Association between risk factors and migraine in Pakistani females.

BACKGROUND: Migraine is a typical cripple issue of the brain identified with cerebral pain which is an indication of numerous health conditions. About 18% of women (27 million) and 6% of men (10 million) are afflicted by migraine in the United States. Based on a case-control study, to explore the different risk factors, causing migraine in females and examine the association between risk factors and migraine. METHODS: A sample of 1055 individuals were selected in different areas of Lahore from September 2019 to March 2020. The information was obtained by using the direct interview method and questionnaire method. Descriptive analysis, bivariate analysis and binary logistic regression analysis were carried out in data analysis. RESULTS: Among 1055 individuals 740 cases and 315 controls were included. In a binary logistic regression model, physical activities, stress, summer season, menstruation and morning were the risk factors that cause migraine and these were found to be positively significant with the odds ratios and 95% confidence interval of odds ratios (1.399; 1.122-1.746), (1.510; 1.187-1.922), (1.595; 1.374-1.851), (1.513; 1.247-1.836) and (1.309; 1.028-1.665) respectively. Nausea, isolation and back head pain were caused by migraine and these were found positively significant with the odds ratios and 95% confidence interval of odds ratios(1.290; 1.122-1.484), (1.882; 1.617-2.190) and (1.285; 1.123-1.471) respectively. CONCLUSIONS: Stress, physical Activities and Menstruation increase the risk of migraine but weight loss, Breakfast, lunch, thirst, injury and Second trimester during pregnancy reduce the risk of migraine.

Serum neurofilament light chain levels in migraine patients: a monocentric case-control study in China.

PURPOSE: Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine. METHODS: A case-control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics. RESULTS: Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant (P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (ß = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged < 45 years and with a migraine course ≥ 10 years have significantly increased sNfL levels. CONCLUSIONS: This is the first study to evaluate sNfL levels in migraine patients. The sNfL levels significantly increased in patients with a migraine course ≥ 10 years. More attention to nerve damage in young patients with a long course of migraine is required.

Non-CGRP Antagonist/Non-Triptan Options for Migraine Disease Treatment: Clinical Considerations.

PURPOSE OF REVIEW: Although the association between CGRP and migraine disease is well-known and studied, therapies can target other pathways to minimize migraine symptoms. It is important to understand the role of these medications as options for migraine treatment and the varied mechanisms by which symptoms can be addressed. In the present investigation, the role of non-CGRP antagonist/non-triptan options for migraine disease therapy is reviewed, including NSAIDs, ß-blockers, calcium channel blockers, antidepressants, and antiepileptics. Pharmacologic therapies for both acute symptoms and prophylaxis are evaluated, and their adverse effects are compared. RECENT FINDINGS: At present, the Food and Drug Association has approved the beta-blockers propranolol and timolol and the anti-epileptic drugs topiramate and divalproex sodium for migraine prevention. Clinicians have other options for evidence-based treatment of episodic migraine attacks. Treatment decisions should consider contraindications, the effectiveness of alternatives, and potential side effects. NSAIDs are effective for the acute treatment of migraine exacerbations with caution for adverse effects such as gastrointestinal upset and renal symptoms. Beta-blockers are effective for migraine attack prophylaxis but are associated with dizziness and fatigue and are contraindicated in patients with certain co-morbidities, including asthma, congestive heart failure, and abnormal cardiac rhythms. Calcium channel blockers do not show enough evidence to be recommended as migraine attack prophylactic therapy. The anti-epileptic drugs topiramate and divalproex sodium and antidepressants venlafaxine and amitriptyline are effective for migraine exacerbation prophylaxis but have associated side effects. The decision for pharmacologic management should ultimately be made following consideration of risk vs. benefit and discussion between patient and physician.

Comparative efficacy of different treatments for menstrual migraine: a systematic review and network meta-analysis.

BACKGROUND: Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine. METHODS: We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies. RESULTS: This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo. CONCLUSIONS: These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.

