The impact of extended-cycle vaginal ring contraception on migraine aura: a retrospective case series

Objective.— To determine whether extended‐cycle dosing of an ultralow dose vaginal ring contraceptive decreases frequency of migraine aura and prevents menstrual related migraine (MRM). Background.— Many women are denied therapy with combined hormonal contraceptives due to published guidelines that recommend against their use in migraine with aura (MwA). The concern is that these products might further elevate the risk of ischemic stroke that accompanies aura. Stroke risk has been reported to vary directly with aura frequency, and aura frequency in turn has been shown to have a direct relationship to estrogen concentration. With the evolution of increasingly lower dosed combined hormonal contraceptives, we now have formulations that – provided that ovulation is inhibited – result in lower peak levels of estrogen than the concentrations attained during the native menstrual cycle. These formulations would thus be expected to result in a lower frequency of migraine aura. Furthermore, as extended‐cycle therapy eliminates monthly estrogen withdrawals, this therapy would likewise be expected to prevent MRM. Methods.— This pilot study is an institutional review board‐approved retrospective database review. We queried our database of 830 women seen in a subspecialty menstrual migraine clinic to identify women who met all inclusion criteria: (1) current history of MwA; (2) confirmed diagnosis of MRM; and (3) treatment with extended‐cycle dosing of a transvaginal ring contraceptive containing 0.120 mg etonogestrel/15 µg ethinyl estradiol. Standardized calendars that specifically document bleeding patterns, headache details, and occurrence of aura are required of all patients in this clinic. Results.— Twenty‐eight women met study criteria, none of whom were smokers. Of these, 5 discontinued use of etonogestrel/ethinyl estradiol within the first month, leaving 23 evaluable subjects. At baseline, subjects averaged 3.23 migraine auras/month (range: 0.1‐12). With extended dosing of the vaginal ring contraceptive, median frequency was reduced to 0.23 auras per month following treatment after a mean observation of 7.8 months (P < .0005). No subject reported an increase in aura frequency. On this regimen, MRM was eliminated in 91.3% of the evaluable subjects. Conclusion.— In this sample of women with both MwA and MRM, use of an extended‐cycle vaginal ring contraceptive was associated with a reduced frequency of migraine aura and with resolution of MRM. This cannot be extrapolated to suggest that stroke risk in MwA will be similarly reduced. Studies to evaluate this relationship are warranted.     

The association between migraine and juvenile stroke: a case-control study

BACKGROUND: Several studies suggest an association between migraine and juvenile stroke. Because of some shortcomings, we designed another case-control study of a homogenous group of patients with juvenile cerebral ischemia. This study is part of a larger German epidemiological research project on the association of migraine with cerebrovascular disease. METHODS: We enrolled 160 consecutive patients under the age of 46 years with first-ever ischemic stroke or transient ischemic attack and 160 strictly sex- and age-matched controls. Patients suffering from arterial dissection, brain hemorrhage, cranial sinus thrombosis, lacunar stroke, or from migrainous infarction were excluded. Migraine was diagnosed according to the criteria of the International Headache Society by the same 2 independent interviewers. For analyzing the data, nonparametric statistical methods including odds ratio and 95% confidence interval were used. RESULTS: Migraine was a significant risk factor for juvenile stroke for the total sample with an odds ratio of 2.11 (confidence interval, 1.16 to 3.82). The odds ratio was even higher in the subgroup under the age of 35 (3.26) and in the female subgroup (2.68). We found migraine to be independent from other vascular risk factors, from etiology, and from the territory of stroke. CONCLUSION: We can confirm the findings of previous studies showing a significant association between migraine and juvenile stroke in women. Furthermore, our data suggest migraine to be an even more significant risk factor for patients under the age of 35 and to be independent from other vascular risk factors.     

