Key studies reporting risk of silent structural brain lesions in people with migraine
| Author (year) | Study design | No of study participants | Objective | Outcome |
| Kruit et al 66 | Cross-sectional, prevalence study of a population-based cohort (CAMERA-1) | 435 | Compare prevalence of brain ILL and WMH in people with migraine and controls from the general population, and to identify migraine characteristics associated with these lesions | MA (n=161) MO (n=134), controls (n=140). 73% women; mean age 48.3 years. Number of deep WMH in migraine compared with controls: MA (OR 2.0; 95% CI 1.0 to 4.3) and MO (OR 2.1; 95 % CI 1.0 to 4.7) compared with controls (OR 1.9). No association between WMH and migraine subtype. An association between WMH and attack frequency:<1 attack per month (OR 1.6; 95% CI 0.8 to 3.5) versus >1 attack per month (OR 2.6; 95% CI 1.2 to 5.7) (p=0.008). Some patients with MA and MO are at increased risk for subclinical lesions in certain brain areas. |
| Scher et al 69 | Population-based cohort (AGES) | 4689 | Determine whether migraine in midlife is associated with increased risk of late-life ILL | MA (n=361), MO (n=209), non-migraine headaches (n=876), controls (n=3243), 57% women, mean age at midlife 50.9 years; mean age at late life 76.2 years. Compared with those not reporting headaches once or more per month, increased risk of late-life ILL in those with midlife MA (adjusted OR 1.4, 95% CI 1.1 to 1.8). The prevalence of infarcts 23.0% for women with MA versus 14.5% for women not reporting headaches (adjusted OR 1.9, 95% CI 1.4 to 2.6), and the prevalence of infarcts in men with MA 19.3% vs 21.3% for men not reporting headaches (adjusted OR 1.0, 95% CI 0.6 to 1.8). P<0.04 for interaction by sex, reflecting an association with cerebellar lesions in women. MO and non-migraine headache not associated with an increased risk of late-life ILL. MA in midlife is associated with late-life vascular disease in the cerebellum and in women. |
| Kurth et al 70 | Population-based, cross-sectional study (EVA-MRI) | 780 | Association between overall and specific headaches with volume of white matter hyperintensities, brain infarcts and cognition | MA (n=17), MO (n=99), non-migraine headache (n=47), controls (n=617). 59% women, mean age 69 years. Number of deep WMH in migraine and non-migraine headache compared with controls; MA (OR 12.4, 95% CI 1.6 to 99.4, p=0.005), MO (OR 1.6, 95% CI 0.9 to 2.7, p=0.11) and non-migraine headache (OR 2.1, 95% CI 1.0 to 4.4, p=0.03) compared with controls (OR 1.0). Adjusted OR was 2.0 (95% CI 1.3 to 3.1, p=0.002) for any history of severe headache. MA also associated with brain infarcts (OR 3.4, 95% CI 1.2 to 9.3). Any history of severe headache associated with increased volume of WMH. MA was the only headache type associated with brain infarcts. Evidence lacking for cognitive impairment for any headache type with or without brain lesions. |
| Palm-Meinders et al 71 | Prospective population-based observational study (CAMERA-2 study) | 435 | Prospectively evaluation of associations of migraine with structure and function of the brain 9 years after initial MRI | MA (n=114), MO (n=89), control (n=83). 71% women, mean age 57 years. Number of deep WMH and ILL in migraine compared with controls: WMH progression (OR 2.1, 95% CI 1.0 to 4.1, p=0.04). ILL progression (OR 7.7, 95% CI 1.0 to 59.5, p=0.05). No association between WMH progression and attack frequency, attack duration, type of attack and antimigraine therapy. No association between ILL progression and migraine subtype and attack frequency. Higher incidence of deep WMH in women with migraine but not significantly higher progression of other MRI-measured brain changes in this follow-up study. No association of migraine with progression of any MRI lesions in men. |
| Bashir et al 67 | Systematic review and meta-analysis | — | Association between migraine and structural changes in the brain—systematic review and meta-analysis | 6 clinic-based and 13 population-based studies WMH showed an association with MA (OR 1.68 95% CI 1.07 to 2.65, p=0.03) but not for MO (OR 1.34; 95% CI 0.96 to 1.87; p=0.08). The association for ILL was greater for MA (OR 1.44; 95% CI 1.02 to 2.03; p=0.04) than for MO, but no association found for MA (p=0.52) and MO (p=0.08) compared with controls. Migraine, particularly MA, may be a risk factor for structural changes in the brain. |
| Hamedani et al 72 | Population-based cohort (ARIC MRI study) | 12 787 | Effect of WMH progression over time in people with migraine | MA (n=422), MO (n=1003), non-migraine headache (n=1280), no headache (n=10 082). 56% women, mean age 60 years. MO cross-sectionally associated with 8.7% greater odds of having WMH score >3 than individuals without headache (adjusted OR=1.87, 95% CI 1.04 to 3.37). People with migraine had an average of 2.65 cm3 more WMH than those without headache (95% CI 0.06 to 5.24). No significant difference in WMH progression over the study period between individuals with and without migraine (95% CI −0.37–3.53). Migraine associated with WMH volume cross-sectionally but not with WMH progression over time. |
| Monteith et al 73 | Prospective population-based cohort | 546 | Association between migraine and subclinical cerebrovascular damage in a diverse older population-based cohort study | No migraine (n=442), migraine (n=104). 59% women, mean age 71 years. Number of subclinical ILL in people with migraine (compared with non-migraine: adjusted OR 2.1, 95% CI 1.0 to 4.2). No association was observed between MO and MA and WMH volume. Migraine may be a risk factor for subclinical brain infarction. |
| Gaist et al 76 | Population-based study of female twins | 345 | Association between migraine with aura and silent ILL and WMH in female twins | MA (n=172), co-twins (n=34), controls (n=139). Compared with controls, cases did not differ with regard to frequency of silent ILL, periventricular WMH score (adjusted mean difference −0.1, 95% CI −0.5 to 0.2) or deep WMH score (adjusted mean difference 0.1, 95% CI −0.8 to 1.1) assessed by Scheltens scale. No evidence of an association between silent brain infarcts, WMH, and MA in female twins. |
| Koppen et al 65 | Population-based study | 282 | Cerebellar function and ischaemic brain lesions in unselected migraine patients and controls from general population | MA (n=111), MO (n=89), non-migraine controls (n=82), 72% female, age range 43–72. Cerebellar ischaemic lesions found in 8.5% of migraine patients and 4% of the controls, which were always located in the posterior lobe, except for one control. With regard to cerebellar tests, there were no differences between MA, MO and controls. Patients with MA and cerebellar ischaemic lesions performed worse on fine motor skills tests than those without lesions (p<0.005). Normal cerebellar function despite increased prevalence of ischaemic lesions in the cerebellar posterior lobe in unselected migraine patients from general population. Except for impaired fine motor skills, these lesions appear to have little functional impact. |
| Uggetti et al 77 | Prospective cohort | 180 | Detect entity of white matter T2-hyperintensities in high selected patients with MA, compared with a group of healthy controls | MA (n=90), controls (n=90), 69% women, mean age 36.8 years. WMH lesions found in 29% of patients with MA and 27% of the controls (p=0.64). No significant difference of incidence of WMH between people with migraine and controls. |
ILL, infarct-like lesions; MA, migraine with aura; MO, migraine without aura; WMH, white matter hyperintensities.