Search

Background and Purpose: Multiple drugs targeting the calcitonin gene‐related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP‐induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan. Experimental Approach: Concentration–response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP‐blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3 μM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations. Key Results: Erenumab shifted the concentration‐response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab. Conclusions and Implications: Gepants have additional effects on top of erenumab for CGRP‐induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: Vestibular migraine is a newly recognised and debilitating condition. This article aims to provide an overview of what is known of vestibular migraine, delineating its diagnostic criteria and presenting some initial management strategies to aid ENT professionals in delivering optimal care when patients first present to the otolaryngology clinic. Method: Although traditionally underdiagnosed, there are now clearly defined diagnostic criteria to aid accurate diagnosis of vestibular migraine. Results: A detailed history and clinical examination are the cornerstone of the diagnostic process, but supportive evidence is required from appropriate audio-vestibular tests and imaging. Conclusion: This is a unique condition that commonly initially presents to ENT. This article provides a summary of diagnostic and management strategies to facilitate early diagnosis and first-line treatment that can be employed in general ENT settings, which may be particularly useful given the limited availability of specialist audio-vestibular medicine and neuro-otology services. [ABSTRACT FROM AUTHOR]

Introduction: The ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) European Union (EU) is part of an overarching population-based study program that also includes the United States and Japan. Here, we report data on the migraine/severe headache burden and the use of acute medication and healthcare resources in Spain and Germany. Methods: OVERCOME (EU) was an online, non-interventional, cross-sectional survey conducted in adults in Spain and Germany between October 2020 and February 2021. A total migraine cohort was established based on health survey participants who reported headache/migraine in the last 12 months AND identified as having migraine based on modified International Classification of Headache Disorders, third edition criteria OR self-reported physician diagnosis. Data were analyzed for the total migraine cohort and the subcohort with moderate to severe headache attacks, with average pain severity ≥ 5 points, pain duration ≥ 4 h, and at least moderate disability due to migraine [Migraine Disability Assessment (MIDAS) score ≥ 11] over the past 3 months. Results: Pain of moderate or severe intensity was the most frequent symptom in the total migraine cohort (n = 19,103/20,756; 92.0%). Proportions of participants reporting severe disability (MIDAS Grade IV), poorer quality of life (QoL; Migraine-Specific QoL Questionnaire), and higher interictal burden (Migraine Interictal Burden Scale-4), generally increased with number of headache days (HDs)/month. Most participants (92.5%) reported current acute migraine/severe headache medication use, although only 39.0% were using triptans. In the moderate to severe attacks subcohort (n = 5547), 48.4% were using triptans, with nonsteroidal anti-inflammatory drugs the most common acute medication. The moderate to severe attacks subcohort also reported poorer QoL and greater pain and disability with increasing HDs/month, although severe interictal burden was reported for ~ 60% of participants regardless of HDs/month. Treatment satisfaction (six-item migraine Treatment Optimization Questionnaire) in those using triptans was generally poor in both total and subcohorts. Conclusion: High migraine-related burden levels were reported, despite use of acute medication. Although triptans are recommended for moderate to severe migraine attacks in Spanish and German guidelines, less than half of participants were using triptans; treatment satisfaction in those using triptans was generally poor. New tailored treatment options may help address unmet needs in current acute treatment. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of galcanezumab has been demonstrated in randomized controlled trials, but evidence about its use under clinical practice conditions is still limited. This study aimed to describe the characteristics of the patients treated with galcanezumab in routine clinical practice in Spain as well as treatment patterns, persistence, and effectiveness. Methods: A retrospective chart review study was carried out in six hospitals. Information of adults with migraine, who started treatment with galcanezumab between November 2019 and September 2021, was analyzed until end or loss of follow-up. Continuous variables were described as mean (standard deviation, SD) and median (interquartile range, IQR), and categorical variables as frequency and percentages. Persistence to treatment was estimated using Kaplan–Meier analysis. Results: A total of 314 patients were analyzed over median follow-up period of 17.5 months (13.8–20.7), with a mean age of 46.3 (12.6), 85% women, 80.6% chronic migraine, and reporting a mean of monthly migraine days of 16.7 (7.8). Overall, 72.9% had comorbid conditions, with anxiety and depression disorders being the most frequent. More than 60% had received ≥ 6 previous preventive drugs, the most common being antiepileptics, antidepressants, and botulinum toxin (95.2%, 89.8% and 84.1%, respectively). Overall, 60.3% of the patients with other preventive treatments maintained them after galcanezumab initiation. The median time on galcanezumab was 14.6 months (9.4–22.8); 95.7%, 82.0%, 76.2% and 59.8% of patients were persistent to treatment at 3, 6, 9 and 12 months, respectively. Of the patients who discontinued (151: 48.1%), 57.6% were due to lack of effectiveness and 31.1% were due to improvement in migraine. The average reduction of monthly migraine days at 3, 6, 9 and 12 months was 7.9 (7.2), 9.1 (7.5), 8.8 (6.6) and 9.0 (6.9) days, respectively. Conclusions: In real clinical practice, galcanezumab is an effective treatment and has a high persistence in patients with migraine, mostly chronic and with multiple use of previous preventive treatments. [ABSTRACT FROM AUTHOR]

Introduction: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Methods: Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. Results: In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex. Conclusions: Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Introduction: Thirty years ago, the first migraine-specific drugs (triptans) appeared. Today two new categories (gepants and ditans) are marketed for acute migraine treatment. That said, is there still a role for conventional therapy? The aim of the present narrative review is to provide an expert overview examining the possible role of the combination paracetamol/caffeine in treatment of acute migraine pain. Methods: To understand possible settings for more appropriate use of paracetamol/caffeine (1000 mg/130 mg) in treatment of acute migraine, a structured literature search was performed using the PubMed database by a panel of experts from major Italian headache centers; articles not referring to migraine pain were excluded from this review; review articles were prioritized. Results: Overall response, even to newer specific and selective trigeminal targeted drugs (TTTs), is not over 60%; thus, there is still room for conventional therapies in acute migraine treatment. The panel identified settings in which the use of paracetamol/caffeine combination to treat acute migraine attacks might offer benefit considering the consolidated use through years, despite the lack of studies directly addressing the efficacy of paracetamol/caffeine in the identified populations: subjects > 65 years of age; presence of cardiovascular (CV) comorbidities; TTTs non-responders; pregnancy and breastfeeding; subjects < 18 years of age; paracetamol/caffeine as add-on therapy. Conclusions: Paracetamol is included in the World Health Organization (WHO) essential drug list and has a high level of popularity among patients. Caffeine enhances the analgesic effect of other drugs including paracetamol. In early treatment of acute migraine pain, prescribing physicians might consider using the paracetamol/caffeine combination among other options. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that an antioxidant diet is a protective factor against migraine. However, the association between zinc, an important antioxidant obtained from the diet, and migraine has received little attention. The purpose of this study was to explore the association between zinc intake with migraine. The present study used cross-sectional data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. Logistic regression models and restricted cubic spline models were performed to explore the association between zinc intake and migraine. A total of 9849 adults aged 20 years or older were included in this study. Zinc intake was negatively associated with migraine. Compared to participants in the lowest group of dietary zinc intake Q1 (≤5.93 mg/day), the adjusted ORs for migraine in Q2 (5.94–8.38 mg/day), Q3 (8.39–11.26 mg/day), Q4 (11.27–15.75 mg/day), and Q5 (≥15.76 mg/day) were 0.73 (95% CI: 0.60–0.89, p = 0.004), 0.72 (95% CI: 0.55–0.95, p = 0.02), 0.76 (95% CI: 0.58–0.99, p = 0.04) and 0.73 (95% CI: 0.50–1.05, p = 0.08), respectively. Our findings also suggested an interaction between zinc intake and age (P for interaction = 0.007). Additionally, the relationship between zinc intake and migraine in adults with 20–50 years was non-linear. A higher zinc intake is significantly associated with a decreased prevalence of migraine, and age can modify the association between them. [ABSTRACT FROM AUTHOR]

