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Background Objective Methods Results Conclusions While headache disorders are linked to low physical activity levels, the impact of depression on this relationship is unclear.To assess how single and comorbid diagnoses of migraine and tension‐type headache (TTH) interact with depression and leisure‐time physical activity (LTPA) levels in The Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil).In this cross‐sectional analysis based on the ELSA‐Brasil baseline data, the relationship of migraine, TTH (both assessed with the International Classification of Headache Disorders, Second Edition), and depression (assessed with the Clinical Interview Schedule–Revised) with LTPA levels (International Physical Activity Questionnaire) was investigated by employing linear regression models. Models were adjusted for sociodemographic, lifestyle, and clinical covariates, and interaction terms were created to examine additive effects of comorbid conditions.Among 14,088 participants, 54.4% (7668/14,088) were female, prevalence rates were: TTH = 39.6% (5573/14,088), migraine = 27.0% (3806/14,088), depression = 0.7% (94/14,088), depression + TTH = 1.1% (148/14,088), and depression + migraine = 2.5% (356/14,088). The mean (standard deviation) LTPA levels across the groups were: no headache + no depression = 148.7 (183.0) min/week, TTH = 133.5 (170.1) min/week, migraine = 110.3 (154.8) min/week, depression = 76.5 (146.3) min/week, depression + TTH = 84.5 (127.7) min/week, and depression + migraine = 64.3 (123.2) min/week. Negative associations were found for depression (β = −55.1, 95% confidence interval [CI] −93.6 to −17.0; p = 0.005), migraine (β = −24.7, 95% CI −33.2 to −15.4; p < 0.001), and TTH (β = −15.5, 95% CI −23.1 to −7.6; p < 0.001) with LTPA. No interaction effect was observed for depression + TTH (β = 36.0, 95% CI −12.6 to 84.6; p = 0.147) and depression + migraine (β = 31.7, 95% CI −11.3 to 74.7; p = 0.149), indicating no additive effect of comorbid conditions on LTPA levels. After adjusting for headache attack frequency, only depression + migraine remained negatively associated with LTPA (β = −38.7, 95% CI −71.6 to −5.8; p = 0.021).Headache disorders and depression were independently and inversely associated with LTPA, with the strongest effects seen in depression alone or comorbid with migraine. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long‐term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression—a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers.To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings.We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer‐reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected.We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting‐state, while others investigated a sensory modality using an evoked or event‐related paradigm with a total of 35 cohort and 3 case studies. Thirty‐two studies focused exclusively on migraine, while the rest reported other primary headache disorders.The findings show an evolution of MEG from a 7‐ to a 306‐channel system and analysis evolving from sensor‐level evoked responses to more advanced source‐level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case–control studies, which could have led to false‐positive findings. More studies are needed to investigate the affective–cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Observational studies have reported inconsistent relationships between migraine and the risk of intracranial aneurysm and subarachnoid hemorrhage (SAH).To determine whether genetic liability to migraine is associated with risk of intracranial aneurysm and aneurysmal SAH.This study was designed as a two‐sample Mendelian randomization (MR) analysis. Genetic associations with migraine were obtained from a large‐scale meta‐analysis of five population and clinic‐based genome‐wide association studies of migraine (102,084 cases and 771,257 controls of European ancestry). Genetic associations with intracranial aneurysm and SAH were obtained from a meta‐analysis of 22 population‐based genome‐wide association studies (7495 cases and 71,934 controls of European ancestry). Findings were corroborated by sensitivity analyses and replicated in an independent sample of combined cases of intracranial aneurysm and SAH (3529 cases and 234,948 controls of Asian ancestry from the Biobank Japan and China Kadoorie Biobanks). In secondary analyses, we investigated the outcomes of extracranial aneurysm in the FinnGen and UK Biobank cohorts (up to 7466 combined cases of thoracic and abdominal aortic aneurysm).Genetic liability to migraine was associated with increased risk of the combined outcome of unruptured intracranial aneurysm and SAH (odds ratio [OR] of outcome per doubling in migraine liability 1.19, 95% confidence interval [CI] 1.06–1.35; p = 0.005). This finding was replicated in an independent sample (OR 1.15, 95% CI 1.02–1.30; p = 0.027), and there were similar associations across the component outcomes of unruptured intracranial aneurysm (OR 1.20, 95% CI 1.01–1.42; p = 0.035) and SAH (OR 1.18, 95% 1.04–1.33; p = 0.008). These findings were consistent in sensitivity analyses robust to violations of the MR assumptions. In reverse MR analyses, genetic liability to intracranial aneurysm was not associated with migraine (OR 1.03, 95% CI 0.99–1.07; p = 0.141). In a secondary analysis, there were similar associations of genetic liability to migraine with all forms of aortic aneurysm (OR for combined thoracic and aortic aneurysm 1.18, 95% CI 1.10–1.27; p = 8.49 × 10−6).Genetic liability to migraine was associated with increased risk of intracranial and extracranial aneurysms, supporting a causal relationship between liability to migraine and these traits. Further work is needed to identify the biological mechanisms and clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To compare the rate and extent of absorption of zavegepant 10 mg (therapeutic dose) or 20 mg (supratherapeutic dose) nasal spray during a migraine attack versus non‐migraine period, assess safety, and explore efficacy and the relationship between zavegepant concentration and therapeutic response.Physiologic changes occurring during a migraine attack could affect the pharmacokinetics of treatments for migraine.This was a Phase 1, multicenter, open‐label, randomized, single‐dose, two‐period, fixed‐sequence, comparative bioavailability study. Participants with a history of 2–8 migraine attacks per month of moderate or severe pain intensity were randomized to a single dose of zavegepant 10 or 20 mg, administered intranasally during a migraine attack (Period 1) and in a non‐migraine period (Period 2). Blood samples were collected pre‐dose and at pre‐specified intervals up to 24 h post‐dose for plasma zavegepant concentration measurement. Safety was monitored throughout, and efficacy (migraine pain intensity score, nausea, photophobia, phonophobia, aura, and functional disability) assessed during Period 1. Plasma zavegepant pharmacokinetic parameters were calculated by standard noncompartmental methods, including maximum plasma concentration (Cmax), area under plasma concentration–time curve from time zero to infinity (AUC0–inf), and time of Cmax (Tmax).A total of 37 participants were evaluable for pharmacokinetics. Following administration of zavegepant 10 mg, geometric mean ratios for Period 1/Period 2 were 82.8% (90% confidence interval [CI] 60.5–113.2) for Cmax and 90.1% (90% CI 70.2–115.5) for AUC0–inf. Following administration of zavegepant 20 mg, geometric mean ratios for Period 1/Period 2 were 72.5% (90% CI 57.9–90.8) for Cmax and 73.4% (90% CI 58.8–91.7) for AUC0–inf. Averaging over the study period, geometric mean ratios for zavegepant 20 mg/10 mg were 142.5% (90% CI 118.6–171.4) for Cmax and 157.0% (90% CI 133.6–184.5) for AUC0–inf. Median Tmax was 0.5 h for both doses regardless of Period. Zavegepant was well tolerated in both study periods and effective during Period 1 at both dose levels. There was no apparent correlation between concentration at 0.5 h or 2 h post‐dose and efficacy outcomes.Zavegepant exposure was comparable during a migraine attack and a non‐migraine period, particularly at the therapeutic dose of 10 mg. When averaging over migraine and non‐migraine periods, there was a less‐than‐dose proportional increase in zavegepant exposure when the dose was doubled from 10 to 20 mg. The median Tmax was 0.5 h regardless of migraine attack or dose. Zavegepant 10 and 20 mg exhibited favorable safety profiles during migraine attacks and non‐migraine periods, and were effective to relieve pain, associated symptoms, and functional disability during migraine attacks, with no apparent correlation between zavegepant concentration and efficacy outcomes. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To evaluate long‐term reductions in acute headache medication (AHM) use with eptinezumab versus placebo in patients with prior preventive migraine treatment failures and medication overuse (MO).Preventive migraine treatment is recommended for patients for whom AHMs have failed and for those who are using excessive amounts of AHM. MO may worsen headache and migraine symptoms in people with migraine; it is a risk factor for disease chronification and/or MO headache.DELIVER was a multicenter, parallel‐group, double‐blind, randomized, placebo‐controlled, phase 3b clinical trial that randomized adults with migraine and two to four prior preventive failures to eptinezumab 100 mg, 300 mg, or placebo infusion every 12 weeks; patients initially given placebo received eptinezumab 100 mg or 300 mg in the extension period. MO was defined according to diagnostic criteria for MO headache in the baseline diary reports. This post hoc analysis of the DELIVER study included change from baseline in AHM days/month of use (ergotamines, triptans, simple or combination analgesics, and opioids; total and select class‐specific use) in the MO population.A total of 890 patients were included in the total population, and 438/890 (49.2%) had MO at baseline. In both the total population and MO population, eptinezumab resulted in greater reductions in total AHM days/month of use during weeks 1–24 than placebo, with triptans showing the largest reduction among AHM classes. Patients switching from placebo to eptinezumab experienced reductions in AHM days/month similar to that of initial eptinezumab treatment. In the extension population, mean (standard error [SE]) changes from baseline in AHM days/month were −4.6 (0.32; 100 mg) and −4.8 (0.32; 300 mg) across weeks 1–4 in patients who received eptinezumab for the entire treatment period and were −4.8 (0.44; placebo–100 mg) and −5.5 (0.44; placebo–300 mg) across weeks 25–28 in patients who switched from placebo to eptinezumab. Mean (SE) changes from baseline in AHM days/month in the extension MO population were −6.5 (0.59; 100 mg) and −6.6 (0.57; 300 mg) across weeks 1–4 in patients who received eptinezumab for the entire treatment period and were −7.1 (0.81; 100 mg) and −8.0 (0.80; 300 mg) across weeks 25–28 in patients who were switched from placebo to eptinezumab. All treatment arms sustained or further reduced AHM use across 18 months of trial participation. Across weeks 1–4, in patients fulfilling criteria for MO at baseline, 68.0% (102/150) of patients treated with eptinezumab 100 mg and 74.7% (109/146) of patients treated with eptinezumab 300 mg reported AHM use below MO thresholds compared to 43.3% (61/141) of patients receiving placebo. In patients with MO at baseline, the proportion of patients without MO remained above 60.0% for all treatment groups during the extension period.Eptinezumab reduced total AHM use more than placebo in patients with prior preventive failures and in patients with MO at baseline; largest reductions were observed for triptans. Robust reductions in AHM use after eptinezumab were sustained or further reduced with up to 18 months of treatment, and most patients no longer met thresholds for MO. [ABSTRACT FROM AUTHOR]