Classifying migraine using PET compressive big data analytics of brain's µ-opioid and D2/D3 dopamine neurotransmission.

Introduction: Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood in vivo. This study examined migraine patients with a novel machine learning (ML) method based on their central µ-opioid and dopamine D2/D3 profiles, the most critical neurotransmitters in the brain for pain perception and its cognitive-motivational interface. Methods: We employed compressive Big Data Analytics (CBDA) to identify migraineurs and healthy controls (HC) in a large positron emission tomography (PET) dataset. 198 PET volumes were obtained from 38 migraineurs and 23 HC during rest and thermal pain challenge. 61 subjects were scanned with the selective µ-opioid receptor (µOR) radiotracer [11C]Carfentanil, and 22 with the selective dopamine D2/D3 receptor (DOR) radiotracer [11C]Raclopride. PET scans were recast into a 1D array of 510,340 voxels with spatial and intensity filtering of non-displaceable binding potential (BPND), representing the receptor availability level. We then performed data reduction and CBDA to power rank the predictive brain voxels. Results: CBDA classified migraineurs from HC with accuracy, sensitivity, and specificity above 90% for whole-brain and region-of-interest (ROI) analyses. The most predictive ROIs for µOR were the insula (anterior), thalamus (pulvinar, medial-dorsal, and ventral lateral/posterior nuclei), and the putamen. The latter, putamen (anterior), was also the most predictive for migraine regarding DOR D2/D3 BPND levels. Discussion: CBDA of endogenous µ-opioid and D2/D3 dopamine dysfunctions in the brain can accurately identify a migraine patient based on their receptor availability across key sensory, motor, and motivational processing regions. Our ML-based findings in the migraineur's brain neurotransmission partly explain the severe impact of migraine suffering and associated neuropsychiatric comorbidities.

A New Hybrid Approach Based on Time Frequency Images and Deep Learning Methods for Diagnosis of Migraine Disease and Investigation of Stimulus Effect.

Migraine is a neurological disorder that is associated with severe headaches and seriously affects the lives of patients. Diagnosing Migraine Disease (MD) can be laborious and time-consuming for specialists. For this reason, systems that can assist specialists in the early diagnosis of MD are important. Although migraine is one of the most common neurological diseases, there are very few studies on the diagnosis of MD, especially electroencephalogram (EEG)-and deep learning (DL)-based studies. For this reason, in this study, a new system has been proposed for the early diagnosis of EEG- and DL-based MD. In the proposed study, EEG signals obtained from the resting state (R), visual stimulus (V), and auditory stimulus (A) from 18 migraine patients and 21 healthy control (HC) groups were used. By applying continuous wavelet transform (CWT) and short-time Fourier transform (STFT) methods to these EEG signals, scalogram-spectrogram images were obtained in the time-frequency (T-F) plane. Then, these images were applied as inputs in three different convolutional neural networks (CNN) architectures (AlexNet, ResNet50, SqueezeNet) that proposed deep convolutional neural network (DCNN) models and classification was performed. The results of the classification process were evaluated, taking into account accuracy (acc.), sensitivity (sens.), specificity (spec.), and performance criteria, and the performances of the preferred methods and models in this study were compared. In this way, the situation, method, and model that showed the most successful performance for the early diagnosis of MD were determined. Although the classification results are close to each other, the resting state, CWT method, and AlexNet classifier showed the most successful performance (Acc: 99.74%, Sens: 99.9%, Spec: 99.52%). We think that the results obtained in this study are promising for the early diagnosis of MD and can be of help to experts.

The holistic approach to the CHRNA7 gene, hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs.

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.

Single-Dose Pharmacokinetics and Safety of Atogepant in Adults With Hepatic Impairment: Results From an Open-Label, Phase 1 Trial.