Background: Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology. Objective: The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study. Methods: The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18 years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41–61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39–57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups. Results: The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30–30) to 15 (12–30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12–30) to 8 (3–22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25–30) to 15 (8–25) from onabot monotherapy and decreased from 25 (15–30) to 12 (4–25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001). Conclusion: Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action. [ABSTRACT FROM AUTHOR]

Headache in intracranial disorders drives significant disability in our patients. Management principles for secondary headaches require a multidisciplinary approach with expertise from the neurological, neuro-ophthalmological, neuroradiological, and neurosurgical specialities. The Pressure of Headache was the theme of the annual United Kingdom CSF Disorders Day and saw speakers and panellists from Australia, Europe, and the United States. Among the topics presented were the newest concepts underpinning idiopathic intracranial hypertension management and spontaneous intracranial hypotension. Advances in our knowledge of cerebrospinal fluid secretion and the visual snow syndrome debate were particular highlights. This review provides a summary of the research on headache disorders that overlap the neuro-ophthalmological axis of care for patients. [ABSTRACT FROM AUTHOR]

Background: Among university students, migraine is notably prevalent and is linked to compromised academic performance and daily functioning. Medical students are a particularly vulnerable category due to the demanding nature of their training, as they are often exposed to headache trigger factors. We therefore aimed to determine the prevalence, characteristics, and healthcare-seeking practices of primary headaches among Italian medical students. Methods: We conducted a cross-sectional study among medical students attending the Università Cattolica del Sacro Cuore in Rome who completed a self-administered questionnaire designed following the International Classification of Headache Disorders-3 criteria. The questionnaire assessed sociodemographic and headache features, healthcare utilization, the use of symptomatic and preventive treatment, and headache trigger factors. Results: Five hundred thirty-six students filled out the questionnaire. The lifetime and last-year prevalence of headache in this cohort was 76.7% (n = 411). Among the students surveyed, migraine had a prevalence of 26.9%, probable migraine of 12.9%, and tension-type headache (TTH)/probable TTH of 36.9%. Two hundred and forty-six students (59.8%) reported that their headache worsened after starting university. All students reporting headache had at least one trigger factor. In students fulfilling the criteria for migraine (n = 144), 137 (95.1%) had previously used acute non-prescription treatments, and eight concurrently used a preventive treatment. Thirty-five students fulfilling the criteria for migraine underwent a brain MRI scan (24.3%), 43 performed a neurological evaluation (29.9%), 36 received a diagnosis of migraine (25%), and 20 (13.9%) accessed the emergency room. Discussion: Migraine and TTH are common among medical students in Italy despite low healthcare resource utilization. These results support the need to promote public health policies and strategies in order to reduce the disability and burden associated with primary headaches among medical students. [ABSTRACT FROM AUTHOR]

Objective: The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification. Methods: This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group). Results: The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07–7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019). Conclusion: Our study substantiates this emerging concept of migraine chronification as an allostatic disorder. [ABSTRACT FROM AUTHOR]

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = −0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = −0.682, p < 0.001, MIDAS: R 2 = −0.880, p < 0.0010) and dural invasion (MIDAS: −53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion. [ABSTRACT FROM AUTHOR]

Since the issuance of the emergency use authorization (EUA) of 3 coronavirus disease 2019 (COVID-19) vaccines, there have been over 180 million individuals fully vaccinated in the United States (US). With the increasing administration of COVID-19 vaccinations, there have been over 550,000 adverse events reported in the Vaccine Adverse Event Reporting System (VAERS) with approximately 230,000 experienced after receipt of the Pfizer-BioNTech COVID-19 Vaccine as of September 23rd 2021. Audio-vestibular symptoms (including Sudden Sensorineural Hearing Loss (SSNHL)) secondary to immunizations has previously been evaluated. However, this report describes the first case of bilateral sudden sensorineural hearing loss potentially due to the Pfizer-BioNTech COVID-19 vaccine. We further review the available literature regarding the treatment of Sudden Sensorineural Hearing Loss, and the association of SSNHL with previous immunizations and COVID-19 infection. Lastly, we hypothesize the underlying potential mechanisms between SSNHL and the Pfizer-BioNTech COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Migraine is one of the leading causes of disability worldwide. Third wave therapies, such as Mindfulness Based Cognitive Therapy for Migraine (MBCT-M), have proven efficacious in reducing headache-related disability. However, research is needed to better understand the change mechanisms involved in these third-wave therapies. Acceptance is a fundamental component of third wave therapies, and more research is warranted on the role of pain acceptance in MBCT-M. It is also valuable to understand the independent roles of the two components of pain acceptance—pain willingness (PW) and activity engagement (AE). The current study is a secondary analysis of a randomized control trial of MBCT-M. Sixty participants were included in the study (MBCT = 31; WL/TAU = 29). Baseline correlations between overall pain acceptance, PW, AE, and headache-related disability were run. Mixed models assessed change from baseline to one-month post-treatment and treatment-by-time interaction for overall pain acceptance, PW, and AE. Mixed models also assessed maintenance of changes at 6-month follow-up in the MBCT-M group. Longitudinal mediation models assessed whether change in pain acceptance, PW, and AE mediated the relationship between treatment and change in headache-related disability. Pain acceptance, PW, and AE were all negatively correlated with headache-related disability at baseline. Pain acceptance, PW, and AE all significantly increased over time in both the waitlist/ treatment-as-usual group (WL/TAU) and the MBCT-M group. Only AE increased more in the MBCT group than the WL/TAU group. Change in pain acceptance, PW, and AE all significantly mediated the relationship between MBCT and change in headache-related disability. The study supports the importance of pain acceptance, specifically the activity engagement component, in MBCT-M. [ABSTRACT FROM AUTHOR]

