Risk Factor For Cryptogenic Stroke Research Articles

Risk factors for the development of cryptogenic stroke and the predictive value of right-to-left shunt in patent foramen ovale.

The purpose of this study was to evaluate the relationship between the right-to-left shunt of the patent foramen ovale and the risk score for paradoxical embolism in cryptogenic stroke, as well as the risk factors for the development of cryptogenic stroke. A retrospective analysis was performed on 257 patients with cryptogenic stroke who were diagnosed and treated in our hospital from February 2020 to January 2022 as a study group, and 98 patients who were diagnosed and treated at the Department of Neurology in our hospital at the same time and excluded from stroke, were selected as the control group. Transcranial Doppler ultrasound acoustic contrast testing was used to grade right-to-left shunts of patent foramen ovale. Clinical information of individuals who had cryptogenic strokes was examined. The correlation between the right-to-left shunt of patent foramen ovale and the risk score for both cryptogenic stroke and paradoxical embolism was analyzed. The factors affecting the occurrence of cryptogenic stroke were investigated. The correlation between right-to-left shunt and paradoxical embolism risk score was explored. Receiver operator characteristic curve (ROC) analysis was used to evaluate each factor's clinical usefulness in predicting the occurrence of cryptogenic stroke. No difference was observed in the history of hypertension, low-density lipoprotein, C-reactive protein and fibrinogen between the control group and the study group (p<0.05). In the study group with patent foramen ovale, the proportion of patients with grades I and II of the right-to-left shunt of patent foramen ovale was significantly lower than that in the control group, while the percentage of patients with grades III and IV was obviously greater than that in the control group (p<0.05). Right-to-left shunt grade, C-reactive protein, and fibrinogen were independent risk factors for cryptogenic stroke by logistic multivariate regression analysis (p<0.05). With an increase in the right-to-left shunt of the patent foramen ovale, patients' risk scores for paradoxical embolism increased considerably (p<0.05). In patients with cryptogenic stroke, the right-to-left shunt grade of the patent foramen ovale was positively connected with the paradoxical embolism risk score (r=0.331, p<0.001). ROC analysis results showed that the areas under the curves (AUC) of right-to-left shunt grading, C-reactive protein, and fibrinogen were 0.651, 0.871, and 0.779, respectively. The combination of the three indexes had an AUC of 0.908, a sensitivity of 87.90%, a specificity of 82.70%, and a Youden index of 0.706, indicating a high predictive value of the combination. The right-to-left shunt of patent foramen ovale was an independent risk factor for cryptogenic stroke, which was positively correlated with the paradoxical embolic risk score. Its combination with clinical serologic indexes had a high clinical value for predicting cryptogenic stroke.

Embolic myocardial infarction associated with patent foramen ovale: a case series

A patent foramen ovale (PFO) is a fairly common mild cardiac defect that causes a shunting across the atrial septum. PFO is also a known risk factor for cryptogenic stroke. Much less frequently, PFO is associated with non-cerebral systemic embolic events. The article describes a case series of paradoxical embolism of the coronary arteries (CA), which caused myocardial infarction (MI). The presence of PFO was confirmed by imaging techniques. Subsequently, the patients underwent successful endovascular closure of the PFO. Thus, paradoxical CA embolism is a rare and underdiagnosed cause of acute MI. It should be considered in patients with MI and a low risk of atherosclerotic coronary artery disease. However, in most cases, it is not possible to verify the source of the embolism. The significance of occluder implantation as one of the treatment tactics requires further clarification.