Objective: To conduct a retrospective cross‐sectional multicenter study to validate the relationships between migraine‐associated symptoms. Background: Symptoms associated with headache—photophobia and phonophobia, nausea, and/or vomiting—are required criteria for migraine diagnosis based on the International Classification of Headache Disorders‐Third Edition (ICHD‐3). However, individuals with migraine report high rates of other symptoms (e.g., lightheadedness, difficulty thinking). We recently completed a single‐center study assessing the relationships between an expanded set of migraine‐associated symptoms. Methods: A pre‐registered cross‐sectional multicenter retrospective analysis was conducted on standardized questionnaire data of youth ages 6–17 years from two headache registries at pediatric tertiary care centers. Cluster Analysis of Migraine‐associated Symptoms (CAMS) was implemented to assess associations between 11 migraine‐associated symptoms. We explored differences between the two centers, and how CAMS was associated with demographics, including sex and age, and headache burden. Results: There were 10,721 participants who were 66.5% female and had a median (interquartile range) age of 13 (10–15) years. The first three CAMS dimensions accounted for 46.5% of the variance and were consistent across sites. The first dimension indicated those reporting any migraine‐associated symptoms were likely to report multiple. The second dimension separated symptoms into those included in ICHD‐3 migraine diagnostic criteria and non‐ICHD symptoms (e.g., lightheadedness, difficulty thinking). The third dimension separated sensory hypersensitivity and vestibular symptoms. An abundance of migraine‐associated symptoms correlated with greater headache severity (Spearman's ρ = 0.18, 95% confidence interval [CI] 0.17–0.20; small effect size) and disability (ρ = 0.26, 95% CI 0.25–0.28; small effect size). We also observed differences in associated symptoms across age and sex. Discussion: Associations between an expanded set of migraine‐associated symptoms are informative for headache burden and reveal intriguing changes across child development and sex. We were able to replicate findings across two centers, indicating that these symptom clusters are inherent to migraine. Plain Language Summary: The presence of symptoms such as light or sound sensitivity, nausea, and vomiting can help clinicians differentiate between migraine and other headache disorders, such as tension‐type headache. However, people with migraine commonly experience symptoms that are not part of migraine diagnostic criteria per the International Classification for Headache Disorders‐Third Edition criteria, including lightheadedness, vision changes, and vertigo. In this study, we found that by considering these other associated symptoms, we were able to better understand the burden of headache in children and adolescents; e.g., we found that having more associated symptoms was associated with more headache severity and greater headache impact in children and teenagers. [ABSTRACT FROM AUTHOR]

Objectives: We used Cluster Analysis of Migraine‐associated Symptoms (CAMS) to critically evaluate current International Classification of Headache Disorders‐Third Edition (ICHD‐3) migraine‐associated symptoms criteria. Background: Diagnostic criteria play a central role in guiding clinical trial inclusion, and therefore available treatments. Migraine and tension‐type headaches (TTH) are differentiated in ICHD‐3 by many headache characteristics, including associated symptoms. A diagnosis of probable migraine indicates some but not all features of migraine are met. Photophobia and phonophobia, or nausea and/or vomiting, are required to meet a diagnosis of migraine; however, CAMS—a model that describes associated symptoms across youth with headache—indicates that a broader range of symptoms contain information about migraine burden. Methods: In this multisite retrospective cross‐sectional study, we evaluated ICHD‐3 migraine criteria. Youth aged 6–17 years with migraine (including probable migraine) or TTH were included in the analysis. We used CAMS to evaluate the migraine‐associated symptom criterion. With CAMS as a guide, we evaluated how changes to the migraine‐associated symptom criterion altered who met the diagnosis of migraine. Results: Of the 9017 participants included in this study, 66.7% were female and had a median (interquartile range) age of 13 (10–15) years. Most participants had migraine or probable migraine (99.0%), and the remainder had TTH (1.0%). A sizable percentage (10.1%) of youth under the umbrella diagnosis of migraine were diagnosed with probable migraine because they did not meet migraine‐associated symptom criterion D; however, many in this group reported several non‐ICHD migraine‐associated symptoms. We explored alterations to criterion D based on CAMS. Allowing for photophobia or phonophobia re‐categorized 55.6% of youth as having migraine, though some only had one symptom. Including lightheadedness or lightheadedness and spinning re‐categorized 19.7% and 25.8% of youth with migraine, respectively, but all of those who were re‐categorized had at least two migraine‐associated symptoms. Conclusion: The ICHD‐3 captures the most prevalent migraine‐associated symptoms; however, many youths with probable migraine who do not meet full criteria due to insufficient associated symptoms nonetheless experience multiple non‐ICHD migraine‐associated symptoms. Changes to criterion D should be considered for the ICHD‐4. Plain Language Summary: For clinicians to make a diagnosis of migraine based on International Classification of Headache Disorders‐Third Edition (ICHD‐3) criteria, patients must have headache‐associated nausea, vomiting, or light and sound sensitivity (criterion D). However, migraine can also be associated with other symptoms like lightheadedness, difficulties with thinking, and vertigo. In this study of youth aged 6–17 years with migraine, probable migraine, or tension‐type headache, we looked at how altering the ICHD‐3 criterion D changed participants' diagnosis based on their symptoms; overall, our results suggest that the next version of ICHD should account for the fact that many youth who do not experience nausea, vomiting, or light and sound sensitivities still experience manyx other migraine associated symptoms. [ABSTRACT FROM AUTHOR]

Objective: Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. Background: Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system‐wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic‐based studies. The VHA is an ideal hospital‐based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. Methods: The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)‐9 or ‐10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. Results: Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008–2019, 24,131 had at least one visit with a CH diagnosis. The 1‐year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non‐headache pain diagnoses. Headache not‐otherwise‐specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5‐year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). Conclusions: To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems. Plain Language Summary: This study describes the epidemiology of cluster headache among all Veterans Health Administration (VHA) enrollees using electronic medical record data from the VHA. We found that during any given 1‐year period, between 0.08–0.10% of women and 0.10–0.18% of men in the VHA were treated for cluster headache. Many of these patients also had co‐occurring disorders including other headache disorders and depression, so more research is needed to find the best ways to treat these patients. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse. Background: Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re‐visits to emergency settings. Methods: A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta‐analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493). Results: From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52–0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01–0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14–0.75), ergot agents (RR 0.44, 95% CI 0.25–0.75), neuroleptics (RR 0.47, 95% CI 0.31–0.71), opioids (RR 0.58; 95% CI 0.35–0.94), or corticosteroids (RR 0.64, 95% CI 0.47–0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01–0.71), combination therapy (RR 0.12, 95% CI 0.02–0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44–0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses. Discussion: Corticosteroids remain the recommended first‐line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events. Plain Language Summary: After leaving the hospital, some patients will have a relapse of migraine pain and may return to the emergency department, but we do not always know why this is or how to best help these patients. While corticosteroids can reduce relapse, we systematically reviewed the direct and indirect evidence for injectable medications to reduce relapse in patients with migraine. The results of our review indicated that (1) the duration of migraine pain and having pain at discharge were associated with relapse, and (2) routinely used medicines besides corticosteroids (e.g., neuroleptics and ergot agents) may be effective in reducing relapse. [ABSTRACT FROM AUTHOR]

Objective: To assess the real‐world effectiveness of ubrogepant by evaluating self‐reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days. Background: Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real‐world effectiveness of ubrogepant. Methods: The UNIVERSE study was an observational, cross‐sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30‐question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant. Results: Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post‐dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function. Conclusions: Ubrogepant demonstrated real‐world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication. Plain Language Summary: Ubrogepant is approved for the acute treatment of migraine in adults. In this study, adults who had used ubrogepant to treat a migraine attack in the previous 14 days responded to survey questions regarding their satisfaction with pain relief, ability to think clearly, and return to normal function. Results indicated that the majority of participants experienced high levels of satisfaction with ubrogepant because most of them said that these areas of their life improved after treatment. [ABSTRACT FROM AUTHOR]

Objective: To study if galcanezumab is effective for vestibular migraine (VM). Background: There are currently no placebo‐controlled trials showing that treatment is effective for VM. Therefore, we performed the first placebo controlled, randomized clinical trial of a calcitonin gene–related peptide–targeted monoclonal antibody for VM. Methods: This was a single site, prospective, double‐blind placebo controlled randomized clinical trial. Key inclusion criteria were as follows: participants aged 18–75 years with a diagnosis of VM or probable VM per Barany Society criteria. The primary outcome was change in VM‐PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) score, and secondary outcomes included change in DHI (Dizziness Handicap Inventory) score, and count of definite dizzy days (DDDs). Participants were randomized 1:1 to 3 months of treatment with galcanezumab or placebo via subcutaneous injection with a pre‐filled syringe, 240 mg the first month, and 120 mg for the second and third months. Results: Forty participants were randomized, and 38 participants were in the modified intent to treat analysis. VM‐PATHI score was reduced 5.1 points (95% confidence interval [CI] −13.0 to 2.7) for placebo (N = 21), and 14.8 points (95% CI −23.0 to −6.5) for galcanezumab (N = 17), a difference of −9.6 (95% CI −20.7 to 1.5, p = 0.044). DHI dropped 8.3 points in the placebo arm (95% CI −15.0 to 1.6), and 22.0 points in the galcanezumab arm (95% CI −31.9 to −12.1), a difference of −13.7 (95% CI −20.4 to −8.5, p = 0.018). The count of DDDs per month dropped from 18 days (standard deviation [SD] 7.6) in the baseline month to 12.5 days (SD 11.2) in month 4 for those in the placebo arm, and from 17.9 days (SD 7.9) in the baseline month to 6.6 days (SD 7.3) in month 4 for those in the galcanezumab arm, a difference of −5.7 days (95% CI −10.7 to −0.7, p = 0.026). No serious adverse events were observed. Conclusions: In this pilot study, galcanezumab was effective in treating VM. Plain Language Summary: Vestibular migraine is a common cause of dizziness. In this study, we investigated whether treatment with a drug called galcanezumab worked better than placebo for treating dizziness. We found that galcanezumab reduced dizziness more than placebo in patients with vestibular migraine. [ABSTRACT FROM AUTHOR]

