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Background: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine., Methods: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database., Results: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10 - 7 ): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10 - 9 ). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure., Conclusion: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology., Trial Registration: Not applicable., (© 2024. The Author(s).)

Purpose of Review: Chronic migraine (CM) is a highly disabling primary headache disorder with a substantial impact on patients' quality of life. Episodic migraine (EM) and CM are dynamic states; CM usually evolves from EM alongside increased headache frequency, comorbidities, and medication overuse, supporting the notion that migraine is a spectrum disorder. This narrative review aims to summarize neuroimaging studies to better understand the pathophysiology of CM., Recent Findings: Positron emission tomography studies have revealed abnormal energy metabolism and metabolic changes in the dorsal rostral pons in individuals with CM, suggesting that this structure has a key role in the pathophysiology of migraine generation and chronification. Magnetic resonance spectroscopy studies have suggested that thalamocortical pathway dysfunction may contribute to migraine chronification, while functional magnetic resonance imaging studies have highlighted that hypothalamic activity may be involved. Recent evidence highlights functional and structural alterations in cortical and subcortical pain-related brain regions in patients with CM. Whether these functional and structural abnormalities of the brain cause migraine chronification or are a consequence of repeated attacks is still debated. In the future, imaging patterns that predict the transformation from EM to CM should be identified., (© 2022. Crown.)

Purpose of Review: This review provides an update on sex differences in chronic migraine (CM), with a focus on clinical characteristics, pathophysiology, and treatments., Recent Findings: Approximately 6.8-7.8% of all migraineurs have CM, with an estimated prevalence of 1.4-2.2% in the general population. The economic burden caused by CM, including medical costs and lost working ability, is threefold higher than that caused by episodic migraine (EM). Notably, the prevalence of migraine is affected by age and sex. Female migraineurs with CM experience higher levels of headache-related disability, including longer headache duration, higher frequency of attacks, and more severely impacted efficiency at work. Sex hormones, including estrogen, testosterone, and progesterone, contribute to the sexually dimorphic characteristics and prevalence of migraine in men and women. Recent neuroimaging studies have indicated that migraine may have a greater impact and cause greater dysfunction in the organization of resting-state functional networks in women. Accumulating evidence suggests that topiramate, Onabotulinumtoxin A and calcitonin gene-related peptide (CGRP) monoclonal antibodies are effective as the preventative treatments for CM. Recent evidence highlights a divergence in the characteristics of CM between male and female populations. The data comparing the treatment response for CM regarding sex are lacking., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Considering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population., Methods: We conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups., Results: We discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM [Formula: see text] 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM., Conclusions: To our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis., (© 2021. The Author(s).)

Background and Objectives: Migraine has been associated with many comorbidities. However, lifestyle factors and the presence of comorbid diseases have not previously been extensively studied in the same sample. This study aimed to compare the prevalence of unhealthy lifestyle factors and comorbid diseases between patients with migraine and migraine-free controls with subgroup analyses to determine the pathophysiology and possible consequences., Methods: This cross-sectional study recruited 1257 patients with migraine between the ages of 20 and 65 years from a headache outpatient clinic in Taiwan and 496 non-migraine controls. All participants completed questionnaires regarding demographics, migraine diagnosis, sleep, headache burden, and medical, pain, and psychiatric conditions. Participants also underwent a structured interview. The associations between comorbidities and migraine were investigated and further stratified by sex and aura., Results: Patients with migraine with aura had an unhealthier lifestyle compared with controls in the form of current smoking status (15.5% [67/431] vs. 11.5% [57/496], p = 0.013). Furthermore, medical- (e.g., thyroid disease; 7.2% [91/1257 vs. 2.8% [14/496]; p = 0.006), psychiatric- (e.g., depression; 6% [76/1257 vs. 2.6% [13/496]; p = 0.031), and pain-related (e.g., fibromyalgia; 8% [101/1257 vs. 3.2% [16/496]; p = 0.006) comorbidities were more prevalent in patients compared with controls. Subgroup analyses revealed that chronic migraine, migraine with aura, and female sex were associated with a greater number of significant comorbidities than episodic migraine, migraine without aura, and male patients with migraine, respectively., Conclusion: Individuals seeking treatment for migraine reported greater levels of smoking and medical, psychiatric, and pain conditions than non-treatment-seeking healthy controls who were recruited from the community. Understanding the relationship between migraine and comorbid diseases may improve medical care as well as the quality of life., (© 2021 American Headache Society.)