Atrial Cardiomyopathy and Cryptogenic Stroke

Background The frequency of cryptogenic stroke (CS) is about 30% of all cases of ischemic stroke (IS). Patients with CS represent a heterogeneous group of patients and require an individualized approach to antithrombotic therapy for secondary prevention. The frequency of development of repeated acute cerebrovascular events in patients with CS is 4.5% per year, which exceeds this indicator in patients with an established pathogenetic variant of IS. Until recently, the dominant point of view, suggesting that the main cause of CS is paroxysmal atrial fibrillation (AF) and for the secondary prevention of IS in this cohort of patients, oral anticoagulants may be more effective than antiplatelet agents, has not been confirmed. The causal relationship between IS and AF is currently not fully understood. Apparently, AF serves as a marker of atrial cardiomyopathy, which is the direct cause of IS. Aim of study Raising the awareness of neurologists about the causes, pathogenetic mechanisms of development and methods for diagnosing IS in patients with atrial cardiomyopathy. Material and methods To achieve this aim, the results of scientific studies on atrial cardiomyopathy as a risk factor for CS were analyzed. The literature search was carried out in electronic search systems Scopus, eLibrary, PubMed using the keywords: ischemic stroke, cryptogenic stroke, atrial cardiomyopathy, pathogenesis of ischemic stroke. Scientific articles published between 1957 and 2021 were selected to be analyzed. And 36% of the analyzed papers on the topic of CS were published no more than 5 years ago. Conclusion The cumulative evidence suggests that atrial fibrillation is not the only cause of embolic events in patients with evidence of atrial dysfunction. Atrial cardiomyopathy can be the cause of thromboembolic syndrome and cryptogenic stroke, even in the absence of atrial fibrillation, therefore, the latter should be considered as a common manifestation of the underlying atrial cardiomyopathy. Since the majority of cardiac thrombi in patients with atrial fibrillation originate in the left atrium, it is likely that patients with atrial cardiomyopathy and cryptogenic stroke represent a group of patients who may be indicated for anticoagulant therapy as a secondary prevention of ischemic stroke and systemic embolism. However, this hypothesis needs to be confirmed.

Multimodality imaging approach of patent foramen ovale: Practical considerations for transient ischemic attack/stroke.

A patent foramen ovale, which is present in up to 25% of the population, is a risk factor for cryptogenic stroke (which accounts for 15%-40% of strokes) and transient ischemic attack via paradoxical embolism. This narrative review focuses on the multimodality imaging approach of the diagnosis and periprocedural guidance of patent foramen ovale, with an emphasis on the use of agitated saline as contrast medium in echocardiography, starting from embryologic aspects. Therefore, we aimed to make a concise and complete presentation of the protocol used for this type of evaluation, along with multimodality imaging approach of the patent foramen ovale and practical considerations for transient ischemic attack/stroke.

The blood pressure variability in patients with cryptogenic stroke

BackgroundIncreased nighttime BP variability (BPV) was associated with stroke. Left atrial (LA) enlargement is the default clinical hallmark of structural remodeling that often occurs in response to LA pressure and volume overload. Blood pressure has proven to be an essential determinant of LA enlargement. We aimed to evaluate the influence of BPV as a risk factor for cryptogenic stroke and highlight the importance of including the (APBM) in the workup for those patients and test the relation between BPV and LA remodeling in these patients, which could be used as a clue to add APM monitoring to their workup. Also, LA remodeling may be a substrate for occult atrial fibrillation (AF). We included Group I (108 consecutive patients with cryptogenic ischemic stroke) and Group II (100 consecutive adult participants without a history of stroke or any structural heart disease). We measured the maximal LA volume index (Max LAVI) and minimal LA volume index (Min LAVI). We calculated the left atrial ejection fraction (LAEF). All the participants were subjected to ABPM.ResultsIn our prospective, cross-sectional cohort study, the patients in Group I had statistically significantly higher Min LAVI and Max LAVI and Less LA EF than Group II, with a P value of (0.001, 0.001, and 0.008), respectively. The Group I patients had higher BPV as measured by SD parameters than patients in Group II, with a P value of 0.001 for all SD parameters. The BPV parameters, as measured by SD parameters, were positively related to the LA remodeling parameters in both groups. After adjusting all variables, we found that age, night systolic SD, and night diastolic SD parameters were independent predictors of LA remodeling.ConclusionsThe patients with cryptogenic stroke had higher short-term BPV, Min LAVI, and Max LAVI but lower LA EF. Careful monitoring of BPV may be of value for both primary and secondary preventions of ischemic stroke.

