Prevalence of patent foramen ovale in a large series of patients with migraine with aura, migraine without aura and cluster headache, and relationship with clinical phenotype

A relationship between migraine and patent foramen ovale (PFO) has been observed in relatively small series of patients so far. Furthermore, the exact mechanism underlying such an association remains unknown. In the present study we determined the prevalence of PFO by contrast–enhanced transcranial Doppler (TCD) in a group of 260 patients with migraine with aura (MA+), 74 patients with migraine without aura (MA–), and 38 patients with cluster headache (CH). One–hundred–sixty–one MA+subjects (61.9%), 12 MA–subjects (16.2%), and 14 CH–subjects (36.8%) were PFO–carriers. The association was independent on the frequency of migraine attacks and complexity of aura. Finally, among the 15 patients who had a history of at least one migraine attack occurring during a Valsalva maneuver only one subject turned out to be PFO–carrier. Our findings confirm previous observations of a link between MA+, CH, and PFO. They also suggest that such an association is independent on migraine clinical phenotype and is probably unrelated to the pathogenic mechanism of paradoxical embolism.     

Relationship between migraine and patent foramen ovale: a study of 121 patients with migraine

BACKGROUND: Migraine is a common neurological disorder, the origins of which remain unknown. Patent foramen ovale (PFO) is considered to have a role in migraine. The relationship between migraine and patent foramen ovale may be stronger in patients suffering from migraine with aura compared to patients with common migraine. OBJECTIVES: The aim of the study was to evaluate the frequency of PFO in patients with migraine with aura (MA+) and compare it with the prevalence of PFO in migraine patients without aura (MA-), and in a healthy age-matched control group. We investigated PFO association with migraine, considering such factors as: A type of migraine aura, frequency of attacks, familial occurrence, sex and age of patients. Patients.-121 patients: 61 patients suffering from migraine with aura, 60 without aura and 65 normal controls. The group of patients with migraine with aura was divided into subgroups regarding to the type of aura. METHODS: In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. RESULTS: The presence of PFO was found in 33/61 (54%) patients with MA(+) compared to 15/60 (25%) without aura and 16/65 (25%) control subjects. The difference between MA(+) patients and MA(-) patients and the difference between MA(+) patients and control group was statistically significant (P < .05). There was no association between type of migraine aura and PFO, as well as we found no association between PFO and frequency of attacks, familial occurrence, sex and age of patients and PFO. CONCLUSIONS: Our findings suggest possible association of migraine with aura and PFO. It seems that PFO does not influence the type of aura and frequency of attacks of migraine as well as it is not associated with familial occurrence of migraine.     

Is migraine associated with right-to-left shunt a separate disease? Results of the SAM study

Migraine with aura (MA) is associated with the persistence of patent foramen ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts than controls, suggesting that right-to-left shunt (RILES) determined by PFO could play a role in triggering migraine attacks. Moreover, some preliminary reports have suggested that PFO closure may give relief to both migraine and aura attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) has clinical features that allow a distinction from shunt-unrelated migraine (SUM), in a prospective, multicentre, observational study (SAM study). We enrolled consecutive MA patients, who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. All were systematically screened for RILES with transcranial Doppler, and for coagulation disorders. Overall, 460 patients were included; the SUM and SAM classes comprised 58% and 42% of patients, respectively. SAM patients were significantly younger (34.1 ± 10 vs. 37.1 ± 11 years), had a more frequent family history of migraine (76% vs. 66%) and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The SAM study suggests that the effect of RILES on migraine features is not relevant. The higher family history of migraine in SAM suggests a possible genetic linkage between migraine and RILES.     

Migraine,patent foramen ovale and migraine triggers

Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MAgroup OR 2.7 [1.02–7.17] and in all migraine patients OR 2.5 [1.01–6.11]. According to our results, patients with migraine who have larger RLS tend to recognize activities that increase the extent of the shunt as a trigger of their migraine attacks.     

