Migraine is a neurological disease with underlying pathology involving altered brain structure and brain function.¹ Advances in neuroimaging techniques have helped investigate both the structural and functional effects of migraine on the human brain.^2-4 Structural imaging techniques such as MRI, magnetic resonance imaging, and computer tomography, CT, can be used to visualize anatomical properties, such as the size and volume of brain structures.² Functional imaging techniques, such as MRI and positron emission tomography, PET, are employed to define regions that are active during specific behaviors and cognitive activities.^2,5 Functional imaging studies may include evaluation of stimuli-induced responses or 'at rest' activity.^5,6

Using these neuroimaging techniques, several studies have reported that migraine is associated with changes to underlying brain structure and function.^7,8 Patients with migraine may displace structural alterations, including reduced density in cortical areas involved in pain processing versus normal controls.^3,9 The nervous system of patients with migraine may also demonstrate functional alterations, where certain brain regions show altered activation and response to painful heat stimulation.⁴ Functional alterations may also underlie migraine non-pain symptoms.¹⁰ For example, in patients who experience visual snow, hypermetabolism was observed in certain regions of the pain network.¹⁰

In some patients, migraine can progress from episodic migraine that is less than 15 headache days per month to chronic migraine defined as 15 headache days per month, or more.^11,12 Migraine frequency can also improve over time¹³. Patients convert from chronic migraine to episodic migraine at a rate of about 26% over two years.¹³ Imaging studies suggest that patients with more severe disease show more pronounced structural and functional neurological changes.^4,14 Studies have found that increased headache-day frequency and longer disease duration are associated with changes in brain structure and function.^4,14 Structural imaging studies in patients with migraine suggest that there is a correlation between increased headache frequency and alterations in grey matter volume, and length of disease history with alterations in neural connectivity and white matter integrity.^14,15 Similarly, increased headache frequency and longer migraine history are associated with increased alterations in functional activation of specific brain regions.^4,16

Another potential implication of uncontrolled migraine is that patients who overuse acute medications to manage their attacks are at the risk of developing mediation overuse headache.12 Approximately 50% of patients who suffer from chronic migraine, that is who have at least 15 headache days per month or more for longer than three months, have medication overuse headache.¹² Analysis of patients with medication overuse headache has shown that these patients also display changes of brain structure and hypometabolism of certain brain regions.^17,18 Structurally, patients with medication overuse headache were found to have grey matter texture abnormalities in a number of regions, including the cerebellar vermis and the left cerebellum.¹⁷ Functionally, hypometabolism of several regions was observed in patients with medication overuse headache, which subsequently returned to near normal three weeks after analgesic withdrawal.¹⁸

If ineffectively controlled, some patients may develop more severe disease characterized by increased frequency or severity of headache or migraine days and the development of medication overuse headache.^11,12 Results from several imaging studies, including those discussed here, suggests that patients with migraine may display altered brain structure and function.^7,8 And, patients who are at the more severe end of the migraine spectrum may experience more pronounced neurological sequelae.^14,17

References:

1. Charles A. Lancet Neurol. 2018; 17(2):174-182.
2. Hirsch GV, et al. Ann Neurosci Psychol. 2015; 2:5.
3. Yu ZB, et al. Medicine (Baltimore). 2016; 95(37):e4824.
4. Schwedt TJ, et al. Cephalalgia. 2014; 34(12):947–958.
5. Crosson B, et al. J Rehabil Res Dev. 2010; 47(2):vii–xxxiv.
6. Van Dijk KRA, et al. J Neurophysiol. 2010; 103:297–321.
7. Rocca MA, et al. Stroke. 2006; 37:1765-1770.
8. Russo A, et al. J Neurol. 2012; 259:1903–1912.
9. Xie Y, et al. Acta Pharmacol Sin. 2009; 30(1):31–41.
10. Schankin CJ, et al. Headache. 2014; 54(6):957-66.
11. Bigal ME, Lipton RB. Curr Neurol Neurosci Rep. 2011; 11:139–148.
12. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1):1-211.
13. Manack A, et al. Neurology. 2011; 76(8):711-718.
14. Kim JH, et al. Cephalalgia. 2008; 28(6):598-604.
15. Chong CD, Schwedt TJ. Cephalalgia. 2015; 35(13):1162-1171.
16. Zhao L, et al. J Headache Pain. 2013; 14:85.
17. Chen Z, et al. J Headache Pain. 2017; 18:112.
18. Fumal A, et al. Brain. 2006; 129:543-550.