Migrene Neden Olan Mekanizmalar ve Patofizyolojiler
Özet
Migren; trigeminovasküler sistemin aktivasyonu, nöropeptitlerin salınımı ve genetik faktörlerin rol oynadığı, tekrarlayan ataklarla seyreden multifaktöriyel bir primer baş ağrısıdır. Beş farklı evreden (prodromal, aura, ağrı, postdrom, interiktal) oluşan bu hastalıkta, kortikal yayılan depresyon (CSD) ve kalsitonin geni ile ilişkili peptit (CGRP) mekanizmaları patofizyolojide anahtar rol oynamaktadır. Atak dönemlerinde hipotalamik aktivasyon, bulantı ve fotofobi gibi semptomlar beyin sapı ve kortikal alanlardaki değişimlerle ilişkilendirilirken; moleküler düzeyde CGRP, serotonin ve dopaminerjik sistemler hedef alınarak triptanlar ve monoklonal antikorlar gibi modern tedaviler geliştirilmiştir. Ayrıca, oksidatif stres ve homosistein artışı gibi faktörlerin tetiklediği endotel hasarı ile vazokonstriksiyon süreçleri, özellikle auralı migren hastalarında subklinik ateroskleroz ve inme riskini etkileyebilmektedir. Genetik çalışmalarda ise yaygın migrenin poligenik yapısı vurgulanırken, nadir görülen Ailesel Hemiplejik Migren (FHM) tablosundan voltaj kapılı iyon kanalları ve taşıma pompalarını kodlayan CACNA1A, ATP1A2 ve SCN1A genlerindeki mutasyonların sorumlu olduğu gösterilmiştir. Sonuç olarak, migren yönetiminde farmakolojik tedavilerin yanı sıra spor, uyku düzeni ve beslenme gibi yaşam tarzı önerilerinin de bütüncül olarak değerlendirilmesi gerekmektedir.
Migraine is a multifactorial primary headache characterized by recurrent attacks, in which the activation of the trigeminovascular system, the release of neuropeptides, and genetic factors play critical roles. In this disease consisting of five distinct phases (prodromal, aura, headache, postdrome, and interictal), cortical spreading depression (CSD) and calcitonin gene-related peptide (CGRP) mechanisms play a pivotal role in the pathophysiology. While symptoms such as hypothalamic activation, nausea, and photophobia during attack periods are associated with changes in the brainstem and cortical areas, modern therapeutics like triptans and monoclonal antibodies have been developed by targeting molecular pathways including CGRP, serotonin, and dopaminergic systems. Furthermore, endothelial damage and vasoconstriction processes triggered by factors such as oxidative stress and elevated homocysteine levels can influence the risk of subclinical atherosclerosis and stroke, particularly in patients with migraine with aura. Genetic research highlights the polygenic nature of common migraine, whereas mutations in the CACNA1A, ATP1A2, and SCN1A genes encoding voltage-gated ion channels and transport pumps have been shown to be responsible for the rare Familial Hemiplegic Migraine (FHM). Consequently, alongside pharmacological treatments, lifestyle recommendations including exercise, regular sleep, and nutrition must be comprehensively evaluated in migraine management.
Referanslar
Goadsby PJ, Lipton RB, Ferrari MD. Migraine — Current Understanding and Treatment. New England Journal of Medicine. 2002;346(4): 257–270. doi:10.1056/nejmra010917
Moulton EA, Burstein R, Tully S, et al. Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS ONE. 2008;3(11): 1–5. doi:10.1371/journal.pone.0003799
Eftekhari S, Warfvinge K, Blixt F, et al. Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. The Journal of Headache and Pain. 2013;14(S1): 2013. doi:10.1186/1129-2377-14-s1-p89
May A. Morphing voxels: The hype around structural imaging of headache patients. Brain. 2009;132(6): 1419–1425. doi:10.1093/brain/awp116
Dai Z, Zhong J, Xiao P, et al. Gray matter correlates of migraine and gender effect: A meta-analysis of voxel-based morphometry studies. Neuroscience. IBRO; 2015;299: 88–96. doi:10.1016/j.neuroscience.2015.04.066
Jia Z, Yu S. Grey matter alterations in migraine: A systematic review and meta-analysis. NeuroImage: Clinical. The Authors; 2017;14: 130–140. doi:10.1016/j.nicl.2017.01.019
