Efficacy of various exercise interventions for migraine treatment: A systematic review and network meta-analysis.

OBJECTIVE: To compare various exercise modalities' efficacy on migraine frequency, intensity, duration, and disability. BACKGROUND: Exercise has been shown to be an effective intervention to reduce migraine symptoms and disability; however, no clear evidence exists regarding the most effective exercise modalities for migraine treatment. METHODS: A systematic review was performed in PubMed, PEDro, Web of Science, and Google Scholar. Clinical trials that analyzed the efficacy of various exercise modalities in addressing the frequency, intensity, duration, and disability of patients with migraine were included. Eight network meta-analyses based on frequentist (F) and Bayesian (B) models were developed to estimate the direct and indirect evidence of various exercise modalities. Standardized mean difference (SMD) and 95% confidence (CI) and credible intervals (CrI) were calculated for each treatment effect based on Hedge's g and p scores to rank the modalities. RESULTS: We included 28 studies with 1501 migraine participants. Yoga (F: SMD -1.30; 95% CI -2.09, -0.51; B: SMD -1.33; 95% CrI -2.21, -0.45), high-intensity aerobic exercise (F: SMD -1.30; 95% CI -2.21, -0.39; B: SMD -1.17; 95% CrI -2.20, -0.20) and moderate-intensity continuous aerobic exercise (F: SMD -1.01; 95% CI -1.63, -0.39; B: SMD -1.06; 95% CrI -1.74, -0.38) were significantly superior to pharmacological treatment alone for decreasing migraine frequency based on both models. Only yoga (F: SMD -1.40; 95% CI -2.41, -0.39; B: SMD -1.41; 95% CrI -2.54, -0.27) was significantly superior to pharmacological treatment alone for reducing migraine intensity. For diminishing migraine duration, high-intensity aerobic exercise (F: SMD -1.64; 95% CI -2.43, -0.85; B: SMD -1.56; 95% CrI -2.59, -0.63) and moderate-intensity continuous aerobic exercise (SMD -0.96; 95% CI -1.50, -0.41; B: SMD -1.00; 95% CrI -1.71, -0.31) were superior to pharmacological treatment alone. CONCLUSION: Very low-quality evidence showed that yoga, high- and moderate-intensity aerobic exercises were the best interventions for reducing migraine frequency and intensity; high- and moderate-intensity aerobic exercises were best for decreasing migraine duration; and moderate-intensity aerobic exercise was best for diminishing disability.

Clinical Evaluation After Discontinuation of Galcanezumab in Japanese Patients with Episodic and Chronic Migraine: Analysis of a Randomized, Placebo-Controlled Trial and Open-label Extension Study.

INTRODUCTION: This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). METHODS: Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months' (primary) or 12/18 months' (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months' post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). RESULTS: The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months' GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months' GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. CONCLUSION: Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02959177 and NCT02959190.

Indian Consensus on the Role of Amitriptyline in Migraine Prophylaxis.

Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however, its role as a first-line medication has been debated. A modified Delphi method was used to develop consensus statements on migraine and its management. The literature review identified knowledge gaps, and two survey rounds were conducted among a panel of experts. Consensus was reached for 12 out of 23 initial survey questions, whereas no consensus was reached for four questions after the deliberation in the second round. The results showed that migraine is highly prevalent among women aged 15-35 years in India. Amitriptyline is an effective monotherapy for prophylactic migraine management, with a recommended initial dose of 5-10 mg. A gradual titration over six months achieves optimal results. Amitriptyline is also safe for managing catamenial migraine and can be used at lower doses during pregnancy to alleviate symptoms. The outcomes of this study emphasize that amitriptyline should be considered as a primary prophylactic treatment for migraine because of its efficacy and safety. The evidence-based consensus achieved is intended to serve as guidance for healthcare practitioners in India, and it is anticipated that such adoption will lead to improvement in patient outcomes and an enhancement in the quality of life for those affected by migraines.

