Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.

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.

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (p=5.12 × 10−9, OR 1.23 [1.150-1.324]) in a genome-wide association study of 2,748 migraineurs from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis p-value of 1.60 × 10−11 (OR 1.18 [1.127 – 1.244]). rs1835740 is located between the astrocyte elevated gene 1 (MTDH/AEG-1) and plasma glutamate carboxypeptidase (PGCP). In an expression quantitative trait study in lymphoblastoid cell lines transcript levels of the MTDH/AEG-1 were found to have a significant correlation to rs1835740. Our data establish rs1835740 as the first genetic risk factor for migraine.

Arch Neurol. 2002 Jun;59(6):1016‐1018 Background: Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura that in half of the families is caused by mutations in the CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is, hemiplegic migraine without affected family members, the contribution of the CACNA1A gene is unknown. Objective: To investigate the involvement of the CACNA1A calcium channel subunit gene in SHM. Methods: We screened 27 patients with SHM for mutations in the CACNA1A gene by a combination of single‐strand conformational polymorphism analysis and sequence analysis. Results: One patient with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed tomography and carried a T666M mutation. Another patient with SHM who had no cerebellar signs carried an R583Q mutation. No mutations or interictal neurological abnormalities were found in the remaining 25 patients with SHM. Conclusions: Most patients with SHM do not have a CACNA1A mutation. The results of this study, combined with the findings reported in the literature, show that the presence of cerebellar symptoms in addition to the hemiplegic attacks increases the chance of finding a CACNA1A mutation. In addition, to our knowledge, we have found a first patient with SHM without cerebellar signs with a mutation. Comment: The story on calcium channelopathies and neurologic disorders becomes ever more complex, as multiple neurologic disorders appear linked to varying forms of calcium‐channel mutations. Professor Ferrari has described links to cerebellar disorders, to a peculiar and severe response to head trauma, and to epilepsy, as well as to familial hemiplegic migraine. Now his group finds that the most frequently found calcium channelopathy mutations are not found in most patients with spontaneous hemiplegic migraine. Does this just mean that other mutations, not yet described, cause a common phenotypic expression? Or are there multiple causes for the hemiplegic migraine syndrome, and not all of them due to calcium channelopathies? SJT

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.