Hu W, Guo J, Chen N, et al. A meta-analysis of voxel-based morphometric studies on migraine. International Journal of Clinical and Experimental Medicine. 2015;8(3): 4311–4319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443181/pdf/ijcem0008-4311.pdf
Sheng LQ, Zhao PW, Ma HR, et al. A lack of consistent brain grey matter alterations in migraine. Brain. 2020;143(6): e45. doi:10.1093/brain/awaa123
Hansen JM, Goadsby PJ, Charles AC. Variability of clinical features in attacks of migraine with aura. Cephalalgia 2016;36(3):216–224. doi:10.1177/0333102415584601
Viana M, Sances G, Ghiotto N, et al. Variability of the characteristics of a migraine attack within patients. Cephalalgia 2016;36(9):825–830. doi:10.1177/0333102415613612
Quintela E, Castillo J, Muñoz P, et al. Premonitory and resolution symptoms in migraine: A prospective study in 100 unselected patients. Cephalalgia. 2006;26(9): 1051–1060. doi:10.1111/j.1468-2982.2006.01157.x
Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: An electronic diary study. Neurology. 2003;60(6): 935–940. doi:10.1212/01.WNL.0000052998.58526.A9
Karsan N, Goadsby PJ. Biological insights from the premonitory symptoms of migraine. Nature Reviews Neurology. Springer US; 2018;14(12): 699–710. doi:10.1038/s41582-018-0098-4
Denuelle M, Fabre N, Payoux P, et al. Hypothalamic activation in spontaneous migraine attacks. Headache. 2007;47(10): 1418–1426. doi:10.1111/j.1526-4610.2007.00776.x
Meylakh N, Marciszewski KK, Di Pietro F, et al. Deep in the brain: Changes in subcortical function immediately preceding a migraine attack. Human Brain Mapping. 2018;39(6): 2651–2663. doi:10.1002/hbm.24030
Schulte LH, May A. The migraine generator revisited: Continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(7): 1987–1993. doi:10.1093/brain/aww097
Maniyar FH, Sprenger T, Monteith T, et al. The premonitory phase of migraine - What can we learn from it? Headache. 2015;55(5): 609–620. doi:10.1111/head.12572
Sand T, Zhitniy N, White LR, et al. Visual evoked potential latency, amplitude and habituation in migraine: A longitudinal study. Clinical Neurophysiology. 2008;119(5): 1020–1027. doi:10.1016/j.clinph.2008.01.009
Kaube H, Keay KA, Hoskin KL, et al. Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following stimulation of the superior sagittal sinus in the cat. Brain Research. Elsevier; 1993;629(1): 95–102. doi:10.1016/0006-8993(93)90486-7
Hoskin KL, Lambert GA, Donaldson C, et al. The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat. Brain Research. 2004;998(1): 91–99. doi:10.1016/j.brainres.2003.11.018
Akerman S, Holland PR, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nature Reviews Neuroscience. Nature Publishing Group; 2011;12(10): 570–584. doi:10.1038/nrn3057
Goadsby PJ, Holland PR. An Update: Pathophysiology of Migraine. 2019;37(4): 651–671
Ashina M, Katsarava Z, Do TP, et al. Migraine: epidemiology and systems of care. The Lancet. 2021;397(10283): 1485–1495. doi:10.1016/S0140-6736(20)32160-7
Russell MB, Iversen HK, Olesen J. Improved description of the migraine aura by a diagnostic aura diary. Cephalalgia. 1994;14(2): 107–117
Hadjikhani N, Sanchez Del Rio M, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(8): 4687–4692. doi:10.1073/pnas.071582498
Leao AAP. Further observations on the spreading depression of activity in the cerebral cortex. J Neurophysiol 1947;10(6):409–414. doi:10.1152/jn.1947.10.6.409
Leao, A.A.P. Spreading depression of activity in the cerebral cortex. J. Neurophysiol. 1944, 7, 359–390
Sugaya, E.; Takato, M.; Noda, Y. Neuronal and glial activity during spreading depression in cerebral cortex of cat. J. Neurophysiol. 1975, 38, 822–841
Kraig, R.P.; Nicholson, C. Extracellular ionic variations during spreading depression. Neuroscience 1978, 3, 1045–1059
Tozzi A, De Iure A, Di Filippo M, et al. Critical role of calcitonin gene-related peptide receptors in cortical spreading depression. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(46): 18985–18990. doi:10.1073/pnas.1215435109
Olesen J, Diener H-C, Husstedt IW, et al. Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine. New England Journal of Medicine. 2004;350(11): 1104–1110. doi:10.1056/nejmoa030505
Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: A randomised, double-blind, placebo-controlled, exploratory phase 2 trial. The Lancet Neurology. Elsevier Ltd; 2014;13(11): 1100–1107. doi:10.1016/S1474-4422(14)70209-1
Dodick DW, Goadsby PJ, Spierings ELH, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: A phase 2, randomised, double-blind, placebo-controlled study. The Lancet Neurology. Elsevier Ltd; 2014;13(9): 885–892. doi:10.1016/S1474-4422(14)70128-0
Dohmen C, Sakowitz OW, Fabricius M, et al. Spreading depolarizations occur in human ischemic stroke with high incidence. Annals of Neurology. 2008;63(6): 720–728. doi:10.1002/ana.21390
Buse DC, Loder EW, Gorman JA, et al. Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: Results of the American Migraine prevalence and prevention (AMPP) study. Headache. 2013;53(8): 1278–1299. doi:10.1111/head.12150
Ashina H, Iljazi A, Al-Khazali HM, et al. Hypersensitivity to Calcitonin Gene–Related Peptide in Post-Traumatic Headache. Annals of Neurology. 2020;88(6): 1220–1228. doi:10.1002/ana.25915
Yiangou A, Mitchell JL, Fisher C, et al. Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation. Headache. 2021;61(1): 157–169. doi:10.1111/head.14026
Yiangou A, Mitchell JL, Vijay V, et al. Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension. Journal of Headache and Pain. The Journal of Headache and Pain; 2020;21(1): 1–8. doi:10.1186/s10194-020-01182-7
Ashina H, Moskowitz MA. Shared biological foundations of post-traumatic headache and migraine. Headache. 2021;61(3): 558–559. doi:10.1111/head.14084
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38(1):1–211. doi:10.1177/0333102417738202
Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: A disorder of sensory processing. Physiological Reviews. 2017;97(2): 553–622. doi:10.1152/physrev.00034.2015
Olesen J, Burstein R, Ashina M, et al. Origin of pain in migraine: evidence for peripheral sensitisation. The Lancet Neurology. Elsevier Ltd; 2009;8(7): 679–690. doi:10.1016/S1474-4422(09)70090-0
Rodriguez E, Sakurai K, Xu J, et al. A craniofacial?specific monosynaptic circuit enables heightened affective pain. Nature Neuroscience. 2017;20(12): 1734–1743. doi:10.1038/s41593-018-0103-7
Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol 2013;75:365–391. doi:10.1146/annurev-physiol-030212-183717
Stankewitz A, Aderjan D, Eippert F, et al. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. Journal of Neuroscience. 2011;31(6): 1937–1943. doi:10.1523/JNEUROSCI. 4496-10.2011
Mo J, Maizels M, Ding M, Ahn AH. Does throbbing pain have a brain signature?Pain 2013;154(7):1150–1155. doi:10.1016/j.pain.2013.02.013
Lipton RB, Buse DC, Saiers J, et al. Frequency and burden of headache-related nausea: Results from the american migraine prevalence and prevention (AMPP) study. Headache. 2013;53(1): 93–103. doi:10.1111/j.1526-4610.2012.02292.x
Maniyar FH, Sprenger T, Schankin C, et al. The origin of nausea in migraine–A PET study. Journal of Headache and Pain. 2014;15(1): 1–6. doi:10.1186/1129-2377-15-84
Giffin NJ, Lipton RB, Silberstein SD, et al. The migraine postdrome. Neurology ®. 2016;87(3): 309–313
Peng KP, May A. Redefining migraine phases – a suggestion based on clinical, physiological, and functional imaging evidence. Cephalalgia. 2020;40(8): 866–870. doi:10.1177/033310241 9898868
Martins IP, Westerfield M, Lopes M, et al. Brain state monitoring for the future prediction of migraine attacks. Cephalalgia 2020;40(3):255–265. doi:10.1177/03331024198 77660
McKendrick AM, Chan YM, Vingrys AJ, et al. Daily vision testing can expose the prodromal phase of migraine. Cephalalgia 2018;38(9):1575–1584. doi:10.1177/0333102417741130
Skorobogatykh K, Van Hoogstraten WS, Degan D, et al. Functional connectivity studies in migraine: What have we learned? Journal of Headache and Pain. The Journal of Headache and Pain; 2019;20(1). doi:10.1186/s10194-019-1047-3
Xue T, Yuan K, Cheng P, et al. Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura. NMR in Biomedicine. 2013;26(9): 1051–1058. doi:10.1002/nbm.2917
