Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

Proteome-wide Mendelian randomization identified potential drug targets for migraine.

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

[Altered functional connectivity of parietal opercular 2 in patients with vestibular migraine: a resting-state fMRI study].

Objective: To investigate the differences in resting-state functional connectivity (FC) between patients with vestibular migraine (VM) and migraine without aura (MwoA) in order to infer the possible neuroimaging mechanisms of VM. Methods: Thirty VM patients admitted to the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from December 2019 to December 2022 were selected as the experimental group (EG) (6 males and 24 females, with mean age of 38.3 years) and 26 MwoA patients as the control group (7 males and 19 females, mean age 35.5 years). General demographic and clinical data such as gender, age, year of education, course of disease and frequency of attacks were collected for all the patients, as well as data of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), headache Visual Arialogue Scale (VAS), Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment Questionnaire (MIDAS). VM patients were also assessed by Dizziness Handicap Inventory (DHI), dizziness VAS and Vestibular Disorders Activities of Daily Living (VADL) scales. All patients underwent resting-sate functional Magnetic Resonance Imaging (fMRI) scans. Bilateral parietal opercular cortex 2 (OP2) and primary visual cortex (V1) were used as regions of interests (ROIs). Differences in FC between ROIs and other brain regions were calculated between the two groups. In view of the brain regions with significant differences, z-values of FC were extracted for each subject in the EG, and Pearson partial correlation analysis was conducted between z-values of FC and clinical characteristics of patients, P<0.05 was considered to have significant correlation. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in gender, age, years of education, course of disease, frequency of attack and scores of MoCA, HAMA and HAMD between the two groups (P>0.05). Headache VAS, HIT-6 and MIDAS scores in VM patients were significantly lower than those in MwoA patients (P<0.05). Compared with MwoA patients, the FC between left OP2 and bilateral precuneus and left thalamus was significantly increased in VM patients, and the FC between right OP2 and left thalamus and right anterior cingulate gyrus were significantly increased (P<0.05, False Discovery Rate correction). Correlation analysis showed that the FC between left OP2 and left precuneus was positively correlated with DHI score in VM patients (P=0.007, r=0.480), and the FC between right OP2 and left thalamus was positively correlated with the disease course in VM patients (P=0.015, r=0.439). Conclusions: The pathogenesis of VM may be related to the altered FC of vestibular, pain and visual-motor networks, abnormalities of these neural pathways may be important imaging biomarkers of VM pathogenesis.

Enhanced audiovisual associative pair learning in migraine without aura in adult patients: An unexpected finding.

BACKGROUND: Altered sensory processing in migraine has been demonstrated by several studies in unimodal, and especially visual, tasks. While there is some limited evidence hinting at potential alterations in multisensory processing among migraine sufferers, this aspect remains relatively unexplored. This study investigated the interictal cognitive performance of migraine patients without aura compared to matched controls, focusing on associative learning, recall, and transfer abilities through the Sound-Face Test, an audiovisual test based on the principles of the Rutgers Acquired Equivalence Test. MATERIALS AND METHODS: The performance of 42 volunteering migraine patients was compared to the data of 42 matched controls, selected from a database of healthy volunteers who had taken the test earlier. The study aimed to compare the groups' performance in learning, recall, and the ability to transfer learned associations. RESULTS: Migraine patients demonstrated significantly superior associative learning as compared to controls, requiring fewer trials, and making fewer errors during the acquisition phase. However, no significant differences were observed in retrieval error ratios, generalization error ratios, or reaction times between migraine patients and controls in later stages of the test. CONCLUSION: The results of our study support those of previous investigations, which concluded that multisensory processing exhibits a unique pattern in migraine. The specific finding that associative audiovisual pair learning is more effective in adult migraine patients than in matched controls is unexpected. If the phenomenon is not an artifact, it may be assumed to be a combined result of the hypersensitivity present in migraine and the sensory threshold-lowering effect of multisensory integration.