Patent foramen ovale as a cause of cryptogenic ischemic stroke

A patent foramen ovale from an anatomical and physiological point of view is a normal communication between the atria, which is present in utero and allows oxygenated placental blood to reach the fetal arterial circulation. With incomplete postpartum fusion of the primary and secondary septa, a patent foramen ovale is formed. In the last two decades, clinical interest in the problem of the patent foramen ovale is dictated by the fact that its role in the development of such clinical syndromes as ischemic stroke, myocardial infarction, pulmonary embolism, migraine and decompression sickness of divers has been established, as well as the introduction of endovascular techniques for endovascular transcatheter closure of the atrial septal defect. It was found that the frequency of patent foramen ovale detection in patients with cryptogenic stroke is on average 2 times higher than in patients with an established cause of ischemic stroke and ranges from 40% to 50%.Aim of study. Raising awareness of neurologists about the causes, pathogenetic mechanisms of development, methods of diagnosis and treatment of ischemic stroke in patients with patent foramen ovale.Material and methods. To achieve this goal, the results of scientific research devoted to patent foramen ovale as a risk factor for cryptogenic stroke were analyzed. The literature search was carried out in electronic search engines Scopus, eLibrary, PubMed using the keywords: «ischemic stroke», «cryptogenic stroke», «patent foramen ovale», «pathogenesis of ischemic stroke». Scientific articles published between 1878 and 2021 were selected for analysis. 31% of the analyzed works are not older than 5 years.Conclusion. The patent foramen ovale is etiologically associated with cryptogenic stroke. Possible mechanisms of ischemic stroke in patent foramen ovale patients include in situ thrombosis, paradoxical embolism, and atrial arrhythmias. Transcatheter endovascular closure of patent foramen ovale with anatomical signs of a high risk of cerebrovascular events in combination with antiplatelet therapy are indicated for patients with cryptogenic stroke aged 18 to 60 years as an optimal means of secondary prevention of ischemic stroke.

Short-term results of percutaneous closure of a patent foramen ovale guided by transoesophageal echocardiography in patients with cryptogenic stroke: a retrospective study

BackgroundA patent foramen ovale (PFO) is a risk factor for cryptogenic stroke (CS), and interventional therapy for PFO can reduce the recurrence rate of CS. However, interventional therapies are primarily guided by X-ray imaging, and data on regular post-surgical follow-up with the transthoracic ultrasound foaming test (UFT) are rare. Thus, this study aimed to assess the short-term (12 months) results of PFO occlusion guided by transoesophageal echocardiography (TEE) and the results of regular UFTs.MethodsClinical records, echocardiographic data, and UFT results of 75 patients who underwent interventional therapy for PFO and CS were retrospectively analysed. The patients were grouped according to their preoperative UFT results: group A (n = 21), small volume of right-to-left shunts; group B (n = 22), moderate volume of right-to-left shunts; and group C (n = 32), large volume of right-to-left shunts. All patients were treated with an Amplatzer occluder under TEE guidance. UFT follow-up was conducted regularly until 12 months after surgery.ResultsNo significant differences in preoperative data, length of hospital stay, or operative time were noted between the groups (p > 0.05). The length of the PFO and diameter of the occluder differed between the groups as follows: group A = group B < group C (p < 0.001). Notably, 1 patient in group C developed recurrent stroke 11 months postoperatively, and 2 patients in group C developed atrial arrhythmia, which improved after 3 months of antiarrhythmic treatment. However, 19 patients still had positive UFT results 12 months postoperatively. Furthermore, the positive UFT rate 12 months postoperatively differed between the groups as follows: group A = group B < group C (p < 0.05). A preoperative large-volume shunt was negatively associated with a negative UFT rate 12 months postoperatively (OR = 0.255, 95% CI: 0.104–0.625).ConclusionsIn patients with PFO and CS, interventional therapy guided by TEE could lead to satisfactory short-term (12 months) outcomes. Although the positive UFT rate gradually decreased, some patients still had positive UFT results 12 months postoperatively. Preoperatively, a large volume of right-to-left shunts and a longer PFO were the two risk factors for positive UFT results postoperatively. Further studies are required to clarify the relationship between postoperative positive UFT results and stroke recurrence.

