The role of patent foramen ovale (PFO) in stroke was debated for decades. Randomized clinical trials (RCTs) have shown fewer recurrent events after PFO closure in patients with cryptogenic stroke (CS). However, in clinical practice, treating stroke patients with coexisting PFO raises some questions. This brief review summarizes current knowledge and challenges in handling stroke patients with PFO and identifies issues for future research. The rationale for PFO closure was initially based on the concept of paradoxical embolism from deep vein thrombosis (DVT). However, RCTs did not consider such details, limiting their impact from a pathophysiological perspective. Only a few studies explored the coexistence of PFO and DVT in CS with varying results. Consequently, the PFO itself might play a role as a prothrombotic structure. Transesophageal echocardiography thus appears most appropriate for PFO detection, while a large shunt size or an associated atrial septum aneurysm qualify for a high-risk PFO. For drug-based treatment alone, studies did not find a definite superiority of oral anticoagulation over antiplatelet therapy. Remarkably, drug-based treatment in addition to PFO closure was not standardized in RCTs. The available literature rarely considers patients with transient ischemic attack (TIA), over 60 years of age, and competing etiologies like atrial fibrillation. In summary, RCTs suggest efficacy for closure of high-risk PFO only in a small subgroup of stroke patients. However, research is also needed to reevaluate the pathophysiological concept of PFO-related stroke and establish strategies for older and TIA patients and those with competing risk factors or low-risk PFO.

Background: Stroke is a leading cause of significant physical, cognitive, and psychiatric morbidity. One risk factor for stroke is paradoxical embolization through a patent foramen ovale (PFO). In cardiac clinical practice, power M-mode Transcranial Doppler (TCD) evaluation is the gold standard for diagnosis of PFO, or right-to-left cardiac shunt (RLS). Brain micro-embolization due to diagnostic bubble contrast echocardiography may cause neurological symptoms in patients with PFO. However, the neurocognitive effects of TCD have not been studied. Objective: The purpose of this study was to evaluate cognitive outcomes in patients who undergo routine diagnostic bubble contrast TCD. The aims of the study were (1) to determine if cognitive function declines pre- to post-TCD evaluation and, (2) to assess the relationship between cognitive function and severity of the RLS measured using the Spencer Grading System. Methods: One hundred and four participants referred to Sorensen Cardiovascular Group for diagnosis of RLS were evaluated for changes in cognitive functioning at three time points. A dual baseline (pre-test and baseline test) was administered to mitigate practice effects between the first and second administrations. All pre and post-TCD comparisons were analyzed using the baseline test and post-TCD test, controlling for the effects of practice, if present. Results: Practice effects were observed for the working memory task, with significant improvement in working memory scores occurring between the first (pre-test) and second (baseline) administrations. The main effect for shunt group (no shunt vs. moderate-to-severe shunt) and the shunt group by time interactions were not significant for processing speed, attention, or working memory, adjusting for practice effects, age, and education. Migraine did not predict group status for mood or shunt variables. Conclusion: Cardiac patients with both small and large RLS did not experience a decline in processing speed, attention, or working memory ability following TCD, suggesting that TCD-induced microemboli do not result in immediate cognitive deficits in these domains. These findings support the use of TCD for routine evaluation of PFO, even in patients with severe RLS, although findings are limited to young (30s), medically healthy, predominately Caucasian individuals assessed immediately following TCD. Results do not exclude the possibility of cognitive impairment at follow-up, on other cognitive tests, or in other cognitive domains.