Semin Neurol 2019; 39(06): 739-748
DOI: 10.1055/s-0039-1700525
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Migraine Aura: Pathophysiology, Mimics, and Treatment Options

Clare L. Fraser
1   Save Sight Institute, Discipline of Ophthalmology, Faculty of Health and Medicine, The University of Sydney, Australia
,
Jenny L. Hepschke
1   Save Sight Institute, Discipline of Ophthalmology, Faculty of Health and Medicine, The University of Sydney, Australia
2   Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia
,
Bronwyn Jenkins
3   Department of Neurology, Royal North Shore Hospital, Sydney, Australia
,
Sashank Prasad
4   Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
17 December 2019 (online)

Abstract

Recent insights into the clinical presentation and pathophysiology of migraine aura have paved the way for new treatments for this common but frequently debilitating condition. Marked efflux of cellular potassium and glutamate contributes to the cortical spreading depression that forms the electrophysiological basis of migraine aura phenomena. Secondary vascular perturbations also contribute to the various symptoms of a migraine attack. Calcitonin gene-related peptide (CGRP) plays a key role in many of these steps, and a growing class of CGRP-antagonists have emerged as a novel, efficacious preventative therapy. It is still not fully understood why a preponderance of migraine aura symptoms is visual, and this issue is an active area of research. In addition, the pathophysiological changes responsible for visual snow syndrome are under investigation. Before diagnosing a patient with migraine aura, it is important to consider the differential diagnosis of transient visual phenomena, with attention to clinical features that may suggest conditions such as retinal disorders, transient ischemic attack, or occipital epilepsy.

 
  • References

  • 1 Charles A, Hansen JM. Migraine aura: new ideas about cause, classification, and clinical significance. Curr Opin Neurol 2015; 28 (03) 255-260
  • 2 Headache Classification Committee of the International Headache Society (HIS). The international classification of headache disorders. 3rd edition (beta version). Cephalalgia 2013; 33 (09) 629-808
  • 3 Yeh WZ, Blizzard L, Taylor BV. What is the actual prevalence of migraine?. Brain Behav 2018; 8 (06) e00950
  • 4 DeLange JM, Cutrer FM. Our evolving understanding of migraine with aura. Curr Pain Headache Rep 2014; 18 (10) 453
  • 5 Quintana S, Genovese A, Rausa F, Manzoni GC, Torelli P. Migraine with typical aura: clinical features and their relationship with sex and age of onset. Results from the analysis of a large case series. Neurol Sci 2018; 39 (Suppl. 01) 135-136
  • 6 Ahmed M, Boyd C, Vavilikolanu R, Rafique B. Visual symptoms and childhood migraine: Qualitative analysis of duration, location, spread, mobility, colour and pattern. Cephalalgia 2018; 38 (14) 2017-2025
  • 7 Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 2017; 97 (02) 553-622
  • 8 Kelman L. The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. Headache 2004; 44 (09) 865-872
  • 9 Eikermann-Haerter K, Negro A, Ayata C. Spreading depression and the clinical correlates of migraine. Rev Neurosci 2013; 24 (04) 353-363
  • 10 Airy H. On a distinct form of transient hemianopsia. Philos Trans R Soc Lond 1870; 160: 247-270
  • 11 Hansen JM, Goadsby PJ, Charles AC. Variability of clinical features in attacks of migraine with aura. Cephalalgia 2016; 36 (03) 216-224