Patent foramen ovale and migraine: Association, causation, and implications of clinical trials

Patent foramen ovale (PFO) appears to be associated with migraine with aura (MA), probably through cardiac shunting. PFOs may also be comorbid with cryptogenic strokes. Although multiple open-label, retrospective, and case-controlled studies have noted sometimes dramatic reductions of MA after PFO closure, the only prospective sham-controlled study of PFO closure for MA, MIST, was negative for all primary and secondary measures of migraine improvement. MIST did demonstrate an association between MA and severe PFO shunts prospectively. Difficulty with recruitment closed the MIST II and ESCAPE trials; the PREMIUM and PRIMA randomized controlled trials are ongoing at the time of this writing.     

卵圆孔未闭经胸超声心动图声学造影及经食管超声心动图的单中心诊断数据分析

目的对卵圆孔未闭（PFO）的经胸超声心动图声学造影（cTTE）及经食管超声心动图（TEE）诊断数据进行分析,探讨cTTE和TEE检查的结果和临床意义。 方法回顾性选取2014年8月至2019年6月疑诊PFO相关疾病、在解放军总医院第一医学中心超声诊断科行cTTE及TEE检查的患者1164例。分析TEE、cTTE及二者联合方法对PFO的检出率,cTTE对右向左分流起源以及分流量的诊断评估结果,TEE对PFO形态结构特点的诊断结果。 结果1164例患者分为先兆偏头痛（MA）组314例、无先兆偏头痛（MO）组219例、隐源性脑梗死（CCI）和（或）短暂性脑缺血发作（TIA）组279例和其他病变组352例。cTTE和（或）TTE检出PFO 282例（282/1164,24.2%）。4组不同临床分组间PFO检出率差异有统计学意义（χ²=17.94,P<0.001）,其中MA患者PFO检出率最高（98/314,31.2%）。1164例患者中764例接受了cTTE检查,检出PFO170例（170/764,22.3%）;816例患者接受了TEE检查,检出PFO 221例（221/816,27.1%）。412例患者接受了cTTE和TEE联合检查,检出PFO125例（125/412,30.3%）。接受cTTE检查的764例患者中,cTTE检出右向左分流者474例（474/764,62.0%）。其中170例PFO右向左分流患者中,分流量为大量者居多（101/170,59.4%）;383例肺循环右向左分流患者中,分流量为少量者居多（185/383,48.3%）;79例二者合并存在者,分流量为大量者居多（54/79,68.4%）。TEE检出的221例PFO患者中,均可记录PFO宽度,平均宽度为（1.61±0.92）mm,狭长形态PFO78例,平均长度为（10.53±3.52）mm。TEE检出分流132例,其中左向右分流122例,右向左分流1例,双向分流9例;检出房间隔膨胀瘤14例,左心房房间隔袋20例,瓣膜丝状物41例。 结论MA、CCI和（或）TIA患者PFO检出率高于MO和其他疾病患者。TEE与cTTE联合应用可提高PFO检出率。cTTE对于右向左分流的检出以及右向左分流起源的判断具有重要价值。PFO相关疾病患者中,PFO右向左分流多为大量,半数以上存在肺循环右向左分流,在检查中需注意鉴别。     

偏头痛和隐源性脑卒中患者经食管超声心动图右心声学造影特征分析

目的：分析偏头痛和隐源性脑卒中患者经食管超声心动图右心声学造影(c-TEE)特征,探讨 c-TEE在不同疾病右向左分流类型评估中的作用。方法：选取2018年1月至2018年10月我院收治的疑诊右向左分流相关的偏头痛患者146例,隐源性脑卒中患者167例作为研究对象进行回顾性分析。所有入选患者均完成TEE、c-TEE检查,分析患者一般情况,并比较两组间TEE及c-TEE右向左分流阳性结果及c-TEE左房内微气泡来源、分流程度等特征。结果：偏头痛组女性居多,且年龄小于隐源性脑卒中患者(P均＜0.05)。TEE观察到隐源性脑卒中组PFO 患者82例,偏头痛组32例,均未发现肺静脉异常;c-TEE检查中偏头痛组肺相关右向左分流(P-RLS)66例,PFO相关右向左分流(PFO-RLS)80例;隐源性脑卒中组P-RLS 71例,PFO-RLS 96例,c-TEE在偏头痛组的PFO检出率明显高于TEE(P＜0.05),隐源性脑卒中组无明显统计学差异(P>0.05)。两组间c-TEE检查不同类型右向左分流比例无统计学差异(P>0.05),但偏头痛组1级RLS(65/127,51%)显著高于隐源性卒中组(38/153,25%,P＜0.05),其中偏头痛患者的P-RLS和PFO-RLS均显著高于隐源性脑卒中患者( P均＜0.05);隐源性卒中组3级RLS比例 (51/153,33%)显著高于偏头痛组 (22/127,18%)(P＜0.05),其中隐源性脑卒中组PFO-RLS显著高于偏头痛组(P＜0.05)。结论： c-TEE可明确偏头痛和隐源性脑卒中患者右向左分流来源并进行半定量分析,为病因学诊断提供可靠的影像学依据。     

Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ²=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=?2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.     

Microembolic Air Load During Contrast‐Transcranial Doppler: A Trigger for Migraine With Aura?

(Headache 2010;50:1320‐1327) Background.— There is a well‐known association between migraine with aura (MA) and right‐to‐left shunt (RILES) because of patent foramen ovale (PFO). The occurrence of MA attacks after microbubble (MB) injection during contrast‐enhanced transcranial Doppler (ce‐TCD) has been recently described. Objectives.— The aim of this study was to analyze the prevalence of RILES in a consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce‐TCD. Methods.— A total of 159 consecutive MA patients underwent ce‐TCD with air‐mixed saline to disclose RILES. RILES was characterized in terms of MB amount (small‐moderate or large) and occurrence at rest and/or during Valsalva maneuver (permanent or latent). Results.— RILES was revealed in 79/159 patients (～50%). Permanent RILES were detected in 56/79 (71%) and latent RILES in 23/79 (29%) MA patients. The occurrence of a typical MA attack was overall observed in 12/159 patients (7.5%; 95% CI: 4‐12.8%), but arose only in RILES‐positive ones, immediately after ce‐TCD (12/79; 15.2%; P < .001). All 12 patients had permanent RILES (12/56; 21.4%; P = .015) and MA attack was mostly observed in large RILES‐positive patients, even without statistical significance (P = .118). Conclusions.— Microembolic air load could act as a trigger of MA attack. According to recent studies and to the clinical characteristics observed in our patients, microembolization because of MB injection might provoke a decrease in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, MA attack. Larger and prospective studies will be necessary to confirm our data and observe a wider correlation.     

Two-dimensional echocardiography using second harmonic imaging for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies

Right-to-left shunting (RLS), usually through a patent foramen ovale (PFO), has been associated with migraine, cryptogenic stroke and hypoxemia. With emerging observational studies and clinical trials on the subject of PFO, there is a need for accurate diagnosis of PFO in patients being considered for transcatheter closure. While transesophageal echo (TEE) bubble study is the current standard reference for diagnosing PFO, transthoracic echo with second harmonic imaging (TTE-HI) may be a preferable screening test for RLS due to its high accuracy and non-invasiveness. The aim of this meta-analysis was to determine the accuracy of TTE-HI compared to TEE as the reference. A systematic review of Medline, Cochrane and Embase was done for all the prospective studies assessing for intracardiac RLS using TTE-HI compared to TEE as the reference; both TTE-HI and TEE were performed with a contrast agent and a maneuver to provoke RLS in all studies. A total of 15 studies with 1995 patients fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TTE-HI were 91 and 93 % respectively. Likewise, the positive and negative likelihood ratios were 13.52 and 0.13 respectively. TTE-HI is a reliable, non-invasive test with proficient diagnostic accuracies. The high sensitivity and specificity of TTE-HI make it a useful initial screening test for RLS. If the precise anatomy is required, then TEE can be obtained before scheduling a patient for transcatheter PFO closure.     

Prevalence of patent foramen ovale in migraine patients with and without aura compared with stroke patients. A transcranial Doppler study

The aim of this study was to investigate the prevalence of patent foramen ovale (PFO) in a consecutive unselected cohort of migraine patients (with and without aura) and compare it with a group of ischaemic young and elderly stroke patients. One hundred and forty-one migraine patients were compared with 330 stroke patients (130 young patients; 200 elderly patients) selected from our hospital stroke data bank. PFO was assessed with transcranial Doppler sonography with i.v. injection of agitated saline. The prevalence of PFO was 51.7% in migraine with aura (MA) patients, 33.7% in migraine without aura (MoA) patients, 33.8% in young stroke patients and 20.5% in elderly stroke patients (P < 0.001). The prevalence of PFO in cryptogenic stroke in young and elderly stroke patients was, respectively, 41.1% and 25% (P = 0.04). The difference between MA and MoA patients was significant (odds ratio = 2.1). The prevalence of PFO in MA patients is higher than in MoA patients and in young cryptogenic stroke patients.     