Oncologic Diseases as a Risk Factor for Cryptogenic Stroke

Background. Acute cerebrovascular accidents in general, and ischemic stroke (IS) in particular, are multifactorial diseases with extremely heterogeneous and numerous risk factors. Currently, despite the development of diagnostic technologies, in approximately 25% of patients with IS, it is not possible to establish the causes and mechanism of its development (the so-called cryptogenic stroke (CS)). As a result, the optimal antithrombotic therapy as a secondary prevention in this group of patients remains unclear. It was found that in 10–20% of patients with CS, a detailed examination reveals oncological disease (OD). It is highly likely that the prevalence of OD-related IS will increase. The US National Cancer Registry has shown a decrease in mortality in patients with the most common forms of OD (lung, breast and prostate cancer). Active OD is a proven risk factor for both IS and other thrombotic events. Nevertheless, about 50% of IS in patients with OD are classified as cryptogenic, which significantly exceeds this indicator in patients without OD. This is associated with the difficulties of intravital diagnosis of the pathogenetic mechanism of IS in patients with OD.Aim of study. Raising the awareness of neurologists about the causes, pathogenetic mechanisms of development and methods of diagnosing IS in patients with OD.Materials and methods. To achieve this goal, the results of scientific research on OD as a risk factor for CS were analyzed. The literature search was carried out in electronic search engines Scopus, eLibrary, PubMed by keywords: ischemic stroke, cryptogenic stroke, cancer, pathogenesis of ischemic stroke. Scientific articles published between 1856 and 2021 were selected for analysis, 45% of the analyzed papers on the topic of CS were published not earlier than 5 years ago.Conclusion. The cause of the development of ischemic stroke can be both the oncological process itself and the means and methods of treating it. Despite the fact that in 10–20% of patients with cryptogenic stroke OD is diagnosed, the question remains whether patients with cryptogenic ischemic stroke should be screened for latent oncological pathology, and if so, how full should the screening be. Typical radiological patterns of ischemic stroke in patients with OD are multiple foci of acute cerebral ischemia in different vascular areas, which may indicate a cardioembolic nature and, in particular, non-bacterial thrombotic endocarditis. Lifetime diagnosis of the causes of cryptogenic stroke in patients with OD is extremely difficult. Since nonbacterial thrombotic endocarditis is one of the leading causes of cryptogenic stroke in the setting of cancer, it is advisable to perform transesophageal echocardiography due to the low sensitivity of transthoracic echocardiography.

Acute Ischemic Stroke Due to Paradoxical Embolism from Spontaneous Thrombosis of Large Varicosity – A Case Report

Paradoxical embolism can have different kinds of manifestation, with cerebrovascular accidents being the most commonly reported. Several studies have proposed that Patent Foramen Ovale (PFO) is a major risk factor for cryptogenic stroke and the mechanism is assumed to be paradoxical embolism. PFO occurs when the foramen ovale fails to close after the birth and a hole is developed between left and right atria. Many cases of embolism through PFO in patients with Deep Vein Thrombosis (DVT) and in patients who received sclerotherapy for varicose vein have been reported. But we present a rare case of spontaneous thrombosis through PFO and associated stroke in a patient with no other significant risk factor than a varicosity in the lower limb. The PFO can act as the conduit for the clot. Many a times, the causes of the stroke like paradoxical embolism may be overseen. In this case, the Trans Esophageal Echocardiography (TEE) confirmed the presence of PFO and clinical examination and doppler of the lower limb revealed the presence of enlarged varicosities. Hence, thorough workups are needed to confirm the etiology and prevent further strokes, especially in the young patients. Also, to avoid such risk, any atrial septal defects must be repaired as early as possible.

Multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia

Background and objectivesAtrial fibrillation is a known risk factor for cryptogenic stroke and therefore requires early detection and prompt management. We investigated predictors of stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia but not atrial fibrillation.Subjects and methodsWe investigated 390 patients (219 men, mean age 67 ± 12 years) diagnosed with stroke and non-sustained atrial tachycardia on 24-h Holter monitoring and recorded the total number of atrial premature contractions identified by the Holter monitor. Multiple atrial premature contractions were defined as atrial premature contractions > 34 beats/day. We analyzed the rates of 5-year freedom from stroke recurrence or atrial fibrillation and investigated independent predictors of stroke recurrence and undiagnosed atrial fibrillation.ResultsThe mean follow-up period was 35 ± 21 months, and the overall stroke recurrence rate was 9.0%. Kaplan–Meier survival analysis revealed that the rate of freedom from stroke recurrence was significantly lower in patients with multiple atrial premature contractions. Also, the patients with multiple atrial premature contractions had higher cumulative incidence rate of new-onset AF (p = 0.019). Multivariate analysis showed that multiple atrial premature contractions (hazard ratio 2.49, 95% confidence interval 1.05–5.88, p = 0.038), cigarette smoking status (hazard ratio 2.66, 95% confidence interval 1.15–6.17, p = 0.022), and the left atrial volume index (hazard ratio 1.05, 95% confidence interval 1.01–1.09, p = 0.020) were significantly associated with stroke recurrence in patients with cryptogenic stroke. However, these factors were not statistically significant predictors of future onset of atrial fibrillation.ConclusionsMultiple atrial premature contractions were significantly correlated with an increased left atrial volume index, which could predict future onset of atrial fibrillation and stroke recurrence. This study showed that multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke without atrial fibrillation.

Patent Foramen Ovale Channel Morphometric Characteristics as Risk Factors for Cryptogenic Stroke

It is still disputable whether the specific morphological properties of the patent foramen ovale (PFO) may contribute to the occurrence of stroke. Therefore, the aim of this study was to evaluate the differences in the morphometric and functional features of the PFO channel in cryptogenic stroke and non‐stroke patients. A total of 106 consecutive patients with cryptogenic stroke and 93 non‐stroke control patients with diagnosed PFO (by transesophageal echocardiography) were analyzed. Multivariate regression logistic analyses indicated PFO channel length change (OR: 2.50 [95%Cl:1.75–3.55], p&lt;0.001), the PFO length/height ratio during the Valsalva maneuver (OR: 0.75 [95%Cl:0.60–0.95], p=0.015), septum primum thickness (OR: 0.34 [95%Cl:0.14–0.80], p=0.013), septum secundum height (OR: 0.91 [95%Cl:0.84–0.98], p=0.013), the presence of an atrial septal aneurysm (OR: 3.38 [95%Cl:1.27–8.97], p=0.014), and large shunt (OR: 2.49 [95%Cl:1.13–5.46], p=0.022) as PFO‐related risk factors for stroke. A MorPFO score was developed (AUC=0.816, SD=0.031), where six factors were included: PFO channel length reduction (≥ 23%) (3 pts), low length/height ratio during the Valsalva maneuver (≤ 2.1) (1 pt), thin septum primum (≤ 1.5mm) (1 pt), short septum secundum (&lt; 5.6mm) (1 pt), presence of an atrial septal aneurysm (1 pt), and large right‐to‐left shunt (1 pt). Patients with scores of 0–2 pts had low‐risk PFO channels, 3–4 pts intermediate‐risk PFO channels, and 5–8 points high‐risk PFO channels. In conclusion transesophageal echocardiography can be used to determine the PFO‐related risk of stroke. MorPFO score may help to identify high‐stroke‐risk PFO channels.

Left ventricular wall motion abnormality is associated with cryptogenic stroke.

Left ventricular wall motion abnormality (LVWMA) unrelated to known cardiac risk factors is an uncertain risk for stroke. We evaluated whether LVWMA was associated with cryptogenic stroke. This retrospective, observational study included 4316 acute ischemic stroke patients, and the association between cryptogenic stroke and LVWMA was examined in comparison with other stroke subtypes. The prevalence of LVWMA was 10.0% in the study population. In a fully adjusted, binary logistic regression, LVWMA was independently associated with cryptogenic stroke compared with stroke from large artery atherosclerosis (odds ratio = 1.627, 95% confidence interval = 1.129-2.345), small vessel occlusion (odds ratio = 1.948, 95% confidence interval = 1.261-3.010), or other causes (odds ratio = 4.950, 95% confidence interval = 1.145-21.412). Meanwhile, the association of LVWMA with cryptogenic stroke was similar to the associations of LVWMA with cardioembolic stroke (odds ratio = 0.758, 95% confidence interval = 0.525-1.094) and stroke with two or more causes (odds ratio = 0.992, 95% confidence interval = 0.609-1.615). In multinomial regression, LVWMA had the strongest association with cardioembolic stroke, followed by cryptogenic stroke and stroke from two or more causes. The strength of the associations with LVWMA then decreased sequentially in patients with large artery atherosclerosis, small vessel occlusion, and other causes. The association of LVWMA with cryptogenic stroke was comparable to that of LVWMA with cardioembolic stroke but stronger than that of LVWMA with non-cardioembolic stroke. LVWMA unrelated to known cardiac risk factors could be considered an independent risk factor for cryptogenic stroke.