Depression, migraine, insomnia, and fibromyalgia are reportedly comorbidities. Nevertheless, no study has evaluated the comorbidity of all four of these disorders. This study aimed to investigate the comorbidity of these four disorders. Cross-sectional analyses were performed using data of the Circannual Change in Headache and Sleep study, an online nationwide population-based survey. Validated questionnaires were used to diagnose the disorders and measure quality of life. The change of clinical characteristics by addition of any comorbidity was analyzed using the Jonckheere–Terpstra trend test. The prevalence rates of depression, migraine, insomnia, and fibromyalgia were 7.2 %, 5.6 %, 13.3 %, and 5.8 %, respectively. Among the 3030 included participants, 494 (16.3 %), 164 (5.4 %), 40 (1.3 %), and 6 (0.2 %) had one, two, three, and four of these conditions, respectively. The number of headache days per 30 days (Jonckheere–Terpstra trend test, p = 0.011) and migraine-related disability (migraine disability assessment score, p = 0.021) increased with an increase in the number of comorbidities but not with the intensity of headache (visual analog scale, p = 0.225) among participants with migraine. The severity of insomnia (Insomnia Severity Index, p < 0.001) and fibromyalgia (fibromyalgia severity score, p = 0.002) increased with additional comorbidities; however, depression (Patient Health Questionnaire-9, p = 0.384) did not show such an increase. The diagnoses of conditions were based on self-reported questionnaires. The findings confirmed significant comorbidity between depression, migraine, insomnia, and fibromyalgia. Health professionals should be aware of the probable comorbidity of depression, migraine, insomnia, and fibromyalgia when caring for individuals with any of these four disorders. • Depression, migraine, insomnia, and fibromyalgia overlap and are highly comorbid. • Addition of depression, migraine, insomnia, or fibromyalgia increases headache days. • More depression, migraine, insomnia, or fibromyalgia; the more migraine disability. • Insomnia and fibromyalgia severity increase with comorbidities. [ABSTRACT FROM AUTHOR]

Medication-overuse headache (MOH), which potentially involves 1–2% of the population, is defined as a headache, on ≥ 15 days a month affected, along with overuse of one or other acute attack medications. MOH presents with significant challenges in the headache community, particularly in clinical settings raising various questions about its pathophysiology. Through a review of the current literature and our clinical experience, we have explored the mechanisms through which MOH may occur, provide an understanding of the current state of treatment and detail some possible views on the understanding and treatment of this condition. We evaluate the variations in treatment methods offered globally and understanding of the disorder. Above all interventions, patient education is crucial, which is underscored by an analysis of the academic publications. Given the condition is preventable, early intervention is imperative and patient awareness is highlighted as key. Globally, there is no uniform treatment methodology, which may be advantageous as approaches need to take local circumstances into account. [ABSTRACT FROM AUTHOR]

Background: Migraine is a disease characterized by headache attacks. The disease is multifactorial in etiology and genetic and environmental factors play role in pathogenesis. Migraine can also be accompanied by psychiatric disorders like neurotism and obsessive compulsive disorder. Stress, hormonal changes and certain food intake can trigger attacks in migraine. Previous studies showed that eating attitudes and disorders are prevalant in patients with migraine. Eating disorders are psychiatric disorders related to abnormal eating habits. Both migraine and eating disorders are common in young women and personality profiles of these patient groups are also similar. A possible relationship which shows that migraine and eating habits are related can lead to a better understanding of disease pathogenesis and subsequently new therapeutic options on both entities. Association of migraine in relation to severity, depression and anxiety and eating habits and disorders were aimed to be investigated in this study. Methods: The study was designed as a prospective, multi-center, case control study. Twenty-one centers from Turkey was involved in the study. The gathered data was collected and evaluated at a single designated center. From a pool of 1200 migraine patients and 958 healthy control group, two groups as patient group and study group was created with PS matching method in relation to age, body-mass index, marital status and employment status. Eating Attitudes Test-26 (EAT-26), Beck's Depression Inventory (BDI) and Beck's Anxiety Inventory (BAI) were applied to both study groups. The data gathered was compared between two groups. Results: EAT-26 scores and the requirement for referral to a psychiatrist due to symptoms related to eating disorder were both statistically significantly higher in patient group compared to control group (p = 0.034 and p = 0.0001 respectively). Patients with migraine had higher scores in both BDI and BAI compared to control group (p = 0.0001 and p = 0.0001 respectively). Severity of pain or frequency of attacks were not found to be related to eating attitudes (r:0.09, p = 0.055). Conclusions: Migraine patients were found to have higher EAT-26, BDI and BAI scores along with a higher rate of referral to a psychiatrist due to symptoms. Results of the study showed that eating habits are altered in migraine patients with higher risk of eating disorders. Depression and anxiety are also found to be common amongst migraine patients. [ABSTRACT FROM AUTHOR]

Background: Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods: The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results: Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions: Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance. [ABSTRACT FROM AUTHOR]

Background: We recently found headache disorders to be highly prevalent among children (aged 6–11 years) and adolescents (aged 12–17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study. Methods: In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country's diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains. Results: The analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores reflected these measures of burden. Conclusions: Headache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials.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®).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.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.In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV‐related contraindications. [ABSTRACT FROM AUTHOR]

Background: Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine. Methods: Anonymized surveys coupled with medical claims data from individuals 19–74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and "other headache disorders"). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions. Results: Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with "Symptoms associated with headache" were "Site of pain" (7.3%), "Headache changes in severity during daily activities" (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were "Stiff shoulders" (13.6%), "Stiff neck" (9.4%), or "Nausea or vomiting" (8.7%), Photophobia" (3.3%) and "Phonophobia" (2.5%). Conclusions: Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of "other headache" was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia. Highlights: It is difficult to correctly identify "symptoms associated with headache" in a single response survey. Surveys with questions regarding photophobia and phonophobia should be carefully designed to help headache classification. It is necessary to educate patients to understand the symptoms of photophobia and phonophobia. [ABSTRACT FROM AUTHOR]

