Skip to main content

Advertisement

Log in

Migraine Aura: Updates in Pathophysiology and Management

  • Headache (R. B. Halker Singh and J. VanderPluym, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To provide an updated review of the pathophysiology, diagnosis, and management of migraine with aura.

Recent Findings

Thalamic and other subcortical regions may play a role in the pathophysiology of migraine. There is inter-patient and intra-patient attack variability in the characteristics of typical aura especially visual aura symptoms. Migraine with brainstem aura may originate cortically. Migraine with retinal aura may be associated with structural and functional changes in the retina.

Summary

Although cortical spreading depression (CSD) continues to be the predominant theory surrounding the pathophysiology of migraine with aura, the exact mechanism of action of CSD and its role in relation of all phases of migraine including features of aura are not fully understood. Novel experimental models and newer diagnostic tools including neuroimaging are currently being used to enhance of understanding of migraine with and without aura. Transient ischemia attacks, stroke, and epilepsy should be considered in your differential diagnosis of migraine with aura. There are no specific therapies for migraine with aura.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dodick DW. A phase-by-phase review of migraine pathophysiology. Headache. 2018;58(Suppl 1):4–16.

    Article  PubMed  Google Scholar 

  2. Leao AAP, Morison RS. Propagation of spreading cortical depression. J Neurophysiol. 1945;8(1):33–45.

    Article  Google Scholar 

  3. Bolay H, Vuralli D, Goadsby PJ. Aura and head pain: relationship and gaps in the translational models. J Headache Pain. 2019;20(1):94 Excellent review highlighting our current understanding of migraine with aura including cortical spreading depression and its limitations.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goadsby PJ, Holland PR. An update: pathophysiology of migraine. Neurol Clin. 2019;37(4):651–71 Excellent review of migraine pathophysiology in all phases including aura phase.

    Article  PubMed  Google Scholar 

  5. Harriott AM, Takizawa T, Chung DY, Chen SP. Spreading depression as a preclinical model of migraine. J Headache Pain. 2019;20(1):45.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chung DY, Sugimoto K, Fischer P, Bohm M, Takizawa T, Sadeghian H, et al. Real-time non-invasive in vivo visible light detection of cortical spreading depolarizations in mice. J Neurosci Methods. 2018;309:143–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Houben T, Loonen IC, Baca SM, Schenke M, Meijer JH, Ferrari MD, et al. Optogenetic induction of cortical spreading depression in anesthetized and freely behaving mice. J Cereb Blood Flow Metab. 2017;37(5):1641–55.

    Article  PubMed  Google Scholar 

  8. Charles A, Hansen JM. Migraine aura: new ideas about cause, classification, and clinical significance. Curr Opin Neurol. 2015;28(3):255–60.

    Article  PubMed  Google Scholar 

  9. Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98(8):4687–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tottene A, Conti R, Fabbro A, Vecchia D, Shapovalova M, Santello M, et al. Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in Ca(v)2.1 knockin migraine mice. Neuron. 2009;61(5):762–73.

    Article  CAS  PubMed  Google Scholar 

  11. Bolay H, Berman NE, Akcali D. Sex-related differences in animal models of migraine headache. Headache. 2011;51(6):891–904.

    Article  PubMed  Google Scholar 

  12. Hadjikhani N, Vincent M. Neuroimaging clues of migraine aura. J Headache Pain. 2019;20(1):32.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Russo A, Silvestro M, Tessitore A, Tedeschi G. Recent insights in migraine with aura: a narrative review of advanced neuroimaging. Headache. 2019;59(4):637–49.

    Article  PubMed  Google Scholar 

  14. Krebs C, Weinberg J, Akesson E, Dilli E. Lippincott illustrated reviews: neuroscience. 2nd ed. Alphen aan den Rijn: Wolters Kluwer; 2017.

    Google Scholar 

  15. Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain. 2014;137(Pt 1):232–41.

    Article  PubMed  Google Scholar 

  16. Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987–93.

    Article  PubMed  Google Scholar 

  17. Hougaard A, Amin FM, Larsson HB, Rostrup E, Ashina M. Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura. Hum Brain Mapp. 2017;38(5):2635–42.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vinogradova LV. Initiation of spreading depression by synaptic and network hyperactivity: insights into trigger mechanisms of migraine aura. Cephalalgia. 2018;38(6):1177–87.

    Article  PubMed  Google Scholar 

  19. Lindblad M, Hougaard A, Amin FM, Ashina M. Can migraine aura be provoked experimentally? A systematic review of potential methods for the provocation of migraine aura. Cephalalgia. 2017;37(1):74–88.