The predictive role of the dietary phytochemical index in relation to the clinical and psychological traits of migraine headaches.

We investigated the relationship between dietary phytochemical index (DPI) and migraine headaches in Iranian patients, analyzing both clinical and psychological traits. A cross-sectional study was conducted using non-obese adults aged 20-50 years who were diagnosed with migraine. The study used a validated 168-item food frequency questionnaire to assess the usual dietary intake of participants. The DPI was calculated using the following formula: [daily energy derived from phytochemical-rich foods (in kJ)/total daily energy intake (in kJ)] × 100. Clinical outcomes of migraine including frequency, duration, and severity of headaches, as well as migraine-related disability were obtained using relevant questionnaires. Moreover, the mental health profile of patients including depression, anxiety, and stress, as well as serum levels of nitric oxide (NO) were measured. A Poisson regression was used for headache frequency. Linear regression analyzed migraine-related outcomes including duration, severity, migraine-related disability, and serum NO levels. In addition, psychological traits were analyzed via logistic regression. A total of 262 individuals (85.5% females) with a mean age of 36.1 years were included in the analysis. The frequency of migraine attacks was lower in patients in the last DPI tertile compared to those in the first DPI tertile both in the crude [incidence rate ratio (IRR) = 0.70, 95% confidence interval (CI) 0.63, 0.78, Ptrend < 0.001] and fully-adjusted models (IRR = 0.84, 95% CI 0.74, 0.96, Ptrend = 0.009). After controlling for potential confounders, an inverse relationship was observed between higher adherence to DPI and migraine-related disability (ß = - 2.48, 95% CI - 4.86, - 0.10, P trend = 0.046). After controlling for potential confounders, no significant relationship was observed between DPI and depression (OR = 0.79, 95% CI 0.42, 1.47, Ptrend = 0.480), anxiety (OR = 1.14, 95% CI 0.61, 2.14, Ptrend = 0.655), and stress (OR = 1.04, 95% CI 0.57, 1.90, Ptrend = 0.876). Higher intakes of phytochemical-rich foods may be associated with lower migraine frequency and improved daily activities among patients. Further studies should confirm our observations and delineate the biological pathways linking phytochemicals and migraine headaches.

Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients.

The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.

Individualized spectral filters alleviate persistent photophobia, headaches and migraines in active duty military and Veterans following brain trauma.

PURPOSE: Consistent with association between photophobia and headache, growing evidence suggests an underlying causal relationship between light sensitivity and central pain. We investigated whether an intervention to regulate light sensitivity by filtering only wavelengths causing difficulties for the specific individual could alleviate headaches/migraines resulting from traumatic brain injury (TBI). METHODS: Secondary data analysis of a clinical database including N = 392 military personnel (97% men, 3% women), ranging in age from 20 to 51 years, diagnosed with TBI, persistent headaches/migraines, and light sensitivity. The average elapsed time from TBI diagnosis to intervention was 3 years. Headache/migraine severity, frequency, medication use, and difficulties related to daily functioning were assessed pre and 4-12 weeks post-intervention with individualized spectral filters. RESULTS: Monthly migraine frequency decreased significantly from an average of 14.8 to 1.9, with 74% reporting no migraines post-intervention. Prescription and over-the-counter medication use decreased by more than 70%. Individuals also reported significant improvement in light sensitivity, headaches/migraine severity, and physical and perceptual symptoms. CONCLUSIONS: Wearing individualized spectral filters was associated with symptom relief, increased subjective quality of reported health and well-being, and decreased objective medication use for TBI-related persistent headaches/migraines. These results support a suggested relationship between dysregulated light sensitivity and central regulation of pain.

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Vestibular migraine and persistent postural perceptual dizziness.

