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The Journal of Headache and Pain
Published in: The Journal of Headache and Pain 1/2019

Open Access 01-12-2019 | Migraine | Review article

Neuroimaging clues of migraine aura

Authors: Nouchine Hadjikhani, Maurice Vincent

Published in: The Journal of Headache and Pain | Issue 1/2019

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Abstract

While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiology of the migraine with aura (MWA) cascade. Here, we review findings pointing to the involvement of cortical spreading depression (CSD) and neuroinflammation in MWA. Whether asymptomatic CSD also happens in some migraine without aura is still under debate. In addition, new evidence points to glial activation in MWA, indicating the involvement of astrocytes in the neuroinflammatory cascade that follows CSD, as well as dural macrophages, supporting the involvement of the trigeminovascular system in migraine pain.
Literature
1.
Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, et al (2013) Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat Genet 45(8):912–917
2.
Hougaard A, Amin FM, Ashina M (2014) Migraine and structural abnormalities in the brain. Curr Opin Neurol 27(3):309–314PubMedCrossRef
3.
May A (2017) Understanding migraine as a cycling brain syndrome: reviewing the evidence from functional imaging. Neurol Sci 38(Suppl 1):125–130PubMedCrossRef
4.
Headache Classification Committee of the International Headache Society (IHS) (2018) The international classification of headache disorders, 3rd edition. Cephalalgia 38(1):1–211CrossRef
5.
Russell MB, Olesen J (1996) A nosographic analysis of the migraine aura in a general population. Brain. 119(Pt 2):355–361PubMedCrossRef
6.
Viana M, Sances G, Linde M, Ghiotto N, Guaschino E, Allena M et al (2017) Clinical features of migraine aura: results from a prospective diary-aided study. Cephalalgia. 37(10):979–989PubMedCrossRef
7.
Lauritzen M (1994) Pathophysiology of the migraine aura. The spreading depression theory. Brain. 117(Pt 1):199–210PubMedCrossRef
8.
Hadjikhani N, Sanchez del Rio M, Wu O, Schwartz D, Bakker D, Fischl B et al (2001) Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 98(8):4687–4692PubMedPubMedCentralCrossRef
9.
Schwedt TJ, Goadsby PJ (2010) 14th international headache congress: basic science highlights. Headache. 50(3):520–526PubMedCrossRef
10.
Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ (2011) Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab 31(1):17–35PubMedCrossRef
11.
Ayata C, Jin HW, Kudo C, Dalkara T, Moskowitz MA (2006) Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol 59(4):652–661PubMedCrossRef
12.
13.
Maurice-Williams RS, Dunwoody G (1988) Late diagnosis of frontal meningiomas presenting with psychiatric symptoms. Br Med J (Clin Res Ed) 296(6639):1785–1786CrossRef
14.
Schwedt TJ, Peplinski J, Garcia-Filion P, Berisha V (2018) Altered speech with migraine attacks: a prospective, longitudinal study of episodic migraine without aura. Cephalalgia
15.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S (2017) Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 97(2):553–622PubMedPubMedCentralCrossRef
16.
Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM (2001) Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Ann Neurol 50(5):582–587PubMedCrossRef
17.
Cao Y, Welch KMA, Aurora S, Vikingstad E (1999) Functional MRI-BOLD of visually triggered headache in patients with migraine. Arch Neurol 56:548–554PubMedCrossRef
18.
Kaube H, Herzog J, Kaufer T, Dichgans M, Diener HC (2000) Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 55(1):139–141PubMedCrossRef
19.
Shibata K, Osawa M, Iwata M (1998) Pattern reversal visual evoked potentials in migraine with aura and migraine aura without headache. Cephalalgia. 18(6):319–323PubMedCrossRef
