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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Kidney Transplant Recipient With Cerebral Paradoxical Embolism Following Recurrent Idiopathic Deep Vein Thrombosis and Pulmonary Embolism: Case Report and Review of the Literature.

Paradoxical embolism occurs when a thrombus crosses an intracardiac defect into the systemic circulation. Here, we present the case of a 35-yearold male kidney transplant recipient with a cerebral paradoxical embolism associated with a spontaneous venous thromboembolism. This patient had recurrent deep venous thrombosis and showering emboli to the lung and paradoxically to the brain through patent foramen ovale, and we treated him successfully. The role of bubble echocardiography was essential in diagnosis to avoid contrast-induced nephropathy. This is the first successfully managed case of a kidney transplant recipient with recurrent idiopathic deep vein thrombosis, pulmonary embolism, and cerebral paradoxical embolism. Bubble echocardiography was an excellent alternative to contrast angiography to avoid nephrotoxicity. Vitamin K antagonists are superior to direct oral anticoagulants, especially among nonadherent/noncompliant patients.

Predictors of recurrent cerebral ischemia after patent foramen ovale closure: A single center observational study.

OBJECTIVES: Transcatheter patent foramen ovale closure lowers recurrent stroke in patients with cryptogenic stroke or transient ischemic attack with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathophysiology remains largely unknown. We sought to evaluate the prevalence of recurrent ischemic neurological events and to assess its predictors after transcatheter patent foramen ovale closure. METHODS: We enrolled consecutive patients who underwent patent foramen ovale closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. Clinical and procedure-related features were collected for each patient. The incidence of recurrent ischemic neurological events was assessed at follow-up. RESULTS: We enrolled a total of 169 patients with mean Risk of Paradoxical Embolism score at hospital admission of 6.4 ± 1.5. The primary indication was previous cryptogenic stroke (94 [55.6 %] subjects), followed by transient ischemic attack (75 [44.4 %]). Among patients with complete outcome data (n= 154), after a median follow-up of 112 months, recurrent cerebral ischemia occurred in 13 [8.4 %], with an annualized rate of 0.92/100 patients. The presence of obesity [OR 5.268, p = 0.018], Risk of Paradoxical Embolism score < 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/ transient ischemic attack after patent foramen ovale closure. CONCLUSIONS: The presence of obesity, Risk of Paradoxical Embolism score < 7 and migraine were independent positive predictors of recurrent ischemic neurological events after patent foramen ovale closure.

Modified Risk of Paradoxical Embolism More Effectively Evaluates the Risk of Stroke Associated with Patent Foramen Ovale.

BACKGROUND: Through an analysis of the risk factors associated with patent foramen ovale (PFO)-related stroke (PS), we aimed to modify the Risk of Paradoxical Embolism (RoPE) to assess the risk of PS. METHODS: A retrospective collection of ischemic stroke (IS) patients with PFO admitted to the Department of Neurology at Beijing Chaoyang Hospital was conducted. The patients were classified into PS and non-PS groups. PS risk factors and RoPE scoring were analyzed based on clinical data, laboratory indicators, and imaging data. Independent risk factors were incorporated into the RoPE scoring system for enhancement. RESULTS: Significant differences were observed between the two groups regarding total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and uric acid levels. The transverse diameter of the left atrium was significantly larger in the non-PS group compared to the PS group. Multivariate logistic regression revealed that higher LDL-C levels and a smaller transverse diameter of the left atrium increased the risk of PS. The modified RoPE score was derived by assigning 1 point each for high LDL-C levels and the absence of transverse diameter enlargement in the left atrium. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves for the classical and modified RoPE score distinguishing PS were 0.661 and 0.798, respectively. CONCLUSION: LDL-C levels and transverse diameter of the left atrium were identified as independent risk factors for PS. The modified RoPE scoring system exhibited superior performance in assessing the risk of PS compared to the original RoPE score.

When a Hypersomnolent Hemodialyzed Patient Actually Has a Rare Stroke: A Case of Artery of Percheron Infarction With Paradoxical Embolism.

