Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study.

BACKGROUND: Previous studies showed that the perimenstrual window is associated with an increased susceptibility to migraine attacks without aura, but had conflicting results regarding attacks with aura. METHODS: We performed a longitudinal E-diary study among 526 premenopausal women with migraine. Differences in occurrence of perimenstrual migraine attacks between women with migraine with aura and without aura were assessed using a mixed effects logistic regression model. Additionally, participants completed a questionnaire about the influence of hormonal milestones on migraine frequency. RESULTS: Prevalence of menstrual migraine did not differ between women with migraine without aura and migraine with aura (59% versus 53%, p = 0.176). The increased risk of migraine attacks without aura during the perimenstrual window was similar for women with migraine without aura (OR[95%CI]:1.53 [1.44-1.62]) and those with migraine with aura (1.53 [1.44-1.62]). The perimenstrual window was not associated with increased risk of migraine aura attacks (1.08 [0.93-1.26], p = 0.314). Women with migraine with aura more often reported increased migraine frequency during pregnancy and breastfeeding compared to women with migraine without aura, but not during hormonal contraception use. CONCLUSION: Sex hormone levels seem to differently affect the trigeminovascular system (migraine headache) and the susceptibility to cortical spreading depolarization (aura). Exclusively migraine attacks without aura should be interpreted as perimenstrual attacks.

Manual acupuncture as prophylaxis for migraine without aura: study protocol for a multi-center, randomized, single-blinded trial.

BACKGROUND: Migraine is a highly prevalent neurological disorder. It is the third most prevalent disorder and the seventh highest cause of disability worldwide. Acupuncture may be a viable prophylactic treatment option for frequent or uncontrolled migraine. Clinical studies comparing acupuncture and placebo acupuncture have not reached a consistent conclusion in confirming whether acupuncture is effective in migraine prophylaxis. The effect of acupuncture mainly depends on acupoints and needles operation. We found that the design of the placebo acupuncture in previous studies included shallow needling at sham acupoints, non-penetrating needling at sham acupoints, and needling at inactive acupuncture points to achieve the inert effect of control group, but the non-penetrating needling at true acupoints was ignored. This randomized controlled trial aims to use true acupoints for non-penetrating acupuncture as control to evaluate the efficacy of manual acupuncture for the prophylaxis of migraine without aura (MWoA). METHODS/DESIGN: This is a single-blinded, randomized, controlled, prospective, multi-center trial with two parallel treatment groups. A total of 198 eligible patients with MWoA will be randomly divided into two groups (1:1 allocation ratio). The intervention group will receive manual acupuncture and the control group will receive placebo acupuncture (non-penetrating). Patients will receive three acupuncture treatment sessions per week for 4 consecutive weeks. All patients will then receive a 12-week follow-up. DISCUSSION: In this study, we are evaluating the efficacy and safety of manual acupuncture in the prophylaxis of MWoA. The placebo control is using non-penetrating needling verum acupoints. It is essential to determine an appropriate control method to ensure the methodological quality of a randomized controlled trial. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (approval no. ChiCTR2000032308 ) in April 2020.

Primary Empty Sella.

Primary empty sella (PES) syndrome is a misnomer as it is not a syndrome but a radiological finding with possible endocrine abnormalities. No specific headache type has been shown to be caused by PES. Endocrine screening may be considered for asymptomatic persons with PES.

Allodynia in Menstrually Related Migraine: Score Assessment by Allodynia Symptom Checklist (ASC-12).

OBJECTIVE: The aim of this study was to compare the allodynia score in headache attacks related and not related to menstruation in women diagnosed with menstrually related migraine without aura. BACKGROUND: Allodynia is an important symptom in migraine and has been associated with migraine chronification. No study has yet compared prospectively allodynia in menstrual vs non-menstrual attacks within the same cohort of patients. METHODS: This is a prospective cohort study, where participants had the 12-item Allodynia Symptom Checklist (ASC-12) assessed after 1, 2, 4, and 24 hours from the onset of migraine attacks in 2 different conditions, with menstrual migraine attack (MM+) and with non-menstrual migraine attack (MM-). RESULTS: A total of 600 women with headache complaints were screened from March 2013 to July 2014 in a headache outpatient or headache tertiary clinic. From these, 55 participants were recruited, and 32 completed the study. Participants' mean age was 27 years, BMI was 22.1, menarche age 12 years, migraine history was 11.5 years, and most women were young (ranged from 17 to 44 years of age), were in higher school (13/32 = 41%), single (20/32 = 63%), and used contraceptives (22/32 = 69%). Multiple pairwise comparisons of ANCOVA's test showed significant higher ASC-12 scores in MM+ group compared to MM- group at 2 hours [mean, 95% CI of difference: 2.3 (0.31, 4.7), P = .049)]. For the ASC-12 categorical scores (absent, mild, moderate, and severe) MM+ yielded higher scores than MM- at 1 hour (z = -3.08, P = .021) and 4 hours (z = -2.97, P = .03). CONCLUSION: This study demonstrated that in the patents from tertiary headache center assessed, menstrual-related migraine attacks augment allodynia scores in the beginning of attacks compared to non-menstrual migraine attacks.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Headache Outcomes After Treatment of Unruptured Intracranial Aneurysm: A Systematic Review and Meta-Analysis.

