Prevalence Of Patent Foramen Ovale In Patients Research Articles

Patent Foramen Ovale (PFO) in Patients of Cryptogenic Stroke AND Transient Ischemic Attack (TIA): A Real World Experience

Background: Stroke, a leading cause of brain tissue damage, presents a significant health concern globally. Cryptogenic stroke (CS), with an unclear origin, poses diagnostic challenges, with the patent foramen ovale (PFO) implicated in some cases. This study aims to investigate PFO prevalence in North India among patients with cryptogenic stroke, addressing current research gaps.
 Objective: To assess PFO occurrence in patients with cryptogenic stroke and Transient Ischemic Attack (TIA) using Echocardiography.
 Methods & Results: This preliminary study analyzed PFO prevalence in patients with CS and TIA from February 2020 to November 2021, involving 25 participants. Descriptive statistics and the Chi-square test were employed. Key findings include a mean age of 44.80±9.13 years, 64% men, and 36% women. Ischemic stroke accounted for 72% of cases, while TIA represented 28%. PFO prevalence was 44%, with no significant gender-PFO association. No correlations were found between stroke type and PFO presence, nor were comorbidities like hypertension and diabetes observed.
 Conclusion: The study highlights a clinically significant distribution of PFO presence but no notable association between stroke type and PFO presence. These findings contribute to understanding PFO's role in cryptogenic stroke and have implications for clinical practice.

Investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.

The mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement. We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO. Among nine participants, primary cancers were breast (n=6), upper gastrointestinal (n=2),and thyroid (n=1). A positive bubble study was identified in 2/9 (22.2%)participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging. In this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

Prospective investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.

e14510 Background: Brain metastases can lead to significant morbidity and mortality in patients with advanced cancer. Preventing metastatic disease to the brain could thus substantially improve outcomes. The mechanism of brain metastasis is incompletely understood. Circulating tumor cells drain to the right heart and through the pulmonary circulation, where they may manifest as lung metastases, and can circulate further to the left heart and then to the brain. However, in patients who develop brain metastases without prior lung involvement, metastatic cells may take an alternate route. We hypothesized that cancer cells may pass directly from the right to left heart via a patent foramen ovale (PFO), akin to paradoxical embolism. The prevalence of PFO is approximately 20-30% in the general population; if further elevated in this population, PFO may play a role in brain metastasis development, and ultimately, prophylactic PFO closure may provide benefit. We conducted a pilot study to investigate whether PFO is associated with brain metastases in patients without prior lung involvement. Methods: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding lung metastases. Participants underwent a transcranial Doppler study to assess for PFO. Agitated saline was injected intravenously at rest and with Valsalva maneuver. High intensity signals were counted in the middle cerebral arteries for 1 minute after each injection. Spencer grade ≥3 indicated a positive study, consistent with the presence of PFO. Results: We accrued 9 participants who met inclusion criteria. Primary cancers were breast (6 participants), upper gastrointestinal (2 participants), and thyroid (1 participant). A positive study was identified in 2/9 (22.2%) participants. One individual was a female with breast cancer who had no preceding extracranial metastases, and the other individual was a male with duodenal adenocarcinoma whose only prior metastatic disease was distant lymphadenopathy, not active at brain metastasis diagnosis. No participants have developed lung metastases as of their most recent imaging. Conclusions: In this prospective pilot study, we found no increased prevalence of PFO in patients who develop brain metastases without preceding lung involvement compared to estimates for the general population. Though a larger study is needed, the development of brain metastases in these patients may reflect tumors’ biological factors directing metastasis organotropism, rather than a structural pathway.

Epidemiology of Patent Foramen Ovale in General Population and in Stroke Patients: A Narrative Review.