Dizziness is a common symptom among patients in primary care, general neurology, and headache clinic practices. Vestibular migraine is conceptualized as a condition of recurrent attacks of vestibular symptoms attributed to migraine. It is now considered the most common cause of spontaneous episodic vertigo. Persistent postural-perceptual dizziness (PPPD) has more recently been defined based on four previous clinical entities as a syndrome of chronic daily dizziness, unsteadiness, or nonspinning vertigo that fluctuates and is exacerbated by postural, motion, or visual factors. Although PPPD is more often precipitated by other conditions causing vertigo, unsteadiness, or dizziness, it is discussed at length in this chapter because vestibular migraine is among the most common triggers for development of PPPD. Pathophysiology of each is incompletely understood, and with lack of biomarkers, the diagnosis of each rests on consensus-derived, symptom-based criteria. Areas of uncertainty exist regarding some overlapping symptoms that may create potential diagnostic confusion between the conditions. This chapter provides a comprehensive review of the current state of vestibular migraine and PPPD, including diagnostic and management guidance for when they occur separately, together, or along with other common comorbidities.

Persistent headache attributed to past ischemic stroke: A prospective cohort study.

OBJECTIVE: To assess the incidence, characteristics, and risk factors for developing persistent headache attributed to past ischemic stroke. BACKGROUND: Although the most recent International Classification of Headache Disorders has recognized the existence of persistent headache attributed to past ischemic stroke, there has been limited research in this area. METHODS: This was a prospective cohort study. We initially assessed patients hospitalized with ischemic stroke admitted within 72 h of symptom onset. All patients underwent diffusion-weighted magnetic resonance imaging. These patients were re-interviewed by telephone 1 year after the stroke. Semi-structured questionnaires, the National Institutes of Health Stroke Scale (NIHSS), and six-item Headache Impact Test were used. RESULTS: A total of 119 participants answered the interview conducted 1 year after the stroke. The mean (standard deviation) age was 64 (13.1) years, 82/119 (68.9%) were female, and the median (interquartile range) NIHSS score was 2 (1.0-4.0). The incidence rate of persistent headache attributed to past ischemic stroke was 12/119 (10.1%; 95% confidence interval [CI] 5.3-17.0%). The most frequent pattern presented was a migraine-like pattern in seven of the 12 (58.3%) patients, which had a substantial/severe impact on five of the 12 (41.7%). For most patients this headache continued, although it began to improve. Previous migraine (odds ratio 7.1, 95% CI 1.06-50.0; p = 0.043) and headache intensity in the acute phase of stroke (odds ratio 1.75, 95% CI 1.13-2.7; p = 0.012) were associated with the occurrence of persistent headache attributed to past ischemic stroke. CONCLUSION: Persistent headache attributed to past ischemic stroke is a frequent complication after stroke. It often has a significant impact on patients' lives and presents a migraine-like pattern as its most frequent phenotype.

Impact of Migraine on Daily Life: Results of the Observational survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME [Japan]) Study.

INTRODUCTION: The impacts of migraine on daily life, including daily activities and fundamental health indicators (sleep and mental health), have not been described in detail for people with migraine in Japan. METHODS: The cross-sectional ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) study was conducted between July and September 2020. Impacts of migraine on housework, family/social/leisure activities, driving, and sleep were assessed using questions from the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire, and Impact of Migraine on Partners and Adolescent Children scales and questions developed for OVERCOME (Japan). The Migraine Interictal Burden Scale (MIBS-4) evaluated burden on days without headaches. Depression and anxiety were assessed with the Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder (GAD-7) scales, respectively. Impacts on daily life were also described across MIDAS/MIBS-4 categories. RESULTS: Among 17,071 respondents with migraine, 24.8% required assistance with housework at least sometimes. Migraine interfered with relationships, leisure, and social activities at least sometimes for 31.8%, 41.6%, and 18.0% of respondents, respectively. Between headache days, 26.8% of respondents worried about planning social/leisure activities at least sometimes. Among respondents living with family (N = 13,548), migraine also had impacts on participation in and enjoyment of family activities. Among respondents who drove (N = 10,921), 43.9% reported that symptoms interfered with driving at least sometimes. Migraine interfered with sleep and mood at least sometimes for 52.7% and 70.7% of respondents, respectively. PHQ-8 and GAD-7 thresholds for clinical depression and anxiety were met by 28.6% and 22.0% of respondents, respectively. Impact of migraine on daily life increased with increasing severity of MIDAS/MIBS-4 categories. CONCLUSION: The burden of migraine on daily activities, sleep, and mental health is substantial for people with migraine in Japan. In clinical practice, it is important to evaluate the impact of migraine on daily life in addition to migraine symptoms.