Successful treatment with traditional Japanese medicine (kampo medicine) Yokukansan as a migraine prophylactic drug: A case report.

RATIONALE: The use of anti-CGRP antibody drugs as migraine preventive drugs is increasing worldwide, but there are still a certain number of cases where antibody drugs are ineffective or cannot be used due to high prices. Conventional prophylactic drugs or traditional Japanese medicine (kampo medicine) are still often used in such cases. However, to date, only limited evidence supports the efficacy of kampo medicine for headaches because these treatments have been used primarily empirically and traditionally. However, in recent years studies have begun to be published that describe the efficacy of kampo medicine for various types of headache. Here, we report the case of a patient who achieved a marked reduction in migraine frequency and severity by prophylactic therapy with the kampo drug yokukansan (TSUMURA Yokukansan Extract Granules). PATIENT CONCERNS AND DIAGNOSES: The patient was a 50-year-old woman. She began to experience headaches around high school age and was diagnosed with migraine without aura at 42 years of age. INTERVENTIONS AND OUTCOMES: She started prophylactic therapy with amitriptyline and topiramate and this treatment reduced the frequency of migraines for several years. However, the frequency began to increase again around 47 years, which is when she presented at our hospital. We achieved a temporary reduction in migraine frequency by adjusting the dose of drugs in her prophylactic therapy regimen, but the frequency increased again around age 49. We then tried monotherapy with the kampo medicine yokukansan, and this markedly reduced migraine frequency and severity over the following year. This therapy has remained effective to date. LESSONS: We speculate that, in this case, migraine without aura was improved by prophylactic therapy with yokukansan due to its action on the glutamatergic system or serotonin system through suppression of orexin-A secretion or its anti-inflammatory effects as reported in previous animal studies. Yokukansan could be a usable kampo medicine for migraine prophylaxis in countries all over the world and should be investigated in a large clinical trial as soon as possible.

Evaluation of retinal perfusion density and foveal avascular zone in migraine subjects with and without aura.

Migraine, classified as a neurovascular disease, has been identified as a potential risk factor for ocular vascular complications. Our study aimed to compare retinal vessel density and perfusion density between subjects with migraine and healthy subjects using optical coherence tomography angiography (OCTA). In this cross-sectional case-control study, we enrolled 30 migraine subjects with aura (MWA), 30 migraine subjects without aura (MWOA) and 30 age and gender-matched healthy controls (HC). The foveal avascular zone (FAZ) in superficial capillary plexus (SCP), Vessel density (VD) and perfusion density (PD) in SCP and deep capillary plexus (DCP) were assessed in a 3 × 3 mm scan of the macula with the swept source OCT. Results indicated that the FAZ of MWA and MWOA subjects was significantly larger from HC. Also, FAZ of MWA was larger from MWOA. VD and PD in both SCP and DCP were significantly reduced in both MWA and MWOA groups compared to HC. However, VD and PD did not show significant differences among MWA and MWOA. Additionally, the duration of disease was the main determinant of the FAZ. In conclusion, the FAZ in the SCP, VD and PD in the SCP and DCP of the macula were affected in both MWA and MWOA. FAZ, specifically, was increased with the evolution of the disease. These findings might contribute to an increased risk of ocular vascular complications among subjects with migraine and could potentially use OCTA as a biomarker for this population.