Atogepant is a selective oral calcitonin gene-related peptide receptor antagonist in development for migraine prevention. Here, we report the pharmacokinetics (PK) and safety of single-dose 60 mg atogepant in participants with severe, moderate, or mild hepatic impairment and matched participants with normal hepatic function from an open-label, parallel-group, single-dose phase 1 trial. Thirty-two participants aged 45 to 72 years were enrolled, which included 8 each with severe, moderate, mild, or no hepatic impairment. All participants completed the study. Atogepant was rapidly absorbed (median time to maximum plasma concentration, ∼2 hours) with an apparent terminal elimination half-life of ∼11 hours. Compared with participants with normal hepatic function, the change in maximum plasma concentrations of atogepant were -4%, -12%, and +9% in participants with severe, moderate, or mild hepatic impairment, respectively. Overall systemic exposures to atogepant were 15% to 38% higher in participants with hepatic impairment compared with those with normal hepatic function, but these differences are not expected to be clinically relevant given the established safety profile of atogepant. Only 1 adverse event was reported: mild rhinorrhea in a participant with moderate hepatic impairment. Overall, atogepant was safe and not associated with any clinically relevant change in PK in participants with severe, moderate, or mild hepatic impairment.

Unmet Needs in Japanese Patients Who Report Insufficient Efficacy with Triptans for Acute Treatment of Migraine: Retrospective Analysis of Real-World Data.

INTRODUCTION: Migraine attacks notably impact people's daily lives, health-related quality of life (HRQoL), and ability to work. Triptans are widely used as acute medication for a migraine attack but are ineffective, poorly tolerated, or contraindicated in some patients. HRQoL and work productivity are therefore likely to pose particular problems for patients whose migraine attacks do not respond sufficiently to triptan acute treatment. This real-world study aimed to determine whether migraine-related HRQoL, disability, and work productivity differed between triptan insufficient responders (TIRs) and sufficient responders (TSRs) receiving this acute treatment for migraine in Japan. METHODS: This was a retrospective analysis of 2017 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting patients with migraine in Japan. Patients had to be receiving a triptan as their sole acute prescribed medication for migraine. TIRs were defined as patients who achieved headache pain freedom within 2 h of taking triptan acute treatment in no more than three of five migraine attacks. Differences in outcomes between TIRs and TSRs were examined in adjusted analyses using a multivariable general linear model. RESULTS: Of 200 patients receiving a triptan as their sole prescribed acute treatment for migraine, 88 (44.0%) were classed as TIRs. Migraine-Specific Quality of Life Questionnaire scores were significantly lower-indicating poorer HRQoL-among TIRs than TSRs, as were mean EuroQol 5-dimension utility and visual analog scale scores (p < 0.05 for comparisons). TIRs also reported significantly (p ≤ 0.003) greater impairment than TSRs across all Work Productivity and Activity Impairment domains, with the exception of work time missed. Migraine disability was higher among TIRs than TSRs. CONCLUSION: Migraine attacks had a negative impact on the HRQoL, disability, and work productivity of people with migraine in Japan reporting insufficient efficacy with acute triptan treatment, highlighting the need for more effective acute treatment options.

Management of Menstrual Migraine.

PURPOSE OF REVIEW: Migraine disease is a neurological brain disorder that has been associated with significant disability and socioeconomic burden affecting women three times more commonly than men. Menstrual migraine is a subclass of migraine disease affecting 42-61% of females living with migraine disease. Menstrual migraine is often far more disabling, of longer duration, and more resistant to treatment. It is crucial to gain a deeper understanding of the ongoing biological changes and have a current awareness of the management of this debilitating form of migraine disease to improve the quality of life of these females living with migraine disease. RECENT FINDINGS: In new treatment options such as devices and with large-scale genome-wide association studies in migraine, genes related to migraine are being identified. This article will review the current literature regarding the pathophysiology, epidemiology, and treatment of menstrual migraine.

Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi Migraine Disease Specific Programme.

BACKGROUND: Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan. METHODS: This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression. RESULTS: Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4, p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16, p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29-2.88; p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05-2.60; p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02-1.06; p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28-0.98; p = 0.044). CONCLUSIONS: Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life.