Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women.

Importance: Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear. Objective: To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors. Design, Setting, and Participants: Female health professionals in the US (the Women's Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018. Exposures: Self-reported migraine with aura compared with migraine without aura or no migraine at baseline. Main Outcomes and Measures: The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort. Results: The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes. Conclusions and Relevance: In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.

Migraine without Aura and Subclinical Atherosclerosis in Young Females: Is Gut Microbiota to Blame?

Background and Objectives: Migraine with aura (MA) could be considered a risk factor for developing atherosclerosis and cardio-vascular events. However, less is known about the relation between migraine without aura (MWA) and atherosclerosis. Our study aimed to assess whether young female migraineurs, with alterations of gut microbiota could associate early atherosclerosis. Materials and Methods: We conducted an exploratory cross-sectional, pilot study concerning 105 consecutive young females having MWA, with recent normal brain scans, that were free of cardio-vascular risk factors, non-smokers, not on oral contraception, not pregnant, and without thyroid or parathyroid diseases, chronic organ failure, cancer, or on probiotic or antibiotic treatment. Consecutive to assessment of gut microbiota, patients were assigned to two groups: dysbiosis positive (n = 45) and dysbiosis negative (n = 60). All study participants underwent clinical examinations with an assessment of migraine severity, body mass index and carotid intima-media thickness (CIMT), as well as laboratory workups. Statistical analysis was performed using a chi-squared test (χ2), a two-tailed t-test and a nonparametric Spearman's correlation test. Results: The dysbiosis positive migraineurs showed a significant increase in CIMT along with several anthropometrical, biological and clinical particularities. Significant positive correlations between dysbiosis and CIMT, glycosylated hemoglobin, migraine severity and duration, tumor necrosis factor-alpha, and body mass index were found. Conclusions: Young female migraineurs with significant alterations of gut microbiota experienced early signs of atherosclerosis and displayed severe migraine disability, as well as multiple biological and clinical particularities.

Evaluation of the effect of topical chamomile (Matricaria chamomilla L.) oleogel as pain relief in migraine without aura: a randomized, double-blind, placebo-controlled, crossover study.

Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48 ± 0.01 µl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p < 0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.

Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital.

INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes.

Insulin resistance in migraineurs: results from a case-control study.

OBJECTIVES: Several studies have suggested an association between migraine and insulin resistance (IR) without adequately addressing the issue according to migraine type. We assessed IR in subjects with migraine with aura (MwA) and migraine without aura (MwoA) to estimate the consistency of the possible association. METHODS: In a case-control study we included case subjects with MwA and MwoA, who were consecutively selected from those referred to our Regional Headache Center from September 2011 to February 2013, and age-matched control subjects selected using general practitioners' databases. IR was calculated by means of the homeostatic model assessment of IR (HOMA-IR), ß-cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) measuring glucose and insulin values in a blood sample collected in the morning after overnight fasting. Data regarding anthropometric measures, comorbidity risk factors, and migraine characteristics were also recorded. RESULTS: We recruited 50 case subjects with MwA (38 women) and 50 with MwoA (40 women) and 50 control subjects (40 women). Proportions of arterial hypertension, cigarette smoking, hypercholesterolemia, use of oral contraceptives, and mean values of the body mass index (BMI) were similar in the three groups. We found significantly different glucose values among and within groups considering case subjects with MwA and MwoA and control subjects (4.9 ± 0.6 vs 4.7 ± 0.5 vs 4.6 ± 0.5 mmol/l; P = 0.018) in the absence of any difference in insulin (53.1 ± 24.0 vs 56.7 ± 34.4 vs 53.8 ± 24.4 pmol/l; P = 0.811), HOMA-IR (1.6 ± 0.8 vs 1.7 ± 1.0 vs 1.6 ± 0.7; P = 0.765), HOMA-B (121.4 ± 71.1 vs 149.2 ± 93.8 vs 162.8 ± 109.7; P = 0.107), and QUICKI (0.36 ± 0.03 vs 0.37 ± 0.03 vs 0.37 ± 0.03; P = 0.877) values. The logistic regression model showed increased odds of MwA in subjects exposed to the highest tertile of glucose values. This association was confirmed in the adjusted model, in which case subjects with MwA were compared with those with MwoA but not with control subjects. CONCLUSIONS: In contrast to what has been shown by the majority of the available studies, the results of our study do not support the association of migraine with IR. As our study was not population-based and several patients had low disease activity, these findings need further confirmation.