Amin FM, Hougaard A, Magon S, et al. Altered thalamic connectivity during spontaneous attacks of migraine without aura: a resting-state fMRI study. Cephalalgia 2018;38(7):1237–1244. doi:10.1177/0333102417729113
Moulton EA, Becerra L, Johnson A, et al. Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. PLoS ONE. 2014;9(4). doi:10.1371/journal.pone.0095508
Chen Z, Chen X, Liu M, et al. Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis. Journal of Headache and Pain. The Journal of Headache and Pain; 2017;18(1): 1–8. doi:10.1186/s10194-017-0722-5
Jin C, Yuan K, Zhao L, et al. Structural and functional abnormalities in migraine patients without aura. NMR in Biomedicine. 2013;26(1): 58–64. doi:10.1002/nbm.2819
Strupf M, Fraunberger B, Messlinger K, Namer B. Cyclic changes in sensations to painful stimuli in migraine patients. Cephalalgia 2019;39(5):585–596. doi:10.1177/0333102418793641
Wattiez AS, Sowers LP, Russo AF. Calcitonin gene-related peptide (CGRP): Role in migraine pathophysiology and therapeutic targeting. Expert Opin Ther Targets. 2020;24(2): 91–100. doi:10.1080/14728222.2020.1724285
Close LN, Eftekhari S, Wang M, et al. Cortical spreading depression as a site of origin for migraine: Role of CGRP. 2019;39(3): 428–434. doi:10.1177/0333102418774299
Recober A, Kuburas A, Zhang Z, et al. Role of calcitonin gene-related peptide in light-aversive behavior: Implications for migraine. Journal of Neuroscience. 2009;29(27): 8798–8804. doi:10.1523/JNEUROSCI.1727-09.2009
Kaiser EA, Rea BJ, Kuburas A, et al. Anti-CGRP antibodies block CGRP-induced diarrhea in mice. Neuropeptides. Elsevier Ltd; 2017;64: 95–99. doi:10.1016/j.npep.2016.11.004
Edvinsson L, Tajti J, Szalárdy L, et al. PACAP and its role in primary headaches. Journal of Headache and Pain. The Journal of Headache and Pain; 2018;19(1): 10194-018-0852–0854. doi:10.1186/s10194-018-0852-4
Villalón CM, VanDenBrink AM. The role of 5-hydroxytryptamine in the pathophysiology of migraine and its relevance to the design of novel treatments. Mini Rev Med Chem 2017;17(11):928–938. doi:10.2174/13895575166661607281210 50
Bartsch T, Levy MJ, Knight YE, et al. Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain. 2004;109(3): 367–378. doi:10.1016/j.pain.2004.02.005
Biswas SK. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxidative Medicine and Cellular Longevity. Hindawi Publishing Corporation; 2016;2016: 1–9. doi:10.1155/2016/5698931
Yildirim S, Akar S, Kuyucu M, et al. Paraoxonase 1 gene polymorphisms, paraoxonase/arylesterase activities and oxidized low-density lipoprotein levels in patients with migraine. Cell Biochemistry and Function. 2011;29(7): 549–554. doi:10.1002/cbf.1785
Borkum JM. The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory. Headache. 2018;58(1): 118–135. doi:10.1111/head.13214
Ghosh J, Joshi G, Pradhan S, et al. Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine. Journal of Neurology. 2010;257(6): 898–904. doi:10.1007/s00415-009-5430-x
Yilmaz Avci A, Akkucuk MH, Torun E, et al. Migraine and subclinical atherosclerosis: endothelial dysfunction biomarkers and carotid intima-media thickness: a case-control study. Neurological Sciences. Neurological Sciences; 2019;40(4): 703–711. doi:10.1007/s10072-019-3710-5
Empl M, Sostak P, Breckner M, et al. T-cell subsets and expression of integrins in peripheral blood of patients with migraine. Cephalalgia. 1999 Oct; 19(8):713-7; discussion 697
Zeller JA, Frahm K, Baron R, et al. Platelet-leukocyte interaction and platelet activation in migraine: A link to ischemic stroke? Journal of Neurology, Neurosurgery and Psychiatry. 2004;75(7): 984–987. doi:10.1136/jnnp.2003.019638
Tietjen GE, Khubchandani J. Platelet dysfunction and stroke in the female migraineur. Current Pain and Headache Reports. 2009;13(5): 386–391. doi:10.1007/s11916-009-0063-4
Gabrielli M, Santarelli L, Addolorato G, et al. High prevalence of antiendothelial cell antibodies in migraine [1]. Headache. 2002;42(5): 385–386. doi:10.1046/j.1526-4610.2002.02114.x