A history of migraine is not a risk factor to develop an ischemic stroke in the elderly

OBJECTIVE: To assess the prevalence of migraine in elderly patients hospitalized with ischemic stroke compared with vascular and nonvascular control groups. BACKGROUND: Migraine is a disease with a presumed vascular mechanism. While migraine is a common complaint of young victims of ischemic stroke, it is unclear whether a current or past history of migraine constitutes a risk factor for developing an ischemic stroke in the elderly. METHODS: We obtained current and past headache history from 100 consecutive patients hospitalized with ischemic stroke (aged 60 years or older) and compared the results with 100 patients hospitalized due to acute myocardial infarction and 100 hospitalized patients with no vascular disease. RESULTS: The sex and the age of the patients did not differ among the groups. The lifetime prevalence of migraine (8% of the patients with ischemic stroke, 8% of the nonvascular controls, and 15% of the patients with acute myocardial infarction) or of all types of headaches (27%, 30%, and 15%, respectively), did not differ significantly between the groups. CONCLUSIONS: Based on the reported history, elderly migraineurs are not at increased risk to develop ischemic stroke.     

Chronic Helicobacter pylori infection and migraine: a case-control study

OBJECTIVE: To determine whether chronic Helicobacter pylori infection is a risk factor for migraine. BACKGROUND: Preliminary studies have shown a high prevalence of Helicobacter pylori infection in patients with primary headaches. METHODS: One hundred three consecutive patients with migraine were enrolled in the study and compared with a group of 103 matched controls. Helicobacter pylori infection was diagnosed by means of both (13)C-urea breath test and serology. RESULTS: Of patients with migraine, 30.1% were positive for Helicobacter pylori, compared with 31.1% of controls (P = NS). The odds ratio for migraine associated with chronic Helicobacter pylori infection was 0.96 (95% confidence interval, 0.51 to 1.80). Demographic, clinical, and psychological characteristics of Helicobacter pylori-positive migraineurs were compared with those of migrainous patients without infection. Helicobacter pylori-positive patients had a significantly (P<.05) lower incidence of food sensitivity than Helicobacter pylori-negative patients. No significant difference was found in any other feature examined. CONCLUSIONS: Our study suggests that chronic Helicobacter pylori infection is not more frequent in patients with migraine than in controls and that infection does not modify clinical features of the disease.     

Association between migraine and headache attributed to stroke: a case-control study

Background.— Several studies were carried out to investigate the occurrence of headache attributed to acute stroke in patients with a lifetime history of migraine. Methods.— In a case–control series of 96 acute stroke patients with a lifetime history of migraine (M+) and 96 stroke patients without (M?), ischemic stroke patients only, without secondary infarction, were selected. The headache attributed to acute ischemic stroke was then analyzed. Results.— (M+) patients complained of headache more often than (M?) patients (P < .0001), mainly in the 24 hours before stroke onset (P < .0001). Migraine‐like features of headache were recognized in a greater proportion of cases in the (M+) patient group with ischemic stroke (P < .018). A preferential brainstem location of ischemic stroke in (M+) patients emerged compared with (M?) patients (P = .014). Discussion.— The high prevalence of headache attributed to stroke in (M+) patients, in a relevant proportion of cases presenting as a sentinel headache, suggests that cerebral ischemia lowers the threshold for head pain more easily in these “susceptible” patients. The most frequent involvement of the brainstem in (M+) patients with ischemic infarction concurs with recent reports that emphasized a greater headache frequency when cerebral infarctions are localized in this structure or deep brain gray matter.     

缺血性脑卒中相关危险因素的病例对照研究

目的评价传统与新型相关危险因素与缺血性脑卒中发病风险的关系。方法采用病例对照研究方法,在华东地区选择401例缺血性脑卒中病例,其中脑血栓形成158例,腔梗243例。和442例正常对照组人群。用问卷调查和体检的方式对缺血性脑卒中相关因素进行收集和分析。结果单因素分析显示:BMI,脑血管病家族史,既往史中的TIA、高血压、糖尿病、冠心病、肾脏疾病,目前血压值(包括收缩压和舒张压),血常规中的白细胞数、中性粒细胞比例,生化指标中的血糖、TG、HDL-C值均提示能增加缺血性脑卒中的发病风险(P0.05)。Logistic回归分析显示:TIA史、高血压、糖尿病、冠心病等既往史能显著增加缺血性脑卒中的患病风险。结论缺血性脑卒中需要采取综合干预措施。新的危险因素不容忽视。影响疾病发生发展的其它危险因素尚需要进一步探讨。     

Genetic abnormalities of the protein C system: shared risk factors in young adults with migraine with aura and with ischemic stroke?