Left-Sided Atrial Septal Pouch is a Risk Factor for Cryptogenic Stroke

The atrial septal pouch is an anatomic variant of the interatrial septum. The morphology of the left-sided septal pouch (LSSP) may favor blood stasis and predispose to thromboembolic events. The aim of this study was to determine the association between LSSP presence and cryptogenic stroke. A total of 126 consecutive patients with cryptogenic stroke and 137 age-matched control patients without stroke were analyzed retrospectively. The presence and dimensions of LSSPs were assessed using transesophageal echocardiography. LSSP was present in 55.6% of patients with cryptogenic stroke and in 40.9% of those without stroke (P=.02). In univariate analysis, patients with LSSP were more likely to have cryptogenic stroke (odds ratio, 1.81; 95% CI, 1.11-2.95; P=.02). After adjusting for other risk factors using multiple logistic regression, the presence of an LSSP was found to be associated with an increased risk for cryptogenic stroke (odds ratio, 2.02; 95% CI, 1.19-3.41; P=.01). There were no statistically significant differences in size of the LSSP between patients with and those without stroke (P>.05). There is an association between the presence of an LSSP and an increased risk for cryptogenic stroke. More attention should be paid to clinical evaluations of LSSPs.

Abstract TP160: May-Thurner Syndrome is Associated With Stroke Due to Paradoxical Embolism

Background: May-Thurner Syndrome (MTS) is a potential risk factor for cryptogenic stroke (CS). While retrospective reports have found important association with MTS in CS, prospective data has been lacking. In this study, we prospectively explored the epidemiology and clinical correlates of MTS patients with cryptogenic stroke. Method: Eligible patients were prospectively recruited in accordance with an IRB-approved protocol. All patients underwent full evaluation of etiopathogenesis of stroke such as MRI/MRA, long-term cardiac telemetry (&gt;30 days), echocardiography, and extensive thrombophilia screen (AT3, FV Leiden, Proteins C and S; prothrombin gene mutations, APLAbs, lipoprotein(a), homocysteine) and 1.5T pelvic MRV. Results: We prospectively recruited 1,131 acute ischemic stroke patients, with 59 patients with PFO-related CS; 15 (40.5%) had May-Thurner anatomy (MTA), and 6 (16.2%) had MTS. MTS pts are younger (36.33±9.95 vs. 53.35±14.78, p=0.011), with a lower trend for BMI (24.40±4.87 V.S. 31.13±8.75, p=0.051, table 1). Lower BMI is predictive of MTS in CS (&lt;=22) with high specificity 93.3% (AUC=0.756, p=0.007). Conclusion: In this prospective study, we found MTA and MTS to be very common in PFO CS patients - especially in younger patients with lower BMI and without traditional stroke risk factors. MTS is a novel risk factor that may aide in the diagnosis of PFO CS, and needs further study.

CRT-800.44 Complex Left Appendage Morphology Is An Independent Risk Factor For Cryptogenic Stroke

The cause of cryptogenic stroke is unknown. Even long term rhythm monitoring has failed to reveal atrial fibrillation.We hypothesized that complex left atrial appendage morphology is independent risk factor for cryptogenic stroke. This is a single-center, retrospective case control study of

Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults.