[Prophylaxis of migraine without aura of liver yang hyperactivity treated with acupuncture at the points selected using the "seven lines of the neck" method: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of prophylaxis on migraine without aura differentiated as liver yang hyperactivity undergoing acupuncture at the points selected using the "seven lines of the neck" method. METHODS: Fifty-eight patients with migraine without aura of liver yang hyperactivity at remission stage were randomly divided into an observation group (29 cases, 3 cases dropped out) and a control group (29 cases, 4 cases dropped out). In the observation group, acupuncture was delivered at Dazhui (GV 14), Fengfu (GV 16), bilateral Fengchi (GB 20), Gongxue (Extra), etc., selected using the "seven lines of the neck" method. In the control group, conventional acupuncture was applied to ashi point, Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5) and others on the affected side. The treatment was given once every other day or every two days, 3 interventions weekly, for consecutive 8 weeks. Before treatment, after 4 and 8 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit), the days of migraine episodes, the frequency of migraine episodes, the score of visual analogue scale (VAS) for pain intensity, and the score of migraine specific quality of life questionnaire (MSQ) were observed in the patients of the two groups. Before treatment and after 8 weeks of treatment, the score of TCM syndrome was observed. After 4 and 8 weeks of treatment and after 4 weeks of treatment completion (follow-up visit), the response rates of 50% reduction in the days and the frequency of migraine episodes were calculated in the two groups. RESULTS: After 4 and 8 weeks of treatment and during follow-up visit, the days and the frequency of migraine episodes were decreased (P<0.01) and VAS scores were declined (P<0.01) when compared with those before treatment in the two groups. The days and the frequency of migraine episodes in the observation group were lower during the follow-up visit (P<0.05) and VAS scores were lower after 8 weeks of treatment and during the follow-up visit (P<0.05) when compared with those in the control group. After 4 and 8 weeks of treatment, and during follow-up visit, the scores of "role function-preventive" and "emotional function" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05). After 8 weeks of treatment and during the follow-up visit, the scores of "role function-restrictive" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05), and the scores of "role function-restrictive" "role function-preventive" and "emotional function" were higher when compared with those before treatment in the control group (P<0.05). After 8 weeks of treatment, the scores of TCM syndrome were decreased in comparison with those before treatment in the two groups (P<0.01). In the observation group, the response rate of 50% reduction in the days of migraine episodes after 8 weeks of treatment and that of the frequency of migraine episodes during the follow-up visit were higher than those of the control group (P<0.05). CONCLUSION: Acupuncture at the points selected using the "seven lines of the neck" method can reduce the days and frequency of migraine episodes and pain intensity, ameliorate the syndrome of TCM and improve the quality of life of the patients with migraine without aura of liver yang hyperactivity.

Investigating the causal association between systemic lupus erythematosus and migraine using Mendelian randomization analysis.

OBJECTIVE: To assess whether systemic lupus erythematosus (SLE) may be genetically causally associated with migraine, including the two primary subtypes: migraine with aura (MWA) and migraine without aura (MWoA). BACKGROUND: The association between SLE and migraine has been investigated extensively. Previous studies have shown a higher prevalence of migraine in patients with SLE, although the exact relationship remains unclear. This study investigated the potential causal association between SLE and migraine using the powerful analytical tool of Mendelian randomization (MR). METHODS: We performed two-sample MR analysis of publicly available summary statistic datasets using inverse variance-weighted (IVW), weighted median, and MR-Egger methods based on an SLE genome-wide association study (GWAS; 5201 cases; 9066 controls; the exposure frequency is 36.5%) as an exposure and migraine GWAS (15,905 cases; 264,662 controls) in individuals with European ancestry as outcomes, focusing on the two migraine subtypes MWA (6780 cases; 264,662 controls) and MWoA (5787 cases; 264,662 controls). Thepleiotropy and heterogeneity were performed. RESULTS: We selected 42 single-nucleotide polymorphisms from SLE GWAS as instrumental variables (IVs) for SLE on migraine, and 41 SNP IVs for SLE on MWA or MWoA. The IVW (odds ratio [OR] = 1.01, 95% confidence interval [CI] = [0.99, 1.03], p = 0.271), weighted median (OR = 1.00, 95% CI = [0.97, 1.03], p = 0.914), and MR-Egger (OR = 1.04, 95% CI = [0.99, 1.09], p = 0.153) methods showed no causal effect of SLE on migraine. A causal effect of SLE was observed on MWA (IVW: OR = 1.05, 95% CI = [1.02, 1.08], p = 0.001; weighted median: OR = 1.05, 95% CI = [1.01, 1.10], p = 0.018; MR-Egger: OR = 1.07, 95% CI = [1.01, 1.14], p = 0.035 and pIVW < 0.017 [Bonferroni correction]) but not MWoA (IVW: OR = 0.99, 95% CI = [0.96, 1.02], p = 0.331; weighted median: OR = 0.98, 95% CI = [0.94, 1.03], p = 0.496; MR-Egger: OR = 1.02, 95% CI = [0.95, 1.09], p = 0.652). The results showed no significant pleiotropy or heterogeneity. CONCLUSION: Our MR analysis demonstrated the complex relationship between SLE and migraine, suggesting a potential effect of SLE on the risk of MWA but not MWoA. These findings can aid in the development of improved subtype-specific management of migraine in patients with SLE.

Napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura: a randomized controlled trial. / æž•é¡¹éƒ¨åŸ‹çº¿æ³•è”åˆé ’çŸ³é ¸ç¾Žæ‰˜æ´›å°”ç‰‡é¢„é˜²æ€§æ²»ç–—æ— å ˆå †åå¤´ç—›ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the efficacy of napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura, and to compare its efficacy with simple napex acupoint thread-embedding and simple metoprolol tartrate tablet. METHODS: A total of 105 patients with migraine without aura were randomized into a combination group (35 cases, 5 cases dropped out), a thread-embedding group (35 cases, 4 cases dropped out) and a western medication group (35 cases, 2 cases dropped out). In the thread-embedding group, napex acupoint thread-embedding was applied at bilateral Fengchi (GB 20) and points of 1.5 cun nearby to the lower edge of spinous process of cervical 2. In the western medication group, metoprolol tartrate tablet was given orally, 12.5 mg a time, twice a day. In the combination group, napex acupoint thread-embedding combined with oral metoprolol tartrate tablet was delivered. The treatment of 8 weeks was required in the 3 groups. The days of headache attacks, frequency of headache attacks, headache severity (visual analogue scale [VAS] score) and the migraine specific quality of life questionnaire version 2.1 (MSQ) score were observed during baseline period (4 weeks before treatment to before treatment), observation period (1-4 weeks and 5-8 weeks in treatment) and follow-up period (1-4 weeks after treatment completion) respectively, the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% were calculated, and the safety was evaluated in the 3 groups. RESULTS: During the observation period and the follow-up period, the days of headache attacks, frequency of headache attacks and headache VAS scores in the 3 groups were reduced compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the days of headache attacks and the frequency of headache attacks in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05); during the observation period (1-4 weeks in treatment), the headache VAS scores in the combination group and the thread-embedding group were lower than that in the western medication group (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the headache VAS scores in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were increased compared with those of the baseline period (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the role prevention scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05); during the follow-up period, the emotion function scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were higher than those in the thread-embedding group and the western medication group (P<0.05). There was no statistical difference in the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% among the 3 groups (P>0.05), and there were no serious adverse reactions in the 3 groups. CONCLUSIONS: Napex acupoint thread-embedding combined with metoprolol tartrate tablet, simple napex acupoint thread-embedding and simple metoprolol tartrate tablet all can reduce the days of headache attacks and the frequency of headache attacks, relieve headache severity and improve the quality of life in patients with migraine without aura. Napex acupoint thread-embedding combined with metoprolol tartrate tablet has a better effect.

