The patent foramen ovale–migraine question

Neurological Sciences - A strong association between migraine with aura and patent foramen ovale (PFO) with shunting has been suggested. Similarly, an association of migraine with aura and...     

偏头痛患者伴发心脏卵圆孔未闭脑血管反应性研究

目的探讨心脏卵圆孔未闭(patent foramen ovale,PFO)与偏头痛的相关性,以及偏头痛伴发PFO患者的脑血管反应性差异。方法利用经颅多普勒超声声学造影(contrast transcranial Doppler,cTCD)及经颅多普勒超声(transcranial Doppler,TCD)屏气实验检查,对照分析西安交通大学第一附属医院神经内科2013-03-2013-10 62例偏头痛患者与43例正常志愿者,伴发PFO结果和脑血管反应性。结果偏头痛组PFO阳性率明显高于正常对照组(51.61%vs 27.91%,P=0.015),PFO阳性的偏头痛患者头痛侧大脑中动脉(middle cerebral artery,MCA)屏气指数(breath holding index,BHI)值明显低于PFO阴性患者(0.82±0.58vs 1.34±0.72,P=0.013)。结果偏头痛与PFO共患率高,偏头痛伴发PFO患者头痛侧脑血管反应性降低。     

The diagnostic iter of patent foramen ovale in migraine patients: an update

Patent foramen ovale (PFO) is a frequent finding in migraine patients. The standard technique for PFO diagnosis is actually trans-oesophageal echocardiography (TEE). It requires the injection of a contrast agent unable to pass the pulmonary filter; hence, it is possible to detect a right-to-left shunt by observing the presence of the contrast medium in the cardiac left compartment. The transcranial Doppler (TCD) device accurately measures the blood flow velocities in different cerebral arteries. It can record microembolic signals (MES) backscattered by microbubbles travelling in the cerebral circulation, and distinguish cardiac shunts from pulmonary shunts. The number of MES is correlated to the entity of the shunt. The near-infrared spectroscopy (NIRS) technique tracks the changes in the concentration of oxygenated and reduced haemoglobin in the brain tissue. PFO is revealed by an alteration of the normal vasoreactivity pattern of the subject during functional stimuli. Magnetic resonance imaging (MRI) provides, at the same time, detailed anatomical information and functional measurements. MRI dynamic perfusion sequences can be used to reliably detect PFO either by visual assessment or by signal-time curves in the pulmonary artery and in the left atrium. A good correlation between TEE and MRI grading scores has been demonstrated, even though the interindividual variability of performing the Valsalva manoeuvre could greatly reduce the sensitivity of the method. Further prospective studies are needed to confirm the PFO MRI grading and to assess the sensitivity and specificity of the method.     

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.     

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.     

Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks

Among 215 patients referred for percutaneous closure of patent foramen ovale (PFO) after presumed paradoxical embolism, we assessed the prevalence of migraine. In the year prior to PFO closure, 48 (22%) patients had migraine, twice the expected prevalence of 10 to 12% in the general European population. In patients with migraine with aura, percutaneous PFO closure reduced the frequency of migraine attacks by 54% (1.2 +/- 0.8 vs 0.6 +/- 0.8 per month; p = 0.001) and in patients with migraine without aura by 62% (1.2 +/- 0.7 vs 0.4 +/- 0.4 per month; p = 0.006). PFO closure did not have an effect on headache frequency in patients with nonmigraine headaches (1.4 +/- 0.9 vs 1.0 +/- 0.9 per month; p = NS).     

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.     

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 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.     