Objectives Background Methods Results Conclusion The primary objective of this study was to evaluate the prevalence of white matter hyperintensities (WMHs) in patients who experience migraine and compare findings between adult male and female patients. Specific symptoms and comorbidities also were analyzed to determine whether they were associated with WMH prevalence or the sex of patients with migraine. We hypothesized that females would have a higher prevalence of WMHs, experience more frequent and more severe migraine headaches, and be more likely to have certain comorbidities associated with migraine than males.An increased prevalence of WMHs in patients with migraine has been proposed, although this relation is not well‐supported by data from population‐based MRI studies. The difference in brain morphology between males and females is of research interest, and females in the general population appear to have a higher prevalence of WMHs. Sex differences and various comorbidities in patients with migraine relative to the number of WMHs on brain imaging have not been fully investigated.This was a cross‐sectional study of 177 patients aged 18 years and older with a diagnosis of migraine who were seen in the Lehigh Valley Fleming Neuroscience Institute's Headache Center between January 1, 2000, and January 1, 2017. Patients' baseline characteristics were extracted from electronic medical records, including demographics, review of systems documentation, and brain imaging from MRI. Variables including headache severity, frequency of head pain, insomnia, and comorbidities (anxiety, depression, diabetes, hyperlipidemia, hypertension, and neck pain) also were analyzed for associations with the presence of WMHs.Females were found to have a significantly higher number of WMHs than males (median 3 [IQR: 0–7] vs. 0 [IQR: 0–3], p = 0.023). Patients with WMHs were significantly more likely than those without WMHs to have hypertension (39.8% of patients with WMHs vs. 20.3% without WMHs, p = 0.011), constipation (20.9% vs. 8.3%, p = 0.034), and sleep disorder (55.7% vs. 37.3%, p = 0.022). Females with migraine were significantly more likely to experience constipation than males (20.0% vs. 2.9%, p = 0.015). None of the migraine characteristics studied (frequency, severity, presence of aura) were different between sexes, nor were they significantly associated with the presence of WMHs.This study suggests that females with migraine may be more likely to have WMHs and experience constipation than males with migraine. Migraine frequency and severity were not different between sexes, nor were they significantly associated with the presence of WMHs. The findings of this study do not support a specific etiology of WMH development in individuals with migraine that differs from findings in the general population. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion To evaluate the real‐world effectiveness of eptinezumab for migraine prevention in Asian patients.Eptinezumab is a monoclonal antibody that targets calcitonin gene‐related peptide (CGRP), a potent vasodilator with an important role in migraine pathophysiology. Although there is robust clinical evidence from pivotal Phase 3 placebo‐controlled trials of the efficacy of eptinezumab for migraine prevention, there are limited data on the real‐world effectiveness of eptinezumab in Asian patient cohorts.This was a non‐interventional, prospective, multisite cohort study of adults with migraine (International Classification of Headache Disorders, 3rd edition criteria) in Singapore who were prescribed eptinezumab (100 mg at baseline and Month 3, administered intravenously) and were followed until Month 6. The primary endpoint was change from baseline in monthly migraine days (MMDs) at Month 3 and Month 6. Secondary endpoints were ≥30% and ≥50% responder rates, and change from baseline in the Headache Impact Test‐6 (HIT‐6), Migraine Disability Assessment (MIDAS), Migraine‐Specific Quality of Life (MSQ), patient‐identified most bothersome symptom (PI‐MBS), acute medication use at Month 3 and Month 6, and safety.Enrolled patients (completed = 29/30) had on average 3.4 (SD 2.9) previous preventive treatments; 29/30 of the patients had trialed at least one previous preventive treatment without benefit. Most had previously trialed oral preventives (87%, 26/30) and anti‐CGRP (70%, 21/30). Relative to baseline, mean MMDs decreased by 4.3 days (95% CI 2.1–6.4; p < 0.001) at Month 3 and 4.9 days (95% CI 2.1–7.7; p < 0.001) at Month 6. At Month 3 and Month 6, 14/30 (47%) and 15/29 (52%) of the patients were ≥30% responders, and 6/30 (20%) and 8/29 (28%) patients were ≥50% responders, respectively. The number of patients with severe life impairment based on the HIT‐6 score (total score 60–78) decreased from 24/30 (80%) at baseline to 19/30 (63%) at Month 3 and 19/29 (66%) at Month 6. The mean MIDAS score decreased by 24.6 points (95% CI 2.82–46.38; p = 0.028) at Month 6, and the mean MSQ score increased by 12.2 points (95% CI 5.18–19.20; p = 0.001) at Month 3 and 13.6 points (95% CI 4.58–22.66; p = 0.004) at Month 6. Most patients reported improvement in the PI‐MBS at Month 3 (73%, 22/30) and Month 6 (55%, 16/29). Acute medication use for headache relief decreased by 3.3 days/month (95% CI 1.0–5.6; p = 0.007) at Month 3 and 4.7 days/month (95% CI 1.7–7.7; p = 0.003) at Month 6. Treatment‐emergent adverse events (TEAEs) were reported in 16/30 (54%) patients, mostly mild/moderate in severity. No serious TEAEs led to treatment discontinuation.Quarterly eptinezumab administration was effective and well‐tolerated in Asian patients with chronic migraine. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Erenumab is a fully human monoclonal antibody that selectively targets the calcitonin gene–related peptide receptor. It has been proven to be safe and efficacious in patients with episodic migraine (EM) and chronic migraine (CM) as demonstrated in phase 2 and 3 clinical trials including patients from Europe, Japan, and the United States. Reversion from CM to EM, as indicated by a reduction in the frequency of headache days, is an important indicator for efficacy outcome, though it has not been analyzed widely in patients with CM to date.Primary results of the DRAGON study demonstrated the efficacy and safety of erenumab in patients with CM from China and other Asian countries. This post hoc analysis evaluated the rate of reversion from CM to EM in the overall population and in subgroups of patients defined by baseline demographic and clinical characteristics (age, body mass index, gender, prior preventive treatment failure, medication overuse status, and disease duration).Reversion from CM to EM was defined as a reduction in headache frequency to < 45 headache days over the 12 weeks of the double‐blind treatment period. In addition, migraine‐related disability and disease impact on functional impairment were assessed within each treatment group in reverters and non‐reverters using the Headache Impact Test‐6 (HIT‐6), Migraine Physical Function Impact Diary (MPFID), and modified Migraine Disability Assessment (mMIDAS).Overall, 557 patients with CM were randomized to monthly erenumab 70 mg (n = 279) or placebo (n = 278), of whom 52.3% (146 of 279) treated with erenumab reverted from CM to EM compared to 41.0% (114 of 278) in the placebo group (odds ratio [OR] 1.59, 95% confidence interval: 1.1–2.2; p = 0.007). Treatment with erenumab resulted in a greater mean change (standard error) from baseline in the HIT‐6 total score for reverters versus non‐reverters compared to placebo (erenumab: −9.5 [0.6] vs. −5.1 [0.5]; placebo: −8.9 [0.7] vs. −4.9 [0.5]). A similar pattern was observed for mMIDAS score in erenumab treatment groups versus placebo (erenumab: −22.1 [1.2] vs. −6.3 [1.8]; placebo: −19.9 [1.3] vs. −7.9 [1.6]). Substantial improvements were reported in MPFID‐Physical Impairment (PI) and Everyday Activities (EA) scores in reverters versus non‐reverters in erenumab treatment groups (MPFID‐PI: −5.9 [0.3] vs. −1.9 [0.6]; MPFID‐EA: −7.9 [0.4] vs. −3.4 [0.6]) and in placebo (MPFID‐PI: −5.4 [0.4] vs. −1.0 [0.5]; MPFID‐EA: −7.1 [0.5] vs. −3.2 [0.5]).This analysis demonstrated that a greater proportion of patients treated with erenumab reverted from CM to EM compared to patients treated with placebo. The reversion from CM to EM was reflected by the greater improvements in patient‐reported outcomes in the erenumab group. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion This study is part of the ODIN‐migraine (Optimization of Diagnostic Instruments in migraine) project. It is a secondary, a priori analysis of previously collected data, and aimed to assess the psychometric properties and factor structure of the Cogniphobia Scale for Headache Disorders (CS‐HD). We aimed to construct a German‐language version and a short version.Cogniphobia is the fear and avoidance of cognitive exertion, which the patient believes triggers or exacerbates headache. High cogniphobia may worsen the course of a headache disorder.The 15‐item CS‐HD was translated into German and back translated in a masked form by a professional translator. Modifications were discussed and carried out in an expert panel. A cross‐sectional online survey including the CS‐HD and further self‐report questionnaires was conducted in a sample of N = 387 persons with migraine (364/387 [94.1%] female, M = 41.0 [SD = 13.0] years, migraine without aura: 152/387 [39.3%], migraine with aura: 85/387 [22.0%], and chronic migraine: 150/387 [38.8%]).Exploratory factor analysis resulted in two clearly interpretable factors (interictal and ictal cogniphobia). Confirmatory factor analysis yielded an acceptable to good model fit (χ2(89) = 117.87, p = 0.022, χ2/df = 1.32, RMSEA = 0.029, SRMR = 0.055, CFI = 0.996, TLI = 0.995). Item response theory‐based analysis resulted in the selection of six items for the short form (CS‐HD‐6). Reliability was acceptable to excellent (interictal cogniphobia subscale: ω = 0.92 [CS‐HD] or ω = 0.77 [CS‐HD‐6]; ictal cogniphobia subscale: ω = 0.77 [CS‐HD] or ω = 0.73 [CS‐HD‐6]). The pattern of correlations with established questionnaires confirmed convergent validity of both the CS‐HD and the CS‐HD‐6.Both the CS‐HD and the CS‐HD‐6 have good psychometric properties and are suitable for the assessment of cogniphobia in migraine. [ABSTRACT FROM AUTHOR]

