Patent Foramen Ovale with Atrial Septal Aneurysm May Contribute to White Matter Lesions in Stroke Patients

Background: Patent foramen ovale (PFO) related stroke has been reported to have higher frequency of hypercoagulable state and “non-specific” subclinical white matter lesions on MRI. While it is interesting to hypothesize that paradoxical embolic events may trigger subclinical infarcts in the setting of prothrombotic state, the associations are unclear. We examined antiphospholipid antibody status, one of the hypercoagulable conditions, with respect to white matter lesions (WMLs) in PFO related stroke to better understand this relationship. Methods: 79 consecutive prospectively recruited non-migrainous PFO-related stroke patients (adjudicated by two vascular neurologists) underwent FLAIR sequence MRI and anticardiolipin antibody IgG, IgM and lupus anticoagulant measurement. Subclinical (or clinically “silent”) white matter lesions (WMLs) were inspected by investigators blind to clinical information using two scales (Fazekas and Scheltens) to insure inter-rater reliability and accuracy. Results: Patients with elevated anticardiolipin titer (n=6; 7.6%; 50% men) had similar age (mean = 53 vs 48) to those with normal titers (n= 73; 92.4%). Of the patients with positive anticardiolipin antibody, mean IgG was 27 GPL (range 21.4-38.6; normal range 0-15); mean IgM was 32.7 MPL (range 22.2-36.6; normal range 0-15), and none had lupus anticoagulant. WMLs were found in both periventricular regions (PV-WML) and in deep white matter (D-WML). Overall, global WML burden is statistically significantly increased in PFO stroke patients with positive anticardiolipin antibody compared to those with negative titers (Fazekas scale - 2.333 vs 1.35 , p < 0.01, Scheltens scale - 2.5 vs 1.54, p < 0.01). This difference remains statistically significant after adjusting for major confounders associated with WML such as diabetes, hypertension, and smoking status. Conclusions: In non-migraineur PFO-related stroke patients with antiphospholipid-associated hypercoagulability, there is greater global WMLs burden than those without any hypercoagulable states. Antiphospholipid antibody positivity may contribute to global burden of WMLs in patients with PFO related stroke, independent of conventional risk factors for WML. WMLs found on MRI FLAIR maybe “footprints” of subclinical embolic events which can potentially be used to follow disease progression and triage more aggressive stroke prevention strategy in this patient population. Further study with a larger disease cohort and other hypercoagulable states are needed to validate these preliminary findings.

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Abstract 2922: Patent Foramen Ovale Is A Cause Of Ischemic Stroke In Patients With Antiphospholipid Syndrome

Stroke ◽

10.1161/str.43.suppl_1.a2922 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Yoshiaki Shimada

Keyword(s):

Ischemic Stroke ◽

Antiphospholipid Syndrome ◽

Patent Foramen Ovale ◽

Multiple Logistic Regression Analysis ◽

Cryptogenic Stroke ◽

Control Group ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

Stroke Patients ◽

Significant Difference

Background: The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis and recurrent fetal loss, and can be an independent risk factor for a first-ever ischemic stroke especially in young female patients. Patent foramen ovale (PFO) has been established as a cause of cryptogenic stroke. Atrial septal aneurysm (ASA) is associated with PFO. Until recently, the precise pathophysiology of APS as causing ischemic stroke has been essentially unknown. In the present study, we investigated the relationship between APS and potential embolic sources including PFO and ASA using transesophageal echocardiography (TEE). Methods: This study was a retrospective case series design. From July 2006 to June 2008, 120 patients with ischemic stroke who admitted to Juntendo University Hospital underwent TEE. In this study period, consecutive ischemic stoke patients diagnosed as APS based on the modified Sapporo criteria were enrolled and classified into APS group. Controls were selected among age- and gender-matched stroke patients without APS who also underwent TEE. We assessed clinical characteristics and presence of embolic sources including PFO and atrial septal aneurysm (ASA) between APS and Control groups. Results: Nine of ischemic stroke patients with APS and 41 controls were included. Primary APS was present in one patient (11.1%) of the APS group, and APS with SLE were found in eight patients (88.9%). There is no significant difference in age, risk factors for ischemic stroke, and MRI findings between two groups. The prevalence of PFO and ASA were significantly higher in APS group compared to Control group (89% vs 41%, P=0.027; 67% vs 20%, P=0.015, respectively). C reactive protein was relatively higher in APS group. Multiple logistic regression analysis showed that PFO (OR: 13.71; 95% CI: 1.01 to 185.62; P=0.049) and ASA (OR: 8.06; 95% CI: 1.17 to 55.59; P=0.034) were independently associated with the APS group. Conclusion: Atrial septal abnormalities including PFO and ASA are strongly associated with APS group, and could be potential embolic sources in ischemic stroke patients with APS.

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Race-Ethnic Differences in Patent Foramen Ovale, Atrial Septal Aneurysm, and Right Atrial Anatomy Among Ischemic Stroke Patients

Stroke ◽

10.1161/01.str.0000085828.67563.42 ◽

2003 ◽

Vol 34 (9) ◽

pp. 2097-2102 ◽

Cited By ~ 35

Author(s):

Carlos J. Rodriguez ◽

Shunichi Homma ◽

Ralph L. Sacco ◽

Marco R. Di Tullio ◽

Robert R. Sciacca ◽

...