Background: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting. Objective: This study aimed to evaluate the effect of extended‐release paracetamol on preventing fasting headaches. Methods: A randomized, open‐label clinical trial investigated the efficacy of extended‐release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self‐reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan. Results: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (β = −0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42–1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12–0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13–0.82). No adverse effects were observed during the study period. Conclusion: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan. Plain Language Summary: Ramadan is a month in which millions of Muslims fast from dawn to dusk; however, fasting during the day (e.g., for 13 hours) may cause headache and discourage individuals from this spiritual practice and can impact normal productivity, especially during the first week as the body adapts. We tested whether taking extended‐release paracetamol before fasting in the morning could avert fasting‐induced headache. Extended‐release paracetamol can be partially beneficial in delaying, but not necessarily preventing, fasting‐induced headache. [Correction added on 12th September 2024, after the first online publication: The Plain Language Summary has been updated.] [ABSTRACT FROM AUTHOR]

Objective: To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Background: Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene–related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head‐to‐head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. Methods: An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000‐305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9–12 in the base case analysis; weeks 1–12 and 9–12 for atogepant and during weeks 9–12 for rimegepant in the scenario analyses). Results: In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9–74.5) for atogepant and 51.8% (95% CI, 42.9–60.6) for rimegepant, compared to 44.1% (95% CI, 39.4–49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1–9.0) for atogepant compared to 13.0 (95% CI, 5.9–75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079–$29,516) for atogepant compared to $73,029 (95% CI, $32,901–$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Conclusions: Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials. Plain Language Summary: No trials have directly compared atogepant to rimegepant for prevention of episodic migraine, so we used data from published clinical trials to conduct an indirect treatment comparison of these two medicines, estimate the number of patients needed to achieve at least a 50% migraine day reduction, and determine the cost of treatment per additional responder. Our results suggested that 5 patients would need to be treated with atogepant to achieve at least a 50% migraine day reduction, compared to 13 with rimegepant. We also estimated that treatment with rimegepant would cost approximately $60,000 more than treatment with atogepant to achieve a ≥50% reduction in migraine days for one patient. [ABSTRACT FROM AUTHOR]

Objective: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine. Background: There are limited evidence‐based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence‐based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence. Methods: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta‐Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta‐analyses, and Hedge's g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta‐analysis were summarized qualitatively. Results: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta‐analyses. After a mean of 2–2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge's g = 0.97, 95% CI 0.58–1.35; p < 0.0001), as did severity (Hedge's g = 1.24, 95% CI 0.55–1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel‐group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta‐analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred. Conclusion: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel‐group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo. Plain Language Summary: The results of our review suggest that onabotulinumtoxinA injections are safe and that they are likely effective for children and adolescents with chronic migraine. However, the available research is generally biased because of study design issues, and it is still uncertain if onabotulinumtoxinA injections have benefits above and beyond the benefits of placebo injections for children and adolescents. Better‐designed research is required to understand if onabotulinumtoxinA injections are more effective than placebo injections in treating children and adolescents with chronic migraine. [ABSTRACT FROM AUTHOR]

Objective: To apply the 2019 joint American Academy of Neurology (AAN) and American Headache Society (AHS) quality measures for headache management to a cohort of neurology resident physicians and then assess outcomes related to guideline adherence. Background: The optimization of headache management is essential to reduce both the individual and systemic impact of these disorders. In 2014, the AAN developed 10 quality measures for evidence‐based management of patients with headache. A workgroup updated and condensed its headache quality measures in 2019, narrowing the set to six measurements, four of which would primarily focus on the management of migraine and two of which would address the management of cluster headache. Methods: This quality improvement study was conducted using a pretest‐posttest study design. A pre‐intervention survey based on retrospective analysis of five clinic notes for adherence to the measures was designed and distributed to all neurology residents (n = 32) at a large, academic tertiary referral center. The intervention included the creation of an electronic medical record template to aid residents in following the measures during clinical encounters, as well as the provision of direct feedback based on pre‐intervention results. Finally, a post‐intervention survey was distributed for completion based on notes written during the intervention period. Analysis was limited to migraine, given the low percentage of cluster headache seen in clinic. Results: An increase in adherence was seen in three of the four migraine‐related quality measures, with the Use of Abortive Medications for Migraine and Documentation of Counseling on Modifiable Lifestyle and Chronification Factors demonstrating statistically significant improvements (75.8% to 88.0% [p = 0.013] and 83.9% to 94.0% [p = 0.029] adherence, respectively). For secondary outcomes, the increase in the utilization of appropriate diagnostic criteria (82.6% to 93.2%, p = 0.018) was significant, and the self‐assessed confidence rating for adherence to guidelines was significant (p < 0.001). Conclusions: This study provides evidence that the quality improvement intervention led to increased adherence to the AAN and AHS migraine‐related measures. It is anticipated that increased adherence may lead to improved patient outcomes. Plain Language Summary: In 2019, the American Academy of Neurology and the American Headache Society worked together to create a set of quality measures to guide clinicians in the care of patients with headache; however, we do not know if these guidelines are being followed. This study aimed to see if resident neurologists at a large academic medical center would better follow these guidelines if they were part of a standardized electronic medical record template. Overall, this study showed that applying the headache quality measures in a real clinical setting is feasible and can improve best‐care practices. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion This study was an open‐label single‐arm clinical trial evaluating the fidelity, feasibility, acceptability, and clinical signal of abbreviated mindfulness‐based cognitive therapy (MBCT‐brief) delivered either via telephone (MBCT‐T) or by video conferencing (MBCT‐V) for people with migraine and comorbid depressive symptoms.Migraine is commonly comorbid with elevated depressive symptoms. MBCT reduces depressive symptoms and shows promise to reduce migraine‐related disability. An abbreviated and remotely delivered version of MBCT could increase access to care.People with migraine and elevated depressive symptoms were recruited from a large urban health system. Participants were assigned in blocks of eight to receive an evidence‐based MBCT‐brief treatment, including eight weekly group classes and home practice delivered via telephone (MBCT‐T) or video (MBCT‐V); MBCT‐T was randomly selected for the first block. Sessions were recorded and coded for treatment fidelity. Feasibility was assessed via session attendance (primary), homework completion, recruitment rate, and survey completion rate. Acceptability was assessed via the eight‐item Client Satisfaction Questionnaire (CSQ‐8; primary), the Credibility/Expectancy Questionnaire (CEQ), the System Usability Scale (SUS), and items assessing survey acceptability. Participants completed the Headache Disability Inventory (HDI) and Quick Inventory of Depressive Symptomatology‐Self Report 16‐item (QIDS‐SR16) at baseline, mid‐treatment, and post‐treatment. Feasibility and acceptability rates were compared to a priori benchmarks.Participants (n = 16) were all female with a mean (standard deviation [SD]) age of 45 (13) years, the majority of whom identified as White (13/16, 81%) and non‐Hispanic (14/16, 88%). The intervention met the a priori criteria set for therapist fidelity to treatment protocol (mean [SD] MBCT‐Treatment Acceptability and Competence Scale Adherence score 2.9 [0.2]), feasibility (mean [SD] session attendance was 7.9/8 [0.3]), and acceptability (mean [SD] CSQ‐8 score 28.8 [3.3]) for the entire sample and for each treatment arm. The usability of the remote‐delivery system was high across study participants (mean [SD] SUS score 84.8 [11.0]). Survey procedures were broadly deemed acceptable, with at least 80% participants either endorsing “Agree” or “Strongly Agree” across all items. Using Wilcoxon tests, we observed significant reductions in both the HDI (pre‐treatment median [interquartile range] score 63 [40, 70] vs. post‐treatment 36 [26, 54], p = 0.004) and the QIDS‐SR16 (pre‐treatment median [interquartile range] score 8 [5, 13] vs. post‐treatment 4 [3, 6], p = 0.003).We found that remotely delivered MBCT‐brief for migraine and depressive symptoms was feasible and acceptable to patients in both the telephone and video modalities. Intervention was associated with significant post‐treatment reductions in headache‐related disability and depressive symptomatology, findings that must be interpreted cautiously in the absence of a control group. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions Reported here are the results of four rimegepant phase I studies, in healthy participants, aimed at determining the in vivo potential of rimegepant (75 mg) for cytochrome P450 (CYP) 3A4‐related drug–drug interactions (DDIs).Rimegepant orally disintegrating tablet (Pfizer Inc., New York, NY, USA) is a calcitonin gene‐related peptide receptor antagonist approved for acute treatment of migraine and preventive treatment of episodic migraine. People with migraine commonly use multiple drug treatments, with the potential for DDIs.Each study was an open‐label, single‐arm, single‐sequence, crossover study. Rimegepant was tested as a victim drug by separate co‐administration of itraconazole (a strong CYP3A4 inhibitor and P‐glycoprotein inhibitor) in Study 1, rifampin (a strong CYP3A4 inducer and moderate CYP2C9 inducer) in Study 2, and fluconazole (a strong CYP2C9 inhibitor and moderate CYP3A4 inhibitor) in Study 3, and as a perpetrator drug by co‐administration with midazolam (a CYP3A4 substrate) in Study 4.Mean values of single‐dose rimegepant maximum concentration (Cmax) and area under the curve from time 0 to infinity (AUC0–inf) increased with itraconazole co‐administration (n = 22) by 1.42‐fold (90% confidence interval [CI] 1.25–1.61) and by 4.14‐fold (90% CI 3.87–4.44), respectively, and decreased with rifampin co‐administration (n = 21) to 36% (90% CI 31.2–41.4%) and to 19% (90% CI 16.3–21.4%), respectively. Co‐administration with fluconazole (n = 23) increased rimegepant mean AUC0–inf by 1.80‐fold (90% CI 1.68–1.93), with no impact on Cmax (1.04‐fold; 90% CI 0.94–1.15). Co‐administration of rimegepant single dose (300 mg; n = 14) or multiple doses (150 mg/day; n = 14) increased the mean Cmax of midazolam by 1.38‐fold (90% CI 1.13–1.67) and 1.53‐fold (90% CI 1.32–1.78), respectively, and the AUC0–inf of midazolam by 1.86‐fold (90% CI 1.58–2.19) and 1.91‐fold (90% CI 1.63–2.25), respectively.Based on the magnitude of DDIs, these studies indicate the following: co‐administration of rimegepant with a strong CYP3A4 inhibitor should be avoided; during co‐administration with a moderate CYP3A4 inhibitor, another dose of rimegepant within 48 h should be avoided; co‐administration of rimegepant with a strong or moderate CYP3A4 inducer should be avoided; CYP2C9 does not play a meaningful role in rimegepant metabolism; and there is no clinically meaningful CYP3A4 inhibition by rimegepant. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex‐specific factors.It has long been hypothesized that inflammation contributes to migraine pathophysiology. This study examined the association between migraine and alleles in the HLA system, a key player in immune response and genetic diversity.We performed a case–control study and included 13,210 individuals with migraine and 86,738 controls. All participants were part of the Danish Blood Donor Study Genomic Cohort. Participants were genotyped and 111 HLA alleles on 15 HLA genes were imputed. We examined the association between HLA alleles and migraine subtypes, considering sex‐specific differences.We found no association between HLA alleles and migraine, neither overall, nor in the sex‐specific analysis. In the migraine subtype analysis, three HLA alleles were associated with migraine without aura; however, these associations could not be replicated in an independent Icelandic cohort (2191 individuals with migraine without aura and 278,858 controls). Furthermore, we found no association between HLA alleles and migraine with aura or chronic migraine.We found no evidence of an association between the HLA system and migraine, suggesting that genetic factors related to the HLA system do not play a significant role in migraine susceptibility. [ABSTRACT FROM AUTHOR]