  • 12 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): 3589-3595
  • 13 Schankin CJ, Viana M, Goadsby PJ. Persistent and repetitive visual disturbances in migraine: a review. Headache 2017; 57 (01) 1-16
  • 14 Perenboom MJL, Zamanipoor Najafabadi AH, Zielman R, Carpay JA, Ferrari MD. Quantifying visual allodynia across migraine subtypes: the Leiden Visual Sensitivity Scale. Pain 2018; 159 (11) 2375-2382
  • 15 Dodick DW. A phase-by-phase review of migraine pathophysiology. Headache 2018; 58 (Suppl. 01) 4-16
  • 16 Hadjikhani N, Sanchez Del Rio M, Wu O. , et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 2001; 98 (08) 4687-4692
  • 17 Charles A, Brennan K. Cortical spreading depression-new insights and persistent questions. Cephalalgia 2009; 29 (10) 1115-1124
  • 18 Karatas H, Erdener SE, Gursoy-Ozdemir Y. , et al. Spreading depression triggers headache by activating neuronal Panx1 channels. Science 2013; 339 (6123): 1092-1095
  • 19 Hartings JA, Bullock MR, Okonkwo DO. , et al; Co-Operative Study on Brain Injury Depolarisations. Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study. Lancet Neurol 2011; 10 (12) 1058-1064
  • 20 Kilic K, Karatas H, Dönmez-Demir B. , et al. Inadequate brain glycogen or sleep increases spreading depression susceptibility. Ann Neurol 2018; 83 (01) 61-73
  • 21 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 (01) 74-88
  • 22 Chen WT, Wang SJ, Fuh JL, Lin CP, Ko YC, Lin YY. Persistent ictal-like visual cortical excitability in chronic migraine. Pain 2011; 152 (02) 254-258
  • 23 Khennouf L, Gesslein B, Brazhe A. , et al. Active role of capillary pericytes during stimulation-induced activity and spreading depolarization. Brain 2018; 141 (07) 2032-2046
  • 24 Close LN, Eftekhari S, Wang M, Charles AC, Russo AF. Cortical spreading depression as a site of origin for migraine: role of CGRP. Cephalalgia 2019; 39 (03) 428-434
  • 25 Giamberardino MA, Affaitati G, Costantini R, Cipollone F, Martelletti P. Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab. J Pain Res 2017; 10: 2751-2760
  • 26 Ashina H, Schytz HW, Ashina M. CGRP in human models of migraine. Handb Exp Pharmacol 2018
  • 27 Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache 2006; 46 (Suppl. 01) S3-S8
  • 28 Lisicki M, D'Ostilio K, Coppola G. , et al. Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials. J Headache Pain 2018; 19 (01) 49
  • 29 Petrušić I, Daković M, Kačar K, Mićić O, Zidverc-Trajković J. Migraine with aura and white matter tract changes. Acta Neurol Belg 2018; 118 (03) 485-491
  • 30 Charles A. The Migraine aura. Continuum (Minneap Minn) 2018; 24 (4, Headache): 1009-1022
  • 31 Andreou A, Sprenger T, Goadsby PJ. Cortical modulation of thalamic function during cortical spreading depression - unraveling a new central mechanism involved in migraine aura. J Headache Pain 2013; 14 (Suppl. 01) 16
  • 32 Wakayama Y, Inoue M, Takahashi J. Aquaporin 1 may be involved in the pathophysiology of migraine: a hypothesis. Headache 2007; 47 (10) 1457-1458
  • 33 Xu GY, Wang F, Jiang X, Tao J. Aquaporin 1, a potential therapeutic target for migraine with aura. Mol Pain 2010; 6: 68
  • 34 Russell MB, Iselius L, Olesen J. Migraine without aura and migraine with aura are inherited disorders. Cephalalgia 1996; 16 (05) 305-309
  • 35 Sutherland HG, Griffiths LR. Genetics of migraine: insights into the molecular basis of migraine disorders. Headache 2017; 57 (04) 537-569