Patent Foramen Ovale: Pivotal Role of Transesophageal Echocardiography in the Indications for Closure,Assessment of Varying Anatomies and Post-procedure Follow-up

Patent foramen ovale (PFO) is present in 15%–30% of the general population and has been associated with various pathologic states, including cryptogenic stroke, platypnea–orthodeoxia syndrome, decompression sickness and migraine with auras. Transesophageal echocardiography (TEE) has a major role in the diagnostic evaluation of PFO, as well as in the post-procedural assessment after transcatheter closure. The goals of this article were to synthesize the echocardiographic transesophageal techniques required for accurate PFO diagnosis and careful anatomic assessment of its anatomic variants, to focus TEE indications for device closure as complementary to clinical indications and to assess the role of TEE in the post-procedure follow-up.     

Osmophobia in primary headaches

This study evaluates osmophobia (defined as an unpleasant perception, during a headache attack, of odours that are non–aversive or even pleasurable outside the attacks) in connection with the diagnosis of primary headaches. We recruited 775 patients from our Headache Centre (566 females, 209 males; age 38±12 years), of whom 477 were migraineurs without aura (MO), 92 with aura (MA), 135 had episodic tension–type headache (ETTH), 44 episodic cluster headache (ECH), 2 chronic paroxysmal hemicrania (CPH) and 25 other primary headaches (OPHs: 12 primary stabbing headaches, 2 primary cough headaches, 3 primary exertional headaches, 2 primary headaches associated with sexual activity, 3 hypnic headaches, 2 primary thunderclap headaches and 1 hemicrania continua). Among them, 43% with MO (205/477), 39% with MA (36/92), and 7% with CH (3/44) reported osmophobia during the attacks; none of the 135 ETTH and 25 OPH patients suffered this symptom. We conclude that osmophobia is a very specific marker to discriminate adequately between migraine (MO and MA) and ETTH; moreover, from this limited series it seems to be a good discriminant also for OPHs, and for CH patients not sharing neurovegetative symptoms with migraine. Therefore, osmophobia should be considered a good candidate as a new criterion for the diagnosis of migraine.     

Cytotoxic T lymphocyte antigen 4 polymorphism 49 (A→G) and migraine

Migraine without aura (MO) and migraine with aura (MA) are disorders involving multiple environmental and genetic factors. The A/G polymorphism located within exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA–4) is associated with several HLA–associated multifactorial diseases. The CTLA–4 family shows a negative control on T–cell proliferation and cytokine production (TNF–α and IL–10). In the present study we investigated the contribution of the candidate gene CTLA–4 in migraine pathophysiology. Included in the study were 96 MO and 39 MA migraine patients and 106 healthy individuals as control group. The results showed no statistical difference of allele frequencies between patient group and control group. These results would indicate no association between MA and MO migraine and CTLA–4 polymorphism, excluding any possible role of the CTLA–4 gene as a genetic factor determining susceptibility to migraine.     

Managing migraine headaches experienced by patients who self–report with menstrually related migraine: a prospective, placebo–controlled study with oral sumatriptan

The objective was to evaluate the efficacy and tolerability of oral sumatriptan (100 mg) in patients who self–reported with menstrually related migraine. A prospective, multicentre, randomised, double–blind, placebocontrolled, two–group crossover study was carried out in 20 UK primary and secondary care surgeries. Of 115 patients with a self–reported history of menstrually related migraine that entered the study, 93 patients completed it. Patients treated all migraine attacks for 2 months with sumatriptan (100 mg) and for 2 months with placebo. The primary endpoint was the proportion of patients reporting headache relief at 4 hours for the first treated attack. Only 11% of patients fulfilled the protocol definition of menstrually related migraine. Patients reported a variable pattern of migraine attacks occurring inside and outside the menstrual window. For the first attack, significantly more patients receiving sumatriptan than placebo reported headache relief for attacks occurring inside (67% vs. 33%, p=0.007) and outside (79% vs. 31%, p<0.001) the menstrual period. Sumatriptan was generally well tolerated. Oral sumatriptan (100 mg) is an effective and well tolerated acute treatment for patients who report menstrually related migraine.     