Introduction: Percutaneous closure of patent foramen ovale (PFO) in selected patients with cryptogenic cerebrovascular ischemic events (CEs) decreases the risk of recurrent stroke; however, optimal patient selection criteria are still under investigation. Candidates for PFO closure are usually selected from the pool of CE patients with a high risk of Paradoxical Embolism (RoPE) score. The RoPE score calculates the probability that PFO is causally related to stroke, based on PFO prevalence in patients with CE compared with that in healthy subjects. The latter has been set at 25% based on the average of autopsy and transesophageal echocardiography (TEE) studies.Methods: We conducted a comprehensive review of studies investigating PFO prevalence in general population and in patients with CE and non-CE using autopsy, TEE, transcranial Doppler (TCD) or transthoracic echocardiography (TTE). Studies were excluded if they (1) reported data from referred subjects with underlying cerebrovascular disease or (2) did not specify etiologically the events.Results: In healthy/control subjects, PFO prevalence was 24.2% (1,872/7,747) in autopsy studies, 23.7% (325/1,369) in TEE, 31.3% (111/355) in TCD, and 14.7% (186/1,267) in TTE studies. All diagnostic modalities included PFO prevalence was higher in CE compared with healthy/control population [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.5–3.8] and compared with non-CE (OR = 2.3, 95% CI = 2.0–2.6). In patients with CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (48.9 vs. 27.3%, p < 0.0001, OR = 2.6 with 95% CI = 2.0–3.3) or TCD (58.1 vs. 41%, OR = 1.9, 95% CI = 1.6–2.5), but not TTE (53.3 vs. 37.5%, p = 0.16). Regarding non-CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (20 vs. 12.9%, OR = 1.7, 95% CI = 1.0–2.8) but not TTE (10.4 vs. 7.8%, p = 0.75) or TCD (22.8 vs. 20.1%, p = 0.56).Conclusions: Given the limitations of autopsy and TEE studies, there is good reason not to take a fixed 25% PFO prevalence for granted. The estimation of degree of causality may be underestimated or overestimated in populations with PFO prevalence significantly lower or higher than the established. Given the high sensitivity, non-invasive nature, low cost, and repeatability of TCD, future large-scale TCD-based studies should investigate potential heterogeneity in PFO prevalence in different healthy racial/ethnic populations.

Prevalence of patent foramen ovale in the Greek population is high and impacts on the interpretation of the risk of paradoxical embolism (RoPE) score.

Background:The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely.Methods:Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11–20), and small (⩽10).Results:PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS (p = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124); p = 0.1] and to nonCS [7.1% (4/56), p = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9–10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was <33%.Conclusions:PFO prevalence in the Greek population is much higher than the widely accepted 25%. PFO may be the cause of stroke in one out of nine Greek patients with CS. Among Greek CS patients who harbor a PFO, the latter is causal in one out of five. The established RoPE score cutoff of ⩾7 for having a probable PFO-associated stroke may overestimate the probability in patients deriving from populations with high PFO prevalence.

Abstract TMP88: Prevalence of Right-to-left Cardiac Shunt in the Greek Population is High and Impacts on the Interpretation of the Risk of Paradoxical Embolism (RoPE) Score

Introduction: The RoPE score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFO-af), based on PFO prevalence in patients with cryptogenic stroke compared with that in control subjects. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely. Since PFO prevalence in Greeks remains unknown, we aimed to define it and to calculate PFO-af stratified by RoPE score in a cohort of patients with embolic stroke of undetermined source (ESUS). Methods: Right-to-left cardiac shunt (RLS) was detected according to the international consensus criteria in healthy subjects (H, n=115, women=65) and patients with ESUS (n=84, women=42) ≤55 years old. Each subject underwent unilateral middle cerebral artery transcranial Doppler (TCD) recording (Sonaratek, Natus) with a 2-MHz probe after infusion of agitated saline, at rest and after a controlled Valsalva maneuver. We characterized RLS as large (&gt;20 microbubbles or curtain), moderate (10&lt;x≤20) and minimal (≤10). Statistical comparisons were performed using the Fisher’s exact test. We dichotomized patients with ESUS and PFO into high (&gt;median) and low (≤median) RoPE score groups and calculated the corresponding PFO-af. Results: RLS was detected in 43.5% (50/115) of H and 50% (42/84) of ESUS. Large RLS tended to occur more often in ESUS compared to H [29.8% (25/84)] vs 18.3% (21/115); p=0.06]. The RoPE score median in patients with ESUS and RLS was 8 (interquartile range: 7,9). Patients with high RoPE score (9-10) had PFO-af of 64.4 whereas patients with low score (0-8) had PFO-af of 4.4. For any individual stratum up to RopE score 6, the PFO-af was null. Conclusions: The prevalence of RLS in Greeks is quite higher than the average used by the RoPE study. Despite a 50% chance of having RLS of any size, patients with ESUS have large RLS at least 60% more often than the general population. We suggest that optimal calculation of the PFO-af corresponding to RoPE score strata relies on the accurate estimation of PFO prevalence in national/ethnic populations. The proposed RoPE score cutoff of &gt;6 for having a probable PFO-related stroke may overestimate the probability in patients deriving from populations with high RLS prevalence.

