Article Text

Download PDFPDF
Refractory migraine: a cerebrovascular disease?
  1. David Fiorella1,2,
  2. Adam S Arthur3,4,
  3. Hsiangkuo Yuan5,
  4. Pervinder Bhogal6,
  5. Nitin Goyal3,
  6. Nicolas K Khattar7,
  7. Felipe C Albuquerque8,
  8. Ashutosh P Jadhav9,
  9. Joshua S Catapano10,
  10. Stephen Silberstein5
  1. 1 Department of Neurosurgery, Stony Brook University, Stony Brook, New York, USA
  2. 2 SUNY SB, Stony Brook, New York, USA
  3. 3 Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee, USA
  4. 4 Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
  5. 5 Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  6. 6 Royal London Hospital, London, UK
  7. 7 Department of Neurosurgery, University of Louisville School of Medicine, Louisiville, Kentucky, USA
  8. 8 Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA
  9. 9 Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA
  10. 10 Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA
  1. Correspondence to Dr Felipe C Albuquerque, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ 85013, USA; Felipe.Albuquerque{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Definition, prevalence, and costs

Migraine is a common and disabling neurological disorder that is estimated to affect nearly 40 million people in the USA and 10% of people worldwide.1 The cost of migraine is extraordinary. The estimated annual US healthcare costs in 2010 for migraine were associated with outpatient visits ($3.2 billion), ER visits ($700 million), and inpatient hospitalizations ($375 million), and have continued to increase yearly since then.2

The term ‘refractory migraine’ is typically used to describe migraine that persists despite treatment.3 This can be most rigorously defined as patients who have failed to respond to two of the available preventative medication classes plus either onabotulinumtoxinA (Botox; Abbvie, Chicago, IL), calcitonin gene-related peptide (CGRP) receptor antagonists (gepants, eg, ubrogepant, atogepant, rimegepant), or CGRP monoclonal antibodies; and suffer from at least eight debilitating headache days per month for at least 6 consecutive months. Status migrainosus describes an unremitting migraine attack that does not respond to medications, lasting 72 hours or more.4

The prevalence of refractory migraine varies widely in different epidemiological studies, but is estimated to affect between 5–30% of migraine sufferers5—translating to between 2 and 12 million patients in the USA per year. The incidence of migraine and refractory migraine far outstrips the incidence of any diseases we commonly see in practice as cerebrovascular physicians.

Evidence for a neurovascular etiology

The role of the neurovasculature in migraine remains a controversial and complex area fraught with inconsistent and conflicting observations.6 The effectiveness of vasoconstricting ergotamines, one of the original and primary treatments for migraine, formed the basis for the notion that vasodilation plays a role in migraine pathogenesis.7 8 Similarly, the ability of vasodilatory medications to reliably induce migraines in susceptible patients further substantiated this hypothesis.9 10

The middle meningeal artery (MMA) has specifically been a focus of many of these …

View Full Text


  • X @AdamArthurMD, @ashupjadhav

  • Contributors All authors contributed equally.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.