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White Matter Hyperintensities in Migraine: a Review

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White Matter Hyperintensities in Migraine: a Review Precision and Future Medicine 2019;3(4):146-157 REVIEW https://doi.org/10.23838/pfm.2019.00128 ARTICLE pISSN: 2508-7940 · eISSN: 2508-7959 White matter hyperintensities in migraine: a review 1 2 1 Mi Ji Lee , Sujin Moon , Chin-Sang Chung 1 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 CHA University School of Medicine, Seongnam, Korea Received: October 6, 2019 Revised: November 28, 2019 Accepted: December 3, 2019 ABSTRACT Migraine is a neurological disorder characterized by recurrent spells of headache ac- Corresponding author: Mi Ji Lee companied by brain symptoms such as nausea, vomiting, photophobia, and phono- Department of Neurology, phobia. White matter hyperintensity (WMH) is the most frequent radiological abnormal- Samsung Medical Center, ity observed in migraineurs. Older studies have reported that the prevalence of WMH is Sungkyunkwan University about 30% in migraineurs, while latest studies using advanced technology show that School of Medicine, 81 Irwon- WMHs are present in about 70% of young (age < 50 years), vascular risk factor-free pa- ro, Gangnam-gu, Seoul 06351, tients with migraine. Population-based studies on elderlies reported conflicting results Korea on the association between migraine and WMH, but deep WMHs were greater in studies Tel: +82-2-3410-3599 of the younger population. Data are also conflicting on whether headache characteris- E-mail: [email protected] tics, migraine type, disease duration, or headache frequency are associated with WMH. Current evidence suggests that a greater deep WMH burden is associated with intracra- nial and extracranial vascular function. The clinical implication of WMH has not been well studied in relation to migraine, but it is generally not associated with cognitive dys- function in patients with migraine. Current understanding of WMHs is limited; we herein suggest some tips for improvement in research methods that will bring a better under- standing of both the pathophysiology and the consequence of WMH development in patients with migraine. Keywords: Ischemia; Magnetic resonance imaging; Migraine with aura; Migraine with- out aura; Stroke; White matter INTRODUCTION Migraine is a neurological disorder characterized by recurrent episodes of headache that is ac- companied by brain symptoms such as nausea, vomiting, photophobia, and phonophobia. About 10% of the world’s population has migraine [1]. The impact of migraine is substantial; it This is an Open Access article has been ranked among the top leading causes of disability in the Global Burden of Disease distributed under the terms of the study 2016 [2]. Creative Commons Attribution Not only is migraine a disorder causing headache-related impact, it also contributes to a Non-Commercial License (http:// creativecommons.org/licenses/ higher risk of cardiovascular outcomes such as stroke, ischemic heart disease, and all-cause by-nc/4.0/). death [3-7]. The association between migraine and stroke has been particularly well recog- 146 Copyright © 2019 Sungkyunkwan University School of Medicine Mi Ji Lee, et al. nized. Several population-based studies reported an in- modern studies, the prevalence of WMH is about 50% in the creased risk of stroke in migraineurs. Especially, subgroups general population aged 44 to 48 years and increases to 90% of migraine with aura (MWA) and female migraineurs carry a in people aged 64 to 74 years [14]. In contrast, younger peo- higher risk of ischemic and hemorrhagic strokes [4,6]. ple do not frequently exhibit WMHs. The risk of having WMH However, clinical or translational studies on the mecha- is tenfold higher in people aged 55 years or older compared nism and prevention of stroke in migraineurs have rarely to that in those aged less than that [15]. been conducted. This is because the absolute incidence of stroke is low; hence, a long observation period and a huge TYPES OF WMH: PERIVENTRICULAR sample size are required in observational studies using stroke WMH AND DEEP WMH as an outcome. Instead, understanding the white matter hy- perintensity (WMH) may contribute to knowledge about the WMHs are classified into two types: periventricular and deep mechanism of ischemic stroke in migraineurs. WMH refers to WMHs. Periventricular WMHs refer to hyperintensities sur- abnormal signal changes in white matter in T2-based brain rounding the ventricles, and deep WMHs are located in deep magnetic resonance imaging (MRI) [8]. The pathophysiology and juxtacortical white matter [10,16,17]. Risk factors and of WMH is not exactly understood and may be heterogenous, clinical implications may be different between the two types but ischemic insult