Migraine, particularly migraine with aura (MA), may be a risk factor for ischemic stroke (IS). The reasons for this association are unknown. We investigated the presence of genetic abnormalities of the protein C system in 83 MA patients, 31 IS patients, and 124 healthy controls, all aged under 45 years. We found an increased frequency of activated protein C resistance due to Arg5O6Gln factor V mutation, and of protein S deficiency in both disorders, with figures higher than those reported in the general population and significantly different from those found in controls. These prothrombotic genetic abnormalities may be shared risk factors in IS and MA, and may play a role in increasing the risk of cerebrovascular disease in migraineurs.     

Association between migraine and risk of venous thromboembolism: A nationwide cohort study

Background .—The link between arterial thromboembolism and migraine is well‐documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. Methods. —We conducted a cohort study accessing a nationwide claims‐based database with an adult cohort of 102,159 neurologist‐diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. Results .—During a mean follow‐up period of 4.2 years, VTE developed in 226 patients (460,047 person‐years) in the migraine cohort and in 203 subjects (462,401 person‐years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92–1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40–4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population

The clinical characteristics of migraine without aura (MO) and migraine with aura (MA) were compared in 484 migraineurs from the general population. We used the criteria of the International Headache Society. The lifetime prevalence of MO was 14.7% with a M:F ratio of 1:2.2; that of MA was 7.9% with a M:F ratio of 1:1.5. The female preponderance was significant in both MO and MA. The female preponderance was present in all age groups in MA, but was first apparent after menarche in MO, suggesting that female hormones are an initiating factor in MO, but not likely so in MA. The age at onset of MO followed a normal distribution, whereas the age at onset of MA was bimodally distributed, which could be explained by a composition of two normal distributions. The estimated separation between the two groups of MA was at age 26 years among the females and age 31 years among the males. The observed number of persons with co-occurrence of MO and MA was not significantly different from the expected number. The specificity and importance of premonitory symptoms are questioned, but prospective studies are needed. Bright light was a precipitating factor in MA, but not in MO. Menstruation was a precipitating factor in MO, but not likely in MA. Both MO and MA improved during pregnancy. The clinical differences indicate that MO and MA are distinct entities.     

Valsalva maneuver as migraine inducer: a case report of a woman with patent foramen ovale and an ischemic stroke

The association between patent foramen ovale, ischemic stroke, and migraine with aura is well known. It is, however, complicated and generates a considerable debate about the features and clinical consequences of the phenomenon. We report a case of a woman for whom patent foramen ovale has possibly acted as an inducer of both migraine attacks and ischemic stroke.     

Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized,double-blind,placebo-controlled study

Magnesium sulphate has been used in the acute treatment of migraines; some studies found it to be a highly effective medication in the acute control of migraine pain and associated symptoms. This randomized, double-blind, placebo-controlled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura. Sixty patients in each group were assigned at random to receive magnesium sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used seven parameters of analgesic evaluation and an analogue scale to assess nausea, photophobia and phonophobia. In the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and number needed to treat was 5.98 at 1 h. There was also no statistical difference in relief of nausea. We did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate. In the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo 1 h after the administration of medication. Our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura, or as an adjuvant therapy for associated symptoms in patients with migraine without aura.     

Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke

BACKGROUND: The role of inherited prothrombotic conditions, including factor V Leiden (FV G1691A), prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T genotype, in the pathogenesis of ischemic stroke is not well established. The effects of these factors may be potentiated by the use of oral contraceptives, analogous to observations in venous thrombosis. METHODS: Patients (n = 193) were women aged 20-49 years with ischemic stroke. Controls (n = 767) were women without arterial thrombosis stratified for age, calendar year of the index event, and residence. The relative risk of ischemic stroke was estimated with unconditional logistic regression, adjusted for stratification variables. FINDINGS: Factor V Leiden and MTHFR 677TT were more common in patients than in controls [odds ratio (OR): 1.8; 95% confidence interval (CI): 0.9-3.6 respectively OR: 1.5; 95% CI: 0.9-2.6]. The frequency of prothrombin G20210A was similar in cases and controls. Carriers of FV Leiden using oral contraceptives had a 11.2-fold (95% CI: 4.3-29.0) higher risk of ischemic stroke than women without either risk factor. Women with MTHFR 677TT using oral contraceptives had a 5.4-fold (95% CI: 2.4-12.0) higher risk than women without these risk factors. INTERPRETATION: These data suggest that carriers of FV Leiden or MTHFR 677TT who use oral contraceptives have an increased risk of ischemic stroke. When these findings are confirmed, a cost-effectiveness analysis should indicate whether ischemic stroke could be prevented with genetic testing before the start of oral contraceptives.     