A importância da alimentação e nutrição para indivíduos com enxaqueca / La importancia de la alimentación y nutrición para personas con jaqueca / The importance of food and nutrition for people with chronic migraines

Introdução: As cefaleias são consideradas um importante problema de saúde pública e estima-se que são a segunda queixa mais comum de dor, sendo a enxaqueca uma das mais presentes. O tratamento da enxaqueca pode ser sintomático ou profilático, a fim de reduzir os sintomas em períodos de crise e evitar que novas crises se instalem, destacando a importância da adoção de hábitos saudáveis e uma alimentação equilibrada. Objetivo: O objetivo deste estudo foi realizar uma revisão integrativa da literatura, destacando os principais achados sobre a importância da alimentação e nutrição para indivíduos acometidos pela enxaqueca. Metodologia: foi realizado um levantamento de estudos nas bases de dados: Biblioteca Virtual em Saúde (BVS); Medline, LILACS, SciELO e Google Acadêmico, além de ter sido considerada a lista de referências dos trabalhos consultados, utilizando a estratégia PECO, onde P (population) indica a população, a letra E (exposure) exposição, C (comparison) comparação e a letra O (outcome) se refere aos desfechos esperados, assim gerou a pergunta norteadora do estudo: "Qual é a importância da alimentação e nutrição para indivíduos com enxaqueca?". Resultados: Foram selecionados 15 estudos para a produção do presente trabalho e foi realizada uma síntese descritiva dos resultados obtidos da relação e influência de hábitos alimentares com a enxaqueca. Conclusões: Conclui-se que os hábitos alimentares e a nutrição adequada têm grande influência e importância para indivíduos com enxaqueca, pois dessa forma, podem reduzir os sintomas apresentados e crises, já que as substâncias presentes nos alimentos estão relacionadas com o início e intensificação das crises (AU).

Introduction: Headaches are considered an important public health problem and are estimated to be the second most common pain complaint, with migraines being one of the most common. Migraine treatment is symptomatic and prophylactic to reduce symptoms when an attack starts and prevent new ones from forming, highlighting the importance of adopting healthy habits and a balanced diet. Objective: The purpose of this study was to carry out an integrative review of the literature in order to highlight the main findings on the influence of eating habits and the importance of nutrition for migraine patients. Methodology:A survey study was performed in the following databases: Virtual Health Library (VHL); Medline, LILACS, SciELO, and Google Scholar, in addition to considering the reference list of the consulted works. The PECO P (population) E (exposure) C (comparison) O (outcome) strategy was used, which generated the guiding question of the study: 'How important is food and nutrition for people with chronic migraines?'. Results:A total of 15 studies were selected to analyze in this work and a descriptive synthesis of the results was performed on the relationship and influence of eating habits of people with chronic migraines. Conclusions:It was concluded that eating habits and adequate nutrition have great influence and importance for migraine patients, as they are one of the main culprits of triggering and intensifying attacks (AU).

Introducción: Las cefaleas son consideradas un importante problema de salud pública y se estima que son la segunda queja más común de dolor, siendo la jaqueca una de las más frecuentes. El tratamiento de la jaqueca puede ser sintomático o profiláctico, con el fin de reducir los síntomas en periodos de crisis y evitar que nuevas ocurran, destacando la importancia de una adopción de hábitos saludables y una alimentación equilibrada. Objetivo: El objetivo de este estudio fue realizar una revisión integrativa de la literatura, destacando los principales hallazgos sobre la importancia de la alimentación y nutrición en personas afectadas por la jaqueca. Metodología: Fue realizada una investigación de los estudios en las bases de dados: Biblioteca Virtual en Salud (BVS); Medline, LILACS, SciELO y Google Académico, además de considerar la lista de referencias de los trabajos consultados, utilizando la estrategia PECO, donde P (population) indica la población, la letra E (exposure) exposición, C (comparison) comparación y la letra O (outcome) se refiere a los resultados esperados, así fue generada la pregunta guía del estudio: "¿Cuál es la importancia de la alimentación y nutrición para las personas con jaqueca?" Resultados: Fueron seccionados 15 estudios para la producción del presente trabajo y fue realizada una síntesis descriptiva de los resultados obtenidos de la relación e influencia de los hábitos alimentarios con la jaqueca. Conclusiones: Se concluye que los hábitos alimentarios y la nutrición adecuada tienen gran influencia e importancia para las personas conjaqueca, pues de esta forma, pueden reducir los síntomas presentados y crisis, ya que las sustancias presentes en los alimentos están relacionadas con el inicio e intensificación de las crisis (AU).