A priori, a posteriori, and back again

Cryptogenic stroke (CS) is common, as is patent foramen ovale (PFO). By chance, they overlap frequently. However, if the relationship was just chance, then PFO prevalence in patients with CS would match the general population (approximately 25%). But PFOs are overrepresented in the CS population (approximately 50%). Paradoxical embolism explains this association—the paradox being a venous source thrombus appearing in an artery (via right-to-left shunt). Because of the high background prevalence, a discovered PFO only has a 50:50 chance of actually causing the stroke in an individual patient.1 The physician asks, “Is the PFO relevant? If I can't know, then why should I look?” Ergo, diagnostic nihilism.

Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke.

Individuals with migraine are at higher risk for stroke, but the mechanism has not been established. On the basis of the association between migraine and intracardiac right-to-left shunt, it has been proposed that stroke in migraineurs could be caused by a paradoxical embolus passing through a patent foramen ovale (PFO) or pulmonary arteriovenous malformation. The aim of this study was to determine the prevalence of PFO with right-to-left shunt in patients who presented with cryptogenic stroke and had a history of migraine. Patients between 18 and 60 years old who presented with an ischemic stroke were characterized based on ASCOD phenotyping (atherosclerosis; small-vessel disease; cardiac pathology; other causes; dissection). A migraine diagnosis was identified by reviewing physician notes, and frequent aura was defined if present in at least 50% of attacks. A PFO with right-to-left shunt diagnosis was identified by the presence of a positive bubble contrast study with either transcranial Doppler, transthoracic, or transesophageal echocardiography. Of the 712 patients who presented with ischemic stroke, 127 (18%) were diagnosed as cryptogenic; 68 patients had adequate testing for PFO and a documented migraine history. The prevalence of PFO in patients with cryptogenic stroke without migraine was elevated (59%) compared with the general population (18%). Patients with both cryptogenic stroke and migraine had a higher prevalence of PFO (79%). In patients with cryptogenic stroke who had migraine with frequent aura, the prevalence of PFO was 93%. Only 5 patients (4%) had a history compatible with migrainous infarction. In patients with cryptogenic stroke who have migraine, there is a high prevalence (79%) of PFO with right-to-left shunt. The timing of the stroke in migraineurs is usually not related to a migraine attack. These observations are consistent with the hypothesis that the mechanism of stroke in migraineurs is most likely because of a paradoxical embolus. Future cryptogenic stroke classification schemes should consider including PFO as a separate etiologic category.

To Be or Not to Be Patent: The Relationship Between Migraine and Patent Foramen Ovale.

Migraine is a common neurological disorder with an uncertain pathogenesis. A pathophysiological link has been proposed between the migraine headache and patent foramen ovale (PFO). However, the data about the association of migraine with the presence of PFO are conflicting. The study aims to prospectively investigate the prevalence of PFO in patients with migraine compared with that of control subjects. A total of 203 migraineous patients and 212 control subjects with similar demographic characteristics to that of case subjects regarding age and gender were included in the study. Transthoracic echocardiography with agitated saline injection was used to evaluate the presence of PFO. PFO was judged to be present if any microbubble was seen in the left cardiac chambers within the first 5 cardiac cycles from the maximum right atrial opacification at rest or after provocative maneuvers. Mean age of the patients was 37.2 ± 9.8 years and 93% were female. Migraine with aura was present in 32% (n = 65) of the patients. The prevalence of PFO was similar in patients with migraine and the control subjects (42% vs 44%; odds ratio 0.90, 95% confidence interval 0.61-1.33, P = .61). Likewise, the prevalence of PFO was similar in migraineurs patients with or without aura (41% vs 42%; odds ratio 0.95, 95% confidence interval 0.51-1.76, P = .87). This study suggest that PFO is not more common in patients with migraine compared with healthy subjects. Therefore, our findings suggest that the relationship between migraine headache and the presence of PFO is questionable.

