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OBJECTIVE: Using a double-dummy pilot randomized controlled trial design, we aimed to determine the feasibility and acceptability of comparing remote electrical neuromodulation (REN) to typical care intravenous pharmacologic interventions for the treatment of children and adolescents visiting the emergency department (ED) with migraine, and to compare parallel-group versus crossover trial designs. BACKGROUND: There are limited data to guide the management of migraine in the ED. Children and adolescents are interested in neuromodulation, and specifically REN, for treatment in this setting, but there are no existing data on this approach. METHODS: We employed a double-dummy, double-blind, pilot randomized controlled trial that tested two designs in two phases: a parallel-group design and a crossover design (ClinicalTrials.gov identifier: NCT05102591). The intervention arms consisted of: (i) active REN stimulation with matched normal saline placebo intravenously, and (ii) matched sham REN stimulation, intravenous metoclopramide (0.15 mg/kg, maximum 10 mg), and intravenous ketorolac (0.5 mg/kg, maximum 30 mg). Youth aged 8.0-<18.0 years visiting a Canadian tertiary care pediatric ED with migraine attacks as per criteria B-E of the International Classification of Headache Disorders third edition were eligible. Primary outcomes were focused on trial feasibility and acceptability, and preliminary efficacy and safety data were also collected. RESULTS: A total of 34% (22/65) of those who screened eligible were enrolled. Three participants (14%) withdrew prior to receiving any study interventions. In all, 10 participants were allocated to typical care, and nine to REN. All treated participants (19/19) completed all assessments. Recruitment was higher during the parallel-group phase: 1.1 participants/month versus 0.6 participants/month, and 36% (17/47) versus 28% (five of 18) of screened eligible were enrolled in the parallel-group and crossover phases, respectively. Participants reported positive impressions of REN use in the ED, e.g., higher mean (standard deviation [SD]) levels of interest in using REN only at 3.7 (1.0) versus 2.8 (1.0) in using intravenous interventions only for a future ED visit. Participants and clinical staff reported overall positive impressions regarding the study protocol. Employing an 11-point pain numerical rating scale, the mean (SD) reduction in pain severity score was 2.1 (1.3) and 2.9 (2.9) from baseline to 1 h, and 2.4 (1.6) and 4.0 (3.5) from baseline to 2 h for REN and intravenous interventions, respectively. One participant in the typical care group and none in the REN group experienced adverse events. CONCLUSION: We demonstrated the feasibility and acceptability of our trial protocol and of using REN to treat youth presenting to the ED with migraine. The parallel-group design generated a higher recruitment rate than the crossover design. Our preliminary efficacy and safety data suggest that REN could be non-inferior to typical care, but we were not powered for these outcomes. Further research on REN's use in the ED setting is warranted.

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BACKGROUND AND PURPOSE: Patients presenting at the emergency room (ER) with headache often encounter a hostile atmosphere and experience delays in diagnosis and treatment. The aim of this study was to design a protocol for the ER with the goal of optimizing the care of patients with urgent headache to facilitate diagnosis and expedite treatment. METHODS: A narrative literature review was conducted via a MEDLINE search in October 2021. The "Code Headache" protocol was then developed considering the available characteristics and resources of the ER at a tertiary care center within the Spanish National Public Health system. RESULTS: The Code Headache protocol comprises three assessments: two scales and one checklist. The assessments identify known red flags and stratify patients based on suspected primary/secondary headaches and the need for pain treatment. Initial assessments, performed by the triage nurse, aim to first exclude potentially high morbidity and mortality etiologies (HEAD1 scale) and then expedite appropriate pain management (HEAD2 scale) based on scoring criteria. HEAD1 evaluates vital signs and symptoms of secondary serious headache disorders that can most benefit from earlier identification and treatment, while HEAD2 assesses symptoms indicative of status migrainosus, pain intensity, and vital signs. Subsequently, ER physicians employ a third assessment that reviews red flags for secondary headaches (grouped under the acronym 'PEACE') to guide the selection of complementary tests and aid diagnosis. CONCLUSIONS: The Code Headache protocol is a much needed tool to facilitate quick clinical assessment and improve patient care in the ER. Further validation through comparison with standard clinical practice is warranted.