Cerebrovascular reactivity to hypercapnia in patients with migraine: A dual-echo arterial spin labeling MRI study.

OBJECTIVE: This study aimed to compare cerebrovascular reactivity between patients with migraine and controls using state-of-the-art magnetic resonance imaging (MRI) techniques. BACKGROUND: Migraine is associated with an increased risk of cerebrovascular disease, but the underlying mechanisms are still not fully understood. Impaired cerebrovascular reactivity has been proposed as a link. Previous studies have evaluated cerebrovascular reactivity with different methodologies and results are conflicting. METHODS: In this single-center, observational, case-control study, we included 31 interictal patients with migraine without aura (aged 19-66 years, 17 females) and 31 controls (aged 22-64 years, 18 females) with no history of vascular disease. Global and regional cerebrovascular reactivities were assessed with a dual-echo arterial spin labeling (ASL) 3.0 T MRI scan of the brain which measured the change in cerebral blood flow (CBF) and BOLD (blood oxygen level dependent) signal to inhalation of 5% carbon dioxide. RESULTS: When comparing patients with migraine to controls, cerebrovascular reactivity values were similar between the groups, including mean gray matter CBF-based cerebrovascular reactivity (3.2 ± 0.9 vs 3.4 ± 1% ΔCBF/mmHg CO2 ; p = 0.527), mean gray matter BOLD-based cerebrovascular reactivity (0.18 ± 0.04 vs 0.18 ± 0.04% ΔBOLD/mmHg CO2 ; p = 0.587), and mean white matter BOLD-based cerebrovascular reactivity (0.08 ± 0.03 vs 0.08 ± 0.02% ΔBOLD/mmHg CO2 ; p = 0.621).There was no association of cerebrovascular reactivity with monthly migraine days or migraine disease duration (all analyses p > 0.05). CONCLUSION: Cerebrovascular reactivity to carbon dioxide seems to be preserved in patients with migraine without aura.

Association between patent foramen ovale and migraine: evidence from a resting-state fMRI study.

A relationship between migraine without aura (MO) and patent foramen ovale (PFO) has been observed, but the neural basis underlying this relationship remains elusive. Utilizing independent component analysis via functional magnetic resonance imaging, we examined functional connectivity (FC) within and across networks in 146 patients with MO (75 patients with and 71 patients without PFO) and 70 healthy controls (35 patients each with and without PFO) to elucidate the individual effects of MO and PFO, as well as their interaction, on brain functional networks. The main effect of PFO manifested exclusively in the FC among the visual, auditory, default mode, dorsal attention and salience networks. Furthermore, the interaction effect between MO and PFO was discerned in brain clusters of the left frontoparietal network and lingual gyrus network, as well as the internetwork FC between the left frontoparietal network and the default mode network (DMN), the occipital pole and medial visual networks, and the dorsal attention and salience networks. Our findings suggest that the presence of a PFO shunt in patients with MO is accompanied by various FC changes within and across networks. These changes elucidate the intricate mechanisms linked to PFO-associated migraines and provide a basis for identifying novel noninvasive biomarkers.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

Patients with episodic migraine without aura have an increased rate of delayed discounting.