Keyword(s):

Ischemic Stroke ◽

Ethnic Differences ◽

Patent Foramen Ovale ◽

Right Atrial ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

Stroke Patients

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A Study on the Relationship Between Patent Foramen Ovale and White Matter Lesions in Migraine Patients

10.21203/rs.3.rs-251075/v1 ◽

2021 ◽

Author(s):

Junyan Huo ◽

Mengxia Wan ◽

Nan Li ◽

Juan Wang ◽

Xiao Cai ◽

...

Keyword(s):

White Matter ◽

Transcranial Doppler ◽

Patent Foramen Ovale ◽

White Matter Lesions ◽

Primary Headache ◽

Transcranial Doppler Ultrasound ◽

Foramen Ovale ◽

Significant Difference ◽

The Difference ◽

The Relationship

Abstract Background Migraine is a common clinical primary headache with unclear aetiology. In recent years, studies have shown that migraine is related to patent foramen ovale, and some patients with migraine have white matter lesions. However, the relationship among the three is unclear.Objective To explore the characteristics of white matter lesions (WMLs) in migraine patients with patent foramen ovale and to predict the occurrence of patent foramen ovale through magnetic resonance imaging (MRI) characteristics in patients with migraine.Methods Seventy-seven patients clinically diagnosed with migraine were examined by transcranial Doppler ultrasound (cTCD) and MRI. The patients were grouped according to the presence of WMLs, with matching by age, sex, hypertension, diabetes, PFO and other characteristic data. We observed the MRI fluid attenuation inversion recovery sequence (FLAIR) image and compared and analysed the difference in WMLs between the PFO-positive group and the PFO-negative group.Results There were 42 cases and 35 cases of migraine with and without WMLs, respectively. A statistically significant difference in near-cortical WMLs with PFO in migraine patients was observed (P=0.001). Logistic regression analysis adjusted by age, sex, hypertension and diabetes identified PFO status as the sole determinant for the presence of near-cortical WMLs (OR = 0.14; 95%CI 0.045–0.421; p < 0.001)Conclusion Near-cortical white matter lesions in migraine patients are related to PFO. Transcranial Doppler ultrasonography may reveal more PFO in patients with migraine and near-cortical WMLs.

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Abstract 170: Role of Patent Foramen Ovale in First and Recurrent Childhood Cryptogenic Arterial Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.170 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Evelyn K Shih ◽

Shobha Natarajan ◽

Christine Falkensammer ◽

Lauren A Beslow ◽

Steven R Messe ◽

...

Keyword(s):

Ischemic Stroke ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Stroke Recurrence ◽

Atrial Septal Aneurysm ◽

Control Analysis ◽

Foramen Ovale ◽

Arterial Ischemic Stroke ◽

Stroke Patients ◽

Retrospective Case

Background: Numerous studies in adults have reported a robust association between patent foramen ovale (PFO) and cryptogenic arterial ischemic stroke (AIS), particularly in younger adults. The association between PFO and stroke in children has not been well characterized and the clinical significance of identifying a PFO in a child with first or recurrent cryptogenic stroke is currently unknown. Methods: We performed a retrospective case control analysis of a 10-year prospectively enrolled cohort of children with acute AIS who underwent transthoracic echocardiogram (TTE) as part of their diagnostic evaluation. We compared PFO prevalence in children with cryptogenic stroke to those with known stroke etiologies and to non-stroke controls. We also assessed stroke recurrence risk in children with vs without PFO and assessed PFO features that may confer higher stroke risk. Results: Of 119 children with first-ever AIS, 59 had TTE available for central review, of which 17 were cryptogenic and 42 had a known cause. PFO prevalence was higher in the cryptogenic stroke group (X, 24%) compared to both the known stroke etiology group (Y, 6%, p = 0.05) and non-stroke controls (Z, 8%, p = 0.05). However, 2 year recurrence free survival rates in stroke patients with PFO did not differ from those without PFO (HR 1.58, 95% CI 0.18-13.62, p = 0.68). PFOs in children with AIS vs controls had numerically more right-to-left shunt at rest (7 vs 0) and atrial septal aneurysm (4 vs 0) but the study was underpowered to look at these factors. Conclusions: In our prospectively enrolled cohort of children with AIS, we found the prevalence of PFO to be higher in children with cryptogenic stroke compared to healthy controls and non-cryptogenic stroke patients. The implication of PFO for risk of recurrence and optimal secondary preventative treatment remains uncertain and require further study.

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Abstract T P134: Size of Patent Foramen Ovale and Recurrent Stroke: A Systematic Review and Meta-Analysis

Stroke ◽

10.1161/str.46.suppl_1.tp134 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Georgios Tsivgoulis ◽

Aristeidis H Katsanos ◽

Ramin Zand ◽

Sotirios Giannopoulos ◽

Christina Zompola ◽

...