20.
Schulte LH, May A (2016) The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 139(Pt 7:1987–1993PubMedCrossRef
21.
Viana M, Linde M, Sances G, Ghiotto N, Guaschino E, Allena M et al (2016) Migraine aura symptoms: duration, succession and temporal relationship to headache. Cephalalgia. 36(5):413–421PubMedCrossRef
22.
Viana M, Sances G, Ghiotto N, Guaschino E, Allena M, Nappi G et al (2016) Variability of the characteristics of a migraine attack within patients. Cephalalgia. 36(9):825–830PubMedCrossRef
23.
Hansen JM, Goadsby PJ, Charles AC (2016) Variability of clinical features in attacks of migraine with aura. Cephalalgia. 36(3):216–224PubMedCrossRef
24.
Olesen J, Larsen B, Lauritzen M (1981) Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 9(4):344–352PubMedCrossRef
25.
Olesen J, Tfelt-Hansen P, Henriksen L, Larsen B (1981) The common migraine attack may not be initiated by cerebral ischaemia. Lancet. 2(8244):438–440PubMedCrossRef
26.
Lauritzen M, Skyhoj Olsen T, Lassen NA, Paulson OB (1983) Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol 13(6):633–641PubMedCrossRef
27.
Olesen J, Friberg L, Olsen TS, Iversen HK, Lassen NA, Andersen AR et al (1990) Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol 28(6):791–798PubMedCrossRef
28.
Ranson R, Igarashi H, MacGregor EA, Wilkinson M (1991) The similarities and differences of migraine with aura and migraine without aura: a preliminary study. Cephalalgia. 11(4):189–192PubMedCrossRef
29.
Woods RP, Iacoboni M, Mazziotta JC (1994) Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med 331(25):1689–1692PubMedCrossRef
30.
Sanchez del Rio M, Bakker D, Wu O, Agosti R, Mitsikostas DD, Ostergaard L et al (1999) Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalagia. 19:1–7
31.
Ferrari MD, Haan J, Blokland JA, Arndt JW, Minnee P, Zwinderman AH et al (1995) Cerebral blood flow during migraine attacks without aura and effect of sumatriptan. Arch Neurol 52(2):135–139PubMedCrossRef
32.
Viana M, Sances G, Linde M, Nappi G, Khaliq F, Goadsby PJ et al (2018) Prolonged migraine aura: new insights from a prospective diary-aided study. J Headache Pain 19(1):77PubMedPubMedCentralCrossRef
33.
Bockhorst KH, Smith JM, Smith MI, Bradley DP, Houston GC, Carpenter TA et al (2000) A quantitative analysis of cortical spreading depression events in the feline brain characterized with diffusion-weighted MRI. J Magn Reson Imaging 12(5):722–733PubMedCrossRef
34.
Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8(2):136–142PubMedCrossRef
35.
Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H et al (2004) Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 113(10):1447–1455PubMedPubMedCentralCrossRef
36.
Knotkova H, Pappagallo M (2007) Imaging intracranial plasma extravasation in a migraine patient: a case report. Pain Med 8(4):383–387PubMedCrossRef
37.
Arnold G, Reuter U, Kinze S, Wolf T, Einhaupl KM (1998) Migraine with aura shows gadolinium enhancement which is reversed following prophylactic treatment. Cephalalgia. 18(9):644–646PubMedCrossRef
38.
Weinstein JS, Varallyay CG, Dosa E, Gahramanov S, Hamilton B, Rooney WD et al (2010) Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. J Cereb Blood Flow Metab 30(1):15–35PubMedCrossRef
39.
Amin FM, Hougaard A, Cramer SP, Christensen CE, Wolfram F, Larsson HBW et al (2017) Intact blood-brain barrier during spontaneous attacks of migraine without aura: a 3T DCE-MRI study. Eur J Neurol 24(9):1116–1124PubMedCrossRef
40.
Hougaard A, Amin FM, Christensen CE, Younis S, Wolfram F, Cramer SP et al (2017) Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain. 140(6):1633–1642PubMedCrossRef
41.