OBJECTIVE: This study aimed to explore decision-making impulsivity and its neural mechanisms in patients with episodic migraine without aura (EMoA). BACKGROUND: Previous evidence indicates increased impulsivity and altered reward processing in patients with chronic migraine and medication overuse; however, whether the same holds true for those with EMoA is unclear. METHODS: Patients newly diagnosed with EMoA (n = 51) and healthy controls (HC, n = 45) were recruited. All participants completed delay discounting task, cognitive assessments, a questionnaire for headache profile, and resting-state function magnetic resonance imaging scans. Resting-state functional connectivity (RSFC) between the regions of interest and the entire brain was explored. RESULTS: Patients with EMoA showed a steeper subjective discount rate than HCs (F = 4.74, p = .032), which was positively related to a history of migraines (r = .742, p < .001). RSFC among the ventral striatum (vSTR), ventromedial prefrontal cortex, and occipital cortex was lower in patients with EMoA than in control groups, which was correlated with history (r' = .294, p = .036) and subjective discount rate (r' = .380, p = .006). Additionally, discounting rates and RSFC between the vSTR and occipital regions were significantly abnormal in the triptan group than the non-triptan group. Mediating effect analysis indicated a significant mediating effect in the change in RSFC between the vSTR and occipital status, history of triptan use, and subjective discount rate. CONCLUSION: This study further elucidated that an increase in delayed discounting rate exists in patients with EMoA and is related to the abnormality of the value processing network.

Causal association between systemic lupus erythematosus and the risk of migraine: A Mendelian randomization study.

BACKGROUND: Numerous studies have found that patients with systemic lupus erythematosus (SLE) often have comorbid headache, especially migraine. However, the causal relationship between genetically determined SLE and migraine risk remains unclear. Therefore, we conducted a Mendelian randomization (MR) study to explore this causal association. METHODS: Genome-wide association studies (GWAS) provided the instrumental variables. We selected summary data from GWAS of SLE as exposure (5201 SLE patients and 9066 controls). Both outcome GWAS data were from the Finnish Gene GWAS, including migraine with aura, migraine with aura and triptan purchases, and migraine without aura. The main MR approach was inverse-variance weighted. Pleiotropy and heterogeneity were detected using the MR pleiotropy residual sum and outlier, MR-Egger intercept test, leave-one-out analysis, and Cochran's Q test. RESULTS: There was a significant association between genetically predicted SLE susceptibility and increased risk of migraine with aura [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.02-1.08, p = .001]. The result was consistent when the outcome was migraine with aura and triptan purchases [OR = 1.05, 95% CI = 1.02-1.08, p = .001]. However, we found no association between SLE and migraine without aura. Our MR study showed no pleiotropy or heterogeneity. CONCLUSIONS: Our study indicates that genetic susceptibility to SLE increases the incidence of migraine with aura but not migraine without aura. It is necessary for the routine evaluation and early recognition of migraine in patients with SLE in clinical settings.

Sleep Spindle Alterations in Children With Migraine.

BACKGROUND: The modulation of thalamocortical activity is the most important site of several levels of interference between sleep spindles and migraine. Thalamocortical circuits are responsible for the electrophysiological phenomenon of sleep spindles. Spindle alterations may be used as a beneficial marker in the diagnosis and follow-up of children with migraine. We aimed to formulate the hypothesis that there is a shared mechanism that underlies migraine and sleep spindle activity. METHODS: We analyzed the amplitude, frequency, duration, density, and activity of sleep spindles in non-rapid eye movement stage 2 sleep in patients with migraine without aura when compared with healthy control subjects. RESULTS: The amplitudes of average, slow, and fast sleep spindles were higher in children with migraine without aura (P = 0.020, 0.013, and 0.033, respectively). The frequency of fast spindles was lower in children with migraines without aura when compared with the control group (P = 0.03). Although not statistically significant, the fast sleep spindle duration in the migraine group was shorter (P = 0.055). Multivariate analysis revealed an increased risk of migraine associated with increased mean spindle amplitude and decreased fast spindle frequency and duration. CONCLUSIONS: Our data suggest that spindle alterations may correlate with the vulnerability to develop migraine and may be used as a model for future research about the association between the thalamocortical networks and migraine.

Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study.

OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.

The effectiveness of agomelatine on headache severity and frequency in episodic migraine without aura; a parallel randomized controlled trial study.