    Article  PubMed  Google Scholar 

  20. International Headache Society Classification Committee. The international classification of headache disorders. 3rd edition. Cephalalgia : an international journal of headache. 2018;38:1–211.

  21. Viana M, Sances G, Linde M, Ghiotto N, Guaschino E, Allena M, et al. Clinical features of migraine aura: results from a prospective diary-aided study. Cephalalgia. 2017;37(10):979–89 Excellent review on clinical features of visual aura based on prospective study of 72 patients.

    Article  PubMed  Google Scholar 

  22. Hansen JM, Baca SM, Vanvalkenburgh P, Charles A. Distinctive anatomical and physiological features of migraine aura revealed by 18 years of recording. Brain. 2013;136(Pt 12):3589–95.

    Article  PubMed  Google Scholar 

  23. Viana M, Sances G, Linde M, Nappi G, Khaliq F, Goadsby PJ, et al. Prolonged migraine aura: new insights from a prospective diary-aided study. J Headache Pain. 2018;19(1):77.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Viana M, Tronvik EA, Do TP, Zecca C, Hougaard A. Clinical features of visual migraine aura: a systematic review. J Headache Pain. 2019;20(1):64.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yamani N, Chalmer MA, Olesen J. Migraine with brainstem aura: defining the core syndrome. Brain. 2019;142(12):3868–75.

    Article  PubMed  Google Scholar 

  26. Demarquay G, Ducros A, Montavont A, Mauguiere F. Migraine with brainstem aura: why not a cortical origin? Cephalalgia. 2018;38(10):1687–95.

    Article  PubMed  Google Scholar 

  27. Kirchmann M, Thomsen LL, Olesen J. Basilar-type migraine: clinical, epidemiologic, and genetic features. Neurology. 2006;66(6):880–6.

    Article  PubMed  Google Scholar 

  28. Grosberg BM, Solomon S, Friedman DI, Lipton RB. Retinal migraine reappraised. Cephalalgia. 2006;26(11):1275–86.

    Article  CAS  PubMed  Google Scholar 

  29. El Youssef N, Maalouf N, Mourad A, Saade J, Khoury M. Teaching neuroimages: retinal migraine in action. Neurology. 2018;90(11):e992.

    Article  PubMed  Google Scholar 

  30. Chang M, Phasukkijwatana N, Garrity S, Pineles S, Rahimi M, Sarraf D, et al. Foveal and peripapillary vascular decrement in migraine with aura demonstrated by optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2017;58:5477–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. El-Shazly AAE, Farweez YA, Hamdi MM, El-Sherbiny NE. Pattern visual evoked potential, pattern electroretinogram, and retinal nerve fiber layer thickness in patients with migraine during and after aura. Curr Eye Res. 2017;42(9):1327–32.

    Article  PubMed  Google Scholar 

  32. Kurth T, Chabriat H, Bousser M-G. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11(1):92–100.

    Article  PubMed  Google Scholar 

  33. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. 2011;10(5):457–70.

    Article  PubMed  Google Scholar 

  34. Pelzer N, Haan J, Stam AH, Vijfhuizen LS, Koelewijn SC, Smagge A, et al. Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic mutation. Neurology. 2018;90(7):e575–e82.

    Article  PubMed  Google Scholar 

  35. de Boer I, van den Maagdenberg A, Terwindt GM. Advance in genetics of migraine. Curr Opin Neurol. 2019;32(3):413–21.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet. 2016;48(8):856–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu L, Yu Y, He J, Guo L, Li H, Teng J. Effects of MTHFR C677T and A1298C polymorphisms on migraine susceptibility: a meta-analysis of 26 studies. Headache. 2019;59(6):891–905.

    Article  PubMed  Google Scholar 

  38. Mathew PG, Robertson CE. No laughing matter: gelastic migraine and other unusual headache syndromes. Curr Pain Headache Rep. 2016;20(5):32.

    Article  PubMed  Google Scholar 

  39. Erdal Y, Emre U, Cimen Atalar A, Gunes T. Alien hand syndrome and migraine with aura: a case report. Cephalalgia. 2018;38(13):1984–7.

    Article  PubMed  Google Scholar 

  40. Jion YI, Grosberg BM, Evans RW. Phantosmia and migraine with and without headache. Headache. 2016;56(9):1494–502.

    Article  PubMed  Google Scholar 

  41. Evans RW, Mitsias PD. Headache at onset of acute cerebral ischemia. Headache. 2009;49(6):902–8.

    Article  PubMed  Google Scholar 

  42. Shams P, Plant G. Migraine-like visual aura due to focal cerebral lesions: case series and review. Surv Ophthalmol. 2011;56(2):135–61.

