Search

Objective: To delineate the structural connectome alterations in patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs)., Background: The pathogenesis of migraine chronification remains elusive, with structural brain network changes potentially playing a key role. However, there is a paucity of research employing graph theory analysis to explore changes in the whole brain structural networks in patients with CM and EM., Methods: The individual structural brain connectome of 60 patients with CM, 34 patients with EM, and 39 healthy control participants were constructed by using deterministic diffusion-tensor tractography. Graph metrics including global efficiency, characteristic path length, local efficiency, clustering coefficient, and small-world parameters were evaluated to describe the topologic organization of the white matter structural networks. Additionally, nodal clustering coefficient and efficiency were considered to assess the regional characteristics of the brain connectome. A graph-based statistic was used to assess brain network properties across the groups., Results: Graph theory analysis revealed significant disruptions in the structural brain networks of CM patients, characterized by reduced global efficiency, local efficiency, and increased characteristic path length compared to HCs. Additionally, CM patients exhibited significantly lower local efficiency than EM patients. Notably, the CM group demonstrated marked reductions in local clustering coefficient and nodal local efficiency in the frontal and temporal regions compared with the healthy control group and EM group. Nodal local efficiency can effectively distinguish CM from EM and HCs. Moreover, the disrupted topologic efficiency was significantly associated with attack frequency and MIDAS score in patients with migraine after Bonferroni correction., Conclusion: Decreased structural connectivity in the frontal and temporal regions may serve as a neuroimaging marker for migraine chronification and disease progression, providing valuable insights into the pathophysiology of chronic migraine., Competing Interests: Declarations. Consent for publication: All authors consent for the publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The transesophageal echocardiogram (TEE) is the standard imaging modality for confirming the presence or absence of patent foramen ovale. PFO is a flap valve depending on the pressure change between the left and right atrium, which can help determine whether to open. 3D-TEE was shown to optimize the visualization of PFO. There is a causal association between PFO and unexplained stroke. It seems that 3D-TEE can present a high-risk PFO morphological feature, which seems to show more than just being easier to open., Methods: In total, 134 consecutive patients with cryptogenic stroke or migraine who had suspected PFO and underwent c-TCD, TTE, and c-TEE were included in this study. TEE confirmed the PFO. The right-to-left shunt (RLS) grade of PFO at rest and abdominal compression Valsalva maneuver was detected by c-TEE., Results: The long diameter of FO (1.74 ± 0.3 vs. 1.60 ± 0.4, p = 0.039), the short diameter of FO (1.12 ± 0.3 vs. 1.00 ± 0.3, p = 0.036), perimeter of FO (4.62 ± 0.7 vs. 4.22 ± 1.0, p = 0.026), and area (1.80 ± 0.8 vs. 1.35 ± 0.8, p = 0.05) of the FO were significantly larger in the larger RLS group. In group of CS, a larger proportion of Eustachian valve or a Chiari's network (14.3% vs. 3.5%, p = 0.036), a larger proportion of in the left funnelform (55.1% vs. 16.3%, p < 0.001), a longer length of the PFO tunnel (13.4 ± 4.4 vs. 7.8 ± 2.5, p < 0.001), a lower IVC-PFO angle (16.4 ± 3.4 vs. 20.3 ± 7.7, p = 0.001), a higher proportion of LA multiple exits of the tunnel (46.9% vs. 14.3%, p < 0.001). Multivariate regression analysis showed that male gender (HR: 4.026, 95% CI: 0.883-18.361, p = 0.072), age (HR: 1.076, 95% CI: 1.002-1.155, p = 0.045), the left funnelform (HR: 7.299, 95% CI: 1.585-33.618, p = 0.011), a longer length of the PFO tunnel (HR: 1.843, 95% CI: 1.404-2.418, p < 0.001) and multiple exits of the tunnel of LA (HR: 8.544, 95% CI: 1.595-45.754, p = 0.012) increased the risk of cerebral infarction. The cut-off value calculated by ROC for the diagnosis of high-risk PFO was that the length of the PFO tunnel was 12 mm and the left funnelform combined with multiple exits of the left atrial (sensitivity was 92%, specificity was 90%). The area under the curve of the combined index versus PoPE score (0.932 vs. 0.736) relative to the RoPE score was statistically significant., Conclusions: TEE has shown outstanding advantages in displaying the specific morphological characteristics of PFO. The left funnelform, a longer length of the PFO tunnel, and multiple exits of the tunnel of LA are associated with an increasing risk of CS in anatomical PFO respect., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