Objective: Our primary outcome was to determine the feasibility of patients with post‐traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype. Background: PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH. Methods: This is a single‐arm, prospective, non‐randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine‐like, probable migraine‐like, or non‐migraine‐like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose. Results: A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine‐like: 22/38 [58%], probable migraine‐like: 24/29 [83%], non‐migraine‐like: 6/15 [40%]; p = 0.154). Conclusions: A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine‐specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH. Plain Language Summary: Headache is the most common persistent symptom after traumatic brain injury, yet there are no evidence‐based treatments for post‐traumatic headache (PTH). In this study, we evaluated the ability of individuals with PTH to complete a daily headache diary and their response to treatment with sumatriptan. About 80% of participants completed the daily headache diary, and 72% of headaches resolved within 2 h of taking sumatriptan, so we concluded that a daily headache diary is useful in documenting headache symptoms and sumatriptan may be an effective treatment for PTH. [ABSTRACT FROM AUTHOR]

Objective: To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications. Background: Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial‐and‐error approach is inefficient. Methods: In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow‐up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta‐blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre‐trained a deep neural network, "TabNet," using 145 variables, then employed TabNet‐embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non‐responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held‐out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance. Results: Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta‐blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta‐blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin. Conclusion: We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine‐specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible. Plain Language Summary: Currently, there is no way to predict whether preventive medications, which are medications that may reduce the frequency and severity of headaches, will be helpful to all patients. We used novel artificial intelligence techniques and developed effective tools that can predict how a patient responds to seven different types of migraine preventive medications before the medication is started. We also found that the ways in which patients describe their headache and the types of symptoms they have is important to predict whether the medication will work. [ABSTRACT FROM AUTHOR]

Objective: This cross‐sectional study evaluated de‐identified data from the National Collegiate Athletic Association—Department of Defense Grand Alliance from 2014 to 2020 to determine the prevalence of migraine and migraine medication and to describe differences in migraine prevalence by sex, race, and sport. Background: Epidemiological studies can help identify underdiagnosed and undertreated populations. Understanding migraine prevalence in collegiate student‐athletes is essential for positive healthcare outcomes including development of prevention and treatment plans. Methods: From a concussion baseline assessment, participant's self‐reported demographics (e.g., age, sex, sport), migraine diagnosis (i.e., yes/no), and migraine medication usage (e.g., yes/no, type) determined prevalence of migraine and medication use in collegiate student‐athletes. Results: Migraine was reported in 5.6% (2617/47,060; 95% confidence interval [CI] 5.4%–5.8%) of the student‐athletes, with higher prevalence in females, 7.5% (1319/17,628; 95% CI 7.1%–7.9%), than males, 4.6% (1298/28,116; 95% CI 4.4%–4.9%). Medication usage was reported by 36.2% (947/2617; 95% CI 34.3%–38.0%) of individuals with migraine. Migraine reporting differed by race, with Caucasian reporting highest (5.9%; 1990/33,913; 95% CI 5.6%–6.1%) and Asian the lowest (2.7%; 55/2027; 95% CI 2.1%–3.5%). Women's sports, including golf, gymnastics, and lacrosse, and men's diving and squash had higher migraine reporting than other sports. Conclusion: Caucasian females reported higher rates than other groups and sport influenced rates of migraine diagnosis. Plain Language Summary: Collegiate student‐athletes face unique circumstances that may influence migraine diagnosis and outcomes. From a de‐identified data set provided by the National Collegiate Athletic Association—Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium, migraine was reported in 5.6% of collegiate student‐athletes and 36.2% of those also reported taking a medication. Migraine reporting differed by race and sport, with Caucasian females reporting higher rates of migraine than other groups. [ABSTRACT FROM AUTHOR]