Correlation of Left Atrial Septal Pouch with the Prevalence of Patent Foramen Ovale: A Retrospective Review

Purpose: To determine the prevalence of Left Atrial Septal Pouch (LASP) and assess the association with Patent Foramen Ovale (PFO). Materials and Methods: We retrospectively reviewed 275 cardiac-gated CT examinations at Indiana University from January 2010 to June 2012, 160 cardiac CTs performed prior to pulmonary vein ablation, 115 for evaluation of coronary artery evaluation. Consensus readings were performed by two readers on a PACS workstation using the Multiplanar Reformat software to identify the presence or absence of LASP and PFO. PFO was diagnosed by the presence of a contrast jet extending from the left atrium to the right atrium. Results: Overall prevalence of LASP was 24.7% (68 LASPs out of 275 patients). There was no Original Research Article Terpenning et al.; CA, 3(2): 122-129, 2015; Article no.CA.2015.010 123 significant difference regarding the gender and age between patients with and without LASP, pvalues 0.054 and 0.63 respectively. The overall prevalence of PFO in both groups is low 2.2% (6 PFOs out of 275 patients). The prevalence of PFO in patients with LASP was 5.9% (4 out of 68 patients) and was 1.0% (2 PFOs out of 207 patients) in patients without LASP. There was a significant difference in prevalence of PFO between patients with and without LASP, p-value 0.035. Conclusions: LASP is a common finding on cardiac CT, its prevalence not affected by age or gender. Patients with LASP have statistically greater prevalence of PFO than patients without LASP, but the prevalence remains low.

Prevalence of migraine headache in an in-patient stroke population.

Migraine, especially with aura, is a risk factor for ischemic stroke. In this study, we investigated descriptive data and prevalence of migraine in an in-patient stroke population. Patients with acute cerebrovascular disease (CVD) admitted to the stroke unit during a 6-month period were recruited. Prevalence of migraine was assessed using a structured questionnaire. Additional clinical data regarding risk factors for CVD were evaluated for all responding patients. A total of 229 patients received a questionnaire and 175 answers were collected (response frequency of 76.4%). Responders matched the initial cohort regarding distribution of age, sex, and type of stroke. Thirty-six cases (20.6%) fulfilled the criteria for migraine or probable migraine according to the 2nd edition of the International Headache Classification (ICHD-2). Sixty percent of migraine patients had migraine with aura. Stroke patients with migraine were younger (P = 0.007), the presence of patent foramen ovale (PFO) was significantly increased (P = 0.008), and atrial fibrillation was less common (P = 0.048). There were no other differences between patients with and without migraine headache regarding conventional risk factors. The prevalence of migraine in this hospital-based stroke cohort was comparable to the estimated prevalence of migraine usually described in population studies. In our study population, the prevalence of migraine with aura was higher than expected. The increased prevalence of PFO in patients with migraine headache corresponds well to previous population studies.

Elevated left ventricular end-diastolic pressure favours closure of foramen ovale

Objective It has been described that prevalence of patent foramen ovale (PFO) declines with age. Our hypothesis was that persistent high pressures in the left atria (LA), may facilitate closure of PFO and age would not play a role.Methods and results The prevalence of PFO was studied in 201 consecutive patients with suspicion of cardioembolic stroke by contrast transoesophageal echocardiography. Left ventricular end-diastolic pressures (LVEDP) were estimated non-invasively by transthoracic echocardiography. Patients with normal diastolic function (DF) or with diastolic dysfunction (DD) stage I were considered as having normal LVEDP whereas patients with DD stage II or III as having elevated LVEDP. Prevalence of PFO was 42.8% and it was smaller in patients with elevated LVEDP than in patients with normal LVEDP (21.2% vs. 51.7%, P< 0.01). There was a smaller prevalence of PFO in patients with DD stage II than in patients with DD stage I or normal DF (25% vs. 51 and 54%, both P< 0.05). Size of the LA was larger in patients without PFO [34.73 ml/m² (24.14–40.84ml/m²) vs. 27.86 ml/m² (21.37–34.68 ml/m²), P< 0.05]. Mean age was 64.2 years (57.38–75.77) with no diff erence between patients with PFO and without PFO. In multivariate analysis Eustachian valve, atrial septal aneurysm, elevated LVEDP and large LA remained signifi cantly associated (P < 0.05) with PFO.Conclusion Elevated LVEDP and enlargement of LA are negatively associated with PFO. The higher the LVEDP, the lower the prevalence of PFO. Age is not associated with PFO.

