation of PFO prevalence in the whole ischemic stroke population and the identification of a stroke recurrence profile risk in patients with PFO. All consecutive patients admitted for acute ischemic stroke and with a confirmed diagnosis at discharge are eligible cases for the study. Demographic and vascular risk factors are registered. Clinical severity is summarized by the National Institute of Health stroke scale. Echocardiographic and transcranial studies are performed in each patient to detect the presence of PFO. Prevalence of PFO will be calculated with 95 % CIs. Univariate analysis will be performed to detect the correlation of PFO with different registered factors and multivariable analysis with PFO as independent variable. The present study should contribute to better identify the role of PFO in ischemic stroke risk and recurrence-related events. Qualifying findings of the study are represented by the high number of enrolled patients, the prospective methodology of the study and the presence of secondary instrumental endpoints.     

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.     

应用对比经颅多普勒技术评价偏头痛和卵圆孔未闭的关系

目的：观察门诊有先兆偏头痛（MA），无先兆偏头痛（M0）患者和无头痛人群中卵圆孔未闭（PFO）的发生率，以及产生中或大分流PFO的发生率。方法：经受试者同意后，随机抽取我院神经内科门诊从2006年3月至2007年3月就诊的MA患者38例（男14例，女24例），MO患者44例（男15例，女29例），无头痛对照24例（男10例，女14例）。以肘前静脉注射手振生理盐水作为造影剂，并结合Valsaval动作，行经颅多普勒（TCD）监测，诊断PFO并对分流量进行分级。结果：MA组与对照组比，具有PFO者占42％，高于对照组的20％；其中中分流或大分流者高于对照组，差异有统计学意义。MO组具有PFO者也高于对照组，但差异无统计学意义。结论：MA患者比无头痛人群存在较多的PFO，其巾出现中分流或大分流的显著增多。     

Patent foramen ovale detected by near-infrared spectroscopy in patients suffering from migraine with aura

There is an increased prevalence of patent foramen ovale (PFO) in women with migraine with aura (MwA) compared to controls, but the role of PFO in triggering aura is still debated. The aim of this study was to test a group of women suffering from MwA with nearinfrared spectroscopy (NIRS), to assess the NIRS capability of discriminating between subjects with and without PFO. Eighty-eight MwA patients (mean age 37.4±10.7 years, range 16–62 years) underwent NIRS measurement of the cerebral variations of the oxygenated (O₂Hb) and reduced haemoglobin (HHb) during breath-holding. The prevalence of O₂Hb vs. HHb was used to assess the presence of PFO. As a gold standard, the presence of PFO was assessed by transcranial Doppler sonography (TCD). At the TCD analysis 48 patients (55%) showed PFOs, 32 of which were permanent. NIRS correctly detected 36 subjects out of 40 without PFO, and 38 subjects out of 48 having PFO: sensitivity was 79%; specificity was 90%. All the false negatives were permanent shunts. MwA patients with PFO showed a delayed increase in the O₂Hb concentration and a reduced oxygenation with respect to subjects without PFO. NIRS is effective in identifying the presence of PFO in a MwA population, but TCD achieves better diagnostic performances. The NIRS provides additional information about the cerebral vasoreactivity and highlights substantial differences between patients with latent and permanent shunts that warrant further studies.

     

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.     

Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) can benefit from a less invasive diagnostic method than transesophageal echocardiography (TEE). Thirty-three gate power m-mode transcranial Doppler (pmTCD) was evaluated for its accuracy in diagnosis of PFO and utility in evaluating residual intracardiac right-to-left shunt (RLS) following transcatheter closure. METHODS: The sensitivity of pmTCD and single-gate TCD (sgTCD) to detect contrast bubble emboli through RLS was compared during transcatheter PFO closure. During 100 preclosure diagnostic evaluations and in 81 postclosure assessments, embolic tracks on pmTCD were counted following intravenous contrast injections and were graded using a 6-level logarithmic scale. The accuracy of TEE and pmTCD was separately compared to PFO anatomical findings during transcatheter closures. RESULTS: There were significantly more microemboli detectable on pmTCD (322 +/- 166; 95% confidence interval [CI], 388-257) than on sgTCD (186 +/- 109; 95% CI, 229-143; P < .001). McNemar change tests suggest that the diagnostic capabilities of pmTCD and TEE for detecting PFO are comparable and correspond to the anatomical findings determined during cardiac catheterization (P = .69 and .45, respectively). During 6-month postclosure evaluation (mean = 185 days), 66% of the patients demonstrated successful closure without significant RLS (ie, grades 0, I, or II), and 34% were found to have incomplete closure with significant RLS (ie, grades III, IV, or V). CONCLUSIONS: pmTCD provides greater sensitivity to contrast bubble emboli than does sgTCD. Among candidates for transcatheter closure, pmTCD provides an improved noninvasive method for diagnosing PFO and evaluating transcatheter closure.     

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。