Page 79 - Migraine, the heart and the brain

Right-to-left shunts and micro-embolization in migraine
without aura patients (77%) and controls (72%). Small or moderate PAVMs were also not associated with migraine, which was not broken down to migraine with and without aura. Results have to be evaluated with caution, as in this study only few large PFOs and no large PAVMs were found. Apart from the resulting power problem, one important limitation of this study is the limited questionnaire, which could have caused diagnostic bias.
In conclusion, a RLS is associated with migraine with aura. This is true for PFO,
and probably also for PAVM. However, the prevalence of RLS in migraine with aura
patients is increased probably less than two-fold to three-fold compared with
controls, which was initially reported [1,2], as both PFO and PAVM are also common
in the general population [12]. A causal relation between RLS and migraine with 4 aura, as hypothesized by some, can only be shown by well designed randomized shamcontrolled RLS closure trials evaluating migraine frequency. While awaiting
these studies, some recent publications have shown that there may be a reasonable
linking biological mechanism, at least in animal studies.
Emboli triggering migraine attacks
For years, a mechanism linking RLS to migraine with aura was only speculative. One proposed mechanism was the transport through the RLS of unknown venous blood constituents that are normally not (or at decreased levels) present in the arterial circulation. Such postulated constituents were venous (paradoxical) emboli and serotonin [21]. The latest publications supporting the postulated embolic mechanism will be reviewed here. Nozari et al. [22] showed in mice that small particulate or air emboli injected into the carotid artery were able to evoke a cortical spreading depression (CSD) without causing ischemia, hereby linking emboli to migraine aura. It is unknown whether venous originated emboli (having passed through a RLS), as opposed to arterial originated emboli, also could cause CSD. If in humans it could also be demonstrated that small emboli are able to evoke a CSD, blood (vessel) abnormalities would then be acknowledged as a migraine trigger [23]. There are some clinical situations in humans that approximate these animal models. Four different types of emboli in humans will be discussed.
Air emboli causing migraine attacks
Migraine aura occurring during a TCD-c procedure has been reported as case reports [24,25] and recently the occurrence of migraine after a TCD-c procedure was studied prospectively. Caputi et al. [26] showed that among migraineurs with aura
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