Diffusion MRI during migraine with aura attack associated with diagnostic microbubbles injection in subjects with large PFO

The relationship between migraine with aura and patent foramen ovale (PFO) is still debatable. We report 2 cases of migraine with aura attacks after diagnostic microbubble injection for contrast transcranial Doppler (cTCD), in subjects with large PFO. In one case MR images, including diffusion weighted imaging and apparent diffusion coefficient, performed during aura did not show any signal abnormality. Patients with migraine with aura may have an attack during cTCD, probably by a "non-ischemic" mechanism.     

A case of atypical sporadic hemiplegic migraine associated with PFO and hypoplasia of vertebro-basilar system

We describe the case of a patient with atypical hemiplegic migraine and associated basilar symptoms, where a large patent foramen ovale (PFO) and hypoplasia of basilar artery were found. The longer period of 4-year remission of the headache attacks was coincident with the percutaneous PFO closure. When 5 years after, hemiplegic migraine attacks relapsed, with more relevant basilar symptoms, a mild re-opening of PFO was found. The atypical presentation of attacks with basilar symptoms and prolonged hemiplegia does not strictly fit the diagnostic criteria of ICHD-II.     

超声心动图联合右心声学造影在卵圆孔未闭诊断中的价值探讨

目的:探讨经食道超声心动图(transesophageal echocardiography,TEE)、右心声学造影(contrast transthoracic echocardiography,cTTE)在卵圆孔未闭(patent foramen ovale,PFO)诊断中的应用价值.方法:本研究选取2019年8月...     

A prospective study of migraine with aura attacks in a headache clinic population

In order to investigate the prevalence of migraine with aura (MA) attacks according to the criteria set by the International Headache Society (IHS) for diagnosis down to the three-digit level of classification, and to determine the recurrence and possible variability of MA attacks over time, we conducted a 6-15-month-long prospective study on 64 MA patients (42 women and 22 men) consecutively referred for the first time to the University of Parma Headache Centre. At the end of the follow-up period, diagnosis was the same as at the first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the duration of the study, the average number of attacks for each patient was 5.3 +/- 6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent (69.1% of patients), but migraine aura without headache (29.1%) and migraine with prolonged aura (20.0%) were also common; by contrast, basilar migraine and migraine with acute onset aura were reported only by one patient in either case. Migraine aura without headache was statistically significantly more frequent in males than in females. Our study results suggest that in most cases the frequency of recurrent MA attacks is relatively low and provide interesting indications about the prevalence of the different MA subtypes listed in the IHS classification, albeit in a headache clinic population.     

经胸和经食管超声心动图诊断卵圆孔未闭的对比研究

目的 对比研究经胸超声心动图TTE和经食管超声心动图TEE对卵圆孔未闭(patent foramen ovale，PFO)的诊断方法和诊断价值，及对卵圆孔未闭的临床意义。方法 运用经胸及经食管超声心动图检查，诊断卵圆孔未闭24例，根据患者有无合并其他心脏疾患及合并的心脏疾患的血流动力学特点将患者分为卵圆孔未闭组及卵圆孔开放组。结果 经胸超声心动图通过CDFI观察房水平的穿隔血流对卵圆孔未闭的诊断准确率为58．3％。经食管超声心动图检查能对所有患者做出正确诊断。卵圆孔未闭组可见卵圆孔瓣上缘与继发隔之间裂缝，CDFI显示源于卵圆孔瓣与继发隔交界边缘处的穿隔血流；卵圆孔开放组可见卵圆孔瓣上缘与继发隔之间出现回声缺失，但卵圆孔瓣尚完整，CDFI于缺口处探及垂直于房间隔的穿隔分流束。结论 经食管超声心动图是目前卵圆孔未闭诊断金标准的首选方法。卵圆孔未闭可导致反常栓塞，应予以积极治疗。