Cerebral MRI and EEG studies in the initial management of pediatric headaches.

BACKGROUND AND STUDY PURPOSE: High resolution imaging modalities and electroencephalographic studies (EEG) are used in the assessment of children with headaches. We evaluated the role of cerebral MRI (cMRI) and EEG in the initial assessment of children with headache as the chief complaint of initial presentation. METHODS: A retrospective chart analysis was performed at a tertiary University Hospital. RESULTS: 209 patients were included in this study [mean age 11.3 years; male 91 (43.5%); female 118 (56.5%)]. The following types of headaches were seen: Unclassified headache: 23.4%; probable migraine 17.2%, migraine without aura 13.4%, complicated migraine 12.4%, migraine with aura 1.0%; tension-type 15.3%, and cluster headaches 0.5%, and secondary headaches 16.7%. In 93 children (44.5%) abnormal physical/neurological findings were noted (multiple entries possible). On cMRI studies the following findings were seen: Infection of sinuses (7.2%), pineal cysts (2.4%), arachnoidial cyst and Chiari malformation (1.9%), unspecified signal enhancement (1.0%), and pituitary enlargement, inflammatory lesion, angioma, cerebral ischaemia, and intra-cerebral cyst (each 0.5%). Electroencephalographic findings included both focal and generalised abnormal slowing (5.3%) and Spike-wave complexes (3.3%). CONCLUSIONS: Despite abnormal findings on neurological/physical examination in a substantial number of children with headaches, the yield of pathological cMRIs was low. The use of EEG recordings was not contributory to the diagnostic and therapeutic approach. More research is needed to better define those patients who are likely to have an intracranial pathology.

[Worsening of migraine symptoms due to giant pineal cyst apoplexy]. / Agravamiento de un cuadro migrañoso por apoplejía de un quiste pineal gigante.

INTRODUCTION: Although the association between headaches and pineal gland cysts has been suggested on a number of occasions, no precise evidence of exactly what this relation involves has been produced to date. It is known, however, that a cyst in the pineal gland can bring on or worsen headaches, especially if it is large or there has been bleeding, due to obstructive compromise in the third ventricle and the resulting hydrocephalus that is produced. CASE REPORT: A 15 years-old male who had suffered from migraine from the age of 6 years and who suddenly experienced a worsening of his headaches, both as regards their frequency and their intensity, over the previous days; no known precipitating factor appeared to be involved. Magnetic resonance imaging of the brain revealed the presence of a giant cyst in the pineal gland, with a notable amount of blood inside it, which was producing an obstructive hydrocephalus. The decision was made to resort to surgical treatment, with resection of the cyst and placement of a shunt valve. As a result the patient's headaches improved greatly and this improvement continued throughout a six-month follow-up. CONCLUSIONS: Worsening of a headache, in this case migraine, for no apparent cause must make us consider secondary processes, although they may be as rare as the one described here.

Evolução clínica da enxaqueca após oclusão percutânea de forame oval patente / Clinical evolution of migraine after transcatheter patent oval foramen closure

