What is the pathophysiology of status migrainosus?

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Last updated: April 23, 2025 • View editorial policy

From the Research

Status migrainosus is a severe, prolonged migraine attack lasting more than 72 hours without relief, involving persistent activation of the trigeminovascular system and sustained release of inflammatory neuropeptides. The pathophysiology of status migrainosus is complex and not fully understood, but it is believed to involve the persistent activation of the trigeminovascular system, with sustained release of inflammatory neuropeptides like calcitonin gene-related peptide (CGRP) and substance P, as discussed in 1. This leads to prolonged neurogenic inflammation, sensitization of pain pathways, and continuous activation of brainstem nuclei involved in pain processing. Central sensitization occurs in the trigeminal nucleus caudalis and thalamus, making neurons hyperresponsive to normal stimuli, as noted in the general understanding of migraine pathophysiology. Cortical spreading depression, a wave of neuronal depolarization followed by inhibition, may repeatedly trigger or sustain the attack. Serotonergic dysfunction plays a role, with decreased serotonin levels contributing to pain modulation failure. Genetic factors predispose individuals to this condition, while environmental triggers like stress, dehydration, and medication overuse can precipitate and maintain the prolonged attack, as identified in studies such as 2. The blood-brain barrier becomes more permeable during status migrainosus, allowing inflammatory mediators to further perpetuate the pain cycle. This self-sustaining process explains why these attacks are particularly resistant to standard migraine treatments and often require more aggressive interventions like intravenous medications, corticosteroids, or even hospitalization, as outlined in treatment guidelines 3. Key factors to consider in the management of status migrainosus include:

  • The use of parenteral steroid and fluid supply as the first choice in treatment, as recommended in 3
  • The potential benefits of combining a triptan with a NSAID for improved efficacy, as noted in 3
  • The importance of limiting the use of acute treatment to prevent medication-overuse headache, as cautioned in 3
  • The need for personalized and causal therapy for migraine sufferers, as emphasized in 4.

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