Age as a predictive factor for reduced intracranial compliance in patients with headache / Idade como fator preditor de complacência intracraniana reduzida em pacientes com cefaleia

Abstract Background Increased intracranial pressure (ICP) consists of a set of signs and symptoms related to changes in intracranial compliance (ICC) and ICP. Objective This study presents a retrospective analysis of patients who underwent non-invasive monitoring of ICC based on complaints of headache, correlating decreased brain compliance and increased intracranial pressure. Methods Noninvasive ICC monitoring was performed using a Brain4care device, which contains a strain gauge and a recorder connected to a mechanical device that touches the scalp surface in the frontoparietal area lateral to the sagittal suture. This tool monitors the ICP by identifying small changes in skull measurements that are caused by pressure variations, i.e., skull deformation is associated with the detection of changes in mean ICP. A clinical evaluation of 32 patients with complaints of headache occurred from the analysis of their medical records. Results Of the 32 patients initially chosen, it was possible to complete the analysis of 18 due to the availability of data in the medical records. From the non-invasive monitoring of the ICC, the following data were collected: time-to-peak, P2/P1 ratio, age, and gender. From the statistical analysis of age and P2/P1 ratio, it was noted that as age increases, ICC tends to decrease regardless of sex (p < 0.05). Conclusion This study concluded that there is a correlation between changes in intracranial compliance and headache complaints in outpatients. There was also a relationship between age and decreased intracranial compliance but without a specific pain pattern.

Resumo Antecedentes O aumento da pressão intracraniana (PIC) consiste em um conjunto de sinais e sintomas relacionados a mudanças na complacência intracraniana (CIC) e na PIC. Objetivo Este estudo apresenta uma análise retrospectiva de pacientes que foram submetidos ao monitoramento não invasivo da CIC com base em queixas de cefaleia, correlacionando a diminuição da complacência cerebral e o aumento da pressão intracraniana. Métodos O monitoramento não invasivo da CIC foi realizado utilizando um dispositivo Brain4Care, que contém um medidor de tensão e um gravador conectado a um dispositivo mecânico que toca a superfície do couro cabeludo na área frontoparietal lateral à sutura sagital. Esta ferramenta monitora a PIC identificando pequenas alterações nas medidas do crânio que são causadas por variações de pressão, ou seja, a deformação do crânio está associada à detecção de alterações na PIC média. Uma avaliação clínica de 32 pacientes com queixas de cefaleia ocorreu a partir da análise de seus prontuários médicos. Resultados Dos 32 pacientes inicialmente escolhidos, foi possível concluir a análise de 18 devido à disponibilidade de dados nos prontuários médicos. A partir do monitoramento não invasivo da CIC, foram coletados os seguintes dados: time-to-peak, relação P2/P1, idade e sexo. Da análise estatística de idade e relação P2/P1, observou-se que à medida em que a idade aumenta, a CIC tende a diminuir independentemente do sexo (p < 0,05). Conclusão Este estudo concluiu que existe uma correlação entre as mudanças na CIC e a queixa de cefaleia em pacientes ambulatoriais. Houve também uma relação entre idade e diminuição da CIC, mas sem um padrão de dor específico.

Exploring Facial Thermography Patterns in Women with Chronic Migraine.