Research on the neural mechanisms underlying brain asymmetry in patients with migraine patients using fMRI is insufficient. This study proposed using lateralized algorithms for functional connectivity and brain network topology and investigated changes in their lateralization in patients with migraine. In study 1, laterality indices of functional connectivity (LFunctionCorr) and brain network topological properties (LBetweennessCentrality, LDegree, and LStrength) were defined. Differences between migraineurs and normal subjects were compared at whole-brain, half-brain, and region levels. In study 2, laterality indices were used to classify migraine and were validated using independent samples and the segment method for repeatability. In study 3, abnormal brain regions related to migraine were extracted based on the classification results and differences analysis. Study 1 found no significant differences related to in for migraine at the whole-brain level; however, significant differences were identified at the half-brain level for the hemispheric lateralization of the LFunctionCorr, while 11 significantly different brain regions were also identified at the brain region level. Furthermore, the classification accuracy in study 2 was 0.9366. With repeated validation, the accuracy reached 0.8561. Furthermore, after extending the samples according to the segmentation strategy, the classification accuracies were improved to 0.9408 and 0.8585. Study 3 identified 10 crucial brain regions with asymmetrical specificity based on laterality indices distributed across the visual network, the frontoparietal control network, the default mode network, the salience/ventral attention network and the limbic system. The results revealed novel insights and avenues for research into the mechanisms of migraine asymmetry and showed that the laterality indices could be used as a potential diagnostic imaging marker for migraine., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria., Methods: Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18 years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st - Nov. 15th, 2021)., Results: We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42-24.11; p = 0.014)., Conclusions: Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Previous studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear., Methods: We utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970-375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results., Results: Genetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity., Conclusion: This study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention., (© 2024. The Author(s).)

Background: Although gray matter (GM) volume alterations have been extensively documented in previous voxel-based morphometry studies on vestibular migraine (VM), little is known about the impact of this disease on the topological organization of GM morphological networks. This study investigated the altered network patterns of the GM connectome in patients with VM., Methods: In this study, 55 patients with VM and 57 healthy controls (HCs) underwent structural T1-weighted MRI. GM morphological networks were constructed by estimating interregional similarity in the distributions of regional GM volume based on the Kullback-Leibler divergence measure. Graph-theoretical metrics and interregional morphological connectivity were computed and compared between the two groups. Partial correlation analyses were performed between significant GM connectome features and clinical parameters. Logistic regression (LR), support vector machine (SVM), and random forest (RF) classifiers were used to examine the performance of significant GM connectome features in distinguishing patients with VM from HCs., Results: Compared with HCs, patients with VM exhibited increased clustering coefficient and local efficiency, as well as reduced nodal degree and nodal efficiency in the left superior temporal gyrus (STG). Furthermore, we identified one connected component with decreased morphological connectivity strength, and the involved regions were mainly located in the STG, temporal pole, prefrontal cortex, supplementary motor area, cingulum, fusiform gyrus, and cerebellum. In the VM group, several connections in the identified connected component were correlated with clinical measures (i.e., symptoms and emotional scales); however, these correlations did not survive multiple comparison corrections. A combination of significant graph- and connectivity-based features allowed single-subject classification of VM versus HC with significant accuracy of 77.68%, 77.68%, and 72.32% for the LR, SVM, and RF models, respectively., Conclusion: Patients with VM had aberrant GM connectomes in terms of topological properties and network connections, reflecting potential dizziness, pain, and emotional dysfunctions. The identified features could serve as individualized neuroimaging markers of VM., (© 2024. The Author(s).)

Background: Migraine-related perfusion changes are documented but inconsistent across studies due to limited sample size and insufficient phenotyping. The phasic and spatial dynamics across migraine subtypes remains poorly characterized. This study aimed to determine spatiotemporal dynamics of gray matter (GM) perfusion in migraine., Methods: We prospectively recruited episodic (EM) and chronic migraine (CM) patients, diagnosed with the International Headache Society criteria and healthy controls (HCs) between 2021 and 2023 from the headache center in a tertiary medical center, and adjacent communities. Magnetic resonance (3-tesla) arterial spin labeling (ASL) was conducted for whole brain cerebral blood flow (CBF) in all participants. The voxel-wise and whole brain gray matter (GM) CBF were compared between subgroups. Spatial pattern analysis of CBF and its correlations with headache frequency were investigated regarding different migraine phases and subtypes. Sex- and age-adjusted voxel-wise and whole brain GM comparisons were performed between HCs and different EM and CM phases. Spatial pattern analysis was conducted by CBF clusters with phasic differences and spin permutation test. Correlations between headache frequency and CBF were investigated regarding different EM and CM phases., Results: Totally 344 subjects (172 EM, 120 CM, and 52 HCs) were enrolled. Higher CBF in different anatomical locations was identified in ictal EM and CM. The combined panels of the specific locations with altered CBF in ictal EM on receiver operating characteristic curve analysis demonstrated areas under curve of 0.780 (vs. HCs) and 0.811 (vs. preictal EM). The spatial distribution of ictal-interictal CBF alteration of EM and CM were not correlated with each other (p = 0.665; r = - 0.018). Positive correlations between headache frequency and CBF were noted in ictal EM and CM regarding whole GM and specific anatomical locations., Conclusions: Patients with migraine exhibited unique spatiotemporal CBF dynamics across different phases and distinct between subtypes. The findings provide neurobiological insights into how selected anatomical structures engage in a migraine attack and adapt to plastic change of repeated attacks along with chronicity., (© 2024. The Author(s).)