Background and Purpose- While unruptured intracranial aneurysms may be discovered incidentally in the workup of chronic headache, it remains unclear whether their treatment ultimately impacts headache severity. We aim to conduct a systematic review and meta-analysis assessing headache severity after treatment of unruptured intracranial aneurysm. Methods- MEDLINE and EMBASE were systematically reviewed. Results- Data from 7 studies met inclusion criteria (309 nonduplicated patients). The standard mean difference in pre- and post-intervention headache severity was estimated at -0.448 (95% CI, -0.566 to -0.329) under a random effects model. No significant heterogeneity was noted nor was any significant publication bias demonstrated. Conclusions- This is the first systematic review assessing postoperative headache severity following treatment of unruptured intracranial aneurysm. While a significant reduction in headache severity was observed, further investigation into this phenomenon is recommended before it influences clinical practice. Future study should stratify headache outcomes by aneurysm size, location, and treatment modality.

Association between migraine frequency and neural response to emotional faces: An fMRI study.

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Temporal-occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura.

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder characterized by an erroneous perception of the body or the surrounding space. AIWS may be caused by different pathologies, ranging from infections to migraine. We present the case of a 54-year-old man, with a long-time history of migraine without aura, diagnosed with AIWS due to a glioblastoma located in the left temporal-occipital junction. To date, this is the first case of AIWS caused by glioblastoma. This case suggests that to exclude aura-mimic phenomena, a careful diagnostic workup should always be performed even in patients with a long-time history of migraine.

Migraine and percutaneous patent foramen ovale closure: a systematic review and meta-analysis.

BACKGROUND: The association between patent foramen ovale (PFO) and migraine with aura (MA) is well established. However, the benefits of PFO closure are less certain in patients with migraine without aura (MwoA). METHODS: We systematically searched Pubmed for pertinent clinical studies published from January 2000 to July 2015. The primary end-point was the elimination or significant improvement of migraine symptoms after PFO closure. RESULTS: Upon screening an initial list of 315 publications, we identified eight studies that included 546 patients. Overall, our analysis indicated a significant improvement of migraine in 81% of MA cases compared to only 63% of MwoA cases. The summary odds ratio was 2.5 (95% confidence interval 1.09-5.73), and the benefits of PFO closure were significantly greater for patients with MA compared to patients with MwoA (P = 0.03). CONCLUSIONS: The presence of aura provides a reference standard for the clinical selection of patients with migraine for PFO closure intervention.

Clinical characteristics of menstrually related and non-menstrual migraine.

Migraine attacks increase during the perimenstrual period in approximately half of female migraineurs. There are differences in the pathogenesis and clinical features of menstrually related and non-menstrual migraine attacks. The objective of this study was to compare the characteristics of migraine in patients with menstrually related and non-menstrual migraine, and to investigate the differences between premenstrual, menstrual, and late-menstrual migraine attacks. Three-hundred and thirty-two women with migraine without aura were evaluated using questionnaires and diaries to determine the characteristics of headache, preceding and accompanying symptoms, and the relation of migraine attacks and menstruation. One-hundred and sixty-three women had menstrually related migraine without aura (49.1%). Duration of disease and duration of headache were longer (p = 0.002 and p < 0.001, respectively), and nausea, vomiting, phonophobia, and aggravation of headache with physical activity were more frequent in patients with menstrually related migraine (p = 0.005, p = 0.006, p < 0.001 and p = 0.006, respectively). Premonitory symptoms and allodynia were observed more frequently in the menstrually related migraine group (p = 0.012 and p = 0.004, respectively). Perimenstrual migraine attacks occurred premenstrually (days -2 and -1) in 46 patients (25.3%), menstrually (days 1 to 3) in 90 patients (49.4%), and late menstrually (days 4 to 7) in 19 patients (10.4%). Our results showed that the duration of headache was longer and accompanying symptoms were more frequent and diverse in patients with menstrually related migraine without aura, suggesting that these findings may reflect the increase in excitability or susceptibility of the brain in these patients.