(1) Background: Chronic migraine is a debilitating neurological condition affecting millions worldwide. This study delves into the facial point-of-care (POC) thermographic patterns of women with chronic migraine, aiming to shed light on the condition's pathophysiology and diagnostic potential. (2) Methods: Using infrared POC thermography, the facial temperature distribution of 24 female participants with chronic migraine were analyzed. (3) Results: The findings revealed significant temperature asymmetry in women with right-sided unilateral headaches, particularly in the right frontal and temporal regions. Notably, individuals with bilateral pain did not exhibit thermal pattern differences, suggesting potential diagnostic complexities. While these results offer valuable insights, further research with larger samples is warranted (4) Conclusions: Facial thermography holds promise as an adjunctive tool for migraine diagnosis and understanding its neurophysiological basis; however, cautious interpretation is advised, given the need for validation and expanded investigations. Improved diagnostic criteria and treatment strategies may emerge from this ongoing exploration, ultimately enhancing the quality of life of chronic migraine sufferers.

Prevalence and Associated Factors of Depression among Adults Suffering from Migraine in Spain.

Considering the significance of migraine and the limited amount of research conducted on its association with depression in population-based studies in Spain, this study aimed to determine the prevalence and change of depression from 2017 to 2020 among adults with migraine in Spain and to analyze the sociodemographic and health-related variables linked to depression in migraine sufferers. A cross-sectional study on 5329 adults with migraine from the Spanish National Health Survey 2017 and the European Health Survey in Spain 2020 was performed. Binary logistic regression was used to examine the factors related to depression. A total of 26.32% of people with migraine suffered from depression. No significant changes in that prevalence between 2017 and 2020 were observed. The risk factors associated with depression included being between the ages of 25 and 44 (p = 0.018), being separated or divorced (p = 0.033), being unemployed (p < 0.001), not engaging in recreational physical activity (p = 0.016), perceiving one's health as average, poor, or very poor (p < 0.001), experiencing moderate to severe pain in daily activities (p = 0.011, p = 0.004, p < 0.001, respectively), and having 1-2 or ≥3 chronic conditions (p = 0.003, p < 0.001, respectively). Conversely, being married (p = 0.001) and alcohol consumption (p = 0.007) were identified as protective factors.

The history and rationale of the development of new drugs for migraine treatment / A história e os fundamentos do desenvolvimento de novos medicamentos para o tratamento da migrânea

Abstract Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen its individual, social, and economic impact. This is a narrative review of the main drugs used for treating migraine, as well as the experimental models and the theoretical frameworks that led to their development. Ergot derivatives, triptans, non-steroid anti-inflammatory drugs, tricyclic antidepressants, beta-blockers, flunarizine, valproic acid, topiramate, onabotulinumtoxin A, ditans, monoclonal antibodies against CGRP and its receptor, and gepants are discussed. Possible therapeutic targets for the development of new drugs that are under development are also addressed. Many of the drugs currently in use for treating migraine were developed for the treatment of other diseases, but have proven effective for the treatment of migraine, expanding knowledge about the disease. With a better understanding of the pathophysiology of migraine, new drugs have been and continue to be developed specifically for the treatment of this disease.

Resumo A migrânea é uma das doenças mais prevalentes e incapacitantes do mundo. O tratamento da crise de migrânea e o tratamento profilático da doença são essenciais para diminuir o seu impacto individual, social e econômico. Este é um artigo de revisão narrativa. Revisamos as principais drogas usadas para a migrânea e os modelos experimentais e referenciais teóricos que levaram ao seu desenvolvimento. Foram abordados os derivados do ergot, triptanas, anti-inflamatórios não hormonais, antidepressivos tricíclicos, betabloqueadores, flunarizina, ácido valproico, topiramato, toxina onabotulínica do tipo A, os ditans, anticorpos monoclonais contra o CGRP e seu receptor e os gepants. Também foram abordados possíveis alvos terapêuticos para o desenvolvimento de novas drogas e drogas que estão em desenvolvimento para o tratamento da migrânea. Muitas das drogas usadas atualmente foram desenvolvidas para o tratamento de outras doenças e se mostraram efetivas para o tratamento da migrânea. Essas ajudaram a ampliar o conhecimento sobre a doença. Com o melhor entendimento da fisiopatologia da migrânea, novas drogas foram e estão sendo desenvolvidas especificamente para o tratamento dessa doença.

