Risk factors of white matter hyperintensities in migraine patients

Jasem Yousef Al-Hashel 1 2, Raed Alroughani 3, Khaled Gad 4 5, Lamiaa Al-Sarraf 4, Samar Farouk Ahmed 6 7


 

Affiliations

29 April 2022

-

doi: 10.1186/s12883-022-02680-8

Abstract

Background: Migraine frequently is associated with White Matter Hyperintensities (WMHs). We aimed to assess the frequency of WMHs in migraine and to assess their risk factors.

Methods: This is cross-sectional study included 60 migraine patients of both genders, aged between 18 and 55 years. Patients with vascular risk factors were excluded. We also included a matched healthy control group with no migraine. Demographic, clinical data, and serum level of homocysteine were recorded. All subjects underwent brain MRI (3 Tesla).

Results: The mean age was 38.65 years and most of our cohort were female (83.3). A total of 24 migraine patients (40%) had WMHs versus (10%) in the control group, (P < 0.013). Patients with WMHs were significantly older (43.50 + 8.71 versus. 35.92+ 8.55 years, P < 0.001), have a longer disease duration (14.54+ 7.76versus 8.58+ 6.89 years, P < 0.002), higher monthly migraine attacks (9.27+ 4. 31 versus 7.78 + 2.41 P < 0.020) and high serum homocysteine level (11.05+ 5.63 versus 6.36 + 6.27, P < 0.006) compared to those without WMHs. WMHs were more frequent in chronic migraine compared to episodic migraine (75% versus 34.6%; P < 0.030) and migraine with aura compared to those without aura (38.3% versus 29,2; P < 0.001). WMHs were mostly situated in the frontal lobes (83.4%), both hemispheres (70.8%), and mainly subcortically (83.3%).

Conclusion: Older age, longer disease duration, frequent attacks, and high serum homocysteine level are main the risk factors for WMHs in this cohort. The severity or duration of migraine attacks did not increase the frequency of WMHs. The number of WMHs was significantly higher in chronic compared to episodic migraineurs.

Keywords: Chronic migraine; Episodic migraine; Homocysteine; Magnetic resonance imaging; Migraine with aura; Migraine without aura.

Conflict of interest statement

All authors disclose no conflict of interest related to this study.

References

 

