Headache in Women
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ABSTRACT PURPOSE OF REVIEW Women are greatly overrepresented among patients seeking treatment for symptoms of headache pain in general and migraine in particular. Understanding the presentation of headache in women in relation to hormonal changes both during the menstrual cycle and throughout the life span is essential for appropriate diagnosis and treatment. RECENT FINDINGS Although perimenstrual migraine attacks are generally without aura, the diagnosis of migraine with aura has been added to the headache classification for menstrual migraine to account for women with the diagnosis of migraine with aura who experience menstrual migraine attacks. Emerging knowledge regarding the differences between menstrual and nonmenstrual attacks, the variability of attack triggering within and between women, and the response of women with menstrually related migraine to new migraine drug classes is contributing to better understanding and more effective treatment of these particularly burdensome and refractory attacks. Given the burden of migraine, almost one-fourth of women with migraine avoid or delay pregnancy. Women who experience migraine during pregnancy are more likely to have a hypertensive disorder and stroke during pregnancy and/or delivery and the postpartum period. Treatment of headache in general and migraine in particular in pregnancy is challenging because of fetal and maternal risks; however, a 2021 systematic review suggests that triptans and low-dose aspirin may not be associated with fetal/child adverse effects and could be more strongly considered for headache treatment in pregnancy. SUMMARY Headache in general and migraine in particular are extraordinarily common in women of reproductive age and fluctuate with hormonal changes and phases of life. Improved knowledge of the epidemiology, pathophysiology, and response to treatment of perimenstrual attacks is essential for more effective response to this most burdensome headache type. Treatment of headache in pregnancy remains challenging.Keywords:
Triptans
Migraine treatment
Menstruation
Abnormal cerebrovascular regulation has been implicated in the pathogenesis of migraine. Our aim in this study was to evaluate cerebrovascular reactivity to different stimulations in migraine with and without aura. Using bilateral transcranial Doppler, the changes of flow velocity during hypercapnia and mental and motor activity were measured in the middle cerebral adages of 15 controls and 30 patients with migraine with aura (n=l5) or without aura (n=15) in an attack‐free period. Vascular response to all tests was similar in controls and patients. In patients with unilateral headache, no side‐to‐side difference was found. These findings suggest that no alteration of cerebrovascular reactivity exists outside attacks in migraine with and without aura. Further studies with transcranial Doppler considering all intracranial vessels and the comparison with other techniques of flow investigation with better regional resolution are needed to confirm these data.
Transcranial Doppler
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Transcranial Doppler
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To better define a possible genetic basis for migraine with aura (MWA).We investigated the familial occurrence of migraine with aura in a sample of (MWA) subjects recruited from an epidemiologic study of migraine with aura involving the general population. The sample with migraine with aura (n = 26) was selected out of a total of 1392 subjects (842 women and 550 men) representative of the general population aged 18 to 65 years in the southern Italian town of San Severo. A family history of migraine with aura was determined via direct interviews with all living first-degree relatives of the 26 subjects who could be reached by investigators, 119 people: 71 women and 48 men. The diagnosis of migraine with aura was made according to the 1988 International Headache Society (IHS) criteria.Of the 26 subjects with migraine with aura, 7 (6 women and 1 man) had a positive family history, with a total of 7 first-degree relatives affected by the disease (1 mother, 2 fathers, 1 brother, 1 sister, and 2 children). Based on the lifetime prevalence rate of migraine with aura (1.6%) in the San Severo general population, the relative risk of migraine with aura in the first-degree relatives of the subjects was 3.68 (4.16 for women and 2.77 for men).Our subjects' relative risk rate for familial occurrence of migraine with aura was similar to that reported by one investigator, but markedly lower than that reported by another group.
Family aggregation
First-degree relatives
Familial hemiplegic migraine
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Cortical Spreading Depression
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To search for differences in prevalence of a CACNA1E variant between migraine without aura, various phenotypes of migraine with aura, and healthy controls.Familial hemiplegic migraine type 1 (FHM1) is associated with mutations in the CACNA1A gene coding for the alpha 1A (Cav 2.1) pore-forming subunit of P/Q voltage-dependent Ca2+ channels. These mutations are not found in the common forms of migraine with or without aura. The alpha 1E subunit (Cav 2.3) is the counterpart of Cav 2.1 in R-type Ca2+ channels, has different functional properties, and is encoded by the CACNA1E gene.First, we performed a total exon sequencing of the CACNA1E gene in three probands selected because they had no abnormalities in the three FHM genes. In a patient suffering from basilar-type migraine, we identified a single nucleotide polymorphism (SNP) in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760; Minor Allele Frequency 0.2241) hitherto not studied in migraine. In a second step, we determined its occurrence in four groups by direct sequencing on blood genomic DNA: migraine patients without aura (N = 24), with typical aura (N = 55), complex neurological auras (N = 19; hemiplegic aura: N = 15; brain stem aura: N = 4), and healthy controls (N = 102).The Asp859Glu - rs35737760 SNP of the CACNA1E gene was present in 12.7% of control subjects and in 20.4% of the total migraine group. In the migraine group it was significantly over-represented in patients with complex neurological auras (42.1%), OR 4.98 (95% CI: 1.69-14.67, uncorrected P = .005, Bonferroni P = .030, 2-tailed Fisher's exact test). There was no significant difference between migraine with typical aura (10.9%) and controls.We identified a polymorphism in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760) that is more prevalent in hemiplegic and brain stem aura migraine. This missense variant causes a change from aspartate to glutamate at position 859 of the Cav 2.3 protein and might modulate the function of R-type Ca2+ channels. It could thus be relevant for migraine with complex neurological aura, although this remains to be proven.
Familial hemiplegic migraine
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Cortical Spreading Depression
SNP
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Background and objectives To assess the usefulness of the "index vein" for making the diagnosis of migraine aura.Methods 400 patients were included when they: i) presented with an acute neurological deficit, ii) had a brain MRI, and iii) had a discharge diagnosis of migraine aura, ischemic stroke, epileptic seizure or controls (n = 100 per group).Results Compared to stroke (2%), epileptic seizure (4%) and controls (1%), the index vein is more prevalent in migraine aura (17%, p < 0.001). The index vein is highly specific for migraine aura (specificity 97%, 95% CI 95-99). The index vein has a positive predictive value for the diagnosis of migraine aura of 70% (95%CI 48-87). The index vein-score has the ability to diagnose migraine aura with a sensitivity of 94% (95%CI 87.4-97.8) and specificity of 73.5% (95%CI 66.8-79.5) at a cut-off of 4 points.Discussion The index vein serves as a good biomarker for migraine aura in the emergency setting.
Stroke
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Taking medication early on for aborting migraines has proved to be more effective, but trials using triptans during the aura phase have not shown significant effectiveness. Isometheptene compounds are popularly used as an anti-migraine OTC drug. We report a 27-year-old male patient with migraine with aura whose headache attacks were consistently inhibited by an isometheptene compound administered at the early aura phase, while he received no benefits from adequate treatment during the headache phase.
Triptans
Migraine treatment
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Familial hemiplegic migraine
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Transcranial Doppler
Neuroradiology
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The relationship between migraine with aura and patent foramen ovale (PFO) is still debatable. We report 2 cases of migraine with aura attacks after diagnostic microbubble injection for contrast transcranial Doppler (cTCD), in subjects with large PFO. In one case MR images, including diffusion weighted imaging and apparent diffusion coefficient, performed during aura did not show any signal abnormality. Patients with migraine with aura may have an attack during cTCD, probably by a “non‐ischemic” mechanism.
Abnormality
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