We investigated patients with migraine or migraine variants who exhibited focal cerebral hypoperfusion on arterial spin-labeled (ASL) magnetic resonance (MR) imaging along with neurological symptoms. Fourteen patients with migraine demonstrated focal cerebral hypoperfusion. Three other patients did not have a history of recurrent headaches but exhibited comparable cerebral hypoperfusion to migraine patients on ASL-MRI in addition to neurological symptoms. Patients with migraine may present with neurological symptoms associated with cortical spreading depression during, after, or even without a headache phase. Additionally, the isolated neurological symptoms may be caused by a pathophysiology identical to that of migraine but without presenting with recurrent headaches., Competing Interests: No potential conflict of interest relevant to this article was reported.

The management of chronic migraine (CM) underwent a significant shift with the introduction of onabotulinumtoxin A (BoNT-A) injections following the landmark PREEMPT trial in 2010. Despite its efficacy, the existing injection protocol lacks precision, prompting a call for revision in light of modern ultrasound (US)-guided techniques. This article highlights the potential of US-guided injections to enhance accuracy, safety, and efficacy in CM treatment. By providing real-time visualization and addressing anatomical variations, US guidance offers a promising avenue for optimizing BoNT-A delivery, minimizing adverse effects, and ensuring therapeutic success., (© 2024 American Institute of Ultrasound in Medicine.)

Background: Migraine and insomnia are prevalent conditions that often co-occur, each exacerbating the other and substantially impacting the quality of life. The locus coeruleus (LC), a brainstem region responsible for norepinephrine synthesis, participates in pain modulation, sleep/wake cycles, and emotional regulation, rendering it a potential nexus in the comorbidity of migraine and insomnia. Disruptions in the LC-noradrenergic system have been hypothesized to contribute to the comorbidities of migraine and insomnia, although neuroimaging evidence in humans remains scarce. In this study, we aimed to investigate the intrinsic functional connectivity (FC) network of the LC in patients with comorbid migraine and subjective chronic insomnia and patients with migraine with no insomnia (MnI) using resting-state functional magnetic resonance imaging (rs-fMRI) and seed-based FC analyses., Methods: In this cross-sectional study, 30 patients with comorbid migraine and chronic insomnia (MI), 30 patients with MnI, and 30 healthy controls (HCs) were enrolled. Participants underwent neuropsychological testing and rs-fMRI. The LC-FC network was constructed using seed-based voxel-wise FC analysis. To identify group differences in LC-FC networks, voxel-wise covariance analysis was conducted with sex and age as covariates. Subsequently, a partial correlation analysis was conducted to probe the clinical relevance of aberrant LC-FC in patients with MI and MnI., Results: Except for the insomnia score, no other significant difference was detected in demographic characteristics and behavioral performance between the MI and MnI groups. Compared with HCs, patients with MI exhibited altered LC-FC in several brain regions, including the dorsomedial prefrontal cortex (DMPFC), anterior cerebellum, dorsolateral prefrontal cortex (DLPFC), thalamus, and parahippocampal gyrus (PHG). Lower FC between the LC and DLPFC was associated with greater insomnia severity, whereas higher FC between the LC and DMPFC was linked to longer migraine attack duration in the MI group., Conclusion: Our findings reveal the presence of aberrant LC-FC networks in patients with MI, providing neuroimaging evidence of the interplay between these conditions. The identified LC-FC alterations may serve as potential targets for therapeutic interventions and highlight the importance of considering the LC-noradrenergic system in the management of MI., (© 2024. The Author(s).)