PFO and Right-to-Left Shunting in Patients with Obstructive Sleep Apnea

Patent foramen ovale (PFO) with right-to-left shunt has a prevalence of 10% to 34% in the general population. It can cause an ischemic stroke, transient ischemic attack, and paradoxical peripheral or coronary embolization. Its influence on migraine and several other diseases and conditions is currently under debate. Attention has recently been turned to the correlation between PFO and obstructive sleep apnea. Thus far, studies on the prevalence of right-to-left shunts as a surrogate for PFO in these patients were limited by small sample sizes and the results have been conflicting. Here, we evaluate the prevalence of right-to-left shunting (RLS) through transcranial Doppler ultrasound (TCD) in a large patient group with obstructive sleep apnea (OSA). One hundred consecutive patients (mean age 59.5 y) with OSA underwent TCD with intravenous injection of agitated saline. The grading of right-to-left-shunts was in accordance with the Spencer PFO Grading Scale. RLS was detected in 72 of 100 patients (72%). Thirty-four out of these 72 patients (47%) had a shunt grade I or II; 15 (21%) had a shunt Grade III or IV; and 23 (32%) had a large shunt (Grade V or V+). In 47 of 72 patients (65%), a right-to-left shunt was detectable at rest without Valsalva maneuver. The prevalence of a RLS in patients with OSA is high. Provided other intracardiac or pulmonary shunts were absent, the high prevalence of a RLS suggests a high prevalence of PFO in patients with OSA.

Abstract 223: Acute Ischemic Stroke in a 23-Year-Old Patient with Verrucous Endocarditis, Prothrombin Heterozygote Mutation, and a Patent Foramen Ovale: A Case Report and Literature Review

Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. Since the etiology of stroke in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report a case of acute ischemic stroke in a 23 year-old patient with multiple risk factors. Case Report A 23 year-old Spanish female with a history of tobacco abuse was brought to the Emergency room after she had a sudden onset of left-side weakness, slurring of speech, and lost of consciousness for a couple of minutes. Physical examination: left upper and lower extremities were completely flaccid with left facial weakness. MRI of head confirmed a right middle cerebral artery regional acute ischemic stroke. Transesophageal Echocardiogram revealed small granular densities on the mitral leaflets that consistent with atypical verrucous endocarditis and a patent foramen ovale (PFO). Hypercoagulable evaluation confirmed prothrombin gene mutation heterozygote. The erythrocyte sedimentation rate (ESR) was 75 mm/hour. All other tests were either negative or in normal range. Anticoagulation therapy was started with Heparin and then switched to Coumadin with an INR target of 2.5. Aspirin was also initiated. Discussion The differential diagnosis in young people (under 50 years) for potential etiology of ischemic stroke is broader than that for older adults. Atypical causes are more prevalent in this population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease. Verrucous endocarditis is small thrombotic and nonbacterial lesions on the heart valves and endocardium, occurring frequently in systemic lupus erythematosus (SLE). However, hypercoagulable states and malignancy are often associated with the formation of verrucous endocarditis. Lesions are usually clinically silent. An embolic stroke may be the first feature to suggest the diagnosis. Since there was no evidence in malignancy, SLE, and antiphospholipid syndrome for our patient, hypercoagulable states should be considered as one of the risks for verrucous endocarditis. About 1-2% of the general population is heterozygous for the prothrombin gene mutation. In contrast, in Spain rates of 6% have been reported. It carries a 2 to 4 times increase in venous thrombosis and also increases the risk of arterial thrombosis (stroke and heart attack). Additionally, studies also show that inherited thrombophilic disorders in the pathogenesis of ischemic stroke might relate to congenital heart diseases such as Prothrombin G20210A variant and Factor V Leiden G1691A mutation might be associated with PFO. The prevalence of PFO in patients who have stroke of unknown cause may be about 40%. PFO also increases the rate of paradoxical thromboembolic stroke. This is particularly true in patients who have had a stroke at an age less than 50 years. Since our patient presents multiple risks for recurrent ischemic stroke, life-long anticoagulant therapy should be considered. Conclusion Acute ischemic stroke in a 23-years-old patient with verrucous endocarditis, prothrombin heterozygote mutation, and a PFO, but absent SLE has been rarely reported. Beside, the authors conclude that hypercoagulable testing and echocardiogram should be performed in young patients with stroke in order to provide us a better understanding of the etiology and the best treatment options.