Protein Z (PZ) is a vitamin K-dependent plasma protein that exhibits both pro- and anticoagulant properties. Both low and high PZ levels have been linked to ischaemic stroke. Although PZ-lowering gene variants have been found to be less common in ischaemic stroke, the relationship remains unclear. We investigated PZ levels and PROZ variants in a multi-ethnic case-control study of unexplained stroke in participants aged 18 to 64. Plasma PZ was measured in cases (≥2 months post-stroke) and controls. PZ polymorphisms G79A (rs3024735) and A13G (2273971) were genotyped. A combined genetic score (0-4 minor alleles) was created assuming additive effects. A total of 715 individuals (1:1.4 cases:controls) was included. Analyses revealed evidence of a non-linear association. After adjusting for demographic and clinical covariates, PZ levels >2.5 µg/ml (90th %ile) were significantly associated with cryptogenic stroke (OR 2.41 [95 % CI 1.34, 4.34]) as compared with lower levels. Higher genetic score was related to progressively lower levels of PZ, and the presence of four minor alleles was associated with lower odds of stroke (adjusted OR 0.26 [95 % CI 0.07, 0.96]) versus 0 minor alleles. In this multi-ethnic study of young and middle-aged adults, there was evidence of a non-linear positive association between PZ level and unexplained stroke, with a directionally consistent association for genetic variants related to PZ levels and cryptogenic stroke. These findings support elevated PZ levels as a risk factor for cryptogenic stroke.

Patent Foramen Ovale With Atrial Septal Aneurysm Is Strongly Associated With Migraine With Aura: A Large Observational Study.

BackgroundA patent foramen ovale (PFO) with atrial septal aneurysm (ASA) has been identified as a risk factor for cryptogenic stroke. Patients with migraine with aura (MA) appear to be at risk for silent brain infarction, which might be related to the presence of a PFO. However, the association between MA and PFO with ASA has never been reported. We examined this association in a large observational study.Methods and ResultsPatients (>18 years) who underwent an agitated saline transesophageal echocardiography (cTEE) at our outpatient clinics within a timeframe of 4 years were eligible to be included. Before cTEE they received a validated headache questionnaire. Two neurologists diagnosed migraine with or without aura according to the International Headache Criteria. A total of 889 patients (mean age 56.4±14.3 years, 41.7% women) were included. A PFO was present in 23.2%, an isolated ASA in 2.7%, and a PFO with ASA in 6.9%. The occurrence of migraine was 18.9%; the occurrence of MA was 8.1%. The prevalence of PFO with ASA was significantly higher in patients with MA compared to patients without migraine (18.1% vs 6.1%; OR 3.72, 95% CI 1.86‐7.44, P<0.001). However, a PFO without ASA was not significantly associated with MA (OR 1.50, 95% CI 0.79‐2.82, P=0.21). Interestingly, a PFO with ASA was strongly associated with MA (OR 2.71, 95% CI 1.23‐5.95, P=0.01).ConclusionIn this large observational study, PFO with ASA was significantly associated with MA only. PFO closure studies should focus on this specific intra‐atrial anomaly.

Abstract T P158: Prolonged Atrial Electrical Mechanical Delay on Echocardiography in Patients With Cryptogenic Stroke

Backgrounds and Purpose: One quarter of strokes are cryptogenic, and subclinical atrial fibrillation may be a common etiologic factor. Prolonged atrial electrical-mechanical delay was known as a predictor of paroxysmal atrial fibrillation (AF). We evaluated whether the prevalence of prolonged atrial electrical-mechanical delay suggesting the presence of atrial substrates for paroxysmal AF may be higher in patients with cryptogenic stroke. Methods: We retrospectively reviewed data from patients with ischemic stroke who were admitted to our hospital between January 2011 and December 2012, and selected patients with cryptogenic stroke who underwent echocardiography. Patients who underwent echocardiography for health care examination were enrolled in control group. Age, sex and underlying risk factors were matched in two groups. Atrial electrical-mechanical delay (PA interval) was defined as the time interval (msec) from the initiation of P wave on surface electrocardiogram to the initiation of trans-mitral inflow on pulse wave Doppler echocardiogram during late diastole. Clinical significance of PA interval was evaluated. Results: Total 130 patients in cryptogenic stroke group and 130 persons in control group were enrolled. Mean age was 63 ± 11 years and 176 (68%) were male. The PR interval (178 ± 27 vs. 165 ± 27 msec, p &lt; 0.0001) and PA interval (74 ± 15 vs. 61 ± 13 msec, p &lt; 0.0001) were longer in cryptogenic stroke patients. The body mass index (23 ± 3 vs. 24 ± 3, p = 0.043) was lower and mitral E/E’ ratio (8.8 ± 3.0 vs. 8.0 ± 2.6 msec, p &lt; 0.0001) was higher in cryptogenic stroke group. Prolonged PR (OR: 1.019, CI: 1.009 - 1.029, p &lt; 0.0001) and PA (OR: 1.068, CI: 1.045 - 1.093, p &lt; 0.0001) intervals, and lower body mass index (OR: 0.919, CI: 0.846 - 0.998) were risk factors for cryptogenic stroke in univariate logistic regression analysis. Prolonged PA (OR: 1.060, CI: 1.035 - 1.086, p &lt; 0.0001) and PR (OR: 1.019, CI: 1.004 - 1.034, p = 0.011) intervals, and lower body mass index (OR: 0.845, CI: 0.764 - 0.935, p = 0.001) were risk factors for cryptogenic stroke in multivariate logistic regression analysis. Conclusion: The prevalence of prolonged atrial electrical-mechanical delay suggesting atrial substrates for paroxysmal AF was higher in patients with cryptogenic stroke.