The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache. [ABSTRACT FROM AUTHOR]

Background: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. Methods: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. Results: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). Conclusions: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective. [ABSTRACT FROM AUTHOR]

Background: Atogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment. Methods: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety issues. An initial response was defined as ≥50%, ≥75%, or 100% reduction from baseline in MMDs in month 1 for ADVANCE or quarter 1 for the LTS trial. The proportions of participants who continued to experience a response above each response-defining threshold through each subsequent month (for ADVANCE) or each quarter (for LTS) were calculated. Results: In ADVANCE, sustained response rates during months 2 and 3 varied with dose and were as follows: 70.8–81.1% following an initial ≥50% response, 47.3–61.9% following an initial ≥75% response, and 34.8–41.7% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during month 1, more than 79% continued to experience at least a 50% response during both months 2 and 3. During the LTS trial, sustained response rates through quarters 2, 3, and 4 were 84.7% following an initial ≥50% response, 72.6% following an initial ≥75% response, and 37.8% following an initial 100% response. Of those who experienced an initial ≥75% or 100% response during quarter 1, more than 90% continued to experience at least a 50% response through quarters 2, 3, and 4. Conclusion: Over 70% of participants who experienced an initial response with atogepant treatment had a sustained response with continued treatment. Trial registration: ClinicalTrials.gov: NCT03777059 (submitted: December 13, 2018); NCT03700320 (submitted: September 25, 2018). [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza.All consecutive patients who met the definition criteria of influenza‐like illness during the influenza seasons 2010–2011 through 2021–2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage.During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020–2021) and 21.69 cases per 1000 patients (season 2017–2018). The prevalence of headache was 66.1% (95% CI = 65.1%–67.1%), varying between 49.6% (season 2021–2022) and 80.1% (season 2010–2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection.Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionGanglion cell layer thickness (GCLT) may be used as a potential marker for central neural changes. We compared GCLT by using spectral domain optical coherence tomography (SD-OCT) in patients with primary headache disorders and healthy controls. We seek whether there was any difference between the headache groups and whether any clinical parameters correlated to GCLT.Fifty-three primary headache patients, 11 age and sex-matched healthy subjects were included in this cross-sectional study after power analysis. All subjects underwent SD-OCT. The duration of disorder, headache frequency, severity, duration of pain, presence of ocular pain, and accompanying symptoms have been collected.Mean GCLT of the headache group was 15.7 ± 3.8 µm (mean ± standard deviation), and the control group was 17.5 ± 2.4. The difference was not statistically significant. When we compared the controls, migraine and tension-type headache patients’ GCLT values, we found a significant difference (ANOVA, p = 0.001). Migraine patients had thinner GCLT compared to all non-migraine headache patients (p = 0.01). Intraocular pressure values of migraine patients and non-migraine patients were not statistically significantly different (p = 0.13). The only clinical parameter that correlated with GCLT was pain duration (r = −0.43 and p = 0.01). The patients with white matter lesions had thinner GCLT (p = 0.046).Our results suggest that not long-term suffering from pain but migraine pathophysiology itself seems to affect neuroretinal tissue. Pain duration was moderately and inversely correlated to GCLT, meaning that the longer the headache, the thinner the ganglion cell layer is. [ABSTRACT FROM AUTHOR]

Background/Objectives: Alexithymia is characterized by a deficit in identifying and communicating feelings. Emerging evidence suggests that alexithymia is highly prevalent in migraine, in a complex interplay with psychiatric comorbidity. Pericranial/cervical muscle tenderness is a remarkable clinical feature in a large proportion of migraine patients. This pilot study aimed at investigating the relationship between alexithymia and pericranial/cervical muscle tenderness in female migraineurs. Methods: A total of 42 female patients fulfilling the diagnostic criteria for migraine were enrolled into this pilot, observational, cross-sectional study after informed consent was obtained. Each patient underwent a psychological assessment to identify any alexithymia by means of TAS-20, anxiety/mood comorbidity (by means of STAI-Y1 STAI-Y2, BDI-II), and migraine-related disability (by means of HIT-6), and a physical cranial/cervical musculoskeletal examination. Palpation of pericranial and cervical muscles was carried out in the standardized manner. A Cumulative Muscle Tenderness (CUM) score (0–6) was calculated for each patient. A multivariate analysis was performed to investigate any association amongst the TAS-20 score, the CUM score, and the following covariates: BDI-II, STAI-Y1, STAI-Y2, and HIT-6 scores, age, disease duration, monthly migraine days, and average head pain intensity in the previous three months. Results: Overall, 35.6% of the sample had alexithymia. The multivariate analysis detected a linear and independent relationship between the TAS-20 and CUM scores, with a statistically significant (p = 0.017) association. Conclusions: This pilot study suggests that alexithymia plays a role in increasing pericranial/cervical muscle tenderness in migraine, independently from psychiatric comorbidity. A novel therapeutical approach, targeting alexithymia, may well reduce muscular tenderness in female migraineurs. [ABSTRACT FROM AUTHOR]

Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients' satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were "fairly happy", 10.6% were "very happy", and 5.5% were "extremely happy"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease. [ABSTRACT FROM AUTHOR]

The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005 shows potent inhibitory activity in vitro. Here, we assessed the effect of AKU-005 in a migraine animal model based on nitroglycerin (NTG) administration. Male rats were treated with AKU-005 (0.5 mg/kg, i.p.) or vehicle 3 h after receiving NTG (10 mg/kg, i.p.) or NTG vehicle. One hour later, rats were subjected to the open field test followed by the orofacial formalin test. At the end of the test, we collected serum samples for assessing calcitonin gene-related peptide (CGRP) levels as well as meninges, trigeminal ganglia, and brain areas to assess mRNA levels of CGRP and pro-inflammatory cytokines, and endocannabinoid and related lipid levels. AKU-005 reduced NTG-induced hyperalgesia during the orofacial formalin test but did not influence NTG-induced changes in the open field test. It significantly reduced serum levels of CGRP, CGRP, and pro-inflammatory cytokine mRNA levels in the meninges, trigeminal ganglia, and central areas. Surprisingly, AKU-005 caused no change in endocannabinoids and related lipids in the regions evaluated. The present findings suggest that AKU-005 may have anti-migraine effects by reducing CGRP synthesis and release and the associated inflammatory events. This effect, however, does not seem mediated via an interference with the endocannabinoid pathway. [ABSTRACT FROM AUTHOR]

