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Azarbal et al. (1) studied closing patent foramen ovale (PFO) or atrial septal defect (ASD) for prophylaxis of migraine. The accompanying editorial highlights areas of caution (2). Additional concerns are: 1) Both right-to-left shunt (PFO) and left-to-right shunt (ASD) appear associated with migraine (3). 2) Closure of ASD improves left ventricular stroke volume; this physiological variable (3) might be involved in precipitating daily migraines. 3) Following ASD closure, plasma atrial natriuretic peptide levels would decrease (3). 4) Lateralization of headaches is a characteristic feature of migraine (4). With the concept of paradoxical embolization of gas, thrombi, or vasoactive neuromediators (2), these potential precipitants are presumed to be streamed regularly over decades to the same brain parenchymal site or circulatory segment in order to produce lateralizing headache (5). This is highly unlikely as paradoxical emboli are generally directed randomly. 5) Atenolol—a first-line migraine prophylactic—does not readily cross the blood-brain barrier (BBB) or significantly influence either brain neuronal function or circulation (4). 6) Drugs used to manage patients with migraine aura such as nifedipine, furosemide, and verapamil do not readily cross the intact BBB (6). These pharmacological absolutes challenge prevalent concepts of primary involvement of brain in migraine. 7) For a disease that can continue for decades, a follow-up period of 12 months (1) is rather short.
An explanation is required for the characteristic late appearance (in the teens or twenties) or disappearance (second and third trimesters of pregnancy and in later decades), in general, of migraine despite continued presence of PFO/ASD. Second, a high incidence of right-to-left shunt has been seen in cluster headache patients (42.5%, 17 of 40) (7). Cluster headache is a strictly lateralized primary headache; brain ischemia is not implicated in its pathogenesis. Third, migraine-with-aura patients seem to respond far better than migraine-without-aura patients (1). Headaches are less frequent, less severe, and shorter in migraine-with-aura patients. When the frequency of headache attacks is lessened, the possibility of the placebo effect in migraine trials is greater (5).
At this juncture, it is necessary to weigh carefully whether we need more reflection about the basic issues surrounding the apparent link between migraines and PFO/ASD or more clinical trials.
- American College of Cardiology Foundation
- Azarbal B.,
- Tobis J.,
- Suh W.,
- Chan V.,
- Dao C.,
- Gaster R.
- Tsimikas S.
- Gupta V.K.
- Gupta V.K.
- ↵Gupta VK. Management of migraine aura: basic theoretical and clinical reconsiderations. Headache 2005. In press.