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Diagnostic Strategies for Patent Foramen Ovale

Dear Editor: I read with great interest the study by Zito et al.1 regarding the comparison among various diagnostic strategies for patent foramen ovale (PFO) in cryptogenic stroke (CS) and migraine. This article raises some important issues. Epidemiological studies have reported variable incidence of PFO in CS and migraine. The observed differences are due to multiple factors such as patient population, age, and diagnostic method etc. Cerebral embolization is believed to be the underlying pathogenic mechanism. In order to prove this hypothesis demonstration of thrombi in the veins, observing real time migration of a thrombus via the PFO as well as detection of microembolic signals in the intracranial circulation are essential. It is often difficult to establish these essential components owing to various methodological and temporal issues. Ultrasonography and contrast venography are often unrewarding in the detection of thrombus in the deep veins of the legs since it could have already migrated. Furthermore, the latter requires injection of potentially nephrotoxic contrast agents. Magnetic resonance venography, especially of ‘‘larger’’ pelvic veins, could identify some remnants of the thrombi and aid in establishing the origin of the thrombi causing CS and migraine. Transesophageal echocardiography (TEE), considered the gold standard for diagnosing PFO, needs an expert echocardiographer and often poorly tolerated by the patients, mostly due to sedation. Moreover, endoscope in the throat affects patients’ ability for performing an adequate valsalva maneuver. Although, TEE provides anatomical details, the movement of a thrombus through the PFO has rarely been observed in real time.2 Transcranial Doppler (TCD) is a reliable technique and has been reported to be more sensitive and specific than TEE.3,4 To further strengthen the place of TCD, Jeserum et al.5 have recently shown that migraineurs have a higher TCD grade right-to-left shunt despite similar atrial septal characteristics on intracardiac echocardiography. However, diagnosis of PFO by TCD is associated with some methodological issues such as the composition of the contrast mixture,6,7 technique of preparing air–saline contrast mixture,8 number of injections and position of the patient,9 TCD equipment,7 and the grading of the TCD-detected right-to-left shunt.7,10 Low-grade shunts may not have the same clinical relevance as the ‘‘large-grade functional’’ PFO. Therefore, a better grading of PFO is necessary for a better understanding and planning a definitive treatment. There is an urgent need for standardizing the methods for diagnosing as well as grading the ‘‘functional status’’ of PFO. One suggested method could be the use of power M-mode TCD and repetitive evaluations in different body positions with controlled preparation of the ultrasound contrast mixture. One possible solution could be performing TCD simultaneously with TEE.11 The relationship between the size of PFO and its functional–potential is not linear. While TEE may be performed to detect the presence, location, and size of PFO, TCD should be employed to determine its functional grade. Mere diagnosis of the presence of the PFO is not enough to establish its etiopathogenic role in CS and migraine. I believe that to determine its etiological role, ‘‘functional–potential’’ of the PFO needs be established with multimodal diagnostic approach.