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OBJECTIVE: To evaluate, in patients with chronic migraine (CM) in real-world conditions, the persistence, effectiveness, and tolerability of erenumab, fremanezumab, and galcanezumab anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) and the persistence and effects of switching. BACKGROUND: Anti-CGRP mAbs represent a novel therapeutic approach to the management of CM; however, real-world data on persistence, effectiveness, and tolerability, especially after switching, are scarce. METHODS: This was a retrospective observational cohort study including all patients with CM treated with erenumab, fremanezumab, and/or galcanezumab in a tertiary hospital between January 2019 and December 2022. Treatment persistence was measured as the number of days between treatment start and end dates or the end of follow-up and also as a percentage of persistent patients at 3, 6, and 12 months; effectiveness as a ≥50% reduction in monthly migraine days (MMD); and tolerability as the number and type of adverse events. RESULTS: Included were 281 patients (383 treatments) with CM (91.5% [257/281] female) receiving anti-CGRP mAbs. Median (interquartile range [IQR]) treatment persistence was 267 (103-550) days. At 12 months, persistence was greater for the first (66.7%) compared to the second (49.8%) and third (37.2%) anti-CGRP mAb treatments (hazard ratio [HR] = 1.93, 95% confidence interval [CI]: 1.35-2.74; HR = 2.75, 95% CI: 1.69-4.47, respectively). Persistence minimum observed median (IQR) was also greater for the first (291 [112-594] days) compared to both the second (188 [90-403] days; p < 0.001) and third (167 [89-352] days; p < 0.001) anti-CGRP mAb treatments. For the first anti-CGRP mAb treatment, there were no differences in persistence among the different drugs. In terms of effectiveness of the first, second, and third anti-CGRP mAb treatments, a ≥50% reduction in MMD was achieved by 57.6% (117/203), 25.0% (11/44), and 11.8% (2/17) of patients, respectively, at 3 months, and by 55.8% (87/156), 29.6% (8/27), and 12.5% (1/8) of patients, respectively, at 6 months. At 12 months, no significant effectiveness differences were observed among anti-CGRP mAb treatments. As for tolerability, 55 adverse events were reported by 43 (15.3%) patients, mostly mild and leading to treatment discontinuation in only 14 (5.0%) patients. The most common adverse events were constipation, injection site reaction, and pruritus. Erenumab patients (3%, 3/99) experienced a higher rate of discontinuation for constipation. CONCLUSIONS: Our findings showed a 12-month higher treatment persistence with the use of a first anti-CGRP mAb treatment when the switch to a second treatment was due to ineffectiveness or severe side events. This persistence was lower after a second or third anti-CGRP. Additionally, in terms of effectiveness, the first anti-CGRP treatment achieved a higher response in terms of ≥50% reduction in MMD; however, some patients may benefit from a switching strategy. Finally, the tolerability profile for anti-CGRP mAbs was favorable. Further studies are needed to identify predictors of response after switching from the first anti-CGRP mAb treatment.

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OBJECTIVE: This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database. BACKGROUND: Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear. METHODS: This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43). RESULTS: A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05). CONCLUSION: RA was linked to a higher migraine risk, regardless of seropositivity.

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BACKGROUND: The "interictal burden of migraine" (MIB) is a new concept that encompasses the overall impact of the disease between migraine episodes. However, the factors that contribute to this interictal burden are still unclear. OBJECTIVE: This study aimed to identify explanatory factors of interictal burden in patients with migraine. METHODS: This prospective cross-sectional observational including 200 patients with migraine (92% [n = 184] female, with a mean [standard deviation] age of 44.8 [12] years, 53% [n = 106] with chronic migraine) completed a clinical and questionnaire assessment targeting MIB, migraine impact, and depressive and cognitive complaints. RESULTS: More than three-fourths (76% [n = 152]) of patients had moderate-to-severe interictal burden. Higher interictal burden (MIB Scale ≥2) was associated with higher headache frequency (eight vs. 14, p = 0.001) and intensity (headache index score 17.0 vs. 30.0, p = 0.002), higher headache impact (six-item Headache Impact Test score 59.2 vs. 63.9, p = 0.001), and more subjective memory complaints (Subjective Memory Complaints Questionnaire [SMC] score 9.0 vs. 4.5, p = 0.001), as well as anxiety (Hospital Anxiety and Depression Scale (HADS)-Anxiety score 5 vs. 10, p < 0.001) and depression symptoms (HADS-Depression score 5 vs. 8, p < 0.001). Once accounted for these potential explanatory variables, subjective memory complaints and impact of headache during ictal phase remained as individual determinants of the interictal burden, with SMC explaining 15% (odds ratio 1.15, 95% confidence interval 1.03-1.28; p = 0.010) of the interictal burden. CONCLUSION: This finding highlights the need to consider cognitive complaints as part of the construct of interictal burden of these patients to refine the focus of their management.