Introdução: A enxaqueca atinge aproximadamente 18% das mulheres e 6% dos homens. Cerca de 50% dos pacientes com enxaqueca com aura (MA+) e 30% dos sem aura (MA-) são portadores de forame oval patente (FOP), incidência maior que na população geral. Este estudo teve como objetivo avaliar a evolução clínica de pacientes com MA+ e MA- submetidos a oclusão percutânea. Método: Foram incluídos pacientes portadores de enxaqueca crônica refratária a tratamento clínico encaminhados ao Laboratório de Hemodinâmica do Hospital Ecoville, entre agosto de 2006 e maio de 2007, para oclusão do FOP. A cefaléia foi caracterizada clinicamente quanto a intensidade, freqüência, duração e presença de aura, bem como foram avaliados os fatores de co-morbidade. A avaliação complementar foi realizada por meio de ressonância magnética de crânio (RMC), ecocardiografia Doppler transesofágica (ETE) e Doppler transcraniano (DTC), os dois últimos métodos com injeção de microbolhas e manobra de Valsalva. Foram, então, realizados cateterismo cardíaco e oclusão do FOP com prótese. Os pacientes foram acompanhados com reavaliação dos mesmos critérios pré-operatórios. Resultados: No total, foram avaliados sete pacientes (seis do sexo feminino), entre 18 e 65 anos de idade, cinco deles portadores de MA+ (enxaqueca clássica) e outros dois portadores de MA-. Em quatro pacientes foram observadas crises moderadas e em três, crises graves. Todos, exceto um, apresentavam alterações isquêmicas à RMC, quatro apresentavam associação com depressão e um, com doença de Behçet. Todos tinham resultados de ETE e DTC positivos, que foram negativados até três meses após a oclusão. Apenas um paciente não apresentou melhora após o tratamento. Conclusão: Apesar do número ainda pequeno de pacientes, a oclusão percutânea do FOP com prótese parece ser método promissor para o tratamento complementar da enxaqueca.

Background: Migraine is present in 18% of women and 6% of men. 50% of the patients that suffer migraine with aura (MA+) and 30% that suffer migraine without aura (MA-) have Patent Oval Foramen (POF), a larger incidence compared to the general population. This study aimed to evaluate clinical evolution of patients MA+ and MA- that underwent POF closure. Method: The inclusion criterion was patients with chronic migraine without pharmacological therapy response that underwent POF closure between August 2006 and May 2007. Migraine severity was classified by its intensity, frequency, duration and presence of aura, and presence of associated diseases. Further investigation was done by cranial magnetic resonance (CMR), transesophageal echocardiography (TEE) and transcranial doppler (TCD), the last two done with microbubble-enhanced contrast and Valsalva maneuver. After percutaneous treatment, patients were followed-up with the same criteria as before closure. Results: Of the seven patients who underwent POF closure, six were female. Ages ranged between 18 and 65 years of age. Five patients were MA+ and two were MA-. The migraine severity was classified as severe in four cases and moderated in three. All, except one patient, had CMR ischaemic abnormalities. Four patients also had depression and one had Behçet disease. All of them had positive TEE and TCD investigation, that turned out to be negative at the follow-up, three months later. Just one patient did not improve migraine crisis after POF closure. Conclusions: In spite of the low sample number, POF closure seems to be a good adjunct treatment of migraine.

Fibromuscular dysplasia with carotid artery dissection presenting as an isolated hemianopsia.

BACKGROUND: Internal carotid artery (ICA) dissection is a well-known cause of anterior circulation stroke, but its association with posterior circulation stroke has been less commonly reported. The latter situation can arise when there is persistent fetal circulation of the posterior cerebral artery and has, to our knowledge, never been reported in the setting of fibromuscular dysplasia (FMD) involving the ICA. METHODS: A 52-year-old man awoke with severe headache and noted visual loss. Examination confirmed a congruous left homonymous hemianopsia. A head computed tomography scan revealed an acute right posterior parietal infarct. Carotid ultrasonography demonstrated complete occlusion of the right ICA. Conventional angiography confirmed this and was diagnostic of FMD with dissection. A right-sided persistent fetal circulation was also noted. Magnetic resonance imaging revealed right parietal and right occipital infarctions. RESULTS: The patient received ASA and clopidogrel and his visual deficit resolved within days. One year later, he remained asymptomatic and there was no suggestion of FMD in other vascular beds. CONCLUSIONS: Although infrequently reported, carotid disease, including dissection, can be responsible for posterior circulation infarcts. Cervical artery dissection can be related to underlying arteriopathies such as FMD, which must be differentiated from vasculitis and vasospasm.