Study Objectives: While insomnia and migraine are often comorbid, the shared and distinct neuroanatomical substrates underlying these disorders and the brain structures associated with the comorbidity are unknown. We aimed to identify patterns of neuroanatomical substrate alterations associated with migraine and insomnia comorbidity., Methods: High-resolution T1-weighted images were acquired from subjects with insomnia, migraine, and comorbid migraine and insomnia, respectively, and healthy controls (HC). Direct group comparisons with HC followed by conjunction analyses identified shared regional gray matter volume (GMV) alterations between the disorders. To further examine large-scale anatomical network changes, a seed-based structural covariance network (SCN) analysis was applied. Conjunction analyses also identified common SCN alterations in two disease groups, and we further evaluated these shared regional and global neuroanatomical signatures in the comorbid group., Results: Compared with controls, patients with migraine and insomnia showed GMV changes in the cerebellum and the lingual, precentral, and postcentral gyri (PCG). The bilateral PCG were common GMV alteration sites in both groups, with decreased structural covariance integrity observed in the cerebellum. In patients with comorbid migraine and insomnia, shared regional GMV and global SCN changes were consistently observed. The GMV of the right PCG also correlated with sleep quality in these patients., Conclusion: These findings highlight the specific role of the PCG in the shared pathophysiology of insomnia and migraine from a regional and global brain network perspective. These multilevel neuroanatomical changes could be used as potential image markers to decipher the comorbidity of the two disorders., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: Several single-nucleotide polymorphisms (SNPs) are associated with restless legs syndrome (RLS). This study investigated whether or not additional SNP variants increase the risk of RLS in migraineurs and in migraine with aura (MA) and migraine without aura (MoA) subgroups., Methods: Migraineurs with and without RLS were genotyped using an Affymetrix array. We performed association analyses for the entire cohort and the MA and MoA subgroups, which were divided further into episodic migraine (EM) and chronic migraine (CM). Potential correlations between SNPs and clinical indices in migraineurs with RLS were examined by multivariate regression analysis., Results: The rs77234324 and rs79004933 SNPs were found in migraineurs with (P = 2.57E-07) and without (P = 3.03E-07) RLS. The A allele frequency for rs77234324 (on LGR6) was 0.1321 in migraineurs with RLS and 0.0166 in those without RLS (odds ratio, 8.978). The T allele frequency for rs79004933 (in the intergenic region) was 0.1981 in migraineurs with RLS and 0.0446 in those without (odds ratio, 5.281). rs2858654, rs76770509, rs4243475 in UTRN, rs150762626, and rs2668375 were identified in migraine with and without RLS in the MoA subgroup (P = 7.56E-09, P = 2.30E-08, P = 1.19E-07, P = 6.86E-07, and P = 8.05E-07, respectively). There was a suggestion of an association between rs10510331 (P = 1.50E-06) and CM and EM in patients with MoA and RLS. Multivariate regression showed a significant relationship between rs79004933 and the Beck Depression Inventory score., Interpretation: rs77234324 in LGR6 and rs79004933 in the intergenic region were associated with RLS in migraineurs. Five SNPs increased the risk of RLS in patients with MoA., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: The relationships between family history, sex, age at onset, and migraine occurrence have been documented. However, the associations between these factors across different sexes and subgroups of patients have yet to be elucidated. This study evaluated the association between family history and migraine in male and female patients experiencing episodic and chronic migraine with and without aura., Methods: This cross-sectional, case-control study included 299 headache-free controls and 885 patients receiving outpatient treatment for migraine. Participants were classified into episodic (1-14 days/month) and chronic (≥15 days/month) migraine groups., Results: Positive family history was significantly more frequently observed in the episodic group than in the chronic group (49.5% vs. 26%; P < 0.001) in male patients, particularly in male patients without aura (50.3% vs. 21.9%; P = 0.003); it was less frequently observed (58.7% vs. 73.7%; P = 0.048) in female patients with aura. Family history was correlated with an earlier age at onset (20.7 years vs. 22.8 years; P = 0.002), particularly in patients without aura (21 years vs. 23.7 years; P = 0.002), who were women (20.9 years vs. 23.9 years; P = 0.002)., Conclusions: Different patterns of association between family history and migraine can be observed between men and women. A positive family history of migraine is correlated with an earlier age at onset, particularly among female patients without aura., Competing Interests: The authors have declared that no competing interests exist.