Imamura K, Takeshima T, Fusayasu E, Nakashima K (2008) Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache. 48(1):135–139PubMed
42.
Martins-Oliveira A, Speciali JG, Dach F, Marcaccini AM, Goncalves FM, Gerlach RF et al (2009) Different circulating metalloproteinases profiles in women with migraine with and without aura. Clin Chim Acta 408(1–2):60–64PubMedCrossRef
43.
Cui Y, Takashima T, Takashima-Hirano M, Wada Y, Shukuri M, Tamura Y et al (2009) 11C-PK11195 PET for the in vivo evaluation of Neuroinflammation in the rat brain after cortical spreading depression. J Nucl Med 50(11):1904–1911PubMedCrossRef
44.
Gehrmann J, Mies G, Bonnekoh P, Banati R, Iijima T, Kreutzberg GW et al (1993) Microglial reaction in the rat cerebral cortex induced by cortical spreading depression. Brain Pathol 3(1):11–17PubMedCrossRef
45.
Karatas H, Erdener SE, Gursoy-Ozdemir Y, Lule S, Eren-Kocak E, Sen ZD et al (2013) Spreading depression triggers headache by activating neuronal Panx1 channels. Science. 339(6123):1092–1095PubMedCrossRef
46.
Albrecht D, Mainero C, Ichijo E, Ward N, Granziera C, Zurcher NR et al (2019) Imaging of neuroinflammation in migraine with aura - a [11C] PBR28 PET/MR study. Neurology. in press
47.
Markowitz S, Saito K, Moskowitz MA (1987) Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. J Neurosci 7(12):4129–4136PubMedCrossRef
48.
49.
Wahl M, Schilling L, Parsons AA, Kaumann A (1994) Involvement of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in the pial artery dilatation elicited by cortical spreading depression. Brain Res 637(1–2):204–210PubMedCrossRef
50.
Close LN, Eftekhari S, Wang M, Charles AC, Russo AF (2019) Cortical spreading depression as a site of origin for migraine: role of CGRP. Cephalalgia. 39(3):428–434
51.
Zhao J, Levy D (2018) The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K(+) stimulation but not cortical spreading depression-induced afferent sensitization. Pain Rep 3(1):e632PubMed
52.
Goadsby PJ, Edvinsson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 28(2):183–187PubMedCrossRef
53.
Goadsby PJ, Edvinsson L (1993) The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 33(1):48–56PubMedCrossRef
54.
Tepper SJ (2018) History and Review of anti-calcitonin gene-related peptide (CGRP) therapies: from translational research to treatment. Headache. 58(Suppl 3):238–275PubMedCrossRef
55.
van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T et al (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 41(5):701–710PubMedCrossRef
56.
Boulloche N, Denuelle M, Payoux P, Fabre N, Trotter Y, Géraud G (2010) Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain. J Neurol Neurosurg Psychiatry 81:978–984PubMedCrossRef
57.
Denuelle M, Boulloche N, Payoux P, Fabre N, Trotter Y, Geraud G (2011) A PET study of photophobia during spontaneous migraine attacks. Neurology. 76(3):213–218PubMedCrossRef
58.
Lai KL, Liao KK, Fuh JL, Wang SJ (2011) Subcortical hyperexcitability in migraineurs: a high-frequency oscillation study. Can J Neurol Sci 38(2):309–316PubMedCrossRef
59.
Granziera C, Daducci A, Romascano D, Roche A, Helms G, Krueger G, Hadjikhani N (2013) Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T. Cerebellum 12(6):812–8
60.
61.
Dinia L, Bonzano L, Albano B, Finocchi C, Del Sette M, Saitta L et al (2013) White matter lesions progression in migraine with aura: a clinical and MRI longitudinal study. J Neuroimaging 23(1):47–52PubMedCrossRef
62.
Kruit MC, Launer LJ, Ferrari MD, van Buchem MA (2005) Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain. 128(Pt 9:2068–2077PubMedCrossRef
63.
Schmitz N, Admiraal-Behloul F, Arkink EB, Kruit MC, Schoonman GG, Ferrari MD et al (2008) Attack frequency and disease duration as indicators for brain damage in migraine. Headache. 48(7):1044–1055PubMedCrossRef
64.
65.
