Patent foramen ovale is a highly prevalent anomaly occurring in 25% to 30% of the general population. Although it is generally asymptomatic, studies have found associations with ischemic stroke and migraine. The best treatment strategy for patent foramen ovale in the setting of ischemic stroke or migraine has historically been controversial; however, several randomized controlled trials have bolstered the evidence for device intervention in the secondary prevention of ischemic stroke.
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• Although highly prevalent and asymptomatic in the general population, patent foramen ovale is associated with 2 major neurologic conditions: stroke and migraine headache.
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• A direct causality and the pathogenic implication of patent foramen ovale in stroke and migraine occurrence remain to be established.
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• The benefit of transcutaneous patent foramen ovale closure for stroke prevention has been demonstrated in randomized controlled trials including CLOSE, REDUCE, and DEFENSE-PFO.
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• The decision regarding which patients to refer for device closure rests on ruling out a competing stroke mechanism and meeting eligibility criteria for positive trials.
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• Close liaison between neurology and cardiology should occur prior to making a recommendation for patent foramen ovale closure.
Historical note and terminology
In a significant proportion of the general population there are various forms of interatrial communication, such as patent foramen ovale, atrial septal defect, and associated disorders such as atrial septal aneurysm. Patent foramen ovale, as its name suggests, represents the postnatal persistence of the normally present foramen ovale, a flap valve structure formed by the septum primum and septum secundum in the fetus.
Atrial septal defect is a congenital defect in which an open, interatrial communication, devoid of any tissue flap covering the opening occurs. Patent foramen ovales are not considered to be atrial septal defects because no septal tissue is missing (120). Atrial septal aneurysm, first described in the literature by Silver and Dorsey in 1978 refers to the redundant tissue in the region of the fossa ovalis (111). It is present if the base of the aneurysmal protrusion measures at least 1.5 cm in diameter and there is either a fixed protrusion of the fossa ovalis at least 1 to 1.5 cm into an atrium or phasic excursion of the fossa ovalis throughout the cardio-respiratory cycle exceeding 1.5 cm from the plane of the atrial septum (38; 87).
These disorders, although sharing some purported associations with disease states such as paradoxical embolic phenomena and cryptogenic strokes, are not synonymous and have different associated clinical features, complications, and controversies regarding their management. This article will focus on patent foramen ovales and their relationship to neurologic disease states with a brief mentioning of associated atrial abnormalities such as atrial septal defect and atrial septal aneurysm as they pertain to patent foramen ovales. The importance of patent foramen ovale stems from the fact that the scientific literature is replete with studies that imply a causative or associative role for them in various neurologic disorders. These disorders include strokes caused by paradoxical embolic phenomena, cryptogenic strokes, and transient ischemic attacks as well as migraines with aura, cluster headaches, cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cryptogenic and recurrent brain abscesses, obstructive sleep apnea, transient global amnesia, paradoxical air embolisms in neurosurgical patients undergoing surgery in the sitting position, neurologic decompression illness, and the presence of “multiple ischemic brain lesions” in divers, and deep white matter and periventricular white matter hyperintensities (on T2/FLAIR MRI sequences) in patients with Alzheimer dementia (67; 31; 61; 62; 26; 03; 92; 01; 51; 100; 66; 08; 85; 33; 56; 123; 98). In the scientific literature, a significant number of studies and expert opinions question these associations and emphasize that these interatrial communications are for the most part innocent bystanders (34; 108; 71; 77; 93). Needless to say, the relationship of patent foramen ovales to neurologic diseases and the ways to best manage them are controversial issues.
The earliest documentation of paradoxical embolism through a patent foramen ovale is in the 1877 text of Julius Cohnheim followed by the 1880 paper by Moritz Litten (69). In more modern times, a group of investigators based in Paris, France first postulated, in 1988, an important role for patent foramen ovales in young patients (younger than 55 years of age) with cryptogenic stroke based on a case-control study (67).