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BACKGROUND: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). METHODS: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. RESULTS: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10-6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). CONCLUSIONS: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.

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BACKGROUND: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. METHODS: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. RESULTS: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10- 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (ß = -0.551, p = 6.65 × 10- 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. CONCLUSION: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. TRIAL REGISTRATION: Not applicable.

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Chronic migraine is a debilitating headache disorder that is associated with excessive analgesic use. As the long-term use of analgesics could cause additional headaches due to medication overuse, there is a need to probe efficient nonprophylactic alternatives and migraineurs' long-term adherence to such possible treatments. This protocol investigates the integration of neurofeedback and mindfulness which are the two common nonpharmacological therapies for migraines. We offer the use of portable EEG headbands for easy home-based data collection and consistent data access from researchers. In order to evaluate the efficacy of this recommended intervention, this is a protocol for a randomized control trial with a waitlisted group and an intervention group consisting of a daily attention task. The protocol presents important criteria which should be checked for consistency in longitudinal data collection from adults with chronic migraine.

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Background: Migraine, a neurological condition perpetually under investigation, remains shrouded in mystery regarding its underlying causes. While a potential link to Right-to-Left Shunt (RLS) has been postulated, the exact nature of this association remains elusive, necessitating further exploration. Methods: The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and functional connectivity (FC) were employed to investigate functional segregation and functional integration across distinct brain regions. Graph theory-based network analysis was utilized to assess functional networks in migraine patients with RLS. Pearson correlation analysis further explored the relationship between RLS severity and various functional metrics. Results: Compared with migraine patients without RLS, patients with RLS exhibited a significant increase in the ALFF within left middle occipital and superior occipital gyrus; In migraine patients with RLS, significantly reduced brain functional connectivity was found, including the connectivity between default mode network and visual network, ventral attention network, as well as the intra-functional connectivity of somatomotor network and its connection with the limbic network, and also the connectivity between the left rolandic operculum and the right middle cingulate gyrus. Notably, a significantly enhanced functional connectivity between the frontoparietal network and the ventral attention network was found in migraine with RLS; Patients with RLS displayed higher values of the normalized clustering coefficient and greater betweenness centrality in specific regions, including the left precuneus, right insula, and right inferior temporal gyrus. Additionally, these patients displayed a diminished nodal degree in the occipital lobe and reduced nodal efficiency within the fusiform gyrus; Further, the study found positive correlations between ALFF in the temporal lobes, thalamus, left middle occipital, and superior occipital gyrus and RLS severity. Conversely, negative correlations emerged between ALFF in the right inferior frontal gyrus, middle frontal gyrus, and insula and RLS grading. Finally, the study identified a positive correlation between angular gyrus betweenness centrality and RLS severity. Conclusion: RLS-associated brain functional alterations in migraine consisted of local brain regions, connectivity, and networks involved in pain conduction and regulation did exist in migraine with RLS.