Atrial Septal Aneurysm Is Always Linked To Right-Left Shunt and Cardio embolic Risk

Atrial septal aneurysm when associated to other cardiac abnormalities, such as patent foramen ovale, Chiari network or Eustachian Membrane, is a well-known recognised risk factor for cerebral embolism. Aim of study is to assess if isolated atrial septal aneurysm could be considered statistically related to cryptogenic stroke, considering the strong clinical impact that this association could have on these patients outcome. 579 patients were investigated for a suspected patent foramen ovale using transthoracic echocardiography, in order to evaluate the presence of atrial septal aneurysm and to identify other potential cardiac embolic sources. The patients with atrial septal aneurysm underwent transcranic echodoppler and transoesophageal echocardiography examination with contrast solution during Valsalva manoeuvre.209/579 (36%) patients where we made diagnosis of atrial septal aneurysm. In this cohort of patients transcranic echodoppler showed a patent foramen ovale in 114/209 (54%), whereas transoesophageal echocardiography in 111/209 (53%); 6/114 (5%) pa-tients with a positive transcranic echodoppler had a normal transoesophageal echocardiography examination and 3/95 (3%) with normal transcranic echodoppler had a positive transoesophageal echocardiography. Transcranic echodoppler vs. transoesophageal echocardiography sensibility was 97% and specificity 94%. Only 13/98 (13%) of patients with isolated atrial septal aneurysm and 23/111 (26%) with patent foramen ovale had history of cryptogenic stroke. According to our data, isolated atrial septal aneurysm could not be considered an independent risk factor for cryptogenic stroke.

Hyperhomocysteinemia, obesity and cryptogenic stroke

The pathogenic role of hyperhomocysteinemia in cryptogenic stroke is not well established. We aimed to determine homocysteine levels in patients with cryptogenic stroke considering the possible variables that may act as confounders and analyze the influence of obesity on this association. We conducted a case-control study in 123 patients with cryptogenic stroke aged 42 ± 12 years and in 153 control subjects aged 42 ± 13 years. Serum homocysteine was determined by fluorescence polarization immunoassay. Patients showed statistically higher levels of homocysteine, creatinine and higher BMI than controls (p = 0.045, p = 0.014, p = 0.013), respectively. After multivariate adjustment the differences in homocysteine levels disappeared (p = 0.774). When subjects were classified according to the presence or absence of obesity, the differences in the prevalence of hyperhomocysteinemia (homocysteine >15 μM) were highly significant, being higher in patients than in controls (p = 0.009). Likewise, mean values of homocysteine in obese were higher in cases than in controls (16.9 ± 9.5 μM vs. 10.12 ± 2.5 μM; p = 0.020), remaining significant after adjusting for the above mentioned confounders. Although in general, hyperhomocysteinemia does not seem to constitute an independent risk factor for cryptogenic stroke, it significantly increases the risk in obese subjects; therefore it is convenient to decrease its levels in this sub-group to minimize the risk.