INTRODUCTION: Artery of Percheron (AOP) is an uncommon anatomic variant of the arterial supply of the medial thalami. Owing to variable clinical presentation, challenging imaging diagnosis, and its rarity, it is difficult to diagnose AOP infarctions. We present a clinical case of a unique presentation of AOP infarction associated with paradoxical embolism and highlight the atypical clinical manifestations and challenging diagnosis of this stroke syndrome. CASE REPORT: A 58-year-old White female with chronic renal insufficiency on hemodialysis was admitted to our center with a 10-hour course of hypersomnolence and right-sided ataxia. She had normal body temperature, blood pressure, peripheral oxygen saturation, and heart rate and scored 11 points in the Glasgow Coma Scale and 12 points in National Institutes of Health Stroke Scale. Initial brain computerized tomography scan, electrocardiogram, and thoracic radiography were normal; transcranial Doppler ultrasound showed >50% stenosis at the P2 segment of the right posterior cerebral artery, and transthoracic echocardiogram, a patent foramen ovale and thrombus adherent to the hemodialysis catheter. On day 3, she underwent brain magnetic resonance that showed acute ischemic lesions at the paramedian thalami and the superior cerebral peduncles. AOP infarction due to a paradoxical embolism from a patent foramen ovale with a right atrial thrombus was the final diagnosis. CONCLUSIONS: AOP infarctions are a rare type of stroke with elusive clinical presentations and frequently, initial imaging assessment is normal. Early recognition is crucial, and a high index of suspicion is needed to suspect this diagnosis.

[Ischemic stroke associated with patent foramen ovale: hospital database analysis]. / Ishemicheskii insul't, assotsiirovannyi s otkrytym oval'nym oknom: analiz dannykh gospital'nykh registrov.

OBJECTIVE: To analyze clinical and instrumental characteristics of patients with ischemic stroke (IS) due to paradoxical embolism according to the data of hospital registers of Moscow and Perm. MATERIAL AND METHODS: A comprehensive study of 114 patients, aged 18 to 55 years, with IS by the mechanism of paradoxical embolism was carried out. All patients underwent clarification of the cause of IS (electrocardiography, ultrasound scanning of the brachiocephalic arteries, CT or MRI of the brain, CT or MR angiography, transthoracic and/or transesophageal echocardiography). The presence of right-left shunt blood flow (RLS) was confirmed by transcranial dopplerography with a bubble test. The clinical significance of patent foramen ovale (PFO) was assessed according to The PFO-Associated Stroke Causal Likelihood Classification System (PASCAL). RESULTS: Clinical and instrumental characteristics of patients with IS due to paradoxical embolism were obtained from two hospital registries. In both groups, the leading trigger for the development of IS was the Valsalva phenomen (>20%), the share of other provoking factors did not exceed 10%. Significant differences between the analyzed groups related to the ultrasonic characteristics of RLS/PFO: patients with a grade 4 shunt predominated in the Research Center of Neurology (RCN) population, while patients with a grade 3 shunt predominated in the City Clinical Hospital (CCH) №4 group. At the same time, there were twice as many patients with aneurysm of the interatrial septum in the CCH №4 group. In accordance with the PASCAL classification, in 93% of RCN patients, PFO can be considered as a probable cause of IS, while in the CCH No. 4 group, a probable causal relationship was traced only in 51% of cases, in 18% of patients, the role of an anomaly in the development of stroke was unlikely. CONCLUSION: The analysis showed that the primary screening of RLS in a regional vascular center allows classifying PFO as a probable cause of IS in only half of the patients. For a more accurate selection of patients for whom endovascular occlusion of the PFO will be most effective, an in-depth examination in a specialized hospital is recommended.

Venous thromboembolism with renal infarct due to paradoxical embolism.

Paradoxical thromboembolism has variable presentation depending on site of embolisation. An African-American man in his 40s presented with severe abdominal pain, watery stools and exertional dyspnoea. At presentation, he was tachycardic and hypertensive. Labwork showed elevated creatinine with unknown baseline. Urinalysis showed pyuria. A CT scan was unremarkable. He was admitted with working diagnosis of acute viral gastroenteritis and prerenal acute kidney injury and supportive care was instituted. On day 2, the pain migrated to left flank. Renal artery duplex ruled out renovascular hypertension but showed a lack of distal renal perfusion. MRI confirmed a renal infarct with renal artery thrombosis. Transoesophageal echocardiogram confirmed a patent foramen ovale. Simultaneous arterial and venous thrombosis require hypercoagulable workup, including investigation for malignancy, infection or thrombophilia. Rarely, venous thromboembolism can directly cause arterial thrombosis by 'paradoxical thromboembolism'. Given the rarity of renal infarct, high index of clinical suspicion is necessary.

Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale.

INTRODUCTION: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs. METHODS: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup. RESULTS: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011). CONCLUSION: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS.

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.

Active paradoxical and pulmonary emboli in a first trimester pregnancy.

Capturing a paradoxical embolism in real-time has been a challenge in recent literature. We present the unique case of a 33-year-old, G3P2 female at 8 weeks gestation presenting with dyspnea. An active thrombus through an undiagnosed patent foramen ovale was found requiring emergent surgical intervention with a positive outcome. The presence of a deep vein thrombosis, inferior vena caval thrombus, patent foramen ovale, and pulmonary artery thrombi was contemporarily documented. To our knowledge, there is minimal literature with this presentation.

Prevalence of Patent Foramen Ovale in North Indian Cryptogenic Young Strokes.

Background: : Strokes of the undetermined cause or cryptogenic strokes (CS) account for 30-40% of ischemic strokes. Paradoxical embolism secondary to patent foramen ovale (PFO) may be associated with CS. Transcranial Doppler (TCD) with bubble contrast is a noninvasive bedside tool for diagnosis of right-to-left shunt (RLS) with high sensitivity and specificity. Data on the prevalence of PFO in CS in India are lacking. We determined the prevalence of RLS likely secondary to PFO in cryptogenic young strokes of the north Indian population using TCD with bubble contrast. Patients and Methods: : In this hospital-based prospective cross-sectional study, TCD with bubble contrast was performed in 57 young (age 15 > 45 years) CS and 50 healthy controls for the detection of RLS. The risk of paradoxical embolism (RoPE) score was calculated from various variables such as age, presence of cortical stroke on neuroimaging, and absence of vascular risk factors. Results: : 57 young CS and 50 healthy controls were recruited. TCD with bubble contrast was positive in 31% cases vs 6% in controls (P = 0.001). All patients with TCD positive for RLS had superficial cortical infarcts (P = 0.03). The median RoPE score of our patients was 9 (range: 7-10). Conclusions: : There is a high prevalence of RLS likely secondary to PFO in cryptogenic young strokes in north India. TCD with bubble contrast is an excellent bedside tool for the detection of RLS.

Pulmonary embolism and renal artery thrombosis in a patient with patent foramen ovale.

BACKGROUND AND AIM: Paradoxical embolism is a rare condition in which a thrombus migrates from the venous system to the arterial circulation, usually through a patent foramen ovale (PFO). Pulmonary embolism (PE) and isolated occlusion of one renal artery has been seldom reported. METHODS: We describe a case of a 47-year old white man with a one-month history of exertional dyspnea who was admitted to our hospital for  severe pain in the right lumbar region. RESULTS: A computed tomography showed  PE and a thrombotic occlusion of the right renal artery. A trans-thoracic echocardiogram documented a PFO with right to left shunt. Magnetic resonance imaging of the brain and venous compression ultrasonography of the lower extremities were normal. Therapeutic anticoagulation was started. CONCLUSIONS: Pulmonary embolism and thrombotic occlusion of one renal artery is a rare manifestation of paradoxical embolism. Exertional dyspnea is an atypical manifestation of PE and can delay the diagnosis.

Paradoxical embolisation in right-sided infective endocarditis and patent foramen ovale.

Intravenous drug use (IVDU) is a growing public health crisis worldwide. A known complication of IVDU is right-sided infective endocarditis (RSIE) involving the tricuspid valve. As the tricuspid valve is burdened with infectious vegetations, it becomes a potential source of pulmonary and, very rarely, paradoxical systemic emboli. We report two patients with RSIE involving the tricuspid valve presenting with acute change in mental status. Subsequent imaging demonstrated embolisation to the brain in the setting of elevated right atrial pressures and the presence of a patent foramen ovale (PFO) with right-to-left shunting. We employed a strategy of percutaneous closure of PFO, to prevent further embolisation, as a successful bridge to definitive surgical management of RSIE. We emphasise that clinicians should evaluate for intracardiac shunting and pursue transesophageal echocardiography when encountering systemic emboli of unknown origin, particularly in patients with RSIE.