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OBJECTIVE: This study aimed to determine the relationship between migraine prevalence and its diagnostic features in school children. METHODS: This study was conducted on children aged 10-18 year who were randomly selected from 22 middle and 26 high schools. Questionnaires were prepared in Turkish with demographic (9 items) and headache characteristics (ICHD-3rd-based headache screening questionnaire, 11 items). RESULTS: A total of 1450 surveys were properly filled out. Female/male ratio was 798/652 (55%÷45%) and the mean age was 14.4 years ± 2.1. 96.4% of the population in this study. According to the criteria of headache attack number (≥4 attacks), character (pulsatile) and duration (≥1 h), the prevalence of migraine in the studied population was 23.1%. CONCLUSION: Population-based studies are important because they provide information on diagnosing migraine, which is a public health priority in childhood, and contribute to creating the world migraine atlas. Although additional diagnostic clues are needed to determine the prevalence of migraine in childhood, we still widely use headache screening questionnaires based on ICHD-3rd.

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WHAT IS THIS SUMMARY ABOUT?: The Harris Poll Migraine Report Card was a survey about people's experiences and challenges with headaches and migraine. The survey was conducted from December 9, 2021, to January 10, 2022, in the United States. The people who took the survey had frequent headaches/migraine attacks (on 8 or more days per month) and used acute headache/migraine medication to relieve head pain and other symptoms (on 10 or more days per month). This summary focuses on the responses of adults with frequent headaches and frequent acute medication use at the time of the survey or within the few months (not specified) before the survey (and not those who previously had frequent headaches and frequent acute medication use at some point in their life prior to the survey). The group of people who took the survey will be called 'respondents'. The term 'headaches' can mean any type of headache including as part of a migraine attack, a tension type headache, or another unknown headache type. All respondents screened positive for having migraine, so many of the headaches they reported on may have been a migraine headache or part of a migraine attack. WHAT WERE THE RESULTS?: Over 50% of respondents said their headaches affected their overall quality of life. Many respondents wished their healthcare provider who was managing their headaches understood more about how headaches affect their mental well-being, how much pain their headaches cause, and why they get headaches. 80% of respondents had concerns about their overall health. Over 60% of respondents said they have experienced anxiety and/or depression. In this survey, although all respondents were eligible to receive a preventive headache/migraine medication because of their headache frequency, only 15% were taking one. WHAT DO THE RESULTS OF THE SURVEY MEAN?: The findings from this survey showed many ways that headaches/migraine care can improve, including talking about mental and emotional well-being, making sure the treatment plan works and does not have side effects that cannot be tolerated, and trying to prevent headaches/migraine from occurring.

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INTRODUCTION: Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM. METHODS: This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1 month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs). RESULTS: Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7 years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (n = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (N = 31) and second (N = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3 months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported. CONCLUSIONS: This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6 months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified.

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BACKGROUND: Migraine is among the most prevalent and burdensome neurological disorders in the United States based on disability-adjusted life years. Cortical spreading depolarization (SD) is the most likely electrophysiological cause of migraine aura and may be linked to trigeminal nociception. We previously demonstrated, using a minimally invasive optogenetic approach of SD induction (opto-SD), that opto-SD triggers acute periorbital mechanical allodynia that is reversed by 5HT1B/1D receptor agonists, supporting SD-induced activation of migraine-relevant trigeminal pain pathways in mice. Recent data highlight hypothalamic neural circuits in migraine, and SD may activate hypothalamic neurons. Furthermore, neuroanatomical, electrophysiological, and behavioral data suggest a homeostatic analgesic function of hypothalamic neuropeptide hormone, oxytocin. We, therefore, examined the role of hypothalamic paraventricular nucleus (PVN) and oxytocinergic (OXT) signaling in opto-SD-induced trigeminal pain behavior. METHODS: We induced a single opto-SD in adult male and female Thy1-ChR2-YFP transgenic mice and quantified fos immunolabeling in the PVN and supraoptic nucleus (SON) compared with sham controls. Oxytocin expression was also measured in fos-positive neurons in the PVN. Periorbital mechanical allodynia was tested after treatment with selective OXT receptor antagonist L-368,899 (5 to 25 mg/kg i.p.) or vehicle at 1, 2, and 4 h after opto-SD or sham stimulation using von Frey monofilaments. RESULTS: Opto-SD significantly increased the number of fos immunoreactive cells in the PVN and SON as compared to sham stimulation (p < 0.001, p = 0.018, respectively). A subpopulation of fos-positive neurons also stained positive for oxytocin. Opto-SD evoked periorbital mechanical allodynia 1 h after SD (p = 0.001 vs. sham), which recovered quickly within 2 h (p = 0.638). OXT receptor antagonist L-368,899 dose-dependently prolonged SD-induced periorbital allodynia (p < 0.001). L-368,899 did not affect mechanical thresholds in the absence of opto-SD. CONCLUSIONS: These data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration.