    Article  PubMed  Google Scholar 

  43. Rajapakse T, Buchhalter J. The borderland of migraine and epilepsy in children. Headache. 2016;56:1071–80.

    Article  PubMed  Google Scholar 

  44. Bigal ME, Lipton RB, Cohen J, Silberstein SD. Epilepsy and migraine. Epilepsy Behav. 2003;4:13–24.

    Article  Google Scholar 

  45. Terrin A, Toldo G, Ermani M, Mainardi F, Maggioni F. When migraine mimics stroke: a systematic review. Cephalalgia. 2018;38(14):2068–78.

    Article  PubMed  Google Scholar 

  46. Coutts SB, Moreau F, Asdaghi N, Boulanger JM, Camden MC, Campbell BCV, et al. Rate and prognosis of brain ischemia in patients with lower-risk transient or persistent minor neurologic events. JAMA Neurol. 2019;76(12):1439–45. Erratum published January 13, 2020. https://doi.org/10.1001/jamaneurol.2019.3063.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Coutts SB, Moreau F, Asdaghi N, Boulanger JM, Camden MC, Campbell BCV, et al. Rate and prognosis of brain ischemia in patients with lower-risk transient or persistent minor neurologic events [supplemental material]. JAMA Neurol. 2019;76:1439.

    Article  PubMed  PubMed Central  Google Scholar 

  48. West BH, Noureddin N, Mamzhi Y, Low CG, Coluzzi AC, Shih EJ, et al. Frequency of patent foramen ovale and migraine in patients with cryptogenic stroke. Stroke. 2018;49(5):1123–8.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Snijder RJ, Luermans JG, de Heij AH, Thijs V, Schonewille WJ, Van De Bruaene A, et al. Patent foramen ovale with atrial septal aneurysm is strongly associated with migraine with aura: a large observational study. J Am Heart Assoc. 2016;5(12).

  50. Tobis JM, Charles A, Silberstein SD, Sorensen S, Maini B, Horwitz PA, et al. Percutaneous closure of patent foramen Ovale in patients with migraine: the PREMIUM trial. J Am Coll Cardiol. 2017;70(22):2766–74.

    Article  PubMed  Google Scholar 

  51. Hartl E, Remi J, Noachtar S. Two patients with visual aura–migraine, epilepsy, or migralepsy? Headache. 2015;55(8):1148–51.

    Article  PubMed  Google Scholar 

  52. Panayiotopolous CP, Sharoqi A. Occipital seizures imitating migraine aura. J R Soc Med. 1997;90:255–7.

    Article  Google Scholar 

  53. Hartl E, Gonzalez-Victores JA, Remi J, Schankin CJ, Noachtar S. Visual auras in epilepsy and migraine–an analysis of clinical characteristics. Headache. 2017;57(6):908–16.

    Article  PubMed  Google Scholar 

  54. Kingston WS, Schwedt TJ. The relationship between headaches with epileptic and non-epileptic seizures: a narrative review. Curr Pain Headache Rep. 2017;21(3):17.

    Article  PubMed  Google Scholar 

  55. Mastria G, Mancini V, Vigano A, De Sanctis R, Letteri F, Toscano M, et al. Temporal-occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura. Neurocase. 2018;24(5–6):242–4.

    Article  PubMed  Google Scholar 

  56. MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38(9):2438–45.

    Article  PubMed  Google Scholar 

  57. Bousser M-G, Welch KMA. Relation between migraine and stroke. Lancet Neurol. 2005;4(9):533–42.

    Article  PubMed  Google Scholar 

  58. Calhoun AH. Hormonal contraceptives and migraine with aura-is there still a risk? Headache. 2017;57(2):184–93.

    Article  PubMed  Google Scholar 

  59. Sheikh HU, Pavlovic J, Loder E, Burch R. Risk of stroke associated with use of estrogen containing contraceptives in women with migraine: a systematic review. Headache. 2018;58(1):5–21.

    Article  PubMed  Google Scholar 

  60. Champaloux SW, Tepper NK, Monsour M, Curtis KM, Whiteman MK, Marchbanks PA, et al. Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke. Am J Obstet Gynecol. 2017;216(5):489.e1–7.

    Article  CAS  Google Scholar 

  61. Dodick DW. Review of comorbidities and risk factors for development of migraine complications (infarct and chronic migraine). Cephalalgia. 2009;29(Suppl. 3):7–14.