Gaist D, Garde E, Blaabjerg M, Nielsen HH, Kroigard T, Ostergaard K et al (2016) Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study. Brain. 139(Pt 7:2015–2023PubMedPubMedCentralCrossRef
66.
Granziera C, Romascano D, Daducci A, Roche A, Vincent M, Krueger G, Hadjikhani N (2013) Migraineurs without Aura show microstructural abnormalities in the cerebellum and frontal lobe. Cerebellum 12(6):812–8
67.
68.
Granziera C, DaSilva AFM, Snyder J, Tuch DS, Hadjikhani N (2006) Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS Med 3(10):1915–1921CrossRef
69.
Maleki N, Linnman C, Brawn J, Burstein R, Becerra L, Borsook D (2012) Her versus his migraine: multiple sex differences in brain function and structure. Brain. 135(Pt 8:2546–2559PubMedPubMedCentralCrossRef
70.
Gaist D, Hougaard A, Garde E, Reislev NL, Wiwie R, Iversen P et al (2018) Migraine with visual aura associated with thicker visual cortex. Brain. 141(3):776–785PubMedCrossRef
71.
Hougaard A, Amin FM, Arngrim N, Vlachou M, Larsen VA, Larsson HBW et al (2016) Sensory migraine aura is not associated with structural grey matter abnormalities. Neuroimage Clin 11:322–327PubMedPubMedCentralCrossRef
72.
Hadjikhani N, Ward N, Boshyan J, Napadow V, Maeda Y, Truini A, Caramia F, Tinelli E, Mainero C (2013) The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia 33(15):1264–8
73.
Mainero C, Boshyan J, Hadjikhani N (2011) Altered functional MRI resting-state connectivity in the periaqueductal gray networks in migraine. Ann Neurol 70(2):838–845PubMedPubMedCentralCrossRef
74.
Burstein R, Cutrer MF, Yarnitsky D (2000) The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain. 123(Pt 8):1703–1709PubMedCrossRef
75.
Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH (2000) An association between migraine and cutaneous allodynia. Ann Neurol 47(5):614–624PubMedCrossRef
76.
Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML et al (2008) Cutaneous allodynia in the migraine population. Ann Neurol 63(2):148–158PubMedPubMedCentralCrossRef
77.
78.
Doud A, Julius A, Ransom CB (2018) Visual phenomena in occipital lobe epilepsy: “It’s Beautiful!”. JAMA Neurol 75(9):1146–1147
79.
Walker MC, Smith SJ, Sisodiya SM, Shorvon SD (1995) Case of simple partial status epilepticus in occipital lobe epilepsy misdiagnosed as migraine: clinical, electrophysiological, and magnetic resonance imaging characteristics. Epilepsia. 36(12):1233–1236PubMedCrossRef
80.
Panayiotopoulos CP (1999) Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differentiation from migraine. Epileptic Disord 1(4):205–216PubMed
81.
Kramer DR, Fujii T, Ohiorhenuan I, Liu CY (2017) Interplay between cortical spreading depolarization and seizures. Stereotact Funct Neurosurg 95(1):1–5PubMedCrossRef
82.
Ridolfi M, Granato A, Polverino P, Furlanis G, Ukmar M, Zorzenon I et al (2018) Migrainous aura as stroke-mimic: the role of perfusion-computed tomography. Clin Neurol Neurosurg 166:131–135PubMedCrossRef
83.
Floery D, Vosko MR, Fellner FA, Fellner C, Ginthoer C, Gruber F et al (2012) Acute-onset migrainous aura mimicking acute stroke: MR perfusion imaging features. AJNR Am J Neuroradiol 33(8):1546–1552PubMedCrossRef
84.
Kirshner HS (2011) Transient global amnesia: a brief review and update. Curr Neurol Neurosci Rep. 11(6):578–582PubMedCrossRef
85.
Kellner-Weldon F, El-Koussy M, Jung S, Jossen M, Klinger-Gratz PP, Wiest R (2018) Cerebellar Hypoperfusion in migraine attack: incidence and significance. AJNR Am J Neuroradiol. [Epub ahead of print]
Metadata
Title
Neuroimaging clues of migraine aura
Authors
Nouchine Hadjikhani
Maurice Vincent
Publication date
01-12-2019
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2019
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-019-0983-2

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