Stroke recurrence and its prevention in patients with patent foramen ovale

BACKGROUND: It is unclear whether medical or invasive (surgical or catheter interventional) treatment is preferable to prevent recurrence of cerebral ischemia in patients with patent foramen ovale (PFO) as the suspected cause of stroke and what the role of concomitant risk factors is in stroke recurrence. METHODS: Over a period of ten years, 124 patients (mean age 51 +/- 15 years) with cryptogenic cerebral ischemia and PFO were included into the study and prospectively followed over a mean of 52 +/- 32 months. Of these, 83 were treated medically, 34 underwent transcatheter closure, and seven had surgical closure of the foramen. Of the medically treated patients, 11 stopped medication during follow-up. Recurrent ischemic events and risk factors for recurrence were analyzed. RESULTS: Annual stroke recurrence rates were generally low and comparable in catheter and medically treated patients, and in patients who had stopped medication (2.9%/2.1%2.2%/year). Patients suffering from recurrence after transcatheter closure (n = 2) both had residual shunts. No stroke recurrence was observed in the few surgically treated patients. An atrial septal aneurysm was not a predictor of recurrent or multiple strokes (p > 0.05, OR = 0.31, and OR = 0.74). Large shunts and a history of previous ischemic events were considerably more frequent in patients with recurrent strokes (p < 0.05, OR = 5.0, and OR = 4.4). Pulmonary embolism and case fatality rates were significantly higher in patients with stroke recurrence (p < 0.001, and p < 0.01). CONCLUSIONS: The absolute risk of recurrent cerebrovascular events in patients with PFO receiving medical or catheter interventional therapy is low. The small group of untreated patients had a comparably low rate of stroke recurrences. Previous ischemic events and shunt size were risk factors in this observational study. Given conflicting findings across multiple studies, enrollment into a randomized controlled trial would be the optimal choice.     

偏头痛脑白质病变与卵圆孔未闭相关性研究进展

偏头痛是一种临床常见的原发性头痛,严重危害人类健康和患者生活质量。近年研究表明,偏头痛患者脑白质病变发生率高于正常人群,并独立于其他脑血管病危险因素。而卵圆孔未闭在偏头痛尤其是先兆性偏头痛患者中的发生率较高,二者关系密切,但是否存在因果关系尚存争议。卵圆孔未闭可引起反常栓塞,其在偏头痛发病机制中的作用尚不十分清楚。伴或不伴卵圆孔未闭的偏头痛患者脑白质病变是否存在差异,值得研究。     

合并卵圆孔未闭的脑梗死患者临床及磁共振影像特点分析

目的通过分析合并卵圆孔未闭（PFO）的脑梗死患者的临床特点及MRI弥散加权相（diffusion--weightedimaging,MRI—DWI）的病灶形式,探讨其可能发病机制。方法回顾性分析102例合并不同大小心脏PFO的脑梗死患者的临床资料、经食道超声及MRI资料。结果102例合并PFO的急性脑梗死患者按PFO大小分为两组：小PFO组（〈1．9mm）患者49例（48．03％）,而大PFO组（≥2．0mm）患者53例（51．96％）。小PFO组伴发房间隔膨胀瘤3例,大PFO组合并房间隔膨胀瘤7例,差异有统计学意义（P〈0．05）。大PFO组有51例患者（96．23％）心脏超声显示异常的右向左分流,比例高于小PFO组（25例,51．02％,P〈0．001）。所有患者中静脉异常栓子的来源检出率为20．59％。MRI—DwI示梗死主要分布于前循环,以皮质下穿支动脉梗死为主,两组患者的梗死病灶分布无差异。结论不同大小PFO患者的MRI—DWI上脑梗死病灶特点无差异。卵圆孔未闲患者的梗死病灶以皮质下穿支动脉梗死,可能不同于大动脉粥样硬化性脑梗死发病机制。     

Distribution of artificial cerebral microemboli in stroke patients with patent foramen ovale

Abstract

Objectives: Patent foramen ovale (PFO) is considered as an important risk factor for cerebrovascular diseases. Nevertheless, the relationship between the distribution of highintensity transient signals (HITS), resulting from injection of air mixed with saline and detected by transcranial Doppler (TCD), and clinical cerebrovascular syndromes in these patients has not been investigated.

Methods: Using TCD, we screened 40 patients with stroke or transient ischemic attack (TIA), in whom PFO was proven by transesophageal echocariography (TEE). Of these, 30 patients (75%) with artificially produced HITS either in the middle cerebral artery (MCA) or the basilar artery (BA) were included in the analysis.

Results: Nineteen patients had a stroke or TIA in the carotid territory and 11 patients in the vertebro-basilar territory. HITS were found in the MCA in all 30 patients and in 21 of the 30 patients in the BA. Of the latter, ten patients were in the carotid group and 11 patients were in the veretebro-basilar group, p=0.011.

Conclusion: There is a significant association between the distribution of artificial HITS and the clinical cerebrovascular syndromes.