  • 36 Iljazi A, Ayata C, Ashina M, Hougaard A. The role of endothelin in the pathophysiology of migraine-a systematic review. Curr Pain Headache Rep 2018; 22 (04) 27
  • 37 Todd C, Lagman-Bartolome AM, Lay C. Women and migraine: the role of hormones. Curr Neurol Neurosci Rep 2018; 18 (07) 42
  • 38 Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C. Estrogen, migraine, and vascular risk. Neurol Sci 2018; 39 (Suppl. 01) 11-20
  • 39 Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2. Headache 2006; 46 (03) 365-386
  • 40 Pollock CE, Sutherland HG, Maher BH. , et al. The NRP1 migraine risk variant shows evidence of association with menstrual migraine. J Headache Pain 2018; 19 (01) 31
  • 41 Pavlovic JM, Vieira JR, Lipton RB, Bond DS. Association between obesity and migraine in women. Curr Pain Headache Rep 2017; 21 (10) 41
  • 42 Andreeva VA, Galan P, Julia C, Fezeu L, Hercberg S, Kesse-Guyot E. A systematic literature review of observational studies of the bidirectional association between metabolic syndrome and migraine. Diabetes Metab 2019; 45 (01) 11-18
  • 43 Rainero I, Govone F, Gai A, Vacca A, Rubino E. Is migraine primarily a metaboloendocrine disorder?. Curr Pain Headache Rep 2018; 22 (05) 36
  • 44 Becker WJ. Acute migraine treatment. Continuum (Minneap Minn) 2015; 21 (4 Headache): 953-972
  • 45 Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55 (06) 754-762
  • 46 Bates D, Ashford E, Dawson R. , et al; Sumatriptan Aura Study Group. Subcutaneous sumatriptan during the migraine aura. Neurology 1994; 44 (09) 1587-1592
  • 47 Olesen J, Diener HC, Schoenen J, Hettiarachchi J. No effect of eletriptan administration during the aura phase of migraine. Eur J Neurol 2004; 11 (10) 671-677
  • 48 Aurora SK, Barrodale PM, McDonald SA, Jakubowski M, Burstein R. Revisiting the efficacy of sumatriptan therapy during the aura phase of migraine. Headache 2009; 49 (07) 1001-1004
  • 49 Bhatt DK, Gupta S, Jansen-Olesen I, Andrews JS, Olesen J. NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models. Cephalalgia 2013; 33 (02) 87-100
  • 50 Hougaard A, Hauge AW, Guo S, Tfelt-Hansen P. The nitric oxide synthase inhibitor and serotonin-receptor agonist NXN-188 during the aura phase of migraine with aura: a randomized, double-blind, placebo-controlled cross-over study. Scand J Pain 2013; 4 (01) 48-52
  • 51 Afridi SK, Giffin NJ, Kaube H, Goadsby PJ. A randomized controlled trial of intranasal ketamine in migraine with prolonged aura. Neurology 2013; 80 (07) 642-647
  • 52 Lan L, Zhang X, Li X, Rong X, Peng Y. The efficacy of transcranial magnetic stimulation on migraine: a meta-analysis of randomized controlled trails. J Headache Pain 2017; 18 (01) 86
  • 53 Barker AT, Shields K. Transcranial magnetic stimulation: basic principles and clinical applications in migraine. Headache 2017; 57 (03) 517-524
  • 54 Starling AJ, Tepper SJ, Marmura MJ. , et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia 2018; 38 (06) 1038-1048
  • 55 Tassorelli C, Grazzi L, de Tommaso M. , et al; PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: the randomized PRESTO study. Neurology 2018; 91 (04) e364-e373
  • 56 Vgontzas A, Burch R. Episodic migraine with and without aura: key differences and implications for pathophysiology, management, and assessing risks. Curr Pain Headache Rep 2018; 22 (12) 78
  • 57 Shapiro RE. Preventive treatment of migraine. Headache 2012; 52 (Suppl. 02) 65-69