Keyword(s):

Systematic Review ◽

Patent Foramen Ovale ◽

Recurrent Stroke ◽

Meta Analysis ◽

Atrial Septal Aneurysm ◽

Foramen Ovale ◽

Stroke Patients ◽

Cerebrovascular Events ◽

Potential Association ◽

Relationship Of

Background&Purpose: There are contradictory data on the potential association between size of patent foramen ovale (PFO) or coexisting atrial septal aneurysm (ASA) and risk of recurrent stroke. We performed a meta-analysis to evaluate the relationship of PFO size and concomitant ASA with recurrent stroke in medically-treated stroke patients with PFO. Subjects&Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available prospective studies reporting recurrent cerebrovascular events defined as stroke and/or transient ischemic attacks (TIA) in medically treated patients with PFO diagnosed by echocardiography and/or transcranial Doppler (TCD). Shunt size was stratified according to validated transeosophageal (TEE) or TCD criteria as “small”, “moderate” or “large”. Coexisting ASA was diagnosed using TEE criteria. Results: We identified 6 eligible studies including a total of 1,727 patients. PFO size (large vs. moderate-small PFO) was not associated with a combined higher risk of recurrent stroke/TIA (RR=1.27; 95%CI= 0.52-3.08; p=0.60; Figure, Panel A) or a higher risk of recurrent stroke alone (RR=1.14; 95%CI= 0.56-2.32; p=0.72; Figure, Panel B). Coexisting ASA was not associated with a combiner higher risk of recurrent stroke/TIA (RR=1.63; 95%CI= 0.89-2.98; p=0.11; Figure, Panel C). There was no evidence of heterogeneity for all analyses (I squared statistic < 50%, p > 0.1 Cohran Q test) across the included studies. Conclusions: Our meta-analysis failed to detect any association between PFO-size and risk of recurrent cerebrovascular events in medically-treated stroke patients with PFO. Similarly, the presence of ASA was not related to risk of recurrent cerebral ischemia.

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Impaired transport function of the left atrium and left atrial appendage in cryptogenic stroke patients with atrial septal aneurysm and without patent foramen ovale

European Journal of Echocardiography ◽

10.1093/ejechocard/jeq164 ◽

2010 ◽

Vol 12 (2) ◽

pp. 140-147 ◽

Cited By ~ 9

Author(s):

J. O. Na ◽

S. Y. Shin ◽

H. E. Lim ◽

C. U. Choi ◽

S. H. Kim ◽

...

Keyword(s):

Left Atrium ◽

Left Atrial ◽

Patent Foramen Ovale ◽

Left Atrial Appendage ◽

Cryptogenic Stroke ◽

Atrial Appendage ◽

Atrial Septal Aneurysm ◽

Transport Function ◽

Foramen Ovale ◽

Stroke Patients

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Abstract P702: How Many Cryptogenic Stroke Patients Should Be Candidates for Patent Foramen Ovale Closure?

Stroke ◽

10.1161/str.52.suppl_1.p702 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Hidetaka Mitsumura ◽

Tomomichi Kitagawa ◽

Maki Tanabe ◽

Takeo Sato ◽

Hiroki Takatsu ◽

...

Keyword(s):

Ischemic Stroke ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Stroke Recurrence ◽

Atrial Septal Aneurysm ◽

Large Artery ◽

Foramen Ovale ◽

Stroke Patients ◽

Ischemic Lesion ◽

Pfo Closure

Background and Purpose: Recent several studies demonstrated that percutaneous patent foramen ovale (PFO) closure reduced the risk of stroke recurrence for patients with cryptogenic stroke (CS) and PFO. Our aim of this retrospective study is to survey the frequency of CS, which can be an indication of PFO closure. Methods: Subjects were consecutive stroke patients with symptomatic ischemic lesion detected by magnetic resonance imaging. Of them, CS were extracted according to exclusion of small-vessel collusion, large-artery atherosclerosis, cardioembolism, definite case of aortogenic embolism, and distinctive causeof ischemic stroke such as arterial dissection, hypercoagulable state and so on. After that, we selected patients in accordance with clinical guideline of PFO closure recommended by the Japanese Stroke Association (Figure). We analyzed the prevalence of CS with right-to-left shunt (RLS) as a good and recommended candidates for PFO closure. Results: Among 1,374 ischemic stroke patients from October 2012 to September 2019 , CS were 240 patients (83 females, mean age of 66 years, 17% of subjects). Of them, 100 patients (42%) had RLS (PFO; 65, atrial septal defect; 1, pulmonary arteriovenous fistula; 1, positive on transcranial Doppler (not performed in TEE) including 21 cases of definite of paradoxical embolism. In 65 patients of CS with PFO, 30 patients younger than 60 years (13% of CS) were good candidates for PFO closure. Moreover, 22 of 1,374 (1.6%) patients who were recommended candidates had one or more high risk factors of PFO, for example large shunt, atrial septal aneurysm, and the presence of shunt at rest (Figure). Conclusions: In our preliminary survey, 2% of acute ischemic stroke should be PFO closure candidates.

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