What Actually Causes Chronic Migraine? A Mechanistic Reading of Treatment-Resistant Migraine — The clinical pattern that defines treatment-resistant migraine

A patient presents with migraine that has progressively transformed from episodic (fewer than 15 headache days per month) to chronic (15 or more headache days per month, with 8 or more meeting full migraine criteria). The migraines often started in adolescence or early adulthood. They were initially manageable with over-the-counter analgesics and lifestyle modification. Over the following decade, the frequency increased. The duration increased. The intensity worsened. The associated symptoms expanded: visual aura, vestibular features, autonomic instability, gastrointestinal symptoms, severe photophobia and phonophobia, brain fog that persists between attacks. The treatment cascade follows the standard neurological algorithm. Triptans for acute attacks. NSAIDs and combination analgesics. Beta blockers (propranolol, metoprolol) for prevention. Topiramate for prevention. Amitriptyline or other tricyclics. Botulinum toxin injections for chronic migraine. The newer CGRP-targeting antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab). Atogepant, rimegepant, ubrogepant for newer oral options. Many patients respond to one or more of these. Some respond substantially. A significant fraction respond partially or not at all. The CGRP antibody class, which represented a major advance, demonstrates approximately 50 to 60 percent response rates in clinical trials, with response defi