Migraine, botulinum toxin type-A, and the disappearing sebaceous cyst.

Botulinum toxin type-A has been used with increasing frequency as a migraine prophylactic agent. A recent case of ours had an unexpected beneficial effect on a local comorbid condition.

Reversible, strokelike migraine attacks in patients with previous radiation therapy.

We report 2 adults with a past history of radiation therapy to the head for malignancy (one with primary B-cell lymphoma confined to the skull and the other with multiple hemangioendotheliomas) who developed episodes consistent with migraine with and without aura. In addition to more typical migraine attacks and beginning many years after their radiation therapy, both patients have experienced infrequent, stereotyped, prolonged, reversible neurologic deficits associated with headache, occasional seizures, and striking, transient, cortical gadolinium enhancement of the posterior cerebral gyri on MRI. Interictal MRI brain scans show stable abnormalities consistent with the patients' previous radiation therapy. The neurologic deficits often progressed over a few days, sometimes lasted weeks, and completely resolved. Electroencephalograms did not show epileptiform activity. Thorough investigation showed no residual or recurrent tumor and no recognized cause for the patients' attacks. We postulate a causal relationship between the patients' remote radiation therapy and their prolonged, strokelike migraine attacks. Radiation-induced vascular changes could provoke the episodes, with or without an underlying migraine diathesis. Recognition of this syndrome can help avoid invasive testing.

Chiari-associated exertional, cough, and sneeze headache responsive to medical therapy.

Benign exertional headache is coded as a separate entity within the International Headache Society's classification system, but the pathophysiological mechanisms underlying this clinical headache subtype are unknown and possibly are similar to those generating migraine. Coexistence of migraine and benign exertional headache in the same patient is not unusual, and antimigraine pharmacologic treatments are often effective in both headache types. Regardless, optimal management mandates that the clinician exclude any intracranial or systemic disease that could mimic "primary" exertional headache. The same holds for primary headaches induced by coughing or sneezing; congenital malformations or neoplasms, particularly within the posterior fossa, are not rare in these patients. The neurologic examination may not be sufficiently sensitive to detect the offending lesion. We describe a patient with migraine without aura and exertional secondary headache due to Chiari malformation type I whose headaches responded to treatment with propranolol and indomethacin.

Migraine and arterial dissection in a young woman.

Ischemic stroke in young adults is rare (5%-10% of all ischemic strokes) and, in absence of other risk factors, may be associated with migraine. We describe the case of a 34-year-old woman, with a history of migraine without aura, who presented a sudden onset of headache with Horner's syndrome, and in whom neuroimaging showed evidence compatible with fibromuscular dysplasia (FMD) and arterial dissection of the extracranial internal carotid artery (ICA) and the carotid siphon. In our opinion, in young women with a long history of migraine, a careful study of the extracranial and intracranial arteries would be useful, although the cost/benefit ratio does not at present justify such a procedure. Our aim in the future is, therefore, to study a larger sample of migraine patients in order to find those patients who are most at risk of arterial dissection and who should, consequently, be carefully studied.

Diagnóstico diferencial del dolor orofacial II. Asociado a desórdenes neurovasculares, vasculares y musculoesqueléticos / Differential diagnosis of orofacial pain II. Associated with neurovascular, vascular and musculoskeletal disorders

Este es el segundo de tres artículos que tienen como propósito presentar una revisión de la literatura de las condiciones que se han considerado para el establecimiento del diagnóstico diferencial del dolor orofacial. Los desórdenes neurovasculares (migrañas, cefaleas tipo cluster, paroxismo hemicraneano), vasculares (arteritis temporal, carotidinia) y musculoesqueléticos (cefaleas de tipo tensional, desórdenes temporomandibulares, dolor miofascial, fibromialgia, desórdenes espinocervicales) serán revisados