Page 68 - Migraine, the heart and the brain

Chapter 3
only one third of migraineurs have migraine with aura.21 Moreover, in that study, transthoracic echo was used, which is known to have a lower sensitivity to detect RLS compared to TCD-c.27 The second study26 most likely was underpowered, with only 42 participants with migraine with aura and 44 with migraine without aura. Moreover, RLS might have been missed in many participants as the TCD signal was assessed within 10 seconds after injection of contrast, which generally is considered too soon.28 Use of TCD-c, which is more sensitive to detect RLS than the other methods generally used,27 and the longer time window (60 seconds), which increases the chances of detecting very small cardiac shunts, may explain why we found somewhat higher RLS prevalences than were found in other studies.4,6,25,26 Two clinicbased studies29,30 assessed RLS with TCD-c in chronic (high frequent) migraine but with inconsistent ndings: 66%30 vs 37%.29 Control groups such as participants with episodic migraine or participants without migraine were lacking in both studies.
The relationship between RLS and migraine with aura is intriguing and might be explained at least in part by shared genetic factors.31 Alternatively, there might be a direct causal relationship.32 In mice, it was shown that carotid injection of small particles or air emboli injected could evoke CSD,16 the electrophysiologic correlate of migraine aura and a putative trigger for migraine attacks.18 Migraineurs who were injected with agitated saline developed EEG alterations and headache attacks, particularly those with large RLS.17 Finally, in a small open-label study, 87% of migraine patients with RLS had a 50% or greater reduction in migraine frequency when using the emboli-preventing drug clopidogrel.33 It has also been hypothesized that substances like amines and other chemicals might bypass the pulmonary lter in participants with RLS, precipitating migraine attacks in susceptible individuals.11 A direct relationship between RLS and migraine in at least some people is further suggested by our nding that participants with migraine with aura (but not those without aura) more often had ongoing migraine activity if they also had spontaneous RLS. As TCD cannot distinguish between cardiac and pulmonary RLS, we cannot determine which type is most relevantinmigraine.Trialstestingthe migraineattack- reducing effect of closing patent foramen ovale (PFO), the most frequent cause of RLS,11 traditionally included participants with both migraine with and without aura, and participants with Valsalva-induced rather than spontaneous PFO.10–13 Whereas retrospective studies10–12 showed promising results, a prospective, randomized, sham-controlled trial13 failed to show any effect. Interestingly, preliminary results of the open-label but randomized Percutaneous Closure of PFO in Migraine with Aura (PRIMA) trial comparing PFO closure with antimigraine medication suggested
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