MIGRAINE PATHOPHYSIOLOGYAND TREATMENTMECHANISMSDespite its very common prevalence, migraine remains an enigmatic disease. The presence of transientneurological signs in a subgroup of migraineurs has long raised a question that still remainscontroversial:are migraine with and without aura two separate entities, or are they different manifestationsof a similarunderlying mechanism? The answer to this question will impact not only our understanding of migrainepathophysiology, but also the design of prophylactic treatment strategies. We know from previous research that migraine with aura is most probably a disorder linked with corticalspreading depression (CSD). In this project we will explore whether migraine without aura is also linked withCSD. We will build on our preliminary findings of structural changes in migraineurs with and without aura,and seek answers to the following questions: Is migraine a progressive disease? Is silent CSD happening inmigraine without aura? Is silent CSD happening in the cerebellum? Are there specific structural changesrelated to migraine? The first aim proposes to test the hypothesis that similar pathophysiological mechanisms underlie bothtypes of migraine. Building on our preliminary findings showing specific areas of cortical thickening inmigraineurs, we will explore their location andcorrelations with clinical characteristics.
Aim 2 will explorewhether brain changes in migraine are progressive in nature, and whether we can find 'downstream' impactof changes in the cortex in the white matter. We will use diffusion tensor imaging to explore characteristicsof white matter in migraineurs, and test whether, as shown in our preliminary data, these changes areorganized along functional pathways. Finally, in aim 3 we will use anatomical and dynamic imaging toexplore the cerebellum, a structure that appears to be chronically affected in migraine. We will test thehypothesis that CSD may arise silently in the cerebellum, and that consequent clinical and structuralchanges are present in the cerebellum of migraineurs. By pursuing our investigations, we believe that we will be able to continue to identify importantpathophysiological issues with potentially relevant consequences for the development of new therapeuticapproaches for the prevention of migraine.
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