    PubMed  Google Scholar 

  62. World Health Organization. Medical eligibility criteria for contraceptive use. 3rd ed. Geneva: World Health Organization; 2004.

    Google Scholar 

  63. American College of Obstetrics and Gynecology Practice Bulletins. Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol. 2019;133(2):e128–e43.

    Article  Google Scholar 

  64. Tepper NK, Whiteman MK, Zapata LB, Marchbanks PA, Curtis MK. Safety of hormonal contraceptives among women with migraine: a systematic review. Contraception. 2016;94(6):630–40.

    Article  CAS  PubMed  Google Scholar 

  65. Petrusic I, Viana M, Dakovic M, JGoadsby P, Zidverc-Trajkovic J. Proposal for a migraine aura complexity score. Cephalalgia. 2019;39(6):732–41.

    Article  PubMed  Google Scholar 

  66. Vinciguerra L, Cantone M, Lanza G, Bramanti A, Santalucia P, Puglisi V, et al. Migrainous infarction and cerebral vasospasm: case report and literature review. J Pain Res. 2019;12:2941–50.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Laurell K, Artto V, Bendtsen L, Hagen K, Kallela M, Meyer EL, et al. Migrainous infarction: a Nordic multicenter study. Eur J Neurol. 2011;18(10):1220–6.

    Article  CAS  PubMed  Google Scholar 

  68. Wolf ME, Szabo K, Griebe M, Forster A, Gass A, Hennerici MG, et al. Clinical and MRI characteristics of acute migrainous infarction. Neurology. 2011;76:1911–7.

    Article  CAS  PubMed  Google Scholar 

  69. Arboix A, Gonzalez-Peris S, Grive E, Sanchez MJ, Comes E. Cortical laminar necrosis related to migrainous cerebral infarction. World J Clin Cases. 2013;1(8):256–9.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Pringsheim T, Davenport JW, Mackie G, Worthington I, Aubé M, Suzanne CN, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(Suppl 2):S1–2.

    PubMed  Google Scholar 

  71. Artto V, Nissila M, Wessman M, Palotie A, Farkkila M, Kallela M. Treatment of hemiplegic migraine with triptans. Eur J Neurol. 2007;14(9):1053–6.

    Article  CAS  PubMed  Google Scholar 

  72. Mathew PG, Klein BC. Getting to the heart of the matter: migraine, triptans, DHE, ditans, CGRP antibodies, first/second-generation gepants, and cardiovascular risk. Headache. 2019;59(8):1421–6.

    Article  PubMed  Google Scholar 

  73. Hansen J, Goadsby PJ, Charles A. Reduced efficacy of sumatriptan in migraine with aura vs without aura. Neurology. 2015;84:1880–5.

    Article  CAS  PubMed  Google Scholar 

  74. Goadsby PJ, Ferrari MD, Csanyi A, Olesen J, Mills JG, Tonabersat TONSG. Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Cephalalgia. 2009;29(7):742–50.

    Article  CAS  PubMed  Google Scholar 

  75. Anne W, Hauge MSA, Schytz HW, Christensen K, Olesen J. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet Neurol. 2009;8:718–23.

    Article  CAS  Google Scholar 

  76. Hansen JM, Charles A. Differences in treatment response between migraine with aura and migraine without aura: lessons from clinical practice and RCTs. J Headache Pain. 2019;20(1):96 Excellent review of available evidence for treatments in migraine aura.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Cuadrado ML, Aledo-Serrano A, Lopez-Ruiz P, Gutierrez-Viedma A, Fernandez C, Orviz A, et al. Greater occipital nerve block for the acute treatment of prolonged or persistent migraine aura. Cephalalgia. 2017;37(8):812–8.

    Article  PubMed  Google Scholar 

  78. Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30(10):1179–86.

    Article  PubMed  Google Scholar 

  79. Lipton R, Dodick DW, Silberstein S, Saper JR, Aurora SK, Pearlman SH, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010;9:373–80.

    Article  PubMed  Google Scholar 

  80. De Icco R, Bitetto V, Martinelli D, Allena M, Guaschino E, Bottiroli S, et al. Noninvasive peripheral vagal nerve stimulation prevents migraine aura: a case report. Cephalalgia Reports. 2019;2:251581631985560.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Esma Dilli.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lai, J., Dilli, E. Migraine Aura: Updates in Pathophysiology and Management. Curr Neurol Neurosci Rep 20, 17 (2020). https://doi.org/10.1007/s11910-020-01037-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-020-01037-3

Keywords

Navigation