  1. 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. - DOI - PubMed
  2. Steiner TJ, Stovner LJ, Birbeck GL. Migraine: the seventh disabler. Headache. 2013;53(2):227–229. - PubMed
  3. Al-Hashel JY, Ahmed SF, Alroughani R. Prevalence of primary headache disorders in Kuwait. Neuroepidemiology. 2017;48(3–4):138–146. - PubMed
  4. Maleki N, Gollub RL. What have we learned from brain functional connectivity studies in migraine headache? Headache. 2016;56(3):453–461. - PubMed
  5. 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(2):553–622. - PMC - PubMed
  6. Chen Z, Chen X, Liu M, Liu S, Ma L, Yu S. Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine. J Headache Pain. 2017;18(1):1–9. - PMC - PubMed
  7. Zhang J, Su J, Wang M, Zhao Y, Zhang QT, Yao Q, et al. The sensorimotor network dysfunction in migraineurs without aura: a resting-state fMRI study. J Neurol. 2017. 10.1007/s00415-017-8404-4. - PubMed
  8. Neeb L, Bastian K, Villringer K, Israel H, Reuter U, Fiebach JB. Structural gray matter alterations in chronic migraine: implications for a progressive disease? Headache. 2017;57(3):400–416. - PubMed
  9. Kruit MC, van Buchem MA, Hofman PA, Bakkers JT, Terwindt GM, Ferrari MD, Launer LJ. Migraine as a risk factor for subclinical brain lesions. JAMA. 2004;291(4):427–434. - PubMed
  10. Lin J, Wang D, Lan L, Fan Y. Multiple factors involved in the pathogenesis of white matter lesions. Biomed Res Int. 2017;2017:9372050. doi: 10.1155/2017/9372050. - DOI - PMC - PubMed
  11. Trauninger A, Leél-Őssy E, Kamson DO, Pótó L, Aradi M, Kövér F, Imre M, Komáromy H, Erdélyi-Botor S, Patzkó A, Pfund Z. Risk factors of migraine-related brain white matter hyperintensities: an investigation of 186 patients. J Headache Pain. 2011;12(1):97–103. - PMC - PubMed
  12. Toghae M, Rahimian E, Abdollahi M, Shoar S, Naderan M. The prevalence of magnetic resonance imaging hyperintensity in migraine patients and its association with migraine headache characteristics and cardiovascular risk factors. Oman Med J. 2015;30(3):203. - PMC - PubMed
  13. Zhang Q, Datta R, Detre JA, Cucchiara B. White matter lesion burden in migraine with aura may be associated with reduced cerebral blood flow. Cephalalgia. 2017;37(6):517–524. - PubMed
  14. Uggetti C, Squarza S, Longaretti F, Galli A, Di Fiore P, Reganati PF, Campi A, Ardemagni A, Cariati M, Frediani F. Migraine with aura and white matter lesions: an MRI study. Neurol Sci. 2017;38(1):11–13. - PubMed
  15. Friedman DI, Dodick DW. White matter hyperintensities in migraine: reason for optimism. JAMA. 2012;308(18):1920–1921. - PubMed
  16. Kurth T, Mohamed S, Maillard P, Zhu YC, Chabriat H, Mazoyer B, Bousser MG, Dufouil C, Tzourio C. Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study. Bmj. 2011;342. - PMC - PubMed
  17. Eggers AE. Migraine white matter hyperintensities and cerebral microinfarcts are silent cryptogenic strokes and relate to dementia. Med Hypotheses. 2017;102:1–3. - PubMed
  18. Moschiano F, D’Amico D, Usai S, Grazzi L, Di Stefano M, Ciusani E, Erba N, Bussone G. Homocysteine plasma levels in patients with migraine with aura. Neurol Sci. 2008;29(1):173–175. - PubMed
  19. Bautista LE, Arenas IA, Peñuela A, Martinez LX. Total plasma homocysteine level and risk of cardiovascular disease: a meta-analysis of prospective cohort studies. J Clin Epidemiol. 2002;55(9):882–887. - PubMed
  20. Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD. Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet. 2005;365(9455):224–232. - PubMed
  21. Collaboration HS Homocysteine and risk of ischemic heart disease and stroke. JAMA. 2002;288(16):2015–2012. - PubMed
  22. Kara I, Sazci A, Ergul E, Kaya G, Kilic G. Association of the C677T and A1298C polymorphisms in the 5, 10 methylenetetrahydrofolate reductase gene in patients with migraine risk. Mol Brain Res. 2003;111(1–2):84–90. - PubMed
  23. Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009;19(6):422–428. - PubMed
  24. Menon S, Lea RA, Roy B, Hanna M, Wee S, Haupt LM, Oliver C, Griffiths LR. Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation. Pharmacogenet Genomics. 2012;22(10):741–749. - PubMed
  25. Sachdev P, Parslow R, Salonikas C, Lux O, Wen W, Kumar R, Naidoo D, Christensen H, Jorm A. Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men. Arch Neurol. 2004;61(9):1369–1376. - PubMed
  26. Dufouil C, Alpérovitch A, Ducros V, Tzourio C. Homocysteine, white matter hyperintensities, and cognition in healthy elderly people. Ann Neurol. 2003;53(2):214–221. - PubMed
  27. Vermeer SE, Van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, Breteler MM. Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam scan study. Ann Neurol. 2002;51(3):285–289. - PubMed
  28. Aicher B, Peil H, Peil B, Diener HC. Pain measurement: Visual Analogue Scale (VAS) and Verbal Rating Scale (VRS) in clinical trials with OTC analgesics in headache. Cephalalgia. 2012;32(3):185–197. - PubMed