Although migraine belongs to the main causes of disability worldwide, the mechanisms of its pathogenesis are poorly known. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective auxiliary markers to support clinical diagnosis. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. We chose the interictal phase as the episodic migraine patients were recruited from the outpatient clinic and had monthly migraine days as low as 1–2 in many cases. Migraine patients displayed lower urinary levels of 5-HIAA (p < 0.01) and KYNA (p < 0.05), but KYN and QA were enhanced, as compared with the controls (p < 0.05 and 0.001, respectively). Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios (p < 0.001 for all). Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score and monthly migraine and monthly headache days. There was a negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be further explored to assess its suitability as an easy-to-determine marker of migraine. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. Methods: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2–3 vs. 0–1) by log-binomial regression, adjusted for confounders. Results: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454–6880) mm3 in women and 4812 (2842–8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. Conclusions: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research. [ABSTRACT FROM AUTHOR]

Background: The humanized monoclonal antibody galcanezumab is an anti-calcitonin-gene-related-peptide (CGRP) and frequently used for migraine prevention. However, the literature revealed limited data with conflicting results. This study aims to assess the safety and efficacy of galcanezumab in treating patients with episodic or chronic migraine. Methods: We searched for randomized controlled trials till September 2022 from six databases (Cochrane library, Embase, PubMed, Web of Science, Scopus, and Clinicaltrials.gov registry). Our primary outcomes were the change in the number of monthly migraine headache days (MHDs) and adverse events. We extracted the data and analyzed it by RevMan (5.4) software. Results: Eight studies with 4964 patients were included. Galcanezumab (≥ 120 mg) significantly reduced the MHDs for six months in migraine patients compared to placebo. The monthly risk ratio (RR) ranged from − 2.33 to − 1.62 for episodic migraine and − 2.86 to − 2.44 for chronic migraine. The response rate of ≥ 50%, ≥ 75% and 100% were higher with galcanezumab groups. The rate ranged from 1.72 to 4.19 for episodic migraine and 1.84 to 2.47 for chronic migraine. It is generally safe except for injection site safety outcomes (erythema, reaction, pruritis, and swelling), the results were significantly higher with galcanezumab groups. It appears dose independent except for injection site reaction, which showed higher with galcanezumab 120 mg only. Furthermore, any adverse events, serious adverse events (SAE) and that led to discontinuation were higher with galcanezumab 240 mg. Conclusion: Galcanezumab is effective in patients with episodic or chronic migraine after one to six months use. It reduced MHDs and had an effective response rate. Moreover, it is generally safe except for injection site adverse events, and SAE, especially with galcanezumab 240mg. [ABSTRACT FROM AUTHOR]

GPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare G-protein-coupled receptor 37-like 1 (GPR37L1) genetic variants found among 51,289 whole-exome sequences from the DiscovEHR cohort. Rare GPR37L1 coding variants were binned according to predicted pathogenicity and analyzed by sequence kernel association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others. Since associations do not prove causality, rare GPR37L1 variants were functionally analyzed in SK-N-MC cells to evaluate potential signaling differences and pathogenicity. Notably, receptor variants exhibited varying abilities to reduce cAMP levels, activate mitogen-activated protein kinase (MAPK) signaling, and/or upregulate receptor expression in response to the agonist prosaptide (TX14(A)), as compared with the wild-type receptor. In addition to signaling changes, knock-out (KO) of GPR37L1 or expression of certain rare variants altered cellular cholesterol levels, which were also acutely regulated by administration of the agonist TX14(A) via activation of the MAPK pathway. Finally, to simulate the impact of rare nonsense variants found in the large patient cohort, a KO mouse line lacking Gpr37l1 was generated. Although KO animals did not recapitulate an acute migraine phenotype, the loss of this receptor produced sex-specific changes in anxiety-related disorders often seen in chronic migraineurs. Collectively, these observations define the existence of rare GPR37L1 variants associated with neuropsychiatric conditions in the human population and identify the signaling changes contributing to pathological processes. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM. [ABSTRACT FROM AUTHOR]

Background: GABA, a key inhibitory neurotransmitter, has synaptic and extrasynaptic receptors on the postsynaptic neuron. Background GABA, which spills over from the synaptic cleft, acts on extrasynaptic delta subunit containing GABAA receptors. The role of extrasynaptic GABAergic input in migraine is unknown. We investigated the susceptibility to valid migraine-provoking substances with clinically relevant behavioral readouts in Genetic Absence Epilepsy of Rats Strasbourg (GAERS), in which the GABAergic tonus was altered. Subsequently, we screened relevant GABAergic mechanisms in Wistar rats by pharmacological means to identify the mechanisms. Methods: Wistar and GAERS rats were administered nitroglycerin (10 mg/kg) or levcromakalim (1 mg/kg). Mechanical allodynia and photophobia were assessed using von Frey monofilaments and a dark-light box. Effects of GAT-1 blocker tiagabine (5 mg/kg), GABAB receptor agonist baclofen (2 mg/kg), synaptic GABAA receptor agonist diazepam (1 mg/kg), extrasynaptic GABAA receptor agonists gaboxadol (4 mg/kg), and muscimol (0.75 mg/kg), T-type calcium channel blocker ethosuximide (100 mg/kg) or synaptic GABAA receptor antagonist flumazenil (15 mg/kg) on levcromakalim-induced migraine phenotype were screened. Results: Unlike Wistar rats, GAERS exhibited no reduction in mechanical pain thresholds or light aversion following nitroglycerin or levcromakalim injection. Ethosuximide did not reverse the resistant phenotype in GAERS, excluding the role of T-type calcium channel dysfunction in this phenomenon. Tiagabine prevented levcromakalim-induced mechanical allodynia in Wistar rats, suggesting a key role in enhanced GABA spillover. Baclofen did not alleviate mechanical allodynia. Diazepam failed to mitigate levcromakalim-induced migraine phenotype. Additionally, the resistant phenotype in GAERS was not affected by flumazenil. Extrasynaptic GABAA receptor agonists gaboxadol and muscimol inhibited periorbital allodynia in Wistar rats. Conclusion: Our study introduced a rat strain resistant to migraine-provoking agents and signified a critical involvement of extrasynaptic δGABAergic receptors. Extrasynaptic δ GABAA receptors, by mediating constant background inhibition on the excitability of neurons, stand as a novel drug target with a therapeutic potential in migraine. [ABSTRACT FROM AUTHOR]