is the most likely mechanism [9]. [18]. While WMH has been recognized in demented patients, In this paper, we will review the association between WMH and age and hypertension are well known risk factors, and migraine, possible mechanisms, and the current limita- periventricular WMH is more strongly associated with age, tions of knowledge in this field. hypertension, and cognitive decline than deep WMH [18-21]. In contrast, migraine is more associated with deep WMH WHAT IS WMH? [18,22,23]. Different pathologies are also observed; although controversial data exists, most studies indicate that ischemic WMH is a radiological term indicating the areas with increased and hypoxic pathologies are predominant in deep WMHs, signal intensity on T2-weighted MR imaging [8,10]. Although while periventricular WMHs are more linked to increased in- WMH is currently defined based on MRI findings, white matter terstitial fluid probably caused by altered periventricular flu- changes have been recognized since the late 1980s with the id dynamics [24,25]. In this review article, the association be- use of brain computed tomography (CT) [11]. Low-attenuated tween migraine and WMH will be discussed with regard to white matter areas on CT were called leukoaraiosis [12]. With the type of WMHs. advances in neuroimaging techniques, the identification of WMH is easier and more sensitive than before. MIGRAINE AND WMH As mentioned above, WMH is hyperintense on T2-weighted images and best detected on fluid-attenuated inversion recov- While conventional neuroimaging of migraine reveals no di- ery (FLAIR) sequence. Typical WMH is round- or oval-shaped, agnostic findings, WMHs may be the most frequent abnor- hypo or isointense on T1-weighted images and is distributed malities observed in migraineurs. Patients often ask about in the periventricular or deep white matter [8,9]. WMH should the clinical implication of these lesions and their association be differentiated from enlarged perivascular space (Vir- with migraine. However, as WMHs are also common among chow-Robin space), lacunes [13], and other disorders such as the general population of middle-aged and elderlies, it is not multiple sclerosis that can cause white matter lesions [9]. easy to determine whether the increased prevalence of WMHs in migraineurs is attributed to either migraine or the EPIDEMIOLOGY normal aging process. Even if WMHs are purely migraine-re- lated, they may be obscured by age-related changes in sus- WMH is prevalent in the general population and has thus ceptible age groups. In addition, migraine patients with been a frequent cause of neurology consultation in people WMHs are more likely to visit secondary or tertiary hospitals who undergo brain MRI. The incidence of WMH increases to seek a second opinion, which may lead to overestimation with age, especially after midlife. The reported prevalence of of its prevalence in migraineurs. Therefore, the study on WMH differs between studies because the detection of WMH WMH in migraineurs should be interpreted with regard to age is highly dependent on MRI resolution and the size criteria. In and study setting. https://doi.org/10.23838/pfm.2019.00128 147 148 Table 1. Clinic-based studies on white matter hyperintensities in patients with migraine Inclusion criteria Methods No. of subjects Age (mean±SD) WMH prevalence (%) Predom- MR strength/sequence inant Study Vascular (thickness), quantita- type of Age (yr) Migraine MWA MOA Control Migraine MWA MOA Control Migraine MWA MOA Control risk factors tive segmentation if WMH used Fazekas et al. 18–59 1.5T/T2 (5 mm) 38 27 11 15 37.5±13.3 40.5±15.4 35.8±11.9 37.8±5.3 39 53 18 14 Deep (1992, Subgroup Excluded 24 14 33 14 Deep Head ache) < 50 [31] De Benedittis et al. 19–66 Only HT 0.5T/T2 (7 mm) 28 9 19 54 40.1± 13.7 40.0± 15.0 32.1 33.3 31.6 7.4 NA (1995, Headache) and DM [40] excluded inmigraine hyperintensities matter White Rovaris et al. 18–55 1.5T/T2 (5 mm) 16 4 12 17 33.9 36.3 31 33 25 0 (2001, J Neurol Sci) [41] Pavese et al. ≤45 Excluded 0.5T/T2 (5 mm) 129 46 83 50 36.1± 6.5 34.2± 7.8 36.1± 8.0 35.3± 5.9 Deep 21.7 18.1 2 Deep (1994, 19.3 Cephalalgia) [33] Igarashi et al. Unspecified Excluded 0.5T/T2 (10 mm) 91 53 33 98 34.0± 13.6 33.2± 14.6 36.7± 11.9 32.4± 18.2 39.6 43.4 33.3 11.2 NA (1991, Subgroup 51 98 29.4 11.2 Deep Cephalalgia) < 40 [32] Cooney et al. 15–83 Excluded 1.5T or 0.5T/T2 (5 mm) 185 107 78 NA 16.2 NA (1996, Subgroup 126 4.8 NA Headache) < 50 [42] Eidlitz-Markus et al. 2.5–18 1.5T/FLAIR (4 mm) 131 63 10.9± 3.5 10.39± 3.8 10.7 0 Deep http://pfmjournal.org (2013, Cephalalgia) [38] Avci et al. 18–50 Excluded 1.5T/FLAIR (5 mm) 216 73 143 216 32.6±6.7 30.9±7.6 32±4.6 31.9 34.2 30.8 9.7 Deep (2015, JHP) [35] (Continued to the next page) https://doi.org/10.23838/pfm.2019.00128 Table 1.
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