Background: Prior studies have established an association between a history of abuse and more severe migraine presentation. Objectives: This cross‐sectional, observational study of a clinic‐based migraine population used validated measures to elucidate migraine‐specific and migraine‐related burdens among patients with a history of abuse. Methods: Patients with migraine (n = 866) from the American Registry for Migraine Research self‐reported if they had a history of emotional, physical, and/or sexual abuse and completed questionnaires assessing migraine‐related burden: Migraine Disability Assessment, Subjective Cognitive Impairment Scale for Migraine Attacks, Work Productivity and Activity Impairment, Patient‐Reported Outcomes Measurement Information System Pain Interference, Patient Health Questionnaire‐2, and Generalized Anxiety Disorder‐7. Migraine‐related burden in patients with versus without a history of abuse was compared. Subsequently, a mediation analysis evaluated the impact of depression and anxiety symptoms in the relationship between abuse history and migraine burden. Results: A history of abuse was reported by 36.5% (n = 316/866) of participants. After controlling for patient age, sex, years lived with headache, and headache frequency, a history of abuse was significantly associated with more severe migraine‐related disability. The combined burden of depression and anxiety symptoms mediated the relationship. Conclusion: A history of abuse is associated with greater migraine‐related disability. Future studies should determine if identification and management of the psychological and physical sequelae of abuse reduce migraine burden. Plain Language Summary: In this study, we found that patients with migraine who participated in the American Registry for Migraine Research and self‐reported a history of emotional, physical, or sexual abuse had worse migraine‐related burden than patients with migraine without a history of abuse. For example, patients who are survivors of abuse described a greater impact of migraine on their work, day‐to‐day living, and cognition. This increased migraine burden may be because of depression and anxiety, and we wonder if treating the underlying causes of these mental health difficulties might reduce their migraine burden. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To assess patient reported outcomes of patients with migraine receiving preventative medications, and to compare patient reported outcomes and unplanned care of patients on calcitonin gene–related peptide inhibitors (CGRPi) with those on other preventative medications.Patient reported outcome measures can be useful in conditions such as migraine with frequent disability. CGRPi are newer migraine preventative medications that can improve patients’ quality of life.This was a retrospective cohort analysis of Patient Reported Outcomes Measurement Information System (PROMIS) data combined with administrative claims data from a large regional health plan for adult patients (≥18 years) with migraine who were on preventative medications from January 2019 to March 2022. PROMIS scores of patients on CGRPi were compared to scores of patients who switched from other preventative medications to CGRPi (pre vs. post), between patients adherent to CGRPi versus non‐adherent, and changes in all‐cause/migraine‐related unplanned care (emergency department) use by the CGRPi cohort.There were 1245 patients on other preventative medications (antiseizure [532/1245 (43%)], antidepressants [316/1245 (25%)], and beta‐blockers [397/1245 (32%)]), 148 who were on CGRPi, and 112 who had switched from other preventative medications to CGRPi. The mean age was 44 years old, 88% were females, 50% were married, and 75% were on commercial insurance. Patients with migraine had higher T‐scores in pain, fatigue, anxiety, and sleep disturbance than the general population. Patients on CGRPi had a statistically significant reduction in pain T‐scores (60.4 [standard deviation (SD) 7.4] to 58.4 [SD 8.2], p = 0.003) post initiation of medications, especially those who switched from other preventative medications to CGRPi (61.4 [SD 6.9] to 58.7 [SD 8.3], p < 0.001). The pain T‐score reduction occurred only among the adherent group. There was a lower proportion of patients with all‐cause unplanned care among patients on CGRPi (43% [64/148] to 32% [47/148], p < 0.001), but the reduction in migraine‐related unplanned care was not statistically significant (9% [14/148] to 6% [9/148], p = 0.197).Our findings suggest that patients had an improvement in pain reduction scores after initiating CGRPi. PROMIS scores could provide important information about quality‐of‐life improvement for prescribers. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion 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.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.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.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.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. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database.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.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).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).RA was linked to a higher migraine risk, regardless of seropositivity. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion 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.This study aimed to identify explanatory factors of interictal burden in patients with migraine.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.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.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. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To assess changes in real‐world use of acute and preventive medications for migraine over a 12‐month follow‐up period in the United States following initiation of the anti‐calcitonin gene‐related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab.Early assessments of real‐world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow‐up.This retrospective cohort study used data from the IQVIA open‐source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified.Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12‐month pre‐index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti‐CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre‐index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post‐index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12‐month follow‐up period. Similarly, among 173,225 patients with pre‐index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post‐index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12‐month follow‐up period.In this long‐term study, we observed the discontinuation of both acute and preventive medications for migraine post‐erenumab initiation. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion The objective of this pilot study was to assess physical therapists’ (PTs) knowledge and needs regarding headache diagnosis and management.While there is significant research on physical therapy and cervicogenic headache, studies suggest that migraine is often under‐recognized, misdiagnosed, and inadequately treated across society despite its high prevalence and burden. Because migraine commonly includes concurrent neck pain and/or vestibular symptoms, patients with migraine may present to PTs for treatment. Very little is known about PTs' headache and migraine education, knowledge, and clinical practices.A team of headache specialists and PTs adapted a previously used headache knowledge and needs assessment survey to help ascertain PTs' knowledge and needs regarding headache treatment. The cross‐sectional survey was distributed online via Research Electronic Data Capture (REDCap) to PTs within a large healthcare system in Connecticut.An estimated 50.5% (101/200) of PTs invited to complete the survey did so. Only 37.6% (38/101) of respondents reported receiving any formal headache or migraine education in their professional training, leading to knowledge gaps in differentiating and responding to headache subtypes. Only 45.5% (46/101) were able to identify that migraine is characterized by greater pain intensity than tension‐type headache, and 22.8% (23/101) reported not knowing the duration of untreated migraine. When asked about the aspects of care they believe their patients with headache would like to see improved, PTs reported education around prevention and appropriate medication use (61/100 [61.0%]), provider awareness of the degree of disability associated with migraine (51/100 [51.0%]), and diagnostics (47/100 [47.0%]).This sample of PTs from one healthcare system demonstrates knowledge gaps and variations in clinical practice for managing their patients with headache. Future research on integrating additional opportunities for headache education for physical therapists, including evidence‐based behavioral therapies, is needed to ascertain whether it is likely to improve patient care. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project.People living with migraine experience a range of symptoms across the pre‐headache, headache, post‐headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi‐structured qualitative interviews were undertaken to better understand the migraine‐related symptomology from the patient's viewpoint.This concept elicitation study used iterative purposeful sampling to select 40 people with self‐reported medical diagnosis of migraine for interviews that were conducted via audio‐only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase.Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre‐headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post‐headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5).Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non‐cardinal migraine‐related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient‐reported outcome measures for migraine clinical trials. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To describe exploratory endpoints from a previous phase 2b/3 placebo‐controlled trial conducted in Japan and Korea, specifically investigating the effect of fremanezumab or placebo on migraine‐associated symptoms and acute headache medication use in patients with episodic migraine (EM).EM is associated with non‐head pain symptoms, including nausea, vomiting, photophobia, or phonophobia, which contribute substantially to the disease burden, healthcare resource utilization, and impaired quality of life. Current EM treatments include a mix of nonspecific/migraine‐specific acute headache medications, but medication overuse can induce headaches and progression from EM to chronic migraine (CM). In multiple phase 2b/3 trials, the monoclonal antibody fremanezumab significantly reduced the average number of monthly migraine days experienced by patients with EM/CM compared with placebo.This was a prespecified analysis of exploratory endpoints in a multicenter, randomized, double‐blind, placebo‐controlled, phase 2b/3 trial conducted in Japanese and Korean patients with EM (NCT03303092). Patients were randomized to receive fremanezumab, either monthly or quarterly, or matching placebo, administered subcutaneously at 4‐week/28‐day (“monthly”) intervals to maintain blinding. Exploratory endpoints reported here were the mean change from baseline in the number of days/month with (i) the use of any acute headache medication, (ii) the use of any migraine‐specific acute headache medication, (iii) nausea or vomiting, and (iv) photophobia and phonophobia.Overall, 357 Japanese and Korean patients with EM received either monthly (n = 121) or quarterly (n = 119) fremanezumab or placebo (n = 117). Compared with placebo, fremanezumab administered monthly or quarterly was associated with a significant reduction from baseline in the average number of days/month with acute headache medication use over three months (difference vs. placebo −2.81 [95% confidence interval (CI) −3.52, −2.11]; p < 0.001 and −2.79 [95% CI −3.50, −2.08]; p < 0.001, respectively). Similar findings were observed in the monthly average number of days with migraine‐specific acute headache medications (difference vs. placebo with monthly and quarterly fremanezumab, −2.63 [95% CI −3.31, −1.95] for both; p < 0.001), the average number of days/month with nausea or vomiting (difference vs. placebo −1.09 [95% CI −1.60, −0.58]; p < 0.001 for monthly fremanezumab and −1.37 [95% CI −1.88, −0.86]; p < 0.001 for quarterly fremanezumab), and the average number of days with photophobia and phonophobia (difference vs. placebo −1.22 [95% CI −1.80, −0.65]; p < 0.001 and −1.64 [95% CI −2.22, −1.06]; p < 0.001, respectively).Monthly and quarterly administered fremanezumab effectively prevented EM in Japanese and Korean patients. Fremanezumab also improved other disease aspects including the need for acute headache medications and the frequency of migraine‐associated symptoms. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions This study was conducted to assess the efficacy of daily 2000 mg eicosapentaenoic acid (EPA) supplementation in individuals with chronic migraine.Chronic migraine is characterized by a minimum of 15 headache days/month, necessitating a focus on preventive treatment strategies. EPA, a polyunsaturated fatty acid recognized for its anti‐inflammatory properties, is examined for its potential effectiveness in chronic migraine management.A randomized, blinded, placebo‐controlled trial of eligible participants with a confirmed diagnosis of chronic migraine were enrolled. The intervention group received 1000 mg of EPA twice daily for 8 weeks, while the control group received two placebo softgels. Symptoms were recorded at 4 and 8 weeks. The primary outcome was assessed using the Headache Impact Test‐6 to evaluate changes in patients. Secondary outcomes encompassed migraine headache days, headache severity measured via a visual analog scale, and the number of consumed painkillers. Descriptive analyses were reported in mean (± standard deviation [SD]).A total of 60 patients were included in the study and finally, 56 patients completed the study according to the protocol, including 47 (84%) females. The data comparison at baseline did not show any significant difference between the two groups except in the number of patients using valproic acid as prophylaxis (21 patients in the EPA group, and 13 in the placebo group; p = 0.037). The results showed after 8 weeks, a mean (SD) difference of Headache Impact Test‐6 in the EPA and placebo groups was −6.96 (3.34) and −4.43 (5.24), respectively (p = 0.084). Regarding migraine headache days, participants reported a mean (SD) −9.76 (4.15) and −4.60 (4.87) decline in days with headache, respectively (p < 0.001). The number of attacks per month after 8 weeks was 3.0 (95% confidence interval [CI] 2.0–4.0) and 4.0 (95% CI 3.0–6.0), respectively (p < 0.001). Regarding severity, there was no significant difference between the two groups (mean [SD] difference: −0.76 [1.13] and –0.73 [1.04], respectively; p = 0.906). In terms of adverse events, two patients in the EPA group reported intolerable nausea and vomiting, and one patient in the placebo group reported dizziness.This study's findings support the potential of a daily 2000 mg EPA as a prophylactic pharmacotherapy in chronic migraine management, specifically in mitigating migraine attacks, migraine headache days, and overall quality of life. [ABSTRACT FROM AUTHOR]

Objective/Background: Migraine is underdiagnosed. On average, medical students have approximately 3 h of exposure to headache education throughout medical school training. Moreover, some medical students have racially‐based biases in pain. There is a paucity of underrepresented in medicine (UIM) headache practitioners. UIM practitioners are more likely to practice in underserved communities and provider‐patient ethnic concordance may help eliminate healthcare disparities. The Student National Medical Association (SNMA) is an organization committed to supporting current and future UIM medical students and addressing the needs of underserved communities. The goal of this project was to develop and deliver a brief Migraine Diagnosis and Disparities Undergraduate Medical Education Program (MD2UMEP) to increase awareness of migraine diagnosis and disparities in UIM medical students in the SNMA. Methods: For connecting/relationship‐building with SNMA, the SNMA Region V website was reviewed. Calls were made to Wayne State University School of Medicine (WSUSOM) Office of Diversity, Equity, and Inclusion (ODEI) explaining the educational initiative with subsequent emails to the Director of WSUSOM's ODEI followed by a video‐conference meeting (VCM). VCMs were conducted with two SNMA member leaders from WSUSOM. A local and regional presentation/delivery of the MD2UMEP was planned. Communication was maintained electronically. For development/delivery of the MD2UMEP, headache literature was reviewed for key concepts underpinning migraine diagnosis and migraine disparities with a focus on African Americans. Slides with talking points were developed with references. Pre‐ and posttest questions were drafted and made accessible via a QR code. The MD2UMEP was presented and students completed the questionnaires. Descriptive statistics were used to quantify responses. Results: The MD2UMEP work began July 31, 2021, with program delivered in final form on October 1, 2022. A professional relationship was established with SNMA leadership. A MD2UMEP was developed then administered at the 2022 SNMA Region V Medical Education Conference. Headache medicine was introduced to UIM SNMA medical students. Anonymously, nine individuals responded to the MD2UMEP pretest questions. Eight individuals answered the posttest questions. At the program's conclusion, UIM student performance improved on seven of 10 test questions on migraine diagnosis and disparities and remained at 100% on one of 10 test questions. On two of the questions, the number correct remained the same (although percentage overall increased due to the smaller denominator). There was a higher proportion of correct responses on the posttest. Conclusions: There is great need for migraine diagnosis and disparities education among medical students. A new migraine diagnosis and disparities program was developed for medical students. SNMA members were receptive to the MD2UMEP and it strengthened their knowledge of migraine diagnosis and disparities. This program exposed UIM medical students to headache medicine. Plain Language Summary: Although migraine is not diagnosed as much as it should be and preventable health outcome differences (i.e., disparities) in migraine disease are seen in different people based on skin color, medical students in the US only receive about 3 h of headache education throughout their medical school training. To address this problem, we conducted a project to develop a migraine educational program that connected with and taught medical students who are not represented very well in the medical profession about migraine disease and migraine health disparities experienced by Black individuals in the US. We found that those who participated in the program strengthened their knowledge of migraine diagnosis and disparities; therefore, this program may serve as an example for future programs for underrepresented medical students and may be a way to begin to decrease disparities in migraine disease. [ABSTRACT FROM AUTHOR]