Atopic dermatitis and risk of ischemic stroke: A nationwide population-based study

Abstract

Background. Epidemiological studies have shown a strong association between systemic inflammatory diseases, particularly allergic diseases, and cardiovascular diseases. However, the relationship between atopic dermatitis (AD) and ischemic stroke remains unclear.

Method. The study identified 20,323 AD patients and 20,323 comorbidity-matched subjects between 2005 and 2008. The two cohorts were followed until 31 December 2009. Ischemic stroke and other cardiovascular events were determined.

Results. During the follow-up period, 301 (1.48%) patients in the AD cohort and 228 (1.12%) matched subjects experienced ischemic stroke. After multivariate adjustment, patients with AD had a 1.33-fold (95% confidence interval (CI), 1.12–1.59; P = 0.001) increased incidence of ischemic stroke. Adjusted hazard ratios for the risk of ischemic stroke in patients with mild, moderate, and severe AD were 1.20 (95% CI, 1.00–1.45; P = 0.052), 1.64 (95% CI, 1.23–2.19; P = 0.001), and 1.71 (95% CI, 1.15–2.56; P = 0.008), respectively. The log-rank test showed a higher cumulative incidence of ischemic stroke in the severe AD group than in the moderate and mild AD groups during the follow-up period (P < 0.001).

Conclusions. AD may be an independent risk factor for ischemic stroke, and risk of ischemic stroke increases with AD severity.     

Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study

We report a small open pilot study to evaluate the efficacy of lamotrigine (100 mg/day) in the prevention of migraine with aura attacks. We studied 24 patients affected by migraine with aura with a high frequency of attacks. Following a 1-month run-in period, the patients took lamotrigine for 3 months. Mean attack number per month was reduced from 6.1 +/- 4.1 during the run-in period to 0.7 +/- 1.3 at the 3rd month of treatment (p < 0.0001). In 13 out of 21 patients who completed the study, the attacks were completely abolished at the 3rd month of treatment, while only one patient was completely unresponsive to the drug. Lamotrigine seems worthy of a controlled trial as prophylaxis of a migraine with aura.     

Lifetime prevalence of migraine and other headaches lasting 4 or more hours: the Atherosclerosis Risk in Communities (ARIC) study

OBJECTIVES: To evaluate the lifetime prevalence of migraine and other headaches lasting 4 or more hours in a population-based study of older adults. BACKGROUND: Migraine and other headaches not fulfilling migraine criteria are common afflictions. Yet the health and social effects of these conditions have not been fully appreciated, particularly among older adults. METHODS: The study included 12 750 participants in the Atherosclerosis Risk in Communities (ARIC) Study from 4 US communities. Prevalence estimates of a lifetime history of migraine and other headaches lasting 4 or more hours were obtained for race and gender groups. A cross-sectional analysis was done to assess the relationship between headache type, by aura status, and various sociodemographic and health-related indices. RESULTS: Compared to education beyond high school, having completed less than 12 years of education was significantly associated with an increased occurrence of migraine with aura (prevalence odds ratio [POR], 1.47; 95% confidence interval [CI], 1.08 to 2.01). Family income less than $16 000, compared to family income of $75 000 or greater, was significantly associated with migraine with aura (POR, 1.68; 95% CI, 1.07 to 2.64), migraine without aura (POR, 1.56; 95% CI, 1.14 to 2.14), and other headaches with aura (POR, 1.89; 95% CI, 1.14 to 3.13). The prevalence odds ratio was higher in each headache category, particularly for those with an aura, for those with hypertension versus normotension and for those who perceived their general health as poor compared to those whose perception was excellent. CONCLUSIONS: A lifetime history of migraine with aura and other headaches with aura was more common among whites, women, and younger participants. Further investigation of headaches lasting 4 or more hours, particularly by aura status, is warranted.