IGRAINE IS A COMMON, chronic, multifactorial neurovascular disorder typically characterized by recurrent attacks of disabling headache and autonomic nervous system dysfunction (migraine without aura); up to one third of patients also have neurological aura symptoms (migraine with aura). 1,2 Migraine has been suggested to be an independent risk factor for stroke, but the evidence is conflicting and seems to be restricted to certain subpopulations (eg, women with migraine with aura who are younger than 45 years, particularly ones who smoke or use oral contraceptives [OCs]). 3-9 Case reports on patients with so-called migrainous infarction suggest that the posterior circulation territory (PCT) is most commonly affected. 8,9 However, data are lacking on prevalence of subclinical infarcts in a wide spectrum of migraine patients in the general population. Patients with migraine may also be at increased risk of more diffuse subclinical lesions in the deep white matter or periventricular areas that are only detected on neuroimaging. 10-12 Several clinic-based magnetic resonance imaging (MRI) studies have reported this,

Background Previous studies suggested that migraine is a risk factor for brain lesions, but methodological issues hampered drawing definite conclusions. Therefore, we initiated the MRI “CAMERA” study. Procedures We summarize our previously published results. A total of 295 migraineurs and 140 controls were randomly selected from a previously diagnosed population-based sample (n=6039), who underwent an interview, physical examination, and a brain MRI-scan. Findings Migraineurs, notably those with aura, had higher prevalence of subclinical infarcts in the posterior circulation (OR=13.7; 95%CI 1.7–112). Female migraineurs were at independent increased risk of white matter lesions (WML; OR=2.1; 95%CI 1.0–4.1), and migraineurs had a higher prevalence of brainstem hyperintense lesions (4.4% vs. 0.7%, p=0.04). We observed a higher lifetime prevalence of (frequent) syncope and orthostatic insufficiency in migraineurs; future research needs to clarify whether autonomic nervous system dysfunction could explain (part of) the increased risk of WMLs in female migraineurs. Finally, in migraineurs aged <50, compared to controls, we found evidence of increased iron concentration in putamen (p=0.02), globus pallidus (p=0.03) and red nucleus (p=0.03). Higher risks in those with higher attack frequency or longer disease duration were found consistent with a causal relationship between migraine and lesions. Conclusion This summary of our population-based data illustrates that migraine is associated with a significantly increased risk of brain lesions. Longitudinal studies are needed to assess whether these lesions are progressive and have relevant (long-term) functional correlates.

In a previous study, migraine cases from the general population were found to be at significantly increased risk of silent infarct-like lesions in the posterior circulation (PC) territory of the brain, notably in the cerebellum. In this study we describe the clinical and neuroimaging characteristics of migraine cases with and without aura and controls with PC lesions. In total, 39 PC infarct-like lesions represented the majority (65%) of all 60 identified brain infarct-like lesions in the study sample (n = 435 subjects with and without migraine). Most lesions (n = 33) were located in the cerebellum, often multiple, and were round or oval-shaped, with a mean size of 7 mm. The majority (88%) of infratentorial infarct-like lesions had a vascular border zone location in the cerebellum. Prevalence of these border zone lesions differed between controls (0.7%), cases with migraine without aura (2.2%) and cases with migraine with aura (7.5%). Besides higher age, cardiovascular risk factors were not more prevalent in cases with migraine with PC lesions. Presence of these lesions was not associated with supratentorial brain changes, such as white matter lesions. The combination of vascular distribution, deep border zone location, shape, size and imaging characteristics on MRI makes it likely that the lesions have an infarct origin. Previous investigators attributed cases of similar 'very small' cerebellar infarcts in non-migraine patients to a number of different infarct mechanisms. The relevance and likelihood of the aetiological options are placed in the context of known migraine pathophysiology. In addition, the specific involvement of the cerebellum in migraine is discussed. The results suggest that a combination of (possibly migraine attack-related) hypoperfusion and embolism is the likeliest mechanism for PC infarction in migraine, and not atherosclerosis or small-vessel disease.

Our findings report an unbiased quantitative whole brain assessment of morphological abnormalities in migraine. This might help to identify indicators for migraine as a possibly progressive brain disease. In order to reveal the causes and consequences of brain damage in migraine, further neuroimaging studies have to investigate quantitative brain changes in a longitudinal design.