Peroutka SJ. Neurogenic inflammation and migrane: Implications for therapeutics. Molecular Interventions. 2005;5(5): 304–311. doi:10.1124/mi.5.5.10
Mason BN, Russo AF. Vascular contributions to migraine: Time to revisit? Frontiers in Cellular Neuroscience. 2018;12(August): 1–10. doi:10.3389/fncel.2018.00233
Yücel M, Kotan D, Gurol Çiftçi G, Çiftçi IH CH. Serum levels of endocan, claudin-5 and cytokines in migraine. Eur Rev Med Pharmacol. 2016;20: 930–936
Oterino A, Toriello M, Valle N, et al. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache. 2010;50(1): 99–168. doi:10.1111/j.1526-4610.2009.01484.x
Michalak S, Kalinowska-Lyszczarz A, Wegrzyn D, et al. The Levels of Circulating Proangiogenic Factors in Migraineurs. NeuroMolecular Medicine. Springer US; 2017;19(4): 510–517. doi:10.1007/s12017-017-8465-7
Rodríguez-Osorio X, Sobrino T, Brea D, et al. Endothelial progenitor cells: a new key for endothelial dysfunction in migraine. Neurology. 2012 Jul 31; 79(5):474-9
Tietjen GE. Migraine as a systemic vasculopathy. Cephalalgia. 2009 Sep;29(9):987-96. doi: 10.1111/j.1468-2982.2009.01937.x. PMID: 19689607
Iljazi A, Ayata C, Ashina M, et al. The Role of Endothelin in the Pathophysiology of Migraine—a Systematic Review. Current Pain and Headache Reports. 2018;22(4): 1–9. doi:10.1007/s11916-018-0682-8
Tietjen GE, Al-Qasmi MM, Athanas K, et al. Increased von Willebrand factor in migraine. Neurology. 2001;57:334–336
Cesar JM, García-Avello A, Vecino AM, et al. Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol Scand. 1995;91:412–413
Tietjen GE, Herial NA, Utley C, et al. Association of von Willebrand factor activity with ACE I/D and MTHFR C677T polymorphisms in migraine. Cephalalgia. 2009;29:960–968
Tietjen GE, Khubchandani J, Herial N, Palm-Meinders IH, Koppen H TG et al. Migraine and vascular disease biomarkers: a population-based case-control study. Physiology & behavior. 2018;38(3): 511–518. doi:10.1177/0333102417698936.Migraine
Mulder EJ, Van Baal C, Gaist D, et al. Genetic and Environmental Influences on Migraine: A Twin Study Across Six Countries. Twin Research. 2003;6(5): 422–431. doi:10.1375/136905203770326420
Sutherland HG, Albury CL, Griffiths LR. Advances in genetics of migraine. Journal of Headache and Pain. The Journal of Headache and Pain; 2019;20(1): 1–20. doi:10.1186/s10194-019-1017-9
Thomsen LL, Eriksen MK, Romer SF, et al. An epidemiological survey of hemiplegic migraine. Cephalalgia. 2002;22(5): 361–375. doi:10.1046/j.1468-2982.2002.00371.x
Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996;87(3): 543–552. doi:10.1016/S0092-8674(00)81373-2
Grieco GS, Gagliardi S, Ricca I, et al. New CACNA1A deletions are associated to migraine phenotypes. Journal of Headache and Pain. The Journal of Headache and Pain; 2018;19(1): 1–6. doi:10.1186/s10194-018-0891-x
Pereira M da C, Morais S, Sequeiros J, et al. Large-scale functional RNAi Screen in C. elegans identifies TGF-β and notch signaling pathways as modifiers of CACNAIA. ASN Neuro. 2016;8(2): 1–10. doi:10.1177/1759091416637025
Di Lorenzo C, Grieco GS, Santorelli FM. Migraine headache: A review of the molecular genetics of a common disorder. Journal of Headache and Pain. 2012;13(7): 571–580. doi:10.1007/s10194-012-0478-x
Blumenfeld AE, Victorio MC, Berenson FR. Complicated Migraines. Seminars in Pediatric Neurology. Elsevier; 2016;23(1): 18–22. doi:10.1016/j.spen.2016.01.007
Friedrich T, Tavraz NN, Junghans C. ATP1A2 mutations in migraine: Seeing through the facets of an ion pump onto the neurobiology of disease. Frontiers in Physiology. 2016;7(JUN): 1–21. doi:10.3389/fphys.2016.00239
N. Pelzer, D. Blom, A. Stam, L. et al. Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation. Cephalalgia, 37 (2017), pp. 737-755
Dichgans M, Freilinger T, Eckstein G, et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005;366(9483): 371–377. doi:10.1016/S0140-6736(05)66786-4
H.G. Sutherland, C.L. Albury, L.R. Griffiths. Advances in genetics of migraine. J. Headache Pain, 20 (2019), p. 72