Atogepant, an oral calcitonin gene‐related peptide receptor antagonist, is approved for the preventive treatment of migraine. Atogepant is a substrate of P‐glycoprotein (P‐gp), breast cancer resistance protein, organic anion transporting polypeptide transporters, and cytochrome P450 (CYP)3A4 and 2D6. Quinidine is a strong P‐gp and CYP2D6 inhibitor. A phase 1 open‐label study evaluated the effect of P‐gp and CYP2D6 inhibition by quinidine on the pharmacokinetics of atogepant, and the safety and tolerability of atogepant and quinidine gluconate (QG) when co‐administered and when given alone in 33 healthy adults. There was no significant change in the atogepant maximum plasma concentration with QG co‐administration. The overall systemic exposure, the area under the plasma concentration‐time curve (from time 0 to time t or to infinity), of atogepant increased by 25% when co‐administered with QG. However, such an increase was not considered clinically relevant. Atogepant did not alter the mean plasma concentration of quinidine at steady state. The incidence of treatment‐emergent adverse events (TEAEs) was highest when QG was administered alone (42.4%), which was primarily due to QT prolongation. Most TEAEs reported were mild in severity and resolved within 1‐2 days. Co‐administration of atogepant with QG did not result in any unexpected tolerability findings in this phase 1 study in healthy participants. The increase in atogepant exposure during QG co‐administration could be due to inhibition of CYP2D6 (a minor contributor to atogepant clearance) as well as inhibition of P‐gp. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit.Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders.A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16‐month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age‐ and sex‐matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation.In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0–3.2]; p = 0.338).In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA‐induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene–related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP‐25 through western blot analysis to gain insights into the mechanistic action of BoNT/A.BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post‐inflammation, and alterations in CGRP release were evaluated. Changes in SNAP‐25 levels were determined using western blot analysis.Upon CFA‐induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP‐25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A‐treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release.Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP‐25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model. [ABSTRACT FROM AUTHOR]

Objective: The purposes were to (1) describe the prevalence of clinical profiles and modifiers, (2) examine the association between clinical profiles and prolonged recovery, and (3) examine the interaction between clinical profiles and modifiers and prolonged recovery in adolescents with sport-related concussion (SRC). Design: Retrospective, cross-sectional. Setting: Interdisciplinary specialty sports concussion clinic. Patients: Patients (n = 299) aged 12 to 19 years who were diagnosed with SRC within 30 days of injury. Independent Variables: Clinical profiles and modifiers were decided by the clinical judgment of the clinical neuropsychologist and sports medicine physician, using data from the Clinical Profile Screen and information gathered from the clinical interview, neurocognitive, and vestibular and ocular motor testing. Main Outcome Measures: Prolonged recovery was defined as ≥28 days from the date of injury to the date of clearance. Results: The most common clinical profiles were migraine (34.8%) and cognitive–fatigue (23.4%). There were no significant relationships between clinical profiles and prolonged recovery (Wald = 5.89, df = 4, P = 0.21). The presence of a modifier did not significantly affect the relationship between clinical profiles and prolonged recovery (x²= 6.5, df = 5, P = 0.26). The presence of any modifier yielded a 10-day increase in median recovery time within the cognitive/fatigue clinical profile (Wilcoxon rank-sum = 268.5, P = 0.01). Conclusions: Although patients with a clinical profile and modifier may not experience prolonged recovery, they may experience longer recovery time than patients with a clinical profile and no modifier. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to conduct a pilot, randomized controlled trial (RCT) of acceptance--commitment therapy (ACT) among womenwith episodicmigraine, aged 18-65 years, and living in the United States. Background: Biobehavioral treatments have recently been proposed as possible preventive therapies for migraine management. ACT is a third wave biobehavioral therapy focused on acceptance and development of psychological flexibility and is evidence based for use in other chronic pain conditions. However, its use for reducing migraine frequency and disability has been understudied to date. Methods: The authors performed a pilot RCT evaluating ACT versus enhanced usual care (EUC) among adult women with episodic migraine. ACT consisted of eight virtual weekly sessions (for 8 weeks). Primary aims evaluated feasibility, retention, and protocol adherence. Secondary clinical outcomes included changes in migraine days and Migraine Disability Assessment (MIDAS). Results: We were able to successfully recruit 54 women in 15 months, which surpassed our recruitment goal. However, the completion rates of migraine logs and questionnaires at both outcome assessments were lower than anticipated. Among the 17 individuals randomized to EUC, 12 (71%) completed migraine logs and 12 (71%) completed questionnaires at the end of the intervention. In the postintervention follow-up, 11 (65%) individuals completed logs and 11 (65%) completed questionnaires. We observed slightly larger decreases in migraine days for those assigned to ACT from baseline to the end of the intervention, but these differences did not persist during postintervention follow-up. Both groups reported similar decreases in MIDAS over time. Conclusions: Recruitment for a large-scale trial of ACT is feasible. Challenges with remote data collection as well as participant burden during the COVID-19 pandemic resulted in lower than anticipated completion rates. Future studies should focus on decreasing participant burden and streamlining study procedures. Clinical Trials Registration: NCT05003362. [ABSTRACT FROM AUTHOR]

Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days—MHD; monthly migraine days—MMD; acute medication days/month—AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75–17], 70% (14/20) females). The median basal frequencies were 28.8 [20–28] MHD, 18 [10–28] MMD and 10 [7.5–21.2] AMDM. Compared with baseline, at 6 months (n = 20), 11 patients (55%) were responders, with a median reduction in MHD of −20 days/month (p = 0.001). At 12 months (n = 14), eight patients (57.1%) were responders, with a median reduction in MHD of −17.5 days/month (p = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives. [ABSTRACT FROM AUTHOR]

Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Takotsubo syndrome and transient global amnesia can occur simultaneously, not only in the context of acute but also long‐standing emotional stress. Probably, hypothyroidism and migraine make the patient more susceptible to both of these disorders. [ABSTRACT FROM AUTHOR]

Objective: To analyze data from the Chronic Migraine Epidemiology and Outcomes‐International (CaMEO‐I) Study in order to characterize preventive medication use and identify preventive usage gaps among people with migraine across multiple countries. Background: Guidelines for the preventive treatment of migraine are available from scientific organizations in various countries. Although these guidelines differ among countries, eligibility for preventive treatment is generally based on monthly headache day (MHD) frequency and associated disability. The overwhelming majority of people with migraine who are eligible for preventive treatment do not receive it. Methods: The CaMEO‐I Study was a cross‐sectional, observational, web‐based panel survey study performed in six countries: Canada, France, Germany, Japan, the United Kingdom, and the United States. People were invited to complete an online survey in their national language(s) to identify those with migraine according to modified International Classification of Headache Disorders, 3rd edition, criteria. People classified with migraine answered questions about current and ever use of both acute and preventive treatments for migraine. Available preventive medications for migraine differed by country. MHD frequency and associated disability data were collected. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment (i.e., ≥3 monthly MHDs with severe disability, ≥4 MHDs with some disability, or ≥6 MHDs regardless of level of disability). Results: Among 90,613 valid completers of the screening survey, 14,492 met criteria for migraine and completed the full survey, with approximately 2400 respondents from each country. Based on the AHS consensus statement preventive treatment candidacy algorithm, averaging across countries, 36.2% (5246/14,492) of respondents with migraine qualified for preventive treatment. Most respondents (84.5% [4431/5246]) who met criteria for preventive treatment according to the AHS consensus statement were not using a preventive medication at the time of the survey. Moreover, 19.3% (2799/14,492) of respondents had ever used preventive medication (ever users); 58.1% (1625/2799) of respondents who reported ever using a preventive medication for migraine were still taking it. Of the respondents who were currently using a preventive medication, 50.2% (815/1625) still met the criteria for needing preventive treatment based on the AHS consensus statement. Conclusions: Most people with migraine who qualify for preventive treatment are not currently taking it. Additionally, many people currently taking preventive pharmacologic treatment still meet the algorithm criteria for needing preventive treatment, suggesting inadequate benefit from their current regimen. Plain Language Summary: People with migraine who experience frequent headaches or some level of disability may benefit from using a preventive medication for migraine. We collected data on the use of preventive medication for migraine in Canada, France, Germany, Japan, the United Kingdom, and the United States. These data demonstrated that many people who qualified for the use of a preventive treatment in the six participating countries were not currently taking a preventive medication for migraine. [ABSTRACT FROM AUTHOR]