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Association between weight status and migraine in the paediatric population: a systematic review and meta-analysis.

Introduction: An association between weight status and migraine has been previously reported; however, this relationship has only been studied in adults, not in the paediatric population. Objective: To evaluate the association between weight status and migraine in the paediatric population. Methods: We searched PubMed/Medline, Scopus, Web of Science, Ovid Medline, and Embase using a cut-off date of May 2023. We included observational studies that evaluated the association between weight status (underweight, overweight, obese, and excess weight) and migraine in the paediatric population (children and adolescents). Normal weight was the comparator. The outcome was migraine (all types, episodic and chronic). We performed meta-analyses using a random-effects model to estimate the pooled effects for each outcome. Sensitivity analysis was performed based on study design and risk of bias (using the Newcastle-Ottawa Scale). Certainty of evidence was assessed using the GRADE approach. Results: Eight studies (6 cross-sectional, 1 case-control and 1 cohort) covering 16,556 patients were included. The overall certainty of evidence was very low for the association between overweight, obesity, and excess weight with migraine. In the sensitivity analysis, meta-analyses of studies with a low risk of bias found that the overweight population probably had an increased odds of migraine (OR: 1.70; 95% CI: 1.14 to 2.53; I2 = 32.3%, p = 0.224) and that excess weight may increase the odds of migraine (OR: 1.58; 95% CI: 1.06 to 2.35; I2 = 83.7%, p = 0.002). Additionally, cohort and case-control studies found that obesity probably increases the odds of migraine. No studies analysed the association between underweight and migraine. Conclusion: The associations between overweight, obesity, excess weight and migraine were uncertain, but studies with better methodological quality reported increased odds. Future longitudinal studies with proper confounding control are needed to disentangle their causal relationship. Systematic review registration: PROSPERO, identifier CRD42021271533.

Association analysis of serotonin transporter gene polymorphism among the South-Indian migraineurs.

Background: Migraine is a multifactorial neurological disorder characterized by frequent moderate to severe intensity headaches. The genetic variations in synaptic and post-receptor signalling proteins have direct effect on the process of serotonergic neurotransmission. Methods: We aimed to investigate the genetic association of serotonin transporter (SERT) 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism and migraine risk in South-Indian population. A total of 304 subjects with migraine including with aura (MA) and without aura (MO) and 308 controls were included in the present study. The single nucleotide polymorphism (SNP) was detected using polymerase chain reaction (PCR) and confirmed by deoxyribonucleic acid (DNA) sequencing. Results: The genotyping analysis revealed insignificant relationship with migraine subjects when compared with controls (P > 0.05). The minor 'S' allele showed no association with odds ratio (OR) = 1.23 [95% confidence interval (CI): 0.90-1.66], heterozygote with OR = 1.18 (95% CI: 0.82-1.69), and homozygote with OR = 1.51 (95% CI: 0.52-4.35). Conclusion: Further clinical studies are required to validate the results of SERT 5-HTTLPR promoter polymorphism in diverse ethnic descents especially in Asian populations.

Association of dietary patterns with migraine: A matched case-control study.