Objective: Utilize machine learning models to identify factors associated with seeking medical care for migraine. Background: Migraine is a leading cause of disability worldwide, yet many people with migraine do not seek medical care. Methods: The web‐based survey, ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (US), annually recruited demographically representative samples of the US adult population (2018–2020). Respondents with active migraine were identified via a validated diagnostic questionnaire and/or a self‐reported medical diagnosis of migraine, and were then asked if they had consulted a healthcare professional for their headaches in the previous 12 months (i.e., "seeking care"). This included in‐person/telephone/or e‐visit at Primary Care, Specialty Care, or Emergency/Urgent Care locations. Supervised machine learning (Random Forest) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms identified 13/54 sociodemographic and clinical factors most associated with seeking medical care for migraine. Random Forest models complex relationships (including interactions) between predictor variables and a response. LASSO is also an efficient feature selection algorithm. Linear models were used to determine the multivariable association of those factors with seeking care. Results: Among 61,826 persons with migraine, the mean age was 41.7 years (±14.8) and 31,529/61,826 (51.0%) sought medical care for migraine in the previous 12 months. Of those seeking care for migraine, 23,106/31,529 (73.3%) were female, 21,320/31,529 (67.6%) were White, and 28,030/31,529 (88.9%) had health insurance. Severe interictal burden (assessed via the Migraine Interictal Burden Scale‐4, MIBS‐4) occurred in 52.8% (16,657/31,529) of those seeking care and in 23.1% (6991/30,297) of those not seeking care; similar patterns were observed for severe migraine‐related disability (assessed via the Migraine Disability Assessment Scale, MIDAS) (36.7% [11,561/31,529] vs. 14.6% [4434/30,297]) and severe ictal cutaneous allodynia (assessed via the Allodynia Symptom Checklist, ASC‐12) (21.0% [6614/31,529] vs. 7.4% [2230/30,297]). Severe interictal burden (vs. none, OR 2.64, 95% CI [2.5, 2.8]); severe migraine‐related disability (vs. little/none, OR 2.2, 95% CI [2.0, 2.3]); and severe ictal allodynia (vs. none, OR 1.7, 95% CI [1.6, 1.8]) were strongly associated with seeking care for migraine. Conclusions: Seeking medical care for migraine is associated with higher interictal burden, disability, and allodynia. These findings could support interventions to promote care‐seeking among people with migraine, encourage assessment of these factors during consultation, and prioritize these domains in selecting treatments and measuring their benefits. Plain Language Summary: In this study, we looked at factors that related to a person's decision to seek medical care for migraine in a representative sample of over 60,000 adults with migraine in the United States. We found that only about half (51.0%) of the participants reported seeking care for migraine. We also found that people were more likely to seek medical care when migraine got in the way of their lives during and between migraine attacks, and when they had allodynia (pain from stimuli that do not normally cause pain). [ABSTRACT FROM AUTHOR]

Objectives: Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. Background: SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72‐h duration is required before the attack can be treated as SM. Methods: The Refractory Headache Special Interest Group from AHS developed a four‐question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. Results: Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72‐h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti‐inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). Conclusions: Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management. Plain Language Summary: In this research study, we asked members of the American Headache Society how they treat status migrainosus, a very severe migraine attack lasting more than 3 days. Out of the 196 people who answered the survey, most used stronger treatments before the headache lasted 72 h, and the majority preferred to use home‐based treatments to avoid the hospital. The five most common treatments they use are corticosteroids (like dexamethasone), nonsteroidal anti‐inflammatory drugs (like ketorolac), neuroleptics (like prochlorperazine), triptans (like naratriptan), and dihydroergotamine. [ABSTRACT FROM AUTHOR]

Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results: Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise. Plain Language Summary: The American Headache Society led a large, international, multistakeholder process to identify headache research topics that should be prioritized during the next 10 years. With input from headache clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public, 25 research priorities within 8 categories were identified. These research priorities can help guide headache researchers when planning their studies and as benchmarks by which the headache field can measure its progress over time. [ABSTRACT FROM AUTHOR]

Objective: To examine the unique role of migraine aura in predicting day‐to‐day levels of headache‐related disability. Background: Migraine symptoms and psychological variables contribute to headache‐related disability. Migraine aura may be associated with more severe symptom profiles and increased risk of psychiatric comorbidities, but the impact of aura on daily functioning is unknown. The present study sought to evaluate the role of migraine aura in predicting same‐day and subsequent‐day migraine‐related disability while accounting for demographic, headache, and psychological variables. Methods: This was an observational prospective cohort study among 554 adults with migraine. For each participant, data on migraine symptoms and psychological variables were collected daily for 90 days using the N‐1 Headache™ digital app (N = 11,156 total migraine days). Analyses assessed whether the presence of aura predicted daily ratings of migraine‐related disability independently of other headache and psychological variables. Given the number of predictors examined, statistical significance was set at p < 0.01. Results: The mean (standard deviation, range) patient‐level Migraine Disability Assessment questionnaire score across days of the migraine episode was 1.18 (1.03, 0–3). Aura was significantly associated with higher disability ratings on all days of the migraine episode (odds ratio [OR] 1.40, 99% confidence interval [CI] 1.13–1.74; p < 0.001). This relationship remained unchanged after adjusting for patient‐level variables (OR 1.40, 99% CI 1.13–1.73; p < 0.001) and day‐level psychological variables (OR 1.39, 99% CI 1.12–1.73; p < 0.001) but was fully negated after controlling for day‐level headache variables (OR 1.19, 99% CI 0.95–1.49; p = 0.039). Aura on the first day of the episode was associated with increased odds of allodynia (OR 1.87, 99% CI 1.22–2.86; p < 0.001), phonophobia (OR 1.62, 99% CI 1.17–2.25; p < 0.001), photophobia (OR 1.89, 99% CI 1.37–2.59; p < 0.001), and nausea/vomiting (OR 1.54, 99% CI 1.17–2.02; p < 0.001) on all days of the episode, but not episode duration (p = 0.171), peak severity (p = 0.098), or any examined psychological variables (sleep duration [p = 0.733], sleep quality [p = 0.186], stress [p = 0.110], anxiety [p = 0.102], or sadness [p = 0.743]). Conclusion: The presence of aura is predictive of increased headache‐related disability during migraine episodes, but this effect is attributable to associated non‐pain symptoms of migraine. Plain Language Summary: We used daily diary data from a headache app to see how aura was associated with disability from migraine. Aura was associated with worse disability, but this was attributable to other non‐pain symptoms of migraine, not aura itself. These findings add to studies suggesting aura is best viewed as one of many symptoms of migraine. [ABSTRACT FROM AUTHOR]

Objective: To describe the association between day‐to‐day peak pain severity and clinical factors in individuals with chronic migraine (CM). Background: Little is known about how clinical factors relate to day‐to‐day pain severity in individuals with CM. Methods: Adults with CM were enrolled into this observational prospective cohort study that collected daily data about headache, associated symptoms, and lifestyle factors using a digital health platform (N1‐Headache™) for 90 days. "Migraine days" were defined as days in which a headache occurred that had features described by the International Classification of Headache Disorders criteria. On these days, peak pain severity was recorded on a 4‐point scale; on non‐headache days peak pain severity was imputed as "0/none". The associations between peak pain severity and 12 clinical factors were modeled and adjusted for sex, age, daily headache, presence of menstrual bleeding, day of the week, and disability. All numerical and Likert scale variables were standardized prior to analysis. Results: Data were available for 392 participants (35,280 tracked days). The sample was predominantly female (90.6%), with a mean (standard deviation) age of 39.9 (12.8) years. In the final multivariable model with random intercept and slopes, higher than typical self‐reported levels of standardized stress (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04–1.11), standardized irritability (OR 1.05, 95% CI 1.02–1.08), standardized sadness (OR 1.05, 95% CI 1.02–1.07), fatigue (OR 1.25, 95% CI 1.15–1.36), eyestrain (OR 1.38, 95% CI 1.26–1.52), neck pain (OR 1.94, 95% CI 1.76–2.13), skin sensitivity (OR 1.61, 95% CI 1.44–1.80), and dehydration (OR 1.29, 95% CI 1.18–1.42) were associated with higher reported peak pain severity levels, while standardized sleep quality (OR 0.96, 95% CI 0.93–0.99) and standardized waking feeling refreshed (OR 0.84, 95% CI 0.81–0.88) were associated with lower reported peak pain severity levels. The inclusion of a random intercept and random slopes improved upon more parsimonious models and illustrated large differences in individuals' reporting of peak severity according to the levels of the associated clinical factors. Conclusion: Our data showed that the experience of CM, from a pain severity perspective, is complex, related to multiple clinical variables, and highly individualized. These results suggest that future work should aim to study a personalized approach to both medical and behavioral interventions for CM based on which clinical factors relate to the individual's experience of pain severity. Plain Language Summary: People with chronic migraine (CM) have a high frequency of attacks (≥15 days/month), yet little is known about their day‐to‐day experience of pain. We looked at the relationship between 12 clinical factors, including mood, sleep, stress, and day‐to‐day pain severity scores in adults with CM. We found that people's experience of pain severity and its relationship to different clinical factors was very individualized, with a lot of variability between people. [ABSTRACT FROM AUTHOR]