Objective: In this cross‐sectional observational study, we aimed to investigate sensory profiles and multisensory integration processes in women with migraine using virtual dynamic interaction systems. Background: Compared to studies on unimodal sensory processing, fewer studies show that multisensory integration differs in patients with migraine. Multisensory integration of visual, auditory, verbal, and haptic modalities has not been evaluated in migraine. Method s : A 12‐min virtual dynamic interaction game consisting of four parts was played by the participants. During the game, the participants were exposed to either visual stimuli only or multisensory stimuli in which auditory, verbal, and haptic stimuli were added to the visual stimuli. A total of 78 women participants (28 with migraine without aura and 50 healthy controls) were enrolled in this prospective exploratory study. Patients with migraine and healthy participants who met the inclusion criteria were randomized separately into visual and multisensory groups: Migraine multisensory (14 adults), migraine visual (14 adults), healthy multisensory (25 adults), and healthy visual (25 adults). The Sensory Profile Questionnaire was utilized to assess the participants' sensory profiles. The game scores and survey results were analyzed. Results: In visual stimulus, the gaming performance scores of patients with migraine without aura were similar to the healthy controls, at a median (interquartile range [IQR]) of 81.8 (79.5–85.8) and 80.9 (77.1–84.2) (p = 0.149). Error rate of visual stimulus in patients with migraine without aura were comparable to healthy controls, at a median (IQR) of 0.11 (0.08–0.13) and 0.12 (0.10–0.14), respectively (p = 0,166). In multisensory stimulation, average gaming score was lower in patients with migraine without aura compared to healthy individuals (median [IQR] 82.2 [78.8–86.3] vs. 78.6 [74.0–82.4], p = 0.028). In women with migraine, exposure to new sensory modality upon visual stimuli in the fourth, seventh, and tenth rounds (median [IQR] 78.1 [74.1–82.0], 79.7 [77.2–82.5], 76.5 [70.2–82.1]) exhibited lower game scores compared to visual stimuli only (median [IQR] 82.3 [77.9–87.8], 84.2 [79.7–85.6], 80.8 [79.0–85.7], p = 0.044, p = 0.049, p = 0.016). According to the Sensory Profile Questionnaire results, sensory sensitivity, and sensory avoidance scores of patients with migraine (median [IQR] score 45.5 [41.0–54.7] and 47.0 [41.5–51.7]) were significantly higher than healthy participants (median [IQR] score 39.0 [34.0–44.2] and 40.0 [34.0–48.0], p < 0.001, p = 0.001). Conclusion: The virtual dynamic game approach showed for the first time that the gaming performance of patients with migraine without aura was negatively affected by the addition of auditory, verbal, and haptic stimuli onto visual stimuli. Multisensory integration of sensory modalities including haptic stimuli is disturbed even in the interictal period in women with migraine. Virtual games can be employed to assess the impact of sensory problems in the course of the disease. Also, sensory training could be a potential therapy target to improve multisensory processing in migraine. Plain Language Summary: Patients with migraine process sensory information differently from those without migraine, but multisensory integration (MI), or how the nervous system combines information from each of the senses, has not been studied in detail in patients with migraine. In our study, a video game was used to study the MI of four different senses including seeing, hearing, reading, and touching in 28 women with migraine without aura and 50 healthy women. The gaming performance of women with migraine was negatively affected when hearing, reading, and touching were added to the visual video game experience, and patients with migraine experienced impaired MI even when they did not have a migraine attack. [ABSTRACT FROM AUTHOR]

Background: The Headache Impact Test (HIT‐6) is an important patient‐reported outcome measure (PROM) in migraine prevention trials. Objectives: This study aimed to (i) assess the reliability and validity of the Arabic version of HIT‐6 in Arabic‐speaking patients experiencing migraine, and (ii) evaluate the responsiveness of HIT‐6 following migraine preventive therapy. Methods: In this prospective study, patients with migraine (n = 145) were requested to fill out a headache diary, the Arabic version of HIT‐6, and Migraine Disability Assessment Scale (MIDAS) at two time points (baseline and 3 months after initiation of prophylactic treatment). Some respondents (n = 73) were requested to fill out HIT‐6 again 1 week from the baseline for test–retest reliability. The intensity of migraine headache attacks was evaluated using the Visual Analogue Scale (VAS). An anchor‐based method was used to establish the minimal important change (MIC) value and responsiveness of HIT‐6. Results: The total scores of HIT‐6 were significantly correlated to a fair degree with MIDAS (r = 0.41), as well as VAS (r = 0.53), and monthly migraine days (r = 0.38) at the baseline while at the follow‐up (after 3 months), the correlations were of moderate degree with MIDAS scores (r = 0.62) and monthly migraine days (r = 0.60; convergent validity). Reliability estimates of the Arabic HIT‐6 were excellent (Cronbach's α = 0.91 at baseline and 0.89 at follow‐up). The average measure interclass correlation coefficient (ICC) value for the test–retest reliability was 0.96 (95% confidence interval = 0.94–0.98, p < 0.001). The HIT‐6 total score is sensitive to change, being significantly reduced after prophylactic treatment compared to before (effect size = 1.5, standardized response mean = 1.3). A reduction from baseline of 4.5 on HIT‐6 showed the highest responsiveness to predict improvement with an area under the curve equal to 0.66, sensitivity of 80%, specificity of 45%, and significance at 0.021. Changes in the HIT‐6 total score were positively correlated with changes in monthly migraine days (r = 0.40) and VAS scores (r = 0.69) but not with changes in the score of MIDAS (r = 0.07). Conclusion: The Arabic version of HIT‐6 is valid, reliable, and sensitive to detect clinical changes following migraine prophylactic treatment with a MIC of 4.5 points. Plain Language Summary: The Arabic version of the Headache Impact Test (HIT‐6) is a valid, reliable tool in measuring the impact of headache in culturally different Arabic‐speaking patients experiencing migraine. The Arabic version of HIT‐6 is sensitive to detect changes in headache‐related disability following migraine preventive therapy. A change of 4.5 points or more in the total score of the Arabic version of HIT‐6 following migraine preventive therapy represents a clinically important change. [ABSTRACT FROM AUTHOR]