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BACKGROUND: Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain-meninges-bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response. Accordingly, this study examines the upregulation of an inflammatory marker in extra-axial tissues in migraine with visual aura. METHODS: We used simultaneously acquired 11 C-PBR28 PET/MRI data of 18 kDa translocator protein (an inflammatory marker) in MWA patients (n = 11) who experienced headaches and visual aura in the preceding month. We measured mean tracer uptake (SUVR) in four regions of interest comprising the meninges plus the adjacent overlying skull bone (parameningeal tissues, PMT). These data were compared to healthy controls and patients with pain (chronic low-back pain, CLBP). RESULTS: MWA had significantly higher mean SUVR in PMT overlying occipital cortex than both other groups, though not in the PMT overlying three other cortical areas. A positive correlation was also found between the number of visual auras and tracer uptake in occipital PMT. INTERPRETATION: A strong persistent extra-axial inflammatory signal was found in meninges and calvarial bone overlying the occipital lobe in migraine with visual auras. Our findings are reminiscent of CSD-induced meningeal inflammation and provide the first imaging evidence implicating inflammation in the pathophysiology of migraine meningeal symptoms. We suspect that this inflammatory focus results from a signal that migrates from underlying brain and if so, may implicate newly discovered bridging vessels that crosstalk between brain and skull marrow, a finding of potential relevance to migraine plus other neuroinflammatory brain disorders. This article is protected by copyright. All rights reserved.

Original publication




Journal article


Ann Neurol

Publication Date



cortical spreading depression, inflammation, meninges, migraine, migraine visual aura, skull-brain interactions