Migraine has been associated with sleep disturbances. Relationship between sleep quality and migraine frequency is yet to be determined. The present study aimed to investigate sleep disturbances among low-frequency, moderate-frequency, high-frequency, and chronic migraineurs, with and without auras, with well-controlled confounding variables.This cross-sectional controlled study included 357 subjects from an outpatient headache clinic in Taiwan. Standardized questionnaires were utilized to collect demographic, migraine, sleep, depression, anxiety, and restless leg syndrome characteristics in all participants. According to frequency of migraine attacks, patients were divided into 4 groups: with 1 to 4 migraine days per month, 5 to 8 migraine days in a month, 9 to 14 migraine days in a month, and >14 migraine days per month. The Pittsburgh Sleep Quality Index (PSQI) and subgroup items were used to evaluate sleep quality. The association between migraine frequency and sleep quality was investigated using multivariable linear regression and logistic regression.The PSQI total score was highest in patients with high frequent migraine (10.0 ± 3.4) and lowest in controls (7.0 ± 3.4) with a significant trend analysis (P for trend = 0.006). Migraine frequency had an independent effect on the items "Cannot get to sleep within 30 minutes" (P < 0.001), "Wake up in the middle of the night or early morning" (P < 0.001), "Bad dreams" (P = 0.001), "Pain" (P = 0.004), and "Quality of sleep" (P < 0.001). The result showed the effect of migraine frequency in both the aura-present (P for trend = 0.008) and the aura-absent subgroups (P for trend = 0.011).High migraine frequency correlates with poor sleep quality and a higher prevalence of poor sleepers. These associations occur in migraine with aura and without aura.

Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system. Headache has been reported as a subtle symptom of the onset of MS, with a variable frequency of 1.6-28.5%; however, it remains unclear whether headache is a true symptom of MS onset. Here, we report the case of a female patient who had a history of migraine without aura and experienced worsening of migraine-headache symptoms as the initial manifestation of MS. Three similar cases were reported previously; however, unlike this case, those cases had no history of migraine without aura. In our case, we excluded factors that could trigger migraine attacks, such as changes in weather, drugs, alcohol, caffeine withdrawal, stress, fatigue, lack of sleep, hormonal therapy, diet, and hunger. The patient had one episode of MS attack with the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions, including hyperintense lesions in the bilateral periventricular white matter, body of the corpus callosum, and periaqueductal grey matter, as observed on the T2-weighted images obtained at the first brain magnetic resonance imaging. In addition, after the injection of gadolinium contrast, ring enhancement over these lesions was noted in T1-weighted images, which was suggestive of active demyelination. MS was diagnosed according to the McDonald criteria (2010 revision). We conclude that MS with periaqueductal grey matter involvement may present with worsening migraine. It is important to be cautious if any secondary causes exist, especially when the patient has a history of migraine without aura. MS should be one of the differential diagnoses in young women showing a change in headache pattern or poor clinical drug response to migraine treatment accompanied by episodes of focal neurological deficit. Failure to recognize MS may lead to inappropriate treatment and worse prognosis; early diagnosis in patients with MS is essential to improve their clinical outcomes and quality of life.