Objective: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia. Background: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache‐free intervals, leading to a compromised quality of life. Methods: This prospective, case–control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18F‐fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women). Results: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family‐wise error‐corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family‐wise error‐corrected). Conclusions: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine. Plain Language Summary: Migraine attacks are often accompanied by photophobia, and some patients with migraine experience constant glare, even when they do not have a headache. We tried to understand if there are changes in the brains of patients with migraine with photophobia by comparing their brain scans to those of healthy participants. We found that the thalamus had more activity in patients with migraine who experience constant glare compared to patients with migraine who do not. [ABSTRACT FROM AUTHOR]

Objective: This scoping review aimed to summarize current knowledge from twin studies on migraine. Migraine heritability, genetic correlations with migraine comorbid disorders, and the use of discordant twin pairs in migraine research are described. Further, the review considers the unused potential of twin studies in migraine research and reflects on future directions. Background: Twin studies can be used to understand how heritable and environmental factors influence human traits and disorders. The classical twin design compares the resemblance of a trait in monozygotic twins to that in dizygotic twins. The classical twin design can be extended to estimate the genetic correlation between disorders, model causality, and describe differences within discordant twin pairs. Methods: Studies focusing on migraine and using a twin study design were included. The search was performed on the PubMed‐MEDLINE database using the search terms "migraine" AND "twin" OR "twins." It was done in May 2023, rerun in November 2023, and managed with the Covidence software. Results: The search identified 52 twin studies on migraine. In 24 papers, the heritability of migraine was estimated with a classical twin design. Heritability estimates ranged from 0.36 to 0.48 for studies with adults, both men and women, and unspecified migraine. Migraine heritability was predominantly estimated with twin cohorts of North European ancestry, and only two studies examined migraine subtypes. A multilevel classical twin design was used in 11 studies to examine the co‐occurrence between migraine and comorbid disorders. The differences within migraine discordant twin pairs were examined in nine studies. Conclusion: The heritability of migraine was estimated with a classical twin design in twin cohorts from seven different countries, with remarkably similar results across studies. Future studies should include migraine subtypes and twin cohorts of non‐North European ancestry to better reflect the global population. Beyond heritability estimations, the twin method is a valuable tool for understanding causality and describing differences within discordant twin pairs. Despite more than 80 years of twin studies in migraine research, the twin design has a large unused potential to advance our understanding of migraine. Plain Language Summary: This review summarizes what has been learned about the inheritance of migraine from studies with twins. Studies with adults, both men and women, estimated the inheritance of migraine at about 36%–48%. However, most of these studies included twins with North European ancestry, and future studies should include twins from different parts of the world to understand how migraine affects people globally. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. Background: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. Methods: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. Results: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin‐ versus vehicle‐treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. Conclusions: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine‐associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed. Plain Language Summary: The aim of this study was to determine if supportive immune cells in the brains of males and females are altered in an animal model of chronic migraine. Mice in the chronic migraine group showed significant activation of astrocytes, but not microglia, in male and female mice in pain and emotion‐processing brain regions. These results suggest that some supportive cells in the brain may play a role in regulating chronic migraine. [ABSTRACT FROM AUTHOR]

Objective: To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Background: Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug‐device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). Methods: The STOP 101 was a Phase 1 open‐label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open‐label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. Results: In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9–15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4–17.1) at 5 min post‐dose, persisting up to 30 min post‐dose for systolic BP (6.3 mmHg; 95% CI 3.0–9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9–11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non‐serious, vascular treatment‐emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off‐protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. Conclusion: In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV‐related contraindications. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To compare healthcare resource utilization and healthcare costs in patients with migraine with or without a history of misdiagnosis.Despite the high prevalence of migraine, migraine is commonly misdiagnosed. The healthcare resource use and cost burden of a misdiagnosis is unknown.This retrospective cohort study identified adults with an incident migraine diagnosis from the Merative™ Marketscan® Commercial and Medicare Supplemental Databases between June 2018 and 2019. Patients with a diagnosis of commonly considered misdiagnoses (headache, sinusitis, or cervical pain) before their migraine diagnosis were classified as the “misdiagnosed cohort.” Patients in the misdiagnosed cohort were potentially misdiagnosed, then eventually received a correct diagnosis. Patients without a history of commonly considered misdiagnoses prior to their migraine diagnosis were classified as the “correctly diagnosed cohort.” Healthcare resource utilization and healthcare costs were assessed in the period before migraine diagnosis and compared between the cohorts. Outcomes were reported as per patient per month and compared with incidence rate ratios.A total of 29,147 patients comprised the correctly diagnosed cohort and 3841 patients comprised the misdiagnosed cohort and met the inclusion criteria. Patients in the misdiagnosed cohort had statistically significantly higher rates of inpatient admissions (0.02 vs. 0.01, incidence rate ratio [IRR] 1.61, 95% confidence interval [CI] 1.47–1.74), emergency department visits (0.10 vs. 0.05; IRR 1.89, 95% CI 1.79–1.99), neurologist visits (0.12 vs. 0.02; IRR 5.95, 95% CI 5.40–6.57), non‐neurologist outpatient visits (2.64 vs. 1.58; IRR 1.67, 95% CI 1.62–1.72) and prescription fills (2.82 vs. 1.84; IRR 1.53, 95% CI 1.48–1.58) compared to correctly diagnosed patients. Misdiagnosed patients had statistically significantly higher rates of healthcare cost accrual for inpatient admissions ($1362 vs. $518; IRR 2.62, 95% CI 2.50–2.75), emergency department visits ($222 vs. $98; IRR 2.27, 95% CI 2.18–2.36), neurologist visits ($42 vs. $9; IRR 4.39, 95% CI 4.00–4.79), non‐neurologist outpatient visits ($1327 vs. $641; IRR 2.07, 95% CI 1.91–2.24), and prescription fills ($305 vs. $215; IRR 1.41, 95% CI 1.18–1.70) compared to correctly diagnosed patients.Patients with migraine who have a history of misdiagnoses have higher rates of healthcare resource utilization and cost accrual versus those without such history. [ABSTRACT FROM AUTHOR]