A meta-analysis of case-control studies of the association of migraine and patent foramen ovale.

OBJECTIVES: To establish quantitative evidence, we performed the first meta-analysis of case-control studies assessing the relationship between migraine and patent foramen ovale (PFO). METHODS: MEDLINE and EMBASE were searched through April 2015 using PubMed and OVID. Eligible studies were case-control studies reporting PFO (or migraine) prevalence in migraine patients versus no-migraine subjects (or PFO patients versus no-PFO subjects). RESULTS: Of 395 potentially relevant articles screened initially, 21 eligible studies enrolling a total of 5572 participants were identified and included. Pooled analyses demonstrated statistically significant 3.36-fold migraine-with-aura [odds ratio (OR), 3.36; 95% confidence interval (CI), 2.04-5.55; p<0.00001] and 2.46-fold migraine-with/without-aura prevalence (OR, 2.46; 95% CI, 1.55-3.91; p=0.0001) but statistically non-significant 1.30-fold migraine-without-aura prevalence (OR, 1.30; 95% CI, 0.85-1.99; p=0.22) in PFO patients relative to no-PFO subjects. CONCLUSIONS: PFO is associated with 3.4-fold migraine-with-aura and 2.5-fold migraine-with/without-aura prevalence but unassociated with migraine-without-aura prevalence.

Menstrual migraine: an updated review on hormonal causes, prophylaxis and treatment.

INTRODUCTION: In this article, we will discuss pure menstrual migraine without aura (PMM) and menstrually related migraine without aura (MRM). Depending on the frequency and severity of their attacks, patients with PMM will likely need an acute treatment and/or short-term preventive plan. Of note, with the use of acute treatments and short-term preventive therapy there is risk of medication overuse if the patient does have pure menstrual migraine and is being treated for menstrually related migraine. AREAS COVERED: A PubMed, Cochrane Central, Medline, Ovid search provided articles relating to menstrual migraine pathophysiology and treatment. EXPERT OPINION: Long-term daily preventive treatment should be considered for patients with MRM and those with severe PMM. Miniprophylaxis can be used in PMM rather than daily preventive treatment. When considering the use of short-term miniprophylaxis, sumatriptan, zolmitriptan, naratriptan, and frovatriptan have shown efficacy; however, frovatriptan appears to be the triptan of choice based on overall efficacy. Oral contraceptives may be considered if patients do not respond to or cannot tolerate typical migraine preventive medications. In patients with migraine with aura, oral contraceptives should be used with caution as this may add to the risk of stroke in this population.

Nutraceuticals safety and efficacy in migraine without aura in a population of children affected by neurofibromatosis type I.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders with a prevalence of one in 4,000 people worldwide, associated with many neurological comorbidities, such as headache. Despite the high prevalence of headache in this population, little data exist regarding the classification of headaches experienced by patients with NF1. Aim of this study is to verify the efficacy and safety of a nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for prophylaxis in a sample of children affected by NF1 presenting migraine without aura. Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex was orally administered twice a day for 6 months, to 18 school-aged patients with NF1 and presenting symptoms of migraine without aura (10 M, mean age 8.4 ± 1.65). Each patient kept a journal to record: number, intensity (according VAS scale), duration of attacks and concomitant symptoms. In addition, the PedMIDAS scale was administered to assess migraine-related disability. To verify the efficacy of the association, we tested the starting frequency (T0) of headache after 6 months (T1) and then we calculated the migraine frequency delta percentage to express the decrease in monthly frequency. After treatment, a reduction was reported (p < 0.001) in all migraine outcomes (frequency, duration, intensity, and grade of disability). In conclusion, the present study should be considered as the first report on the efficacy and safety of nutraceutical complex containing Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium for the prophylaxis of migraine in children affected by NF1. Our findings suggest that headache symptoms should be considered a therapeutic target independent of primary disorder.

Perceived migraine triggers: do dietary factors play a role?

The present cross-sectional study was designed to assess the frequency of 36 possible triggering factors precipitating a migraine crisis (hormonal, environmental, and dietary) in adult outpatients suffering from migraine attacks. A group of 123 migraine sufferers, aged 43.2 ± 13.9 (mean ± SD) years, including 114 (92.7%) women, 68.3% having migraine without aura, 68.3% reporting pain severe enough to require drug prophylaxis, and 29.3% presenting with hypertension, were evaluated. The most common triggers were stress and fasting, and environmental and hormonal factors were frequently found to precipitate a crisis. More than 90% of the patients reported susceptibility to 5 or more factors, and only 2.4% did not complain about any dietary factor. The large number of triggers detected in the present study emphasises the importance of awareness and avoidance of these factors in the management of patients with migraine.