  • 58 Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol 2006; 59 (04) 652-661
  • 59 Shah DR, Dilwali S, Friedman DI. Migraine aura without headache [corrected]. Curr Pain Headache Rep 2018; 22 (11) 77
  • 60 Lampl C, Buzath A, Klinger D, Neumann K. Lamotrigine in the prophylactic treatment of migraine aura--a pilot study. Cephalalgia 1999; 19 (01) 58-63
  • 61 Pascual J, Caminero AB, Mateos V. , et al. Preventing disturbing migraine aura with lamotrigine: an open study. Headache 2004; 44 (10) 1024-1028
  • 62 Lampl C, Katsarava Z, Diener HC, Limmroth V. Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. J Neurol Neurosurg Psychiatry 2005; 76 (12) 1730-1732
  • 63 Khan S, Olesen A, Ashina M. CGRP, a target for preventive therapy in migraine and cluster headache: Systematic review of clinical data. Cephalalgia 2019; 39 (03) 374-389
  • 64 Rizwan S, Mehmood A, Khalid I. , et al. Polypharmacology approach against migraine with aura and brain edema for the development of an efficient inhibitor and its analogues. Curr Comput Aided Drug Des 2018; 14 (04) 385-390
  • 65 Leimuranta P, Khiroug L, Giniatullin R. Emerging role of (endo)cannabinoids in migraine. Front Pharmacol 2018; 9: 420
  • 66 Andreeva VA, Fezeu LK, Hercberg S, Galan P. Obesity and migraine: effect modification by gender and perceived stress. Neuroepidemiology 2018; 51 (1,2): 25-32
  • 67 Klenofsky B, Pace A, Natbony LR, Sheikh HU. Episodic migraine comorbidities: avoiding pitfalls and taking therapeutic opportunities. Curr Pain Headache Rep 2019; 23 (01) 1
  • 68 Puledda F, Shields K. Non-pharmacological approaches for migraine. Neurotherapeutics 2018; 15 (02) 336-345
  • 69 Martins LB, Rodrigues AMDS, Rodrigues DF, Dos Santos LC, Teixeira AL, Ferreira AVM. Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment. Cephalalgia 2019; 39 (01) 68-76
  • 70 Mahmoud AN, Mentias A, Elgendy AY. , et al. Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects. BMJ Open 2018; 8 (03) e020498
  • 71 Cecchi G, Paolucci M, Ulivi M. , et al. Frequency and clinical implications of hypercoagulability states in a cohort of patients with migraine with aura. Neurol Sci 2018; 39 (Suppl. 01) 99-100
  • 72 Elbadawi A, Barssoum K, Abuzaid AS. , et al. Meta-analysis of randomized trials on percutaneous patent foramen ovale closure for prevention of migraine. Acta Cardiol 2019; 74 (02) 124-129
  • 73 Tobis JM, Charles A, Silberstein SD. , et al. Percutaneous closure of patent foramen ovale in patients with migraine: the PREMIUM trial. J Am Coll Cardiol 2017; 70 (22) 2766-2774
  • 74 Schankin CJ, Goadsby PJ. Visual snow--persistent positive visual phenomenon distinct from migraine aura. Curr Pain Headache Rep 2015; 19 (06) 23
  • 75 Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ. ‘Visual snow’ - a disorder distinct from persistent migraine aura. Brain 2014; 137 (Pt 5): 1419-1428
  • 76 Metzler AI, Robertson CE. Visual snow syndrome: proposed criteria, clinical implications, and pathophysiology. Curr Neurol Neurosci Rep 2018; 18 (08) 52
  • 77 Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology 2002; 58 (06) 885-894
  • 78 Schankin CJ, Maniyar FH, Sprenger T, Chou DE, Eller M, Goadsby PJ. The relation between migraine, typical migraine aura and “visual snow”. Headache 2014; 54 (06) 957-966
  • 79 Lauschke JL, Plant GT, Fraser CL. Visual snow: a thalamocortical dysrhythmia of the visual pathway?. J Clin Neurosci 2016; 28: 123-127
  • 80 Gersztenkorn D, Lee AG. Palinopsia revamped: a systematic review of the literature. Surv Ophthalmol 2015; 60 (01) 1-35