Background: Little is known about the association between dietary patterns and odds of migraine. We aimed to investigate the association between posteriori dietary patterns and migraine odds and migraine-related outcomes using principal component analysis (PCA). Methods: A total of 500 participants enrolled in this age- and sex-matched case-control study. Subjects in the case group were migraine patients who were diagnosed by a neurologist (n = 250) and subjects in the control group were healthy individuals (n = 250). Dietary intake was assessed using a 168-item semi-quantitative Food Frequency Questionnaire (FFQ). Extraction of dietary patterns was performed via PCA. Information on the wide range of covariates and migraine-related outcomes were collected. Results: The 2 major dietary patterns of the "Western diet" and "prudent diet" were extracted using PCA. Those who were in the highest quartile of the prudent diet had the lowest odds of migraine in the fully adjusted model [odds ratio (OR) = 0.10; 95% confidence interval (CI): 0.04-0.21]. Additionally, higher adherence to the Western diet was positively associated with migraine odds (P ˂ 0.001) and this association remained significant and even increased after adjusting a wide range of confounders. Among migraine sufferers, those who had the highest score on the Western diet, had significantly higher attack frequency compared to the patients in the first quartile (15.4 ± 8.9 vs. 12.3 ± 8.6; P = 0.004). Conclusion: The finding of a significant association between the 2 extracted dietary patterns and migraine odds highlights the possible role of diet in both the prevention and stimulation of migraine.

Increased MRI-based Brain Age in chronic migraine patients.

INTRODUCTION: Neuroimaging has revealed that migraine is linked to alterations in both the structure and function of the brain. However, the relationship of these changes with aging has not been studied in detail. Here we employ the Brain Age framework to analyze migraine, by building a machine-learning model that predicts age from neuroimaging data. We hypothesize that migraine patients will exhibit an increased Brain Age Gap (the difference between the predicted age and the chronological age) compared to healthy participants. METHODS: We trained a machine learning model to predict Brain Age from 2,771 T1-weighted magnetic resonance imaging scans of healthy subjects. The processing pipeline included the automatic segmentation of the images, the extraction of 1,479 imaging features (both morphological and intensity-based), harmonization, feature selection and training inside a 10-fold cross-validation scheme. Separate models based only on morphological and intensity features were also trained, and all the Brain Age models were later applied to a discovery cohort composed of 247 subjects, divided into healthy controls (HC, n=82), episodic migraine (EM, n=91), and chronic migraine patients (CM, n=74). RESULTS: CM patients showed an increased Brain Age Gap compared to HC (4.16 vs -0.56 years, P=0.01). A smaller Brain Age Gap was found for EM patients, not reaching statistical significance (1.21 vs -0.56 years, P=0.19). No associations were found between the Brain Age Gap and headache or migraine frequency, or duration of the disease. Brain imaging features that have previously been associated with migraine were among the main drivers of the differences in the predicted age. Also, the separate analysis using only morphological or intensity-based features revealed different patterns in the Brain Age biomarker in patients with migraine. CONCLUSION: The brain-predicted age has shown to be a sensitive biomarker of CM patients and can help reveal distinct aging patterns in migraine.

Effectiveness of intraoral splints in the treatment of migraine and tension-type headache: A systematic review.

OBJECTIVES: The main objective of this systematic review was to assess the effectiveness of intraoral splints in treating migraine and tension-type headaches. MATERIAL AND METHODS: The article search was conducted within seven electronic databases (Medline, PubMed, Embase, CINAHL PLUS with full text, Cochrane Library Trials, Web of Science, and Scopus) with no date limits or language restrictions up to June 12, 2022. Strict inclusion and exclusion criteria were set for article selection. At the same time as data extraction, each study's risk of bias (RoB) was evaluated using the Cochrane tool to assess their RoB. Subsequently, the Cochrane Grading of Recommendations Assessment Development and Evaluation was used to evaluate the certainty of the evidence. RESULTS: Four controlled clinical trials were included. These trials were heterogeneous in terms of (1) diagnosis, (2) design of the intraoral splints, and (3) tools for reporting the results, which made it difficult to compile the data as well as evaluate its quality. Trials reported a reduction in the frequency of headache and pain intensity when using intraoral splints; however, this therapy was not superior to medications. CONCLUSIONS: The evidence is very low for the use of oral splints as a therapeutic alternative to medication in the treatment of migraine and/or tension-type headache.