What Actually Causes Chronic Migraine? A Mechanistic Reading of Treatment-Resistant Migraine — When drivers combine

Most chronic migraine cases have features of more than one driver. Driver 1 (mitochondrial) and Driver 2 (mast cell) frequently combine because the inflammatory tone that drives mast cell activation also produces mitochondrial dysfunction through the CD38 pathway. Driver 2 and Driver 3 frequently combine because Pattern A barrier-driven MCAS is mechanistically the same lesion as the gut-brain axis dysfunction. Driver 4 often emerges as dominant in patients who had Drivers 1, 2, or 3 operating sub-clinically until perimenopause unmasked them.