Ischemic Stroke in Young Patients with Cardiac Abnormalities and Hypercoagulable State: 2 Case Reports and Literature Review to Assess Diagnostic and Prevention Options

Abstract 4663 BackgroundStroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors. Case ReportNo. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke.No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely. DiscussionThe differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS. ConclusionBased on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent. Disclosures:No relevant conflicts of interest to declare.

Cessation of sporadic hemiplegic migraine attacks after patent foramen ovale closure

Patent foramen ovale (PFO) may act as a causal or triggering factor for migraine attacks. A recent quantitative systematic review of the relationship between PFO and migraine has revealed that the already existing data which imply increased prevalence of PFO in patients with migraine attacks, increased prevalence of migraine attacks in patients with PFO, and improvement (even total abolition) of migraine attacks, after PFO closure in migraineurs are supported by little evidence. 3,4 The authors of this review, however, state that no conclusion can be drawn about the efficacy of PFO closure in migraine treatment, as further studies are needed. To our knowledge, we report the first case of a 14-yearold male whose SHM attacks disappeared after PFO closure. The 14-year-old male was admitted urgently to the Department of Developmental Neurology, Medical University of Gdansk, with severe headache (most prominent in fronto-temporal region bilaterally) accompanied by nausea and vomiting preceded by visual disturbances, dysarthria, weakness of the left limbs, and facial asymmetry that appeared about an hour before admission. Twelve months earlier he had been diagnosed in our clinic with probable sporadic hemiplegic migraine (the results of paediatric and neurological examination, neuroimaging, laboratory tests, and electroencephalograph were all negative).

Patent foramen ovale in patients with tension headache: is it as common as in migraineurs? An age- and sex-matched comparative study

The association of patent foramen ovale (PFO) and atrial septal aneurysm (ASA) with migraine headache attack (MHA) has been clearly shown. The same findings have been recently demonstrated also in cluster headache. Although tension-type headaches (TTH) are the most common kind of headache, their association with these atrial septal abnormalities has never been studied before. The study was conducted to clarify whether there was a significant association between the presence of such atrial septal abnormalities and tension headache, when compared with migraineurs. One hundred consecutive patients with migraine and 100 age- and sex-matched subjects with TTH and 50 healthy volunteers with no headache were enrolled in the study and underwent a complete transesophageal echocardiographic study with contrast injections at rest and with the Valsalva maneuver. There was no significant difference between the age and the sex of the participants of the three groups. The overall prevalence of PFO was 23% in patients with TTH and that of large PFOs was only 11%. The 23% prevalence of PFO in patients with TTH was not statistically different from 16% found in our normal control group. Furthermore, we found a significantly higher prevalence of PFO in migraineurs (50%) when compared with patients with tension headache (p < 0.001). This was also true for the collective presence of large PFOs and ASAs (35%) (p < 0.001). Although atrial septal anomalies have an association with MHA, they do not have a significant association with TTH.

Patent foramen ovale in cryptogenic stroke: incidental or pathogenic?

Patent foramen ovale (PFO) is significantly associated with cryptogenic stroke (CS). However, even in patients with CS, a PFO can be an incidental finding. We sought to estimate the probability that a PFO in a patient with CS is incidental. A systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus control subjects with stroke of known cause. Using simple assumptions and Bayes' theorem, we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus control subjects in different age populations, with or without atrial septal aneurysms, and were used to summarize across studies the probability that a PFO in CS is incidental. The summary OR (95% CIs) for PFO in CS versus control subjects was 2.9 (CI, 2.1 to 4.0). The corresponding ORs for young and old patients (< or >or=55 years) were 5.1 (3.3 to 7.8) and 2.0 (>1.0 to 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28% to 39%) in age-inclusive studies, 20% (16% to 25%) in younger patients, and 48% (34% to 66%) in older patients. These probabilities were much lower when an atrial septal aneurysm was present. In patients with otherwise CS, approximately one third of discovered PFOs are likely to be incidental and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an atrial septal aneurysm, suggesting the importance of patient selection in therapeutic decision-making.

Dye dilution and oximetry for detection of patent foramen ovale.

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. 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. 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. 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.

Sex differences in cryptogenic stroke with patent foramen ovale

Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.