Background Methods Results Discussion Slower speaking rates and higher pause rates are found in individuals with migraine or post‐traumatic headache during headache compared to when headache‐free. We aimed to determine whether headache intensity influences the speaking rate and pause rate of participants with migraine or acute post‐traumatic headache (aPTH) following mild traumatic brain injury (mTBI).Using a speech elicitation tool, participants with migraine, aPTH, and healthy controls (HC) submitted speech samples over a period of 3 months. Speaking and pause rates were calculated when participants were headache‐free and when they had mild or moderate headache. In this observational study, speaking and pause rates in participants with migraine and aPTH were compared to HC, controlling for age, sex, and days since mTBI (participants with aPTH only).A total of 2902 longitudinal speech samples from 13 individuals with migraine (mean age = 33.5, SD = 6.6; 12 females/1 male), 43 individuals with aPTH (mean age = 44.4, SD = 13.5; 28 females/15 males), and 56 HC (mean age = 40.8, SD = 13.0; 36 females/20 males) were collected. There was no difference in speaking rate between HC and the combined headache cohort of participants (migraine and aPTH) when they had headache freedom or a mild headache. When participants had moderate intensity headache, their speaking rate was significantly slower compared to that of HC and compared to their speaking rate during mild headache intensity or headache freedom. For the combined headache cohort of participants, pause rates were significantly higher when they had headache freedom or had a headache of mild or moderate intensity relative to HC. Compared to participants' pause rate during headache freedom, their pause rate was significantly higher during mild and moderate headache intensity. Participants with aPTH had significantly slower speaking rates compared to participants with migraine during headache freedom, mild headache intensity, and moderate headache intensity. Participants with aPTH had significantly higher pause rates compared to participants with migraine when experiencing moderate headache intensity.For both aPTH and migraine, more severe headache pain was associated with higher pause rates and slower speaking rates, suggesting that speaking rate and pause rate could serve as objective biomarkers for headache‐related pain. Slower speaking rate in participants with aPTH could reflect additional consequences of TBI‐related effects on motor control and speech production. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To evaluate headache comorbidity in a cohort of patients with functional movement disorders by assessing the prevalence, clinical characteristics, and temporal relationship of headache with the onset of functional symptoms.Functional movement disorders are common and potentially treatable. Although headache is frequent in these patients, few studies have evaluated their headache features.This observational cohort study included consecutive patients with functional movement disorders evaluated in our Functional Movement Disorders Unit between October 2021 and November 2022. Clinical and demographic features from clinical charts were reviewed, and patients completed a self‐administered questionnaire designed by the authors that included headache characteristics, disease duration, treatments received, and the Headache Impact Test‐6. Headache type was classified as per the Classification of Headache Disorders, third edition (ICHD‐3).A total of 51 patients with functional movement disorders were included. Of those, 40 (78%) reported having recurrent headache. Headache intensity was moderate–severe in 33/40 (83%), and about two‐thirds experienced headache >9 days/month. Disability secondary to headache was high (median [interquartile range] Headache Impact Test‐6 score 62 [49–66]). Based on the ICHD‐3, 23/40 (58%) of patients with headache met the criteria for migraine or probable migraine, 11/40 (27%) for tension‐type headache, two of 40 (5%) for new daily persistent headache, and one of 40 (3%) for primary exercise headache, while three of 40 (7%) were unclassifiable. The onset of headache occurred before the functional movement disorder in 28/40 (70%), after the functional movement disorder in five of 40 (12%), and simultaneously in six of 40 (15%). In this last group, four of the six (67%) patients described a daily headache from the onset, and two met the criteria for new daily persistent headache.Headache is a frequent condition in patients with functional movement disorders and an additional burden of disability beyond their motor symptoms. We found that, besides migraine and tension‐type headache, new daily persistent headache may be a comorbid phenotype in patients with functional movement disorders and should be further studied in larger prospective studies. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To explore hidden Markov models (HMMs) as an approach for defining clinically meaningful headache‐frequency‐based groups in migraine.Monthly headache frequency in patients with migraine is known to vary over time. This variation has not been completely characterized and is not well accounted for in the classification of individuals as having chronic or episodic migraine, a diagnosis with potentially significant impacts on the individual. This study investigated variation in reported headache frequency in a migraine population and proposed a model for classifying individuals by frequency while accounting for natural variation.The American Registry for Migraine Research (ARMR) was a longitudinal multisite study of United States adults with migraine. Study participants completed quarterly questionnaires and daily headache diaries. A series of HMMs were fit to monthly headache frequency data calculated from the diary data of ARMR.Changes in monthly headache frequency tended to be small, with 47% of transitions resulting in a change of 0 or 1 day. A substantial portion (24%) of months reflected daily headache with individuals ever reporting daily headache likely to consistently report daily headache. An HMM with four states with mean monthly headache frequency emissions of 3.52 (95% Prediction Interval [PI] 0–8), 10.10 (95% PI 4–17), 20.29 (95% PI 12–28), and constant 28 days/month had the best fit of the models tested. Of sequential month‐to‐month headache frequency transitions, 12% were across the 15‐headache days chronic migraine cutoff. Under the HMM, 38.7% of those transitions involved a change in the HMM state, and the remaining 61.3% of the time, a change in chronic migraine classification was not accompanied by a change in the HMM state.A divide between the second and third states of this model aligns most strongly with the current episodic/chronic distinction, although there is a meaningful overlap between the states that supports the need for flexibility. An HMM has appealing properties for classifying individuals according to their headache frequency while accounting for natural variation in frequency. This empirically derived model may provide an informative classification approach that is more stable than the use of a single cutoff value. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions We assessed whether the effectiveness of monoclonal antibodies (mAbs) targeting the calcitonin gene‐related peptide (CGRP) pathway changes according to the duration of chronic migraine (CM) over 12 months.In most patients, CM is a progressive disease starting with episodic migraine. Longer CM duration might be associated with more difficult treatment, probably because the mechanisms underlying chronicization are strengthened. Therefore, early treatment of CM could lead to better outcomes compared with later treatment.This cohort study included individuals with CM treated with anti‐CGRP mAbs in two tertiary headache centers from April 2019 to May 2023. The primary outcome included a change in monthly migraine days (MMDs) from baseline to the third trimester of treatment, 10–12 months. Secondary outcomes established whether response to anti‐CGRP mAbs has a more rapid onset in individuals with shorter CM duration compared with longer duration; they included change in MMDs, monthly headache days (MHDs), and days and number of intakes of acute medication during each trimester compared to baseline. Additional outcomes included persisting MMDs, MHDs, and days and number of intakes of acute medication during each trimester of treatment. Patients were compared across tertiles of the overall CM duration.The study included 335 individuals with CM, with a median (interquartile range [IQR]) age of 48 (39–57) years; 270 (80.6%) were women. Patients in the highest tertile of CM duration (aged 18–60 years) were older than patients in the lower duration tertiles (0–7 years and 8–18 years, respectively), with a median (IQR) age of 56 (48–64) years compared with 42 (31–50) years, and 48 (39–56)years, respectively (p = 0.025); however, this difference was likely due to a correlation between age and disease duration. The change in MMDs from baseline to the last trimester of treatment (10–12 months) was comparable across tertiles of CM duration (median [IQR] −12 [−18 to −5] days, −12 [−17 to −6] days, and −12 [−18 to −4] days; p = 0.946). No difference emerged in secondary outcomes, suggesting a similar time to onset of anti‐CGRP mAbs effect across all tertiles of CM duration.Our data showed that anti‐CGRP mAbs are effective and have a rapid onset of action in CM regardless of disease duration. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To evaluate preferences for key attributes of injected or infused preventive migraine treatments and assess heterogeneity in preferences among Canadian participants with migraine.Current treatment options for migraine prevention differ in their attributes, including mode of administration, efficacy, and dosing frequency; preferences for such attributes can vary among patients. With the advent of new therapies, evidence demonstrating patient preferences for injected or infused preventive migraine treatments is necessary.Canadian adults self‐reporting a diagnosis of migraine completed a cross‐sectional, internet‐based survey that included a discrete choice experiment. Participants were presented with attributes of preventive migraine treatments, including speed of onset, durability of efficacy, mode of administration, administration setting, and dosing frequency. Latent class analysis (LCA) was used to identify subgroups of patients who differed in their treatment preferences.In total, 200 participants completed the survey. Participants’ treatment preferences were most sensitive to improvements in the durability of effectiveness from “wears off 2 weeks before next dose” to “does not wear off before the next dose” (absolute difference in weights = |−0.95 to 1.07| = 2.02) and improvements from “cranial injections” to “intravenous infusions” (|−1.04 to 0.58| = 1.62); participants equally preferred self‐injection and intravenous infusion from a health‐care provider (mean weight = 0.58 and 0.47, respectively) as a route of administration over cranial injections (mean weight = −1.04). Three subgroups were identified with LCA: group one (n = 103) prioritized fast‐acting and durable therapies, group two (n = 54) expressed aversion to cranial injections, and group three (n = 43) favored treatments administered in a health‐care provider setting.In this sample of Canadian adults with migraine, we showed that durability of effectiveness and mode of administration are key attributes influencing patient preferences for preventive migraine treatments; however, certain groups of patients may differ in their treatment priorities. Our results highlight the need for patient–provider discussions regarding treatment attributes and consideration of patients’ preferences when selecting a preventive migraine treatment. [ABSTRACT FROM AUTHOR]

Objective: To analyze the specificity of calcitonin gene–related peptide (CGRP) levels, we measured alpha‐CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache. Background: Several studies have found an association between migraine and IBD. Methods: In this cross‐sectional study performed in an IBD clinic, morning serum alpha‐CGRP levels were measured by enzyme‐linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC). Results: Alpha‐CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6–73.9] pg/mL) and patients with CM (53.0 [36.7–73.9] pg/mL) compared to HC (37.2 [30.0–51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha‐CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6–73.4] pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 [29.1–76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha‐CGRP levels were further different in patients with IBD with migraine (70.9 [51.8–88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3–73.8] pg/mL; p = 0.049), and patients with IBD with tension‐type headache but without migraine (41.7 [28.5–66.9] pg/mL; p = 0.004), though alpha‐CGRP levels in patients with IBD without migraine (53.7 [32.9–73.5] pg/mL) remained different over HC (p = 0.028). Conclusion: Together with CM, circulating alpha‐CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha‐CGRP levels are not a totally specific migraine biomarker. However, alpha‐CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities. Plain Language Summary: Alpha‐calcitonin gene–related peptide (CGRP) levels may be a potential migraine biomarker, but it is unclear if this is the case because changes in CGRP concentrations can also be present in other conditions. We measured morning serum alpha‐CGRP levels in 96 patients with a recent inflammatory bowel disease (IBD) diagnosis, and compared them to 50 matched healthy participants and 50 matched patients with chronic migraine (CM). We found a significant increase in serum alpha‐CGRP levels in both patients with IBD and CM compared to healthy controls, which we think may reflect chronic inflammation found in IBD; these results offer another example that alpha‐CGRP concentrations are not totally specific for migraine. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to determine the heavy metal and trace element (HMTE) profile in patients with migraine (PwM) and to compare it to that of healthy individuals without migraine. Background: Migraine is a universal disease that affects more than 10% of the world's population; however, its pathophysiology is still obscure. Methods: A total of 100 participants were included in this prospective matched case–control study (50 PwM during acute attack and 50 age‐ and sex‐matched healthy controls). The study was conducted in the university hospital in Yozgat, Turkey, where the inductively coupled plasma mass spectrometry system was used to measure the HMTE profile. The calibration curve was created with 11 points for heavy metals (arsenic [As], cadmium [Cd], cobalt [Co], lead [Pb], mercury [Hg], nickel [Ni], and tin [Sn]) and trace elements (antimony [Sb], chromium [Cr], copper [Cu], iron [Fe], magnesium [Mg], manganese [Mn], molybdenum [Mo], and zinc [Zn]). Results: The median age was 27 (23–37) years, and the female/male ratio was 37/13 for both groups. The PwM group had significantly higher As, Co, Pb, and Ni levels among the heavy metals (p = 0.033, 0.017, 0.022, and 0.021, respectively). Also, PwM had significantly lower Cr, Mg, and Zn levels among the trace elements (p = 0.007, 0.024, and < 0.001, respectively). The only trace element that was elevated in the PwM group was Mn (p = 0.001). The PwM and control groups did not differ in terms of Cd, Sn, Sb, Cu, Fe, and Mo (p = 0.165, 0.997, 0.195, 0.408, 0.440, and 0.252, respectively). Conclusion: Some HMTE parameters are altered in PwM, which may provide additional insight into understanding migraine etiology. Plain Language Summary: Changes in blood levels of heavy metal and trace elements (HMTEs) may contribute to migraine. We compared several different HMTEs in healthy people and patients with migraine (PwM) during an attack and found many differences in HMTEs between healthy people and PwM. We concluded that shifts in blood levels of HMTEs may play a role in migraine, and further research on this topic is needed. [ABSTRACT FROM AUTHOR]

The small molecule calcitonin gene–related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication‐overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo‐controlled trials to rigorously assess this strategy. Plain Language Summary: A new class of migraine medicines, the gepants, does not cause medication‐overuse headache; these drugs can be taken in periods of increased headache risk, even before symptoms begin, to keep headaches from coming on. This new way of treating migraine is called "situational prevention." Experience in clinical practice suggests that treating migraine patients without current symptoms during times of increased headache risk, for example in connection with the menstrual cycle, travel, stress, or relaxation after stress, may be good times for situational prevention, but studies are needed to confirm when this strategy is most likely to be beneficial. [ABSTRACT FROM AUTHOR]