  29. Hung P, Fuh J, Wang S. The application of migraine disability assessment questionnaire (MIDAS) Acta Neurol Taiwanica. 2006;15(1):43. - PubMed
  30. Kosinski M, Bayliss MS, Bjorner JB, Ware JE, Garber WH, Batenhorst A, Cady R, Dahlöf CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6™. Qual Life Res. 2003;12(8):963–974. - PubMed
  31. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal cognitive assessment Moca: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699. - PubMed
  32. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–73. - PubMed
  33. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–173. - PubMed
  34. World Medical Association World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–2194. doi: 10.1001/jama.2013.281053. - DOI - PubMed
  35. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest. 2004;113(10):1447–1455. - PMC - PubMed
  36. Colombo B, Dalla Libera D, Comi G. Brain white matter lesions in migraine: what’s the meaning? Neurol Sci. 2011;32(1):37–40. - PubMed
  37. Yemisci M, Eikermann-Haerter K. Aura and Stroke: relationship and what we have learnt from preclinical models. J Headache Pain. 2019;20(1):1–8. - PMC - PubMed
  38. Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalagia. 2006;26:361–372. - PubMed
  39. Negm M, Housseini AM, Abdelfatah M, Asran A. Relation between migraine pattern and white matter hyperintensities in brain magnetic resonance imaging. Egypt J Neurol Psychiatry Neurosurg. 2018;54(1):1–8. - PMC - PubMed
  40. Le Pira F, Reggio E, Quattrocchi G, Sanfilippo C, Maci T, Cavallaro T, Zappia M. Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions? Headache. 2014;54(1):125–130. - PubMed
  41. Xie H, Zhang Q, Huo K, Liu R, Jian ZJ, Bian YT, Li GL, Zhu D, Zhang LH, Yang J, Luo GG. Association of white matter hyperintensities with migraine features and prognosis. BMC Neurol. 2018;18(1):1–0. - PMC - PubMed
  42. Zhuang FJ, Chen Y, He WB, Cai ZY. Prevalence of white matter hyperintensities increases with age. Neural Regen Res. 2018;13(12):2141–2146. doi: 10.4103/1673-5374.241465. - DOI - PMC - PubMed
  43. Alkhaffaf WH, Naif MM, Ahmed RN. The association of MRI findings in migraine with the headache characteristics and response to treatment. Revista Latinoamericana de Hipertension. 2020;15(5):345–351.
  44. Dobrynina LA, Suslina AD, Gubanova MV, Belopasova AV, Sergeeva AN, Evers S, Gnedovskaya EV, Krotenkova MV. White matter hyperintensity in different migraine subtypes. Sci Rep. 2021;11(1):1–9. - PMC - PubMed
  45. Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet. 2010;375(9718):938–948. - PubMed
  46. Palm-Meinders IH, Koppen H, Terwindt GM, Launer LJ, Konishi J, Moonen JM, Bakkers JT, Hofman PA, van Lew B, Middelkoop HA, van Buchem MA. Structural brain changes in migraine. JAMA. 2012;308(18):1889–1896. - PMC - PubMed
  47. Seneviratne U, Chong W, Billimoria PH. Brain white matter hyperintensities in migraine: clinical and radiological correlates. Clin Neurol Neurosurg. 2013;115(7):1040–1043. - PubMed
  48. Eikermann-Haerter K, Huang SY. White matter lesions in migraine. Am J Pathol. 2021;191(11):1955–1962. - PubMed
  49. Dalkara T, Nozari A, Moskowitz MA. Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol. 2010;9(3):309–317. - PMC - PubMed
  50. Rocca MA, Colombo B, Inglese M, Codella M, Comi G, Filippi M. A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine. J Neurol Neurosurg Psychiatry. 2003;74(4):501–503. - PMC - PubMed
  51. Gavgani SC, Hoseinian MM. Comparative study on homocysteine levels in migraine patients and normal peoples. Ann Biol Res. 2012;3:1804–1807.
  52. Wong TY, Klein R, Sharrett AR, Couper DJ, Klein BE, Liao DP, Hubbard LD, Mosley TH, ARIC investigators, ARIC Investigators Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA. 2002;288(1):67–74. - PubMed
  53. Goadsby PJ. Current concepts of the pathophysiology of migraine. Neurol Clin. 1997;15(1):27–42. - PubMed
  54. Rao R, Tah V, Casas JP, Hingorani A, Whittaker J, Smeeth L, Sharma P. Ischaemic stroke subtypes and their genetic basis: a comprehensive meta-analysis of small and large vessel stroke. Eur Neurol. 2009;61(2):76–86. - PubMed
  55. Swieten JV, HOUT JV, KETEL BV, Hijdra A, Wokke JH, Gijn JV. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly: a morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain. 1991;114(2):761–774. - PubMed
  56. Rościszewska-Żukowska I, Zając-Mnich M, Janik P. Characteristics and clinical correlates of white matter changes in brain magnetic resonance of migraine females. Neurol Neurochir Pol. 2018;52(6):695–703. - PubMed
  57. Sachdev P, Chen X, Wen W. White matter hyperintensities in mid-adult life. Curr Opin Psychiatry. 2008;21(3):268–274. - PubMed

Page Navigation