Dr. Levine of the SUNY Health Science Center at Brooklyn has received honorariums from Genentech for service on a scientific advisory committee and a research grant from Genentech as a principal investigator.)
This article includes discussion of patent foramen ovale, Patent oval foramen, and PFO. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
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 remains unclear. Randomized controlled trials on patent foramen ovale closure showed no benefit for secondary stroke prevention or migraine improvement.
• Although highly prevalent and asymptomatic in the general population, patent foramen ovale is associated with 2 major neurologic conditions: stroke and migraine headache.
• A direct causality and the pathogenic implication of patent foramen ovale in stroke and migraine occurrence remain to be established.
• The best strategy for stroke prevention in patients with patent foramen ovale is controversial.
• The benefit of transcutaneous patent foramen ovale closure for stroke prevention and migraine improvement remains under investigation.
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.Vick 2006). 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 (Silver and Dorsey 1978). 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 (Hanley et al 1985; Mugge et al 1995).
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 (Lechat et al 1988; Di Tullio et al 1992; Klotzsch et al 1996; Knauth et al 1997; Del Sette et al 1998; Anzola et al 1999; Overell et al 2000; Angeli et al 2001; Kawamata et al 2001; Roxas-Timonera et al 2001; Lamy et al 2002; Beelke et al 2003; Morelli et al 2005; Engelhardt et al 2006; Khouzam et al 2006; Wammes-van der Heijden et al 2006; Purandare et al 2008). 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 (Falk 1991; Schwerzmann et al 2001; Maalikjy Akkawi et al 2003; Meissner et al 2006; Petty et al 2006). 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 (Lippmann and Rafferty 1993). 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 (Lechat et al 1988).
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