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Migraine is one of the most common neurological disorders, characterized by moderate-to-severe headache episodes. Autonomic nervous system (ANS) alterations can occur at phases of migraine attack. This study investigates patterns of ANS changes during the pre-ictal night of migraine, utilizing wearable biosensor technology in ten individuals. Various physiological, activity-based, and signal processing metrics were examined to train predictive models and understand the relationship between specific features and migraine occurrences. Data were filtered based on specified criteria for nocturnal sleep, and analysis frames ranging from 5 to 120 min were used to improve the diversity of the training sample and investigate the impact of analysis frame duration on feature significance and migraine prediction. Several models, including XGBoost (Extreme Gradient Boosting), HistGradientBoosting (Histogram-Based Gradient Boosting), Random Forest, SVM, and KNN, were trained on unbalanced data and using cost-sensitive learning with a 5:1 ratio. To evaluate the changes in features during pre-migraine nights and nights before migraine-free days, an analysis of variance (ANOVA) was performed. The results showed that the features of electrodermal activity, skin temperature, and accelerometer exhibited the highest F-statistic values and the most significant p-values in the 5 and 10 min frames, which makes them particularly useful for the early detection of migraines. The generalized prediction model using XGBoost and a 5 min analysis frame achieved 0.806 for accuracy, 0.638 for precision, 0.595 for recall, and 0.607 for F1-score. Despite identifying distinguishing features between pre-migraine and migraine-free nights, the performance of the current model suggests the need for further improvements for clinical application.

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Background: Migraine is characterized by sudden acute episodes of pain, with a global prevalence of 18% among all age groups. It is the second leading cause of years lived with disability worldwide. Prophylactic treatment is important in managing migraine; however, its efficacy and safety are debated. This study aimed to evaluate the efficacy of desvenlafaxine in female patients with migraine. Methods: We conducted a retrospective observational case study involving 10 women diagnosed with migraine who were treated with desvenlafaxine. We measured the number of migraine days per month, average headache duration in minutes, headache severity using a visual analog scale, use of acute medications, and frequency of acute medication use per week. Results: Desvenlafaxine significantly reduced the number of migraine days from 14.70 ± 3.68 at baseline to 2.50 ± 2.50 at follow-up (p < 0.05). The average headache duration dropped from 131.25 ± 32.81 min to 52.50 ± 44.64 min. Headache severity scores improved from 6.80 ± 1.49 at baseline to 0.80 ± 0.92 at follow up, the frequency of acute medication use per week reduced from 3.30 ± 1.49 at baseline to 0.80 ± 0.92, and the frequency of acute medication use decreased from 3.30 ± 1.49 times per week to 0.80 ± 0.92. Conclusions: Desvenlafaxine shows potential as an effective prophylactic therapy for migraine. Larger-scale studies are necessary to further explore its benefits.

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Migraine-related stigma is a pervasive issue impacting nearly half of chronic migraine patients, with significant consequences for their quality of life, disability and mental health. Despite its profound effects, migraine stigma remains under-recognised in both clinical practice and research. This narrative review explores the three primary types of stigmas affecting migraine patients: public, structural and internalised. Public stigma involves negative societal attitudes and stereotypes that trivialise the condition. Structural stigma is reflected in policies that restrict access to necessary care and resources. Internalised stigma occurs when patients absorb these negative views, leading to self-blame and diminished self-worth. Addressing these different types of stigmas is crucial for improving the understanding, diagnosis and treatment of migraine. Educational efforts, advocacy and policy reform are essential strategies in this context. A deep understanding of stigma is vital for developing effective interventions that enhance clinical management and patient quality of life. Ultimately, reducing stigma can lead to better health outcomes and a more comprehensive approach to migraine care.

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BACKGROUND AND PURPOSE: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases. METHODS: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. RESULTS: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). CONCLUSIONS: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.