  • 81 McKendrick AM, Chan YM, Tien M. , et al. Behavioral measures of cortical hyperexcitability assessed in people who experience visual snow. Neurology 2017; 88 (13) 1243-1249
  • 82 Luna S, Lai D, Harris A. Antagonistic relationship between vep potentiation and gamma power in visual snow syndrome. Headache 2018; 58 (01) 138-144
  • 83 Eren O, Rauschel V, Ruscheweyh R, Straube A, Schankin CJ. Evidence of dysfunction in the visual association cortex in visual snow syndrome. Ann Neurol 2018; 84 (06) 946-949
  • 84 Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci 2015; 35 (17) 6619-6629
  • 85 Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015; 14 (01) 65-80
  • 86 Huang J, Zong X, Wilkins A, Jenkins B, Bozoki A, Cao Y. fMRI evidence that precision ophthalmic tints reduce cortical hyperactivation in migraine. Cephalalgia 2011; 31 (08) 925-936
  • 87 Parra J, Lopes da Silva FH, Stroink H, Kalitzin S. Is colour modulation an independent factor in human visual photosensitivity?. Brain 2007; 130 (Pt 6): 1679-1689
  • 88 Unal-Cevik I, Yildiz FG. Visual snow in migraine with aura: further characterization by brain imaging, electrophysiology, and treatment--case report. Headache 2015; 55 (10) 1436-1441
  • 89 Lebedeva ER, Gurary NM, Gilev DV, Christensen AF, Olesen J. Explicit diagnostic criteria for transient ischemic attacks to differentiate it from migraine with aura. Cephalalgia 2018; 38 (08) 1463-1470
  • 90 Waters MJ, Cheong E, Jannes J, Kleinig T. Ischaemic stroke may symptomatically manifest as migraine aura. J Clin Neurosci 2018; 55: 62-64
  • 91 Adcock JE, Panayiotopoulos CP. Occipital lobe seizures and epilepsies. J Clin Neurophysiol 2012; 29 (05) 397-407
  • 92 Halpern JH, Pope Jr HG. Hallucinogen persisting perception disorder: what do we know after 50 years?. Drug Alcohol Depend 2003; 69 (02) 109-119
  • 93 Levi L, Miller NR. Visual illusions associated with previous drug abuse. J Clin Neuroophthalmol 1990; 10 (02) 103-110
  • 94 Abraham HD. Visual phenomenology of the LSD flashback. Arch Gen Psychiatry 1983; 40 (08) 884-889
  • 95 Hermle L, Simon M, Ruchsow M, Geppert M. Hallucinogen-persisting perception disorder. Ther Adv Psychopharmacol 2012; 2 (05) 199-205
  • 96 Gaillard MC, Borruat FX. Persisting visual hallucinations and illusions in previously drug-addicted patients. Klin Monatsbl Augenheilkd 2003; 220 (03) 176-178
  • 97 Lerner AG, Oyefe I, Isaacs G, Sigal M. Naltrexone treatment of hallucinogen persisting perception disorder. Am J Psychiatry 1997; 154 (03) 437
  • 98 Schadlu AP, Schadlu R, Shepherd III JB. Charles Bonnet syndrome: a review. Curr Opin Ophthalmol 2009; 20 (03) 219-222
  • 99 Grange L, Dalal M, Nussenblatt RB, Sen HN. Autoimmune retinopathy. Am J Ophthalmol 2014; 157 (02) 266-272.e1
  • 100 Roels D, Ueno S, Talianu CD, Draganova D, Kondo M, Leroy BP. Unilateral cancer-associated retinopathy: diagnosis, serology and treatment. Doc Ophthalmol 2017; 135 (03) 233-240
  • 101 Khan N, Huang JJ, Foster CS. Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome. Semin Ophthalmol 2006; 21 (03) 135-141
  • 102 Grewal DS, Fishman GA, Jampol LM. Autoimmune retinopathy and antiretinal antibodies: a review. Retina 2014; 34 (05) 827-845
  • 103 v M FdeL, W H; L VMF. Relevance of excitable media theory and retinal spreading depression experiments in preclinical pharmacological research. Curr Neuropharmacol 2014; 12 (05) 413-433