Características clínicas de los pacientes con migraña del Servicio de Neurología de la Clínica Internacional / Clinical characteristics of patients with migraine at the Servicio de Neurologia at the Clinica Internacional

Objetivo: Identificar las características demográficas y clínicas de pacientes con migraña de la Clínica Internacional (CI). Sujetos y métodos: Se evaluaron pacientes con migraña que acudieron al consultorio externo de neurología de la CI. Resultados: Fueron diagnosticados con migraña 64 pacientes. El 78.12% fueron mujeres, con 32.62 años de edad promedio. Reportaron grado de instrucción superior 35 pacientes (54.69%), secundaria 26 (40.63%) y primaria 3 (4.69%). Reportaron crisis mensuales 14 pacientes (21.88%), semanales 40 (62.50%) y variables 10 (15.62%). La hora más frecuente de presentación fueron las tardes en 11 pacientes (17.18%), mañanas 10(15.62%), noches 9 (14.06%) y variable 34 (53.12%). Las crisis duraron 2 horas en 32 (50.00%), 1 día en 11 (17.18%), >1 día en 11 (17.18%) y variables en 7(10.94%). Tuvieron dolor tipo opresivo 23 pacientes (35.94%), pulsatil 33 (51.56%), punzada 39 (60.94%), quemazón 17(26.56%) y variables 2 (3.13%). Alteraron sus actividades por crisis 45 pacientes (70.31%), continuaron sus actividades 16 (25.00%) y variables 4 (6.25%). El 92.19% tuvieron antecedente familiar de migraña. El factor precipitante de migraña más frecuente fue el ruido en 82.81% de pacientes, el factor aliviador más frecuente fue el sueño en 75.00%. Conclusiones: La mayoría de pacientes fueron mujeres, con crisis semanales, de presentación variable, con antecedentes familiares de migraña, alterando sus actividades habituales.

Objective: Identify demographic and clinical characteristics of patients with migraine of International Clinic (CI). Subjects and methods: we evaluated the Migraine patients who attended the outpatient clinic of neurology at the CI. Results: Migraine was diagnosed in 64 patients. The 78.12% were women, average age 32.62 years. Reported Higher educational attainment 35 patients (54.69%), secondary 26 (40.63%) and primary 3 (4.69%). Reported monthly crisis 14 patients (21.88%), weekly 40 (62.50%) and variable 10 (15.62%). The time of presentation were more frequent in evenings in 11 patients (17.18%), morning 10 (15.62%), nights 9 (14.06%) and variable in 34 (53.12%). The crisis lasted 2 hours in 32 (50.00%), 1 day in 11 (17.18%), >1 day in 11 (17.18%) and variables in 7(10.94%). The type of pain was squeezing in 23 patients (35.94%), pulsatile 33 (51.56%), stitch 39 (60.94%), burning 17 (26.56%) and variable 2 (3.13%). The pain altered their activities in 45 patients (70.31%), continued their activities 16 (25.00%) and variables 4 (6.25%). The 92.19% had family history of migraine. The most frequent precipitating factor of migraine was noise in 82.81% of patients; the most common soothing factor was sleep at 75.00%. Conclusions: Most patients were women, with weekly crisis, variable presentation, family history of migraine, altering their normal activities.

Almotriptan for menstrually related migraine.

INTRODUCTION: Approximately 50% of migrainous women associate their headache temporally to menses. Menstrually related migraine (MRM) is a disabling form of migraine characterized by attacks that are generally longer, more severe and less drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it is important to find an appropriate treatment option for women suffering from this condition. AREAS COVERED: This paper provides an overview of the clinical features of MRM, with special attention on the use of almotriptan for its treatment. Four studies on almotriptan in the treatment of MRM are present in the medical literature. Two report post hoc analyses of data derived from larger studies on the use of almotriptan for migraine treatment. One reports the results from a study specifically dedicated to MRM and one illustrates a subanalysis on the accompanying symptomatology. EXPERT OPINION: Evidence demonstrates that almotriptan is a molecule with a high efficacy in the treatment of MRM and with an excellent tolerability profile when compared with other triptans. Moreover, it shows a proven ability to control migraine-associated symptoms. All these qualities play a decidedly positive role in making almotriptan a product of choice for the treatment of MRM.