BACKGROUND: Migraine is a headache disorder that affects public health and reduces the patient's quality of life. Preventive medication is necessary to prevent acute attacks and medication overuse headaches (MOH). Agomelatine is a melatonin antagonist. AIMS: This study aimed to determine the effectiveness of agomelatine on the severity and frequency of migraine attacks. METHODS: The study is a parallel randomized controlled trial with two groups of intervention and control. 400 patients were evaluated. Eligible individuals, including those with episodic migraine headaches without aura between the ages of 18 and 60 years who did not receive preventive treatment beforehand, were enrolled. Also, patients did not receive any specific medications for other diseases. Among these, 100 people met the inclusion criteria and entered the study. These subjects were randomly assigned to one of the two groups. The intervention group received 25 mg of agomelatine daily and the control group received B1. In this study, the effect of agomelatine on the frequency and severity of attacks, mean monthly migraine days (MMD), and migraine disability assessment (MIDAS), were assessed. The study was triple-blind and after three months, a post-test was performed. Data were analyzed using SPSS software. RESULTS: A total of 100 patients were randomly assigned to either intervention or control groups. The prescriber physician and the data collector did not know about the allocation of patients to groups. Before the intervention, there was no significant difference in the headache frequency per month (t=-0.182, df = 98, p = 0.85), mean MMD (p = 0.17), headache severity (p = 0.076), and MIDAS (p = 0.091). After the study, there was a significant difference between the two groups in terms of the headache frequency per month (p = 0.009), and mean of MMD (p = 0.025). There was also a significant difference between pretest and posttest in two groups in the headache severity (p < 0.001) and MIDAS (p < 0.001). CONCLUSION: Agomelatine can be used as a preventive medication for migraine without aura. It is suggested that agomelatine be studied in comparison with other preventive drugs for patients with migraine. TRIAL RETROSPECTIVELY REGISTRATION: Trial Retrospectively registration= IRCT20230303057599N1. Date: 2023-5-24 The present study is a residency thesis approved by the Tehran University of Medical Sciences.

Mendelian randomization study of lipid metabolism characteristics and migraine risk.

BACKGROUND: The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk. METHODS: Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk. RESULTS: Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000). CONCLUSIONS: There is a relationship between lipid metabolism characteristics and migraine risk. SIGNIFICANCE: Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

Altered Neuromagnetic Activity in the Default Mode Network in Migraine and Its Subgroups (Episodic Migraine and Chronic Migraine).

BACKGROUND: The differences in the resting state spectral power and functional connectivity of the default mode network between people with migraine without aura (MwoA) and its subgroups differentiated by frequency (episodic migraine (EM) and chronic migraine (CM)) and healthy controls (HC) were investigated using magnetoencephalography. METHODS: In the resting state, the topological spatial structure of the brain in 33 MwoA patients and 22 HC was first studied using magnetoencephalography, followed by probing the neuroelectrical activity of 17 CM and 16 EM patients, to identify damage to their default mode network (DMN). The techniques used to investigate both spectral power and functional connectivity were minimum-paradigm estimation combined with Welch's technique and corrected amplitude envelope correlation. RESULTS: The differences between MwoA and its subgroups (CM and EM) and HC based on spectral power were mainly in the delta, theta, and alpha bands, while the differences in functional connectivity were primarily in the delta, alpha, and beta bands. In the delta and theta bands, the spectral power of MwoA and its subgroups (CM and EM) was higher than in the HC group. The spectral power of MwoA and its subgroups (CM and EM) was lower in the alpha band. In terms of functional connectivity, the corrected amplitude envelope correlation of MwoA and its subgroups (CM and EM) was lower than the HC group in the bands with spectral differences. People with EM and CM differed in the spectral power in the left medial prefrontal cortex and the right lateral temporal cortex in the alpha band, where correlation analysis and logistic regression analysis showed that the intensity of the spectral power of the left medial prefrontal cortex was negatively correlated with headache frequency. CONCLUSIONS: The spectral power of the left medial prefrontal cortex in the alpha band may serve as a biomarker that is associated with the number of monthly headache attacks and may be a potential neuromodulatory target for controlling migraine chronicity.