Migraine Genetics: Part<scp>II</scp>

Silberstein, Stephen D.; Dodick, David W.

doi:10.1111/head.12169

Cited by 53 publications

(54 citation statements)

References 89 publications

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“…25 Further research may reveal subtypes of migraine, often with aura, at risk for stroke and vascular complications. 26 The mechanisms explaining why migraine was associated with vascular events only in smokers in our population are unclear. Statistically, we could Multivariable-adjusted hazard ratios show the influence of vascular risk factors on the association between migraine and stroke outcomes.…”

Section: Resultsmentioning

confidence: 77%

Migraine and risk of stroke in older adults

et al. 2015

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Objective: To examine the association between migraine and stroke/vascular outcomes in a racially/ethnically diverse, older cohort.Methods: Participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders, second edition. We estimated the association between migraine and combined vascular events including stroke and stroke only over a mean follow-up of 11 years, using Cox models adjusted for sociodemographic and vascular risk factors.Results: Of 1,292 participants (mean age 68 6 9 years) with migraine data followed prospectively for vascular events, 262 patients (20%) had migraine and 75 (6%) had migraine with aura. No association was found between migraine (with or without aura) and risk of either stroke or combined cardiovascular events. There was an interaction between migraine and current smoking (p 5 0.02 in relation to stroke and p 5 0.03 for combined vascular events), such that those with migraine and smoking were at an increased risk. The hazard ratio of stroke for migraine among current smokers was 3.17 (95% confidence interval [CI] 1.13-8.85) and among current nonsmokers was 0.77 (95% CI 0.44-1.35). In relation to combined vascular events, the hazard ratio for migraine vs no migraine among current smokers was 1.83 (95% CI 0.89-3.75) and among current nonsmokers was 0.63 (95% CI 0.43-0.94). Conclusion:In our racially/ethnically diverse population-based cohort, migraine was associated with an increased risk of stroke among active smokers but not among nonsmokers. Migraine is a complex neurovascular syndrome resulting in an unstable trigeminal vascular system. It has been suggested that migraine and stroke exist on a continuum, and the vascular system may have important secondary consequences in migraine.1 While the vascular theory of migraine has been disproved, migraine with aura, mostly in women younger than 45 years, has been shown to be an independent risk factor for ischemic stroke.2 Some studies also suggest that migraine is associated with an unfavorable cardiovascular risk profile, cardiovascular disease events, and vascular death.3-8 However, there are no reliable indicators to predict which migraineurs will develop cerebrovascular ischemic insults and other vascular events. Moreover, migraine may be a potentially modifiable vascular risk factor, requiring further exploration in high-risk populations.The objective of this study was to assess the association between migraine, including both migraine with and without aura, and stroke in the Northern Manhattan Study (NOMAS), an ethnically diverse, older, community-based cohort. As a secondary aim, we also explored the association between migraine and vascular events/mortality.

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Section: Resultsmentioning

confidence: 77%

Migraine and risk of stroke in older adults

et al. 2015

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“…CSD is a short-lasting propagating wave of cellular depolarization followed by a long-lasting suppression of the neuronal activity that is believed to be the basis for the migraine aura (7). The likelihood of CSD is increased by hyperexcitability of the neuronal network (8,9). In FHM1, Ca V 2.1 mutations induce a gain-of-function resulting in enhanced glutamate release and facilitated CSD.…”

Section: Introductionmentioning

confidence: 99%

Early-onset familial hemiplegic migraine due to a novel SCN1A mutation

et al. 2016

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IntroductionFamilial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura. The FHM3 subtype is caused by mutations in SCN1A, which is also the most frequent epilepsy gene encoding the voltage-gated Na+ channel NaV1.1. The aim of this study was to explore the clinical, genetic and pathogenetic features of a pure FHM3 family.MethodsA three-generation family was enrolled in this study for genetic testing and assessment of clinical features. Whole cell patch-clamp was performed to determine the functions of identified mutant NaV1.1 channels, which were transiently expressed in human tsA201 cells together with β1 and β2 subunits.Results and conclusionsWe identified a novel SCN1A (p.Leu1624Pro) mutation in a pure FHM family with notably early-onset attacks at mean age of 7. L1624P locates in S3 of domain IV, the same domain as two of four known pure FHM3 mutations. Compared to WT channels, L1624P displayed an increased threshold-near persistent current in addition to other gain-of-function features such as: a slowing of fast inactivation, a positive shift in steady-state inactivation, a faster recovery and higher channel availability during repetitive stimulation. Similar to the known FHM3 mutations, this novel mutation predicts hyperexcitability of GABAergic inhibitory neurons.

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“…Mutations in the SCN1A gene are responsible for the third type of FHM, FHM III. This gene encodes the α1 subunit of the neuronal Nav1.1 voltage-gated sodium channels [90], and leads to accelerated recovery of the channel from fast inactivation, leading to a higher firing rate [91]. These data indicate that FHM mutations can result in cortical hyperexcitability, suggesting that this phenomenon may also be involved in the formation of simple migraine.…”

Section: Cortical Hyperexcitability In Migrainementioning

confidence: 83%

Tryptophan Catabolites and Migraine

Bohár

Párdutz

Vécsei

2016

CPD

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Abstract:Migraine is a highly disabling neurological condition affecting around 15% of the population worldwide.Decades of intensive research shed some light on diseases pathomechanism, but information is still missing about the initiation of the attack. In the past century, serotonin emerged as the main target of both basic and therapeutic research. As a result, the triptans, the only approved migraine specific drugs were developed. The involvement of glutamatergic mechanism in migraine headache development such as cortical hyperexcitability, and cortical spreading depression as the pathological correlate of migraine aura called the attention to the kynurenine pathway in migraine pathomechanism. The serotonin and kynurenine pathways are closely connected, as they both are the metabolic routes of the amino acid tryptophan. Kynurenine catabolites are important participants in glutamatergic neurotransmission, regulation also nociceptive processing of the trigeminal system. The current work attempts to collect recent data on both serotonin and kynurenine research related to migraine and emphasizes the importance of further research on this topic.

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Migraine Genetics: PartII

Cited by 53 publications

References 89 publications

Migraine and risk of stroke in older adults

Migraine and risk of stroke in older adults

Early-onset familial hemiplegic migraine due to a novel SCN1A mutation

Tryptophan Catabolites and Migraine

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