Right-to-left shunt (RLS) caused by patent foramen ovale (PFO) and pulmonary arteriovenous malformations (PAVM) have been associated with a variety of diseases, and reliable techniques for detecting RLS are essential for diagnosis. This study aimed to compare the diagnostic accuracy of multimodal ultrasound imaging, including transthoracic echocardiography (TTE) plus contrast transthoracic echocardiography (CTTE) and transesophageal echocardiography (TEE) plus contrast transesophageal echocardiography (CTEE) for PFO and PAVM in patients with cryptogenic stroke or migraine. This prospective study enrolled patients with cryptogenic stroke or migraine admitted to First Hospital of Shanxi Medical University between July 2018 and April 2023. The TTE + CTTE + TEE + CTEE multimodal ultrasound imaging was defined as the gold standard. A total of 230 patients with cryptogenic stroke (108) or migraine (122) were enrolled. The TEE + CTEE generated a better area under the receiver operator characteristic (ROC) curves (AUC) than TTE + CTTE [0.995 (0.988-1.000) vs 0.975 (0.767-0.984), P < .001], indicating better identification of PFO and PAVM. The sensitivity and specificity of the TTE + CTTE were 89.4% and 85.7%, respectively, whereas the sensitivity and specificity of TEE + CTEE were 99.1% and 100%, respectively. The missed diagnosis rate of TTE + CTTE and TEE + CTEE was 65.7 % and 12.5%, respectively. The combination of TEE + CTEE may be a more reliable and sensitive tool to detect PFO and PAVM than TTE + CTTE in patients with cryptogenic stroke or migraine., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Screening for patent foramen ovale (PFO) in patients with ischemic neurological events is becoming more common., Objectives: This study aimed to evaluate clinical characteristics and atrial septum anatomy in relation to age and presence of PFO, as well as factors associated with a history of stroke in patients assessed for cardiac causes of ischemic neurological events., Patients and Methods: A total of 817 patients with a history of neurological episodes (stroke, transient ischemic attack [TIA], or migraine) were prescreened using transcranial Doppler ultrasound. Transesophageal contrast echocardiography (TEE) was employed to confirm PFO and assess the anatomy of the atrial septum and right atrium., Results: Among the patients, 28% had ischemic stroke, 31% had TIA, and 49% had migraines. PFO was confirmed in 79% of the patients. Regardless of the analyzed age group, PFO was associated with higher prevalence of TIA, migraine and syncope history, atrial septal aneurysm (ASA), and Chiari network. There were fewer women in the PFO group, but only in the population aged 45 years or under. Patient age, male sex, typical cardiovascular risk factors, and the presence of ASA were associated with a history of stroke., Conclusions: In patients with ischemic neurological events who were prescreened for PFO, confirmation of PFO on TEE was associated with a higher prevalence of TIA, migraine, syncope, Chiari network, and ASA. Advanced age, typical cardiovascular risk factors, and ASA were associated with stroke history in the study population.

Background: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls., Methods: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM., Results: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine., Conclusions: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology., (© 2024. The Author(s).)

Background: Migraine is a primary headache defined as moderate-to-severe pain lasting 4 to 72 h, ranking 2nd among the disabling conditions for both genders regardless of the age and the greater occipital nerve (GON) block has been reported as an efficient treatment method for migraine. The present study aims to evaluate and compare the efficiency of the two methods of GON block, i.e., the ultrasound (US)-guided technique and the landmark-based technique., Method: Having a prospective and randomized design, the study assigned the patients with chronic migraine into two groups after which a neurologist performed landmark-based GON block in the first group while an algologist performed US-guided GON block in the second group. During the 3-month follow-up period, the number of days with pain, the duration of pain, the number of analgesic drugs taken in a month, and Visual Analogue Scale (VAS) scores were compared with the values ​​before treatment and at the 1st week, 1st month, and 3rd month after treatment., Results: US-guided GON block group included 34 patients while there were 32 patients in the landmark-based GON block group. US-guided GON block group showed significantly reduced VAS scores and frequency of attacks compared to the landmark-based GON block group at Month 1 after the procedure. After a 3-month follow-up period of the two groups, the frequency of attacks, analgesic intake and the duration of attacks were lower in both groups compared to the baseline. At 3-month follow-up, the mean of VAS scores decreased from 9,47 ± 2,69 to 4,67 ± 1,9 in US-guided GON block group and from 9,46 ± 0,98 to 7 ± 2,5 in the landmark-based GON block group., Conclusion: It was determined that both US-guided and landmark-based GON block were efficient techniques in patients with chronic migraine. US-guided GON block technique resulted in lower VAS scores, shorter durations of pain, lower frequencies of attack, and lower intake of analgesics compared to the landmark-based GON block technique., (© 2024. The Author(s).)

Background: Recent studies suggested that persons with migraine might be at higher risk of structural brain changes, including cerebral small vessel disease and atrophy. However, findings in the literature are inconsistent, with variations observed in the direction, magnitude, and population characteristics of reported effects, and large-scale population-based evidence remains scarce. Hence, we investigated the association of migraine with structural brain changes in a middle-aged and elderly population., Methods: Within the population-based Rotterdam Study, lifetime history of migraine was assessed using a validated questionnaire between 2006 and 2011. Magnetic resonance imaging of the brain was performed in 4920 participants (median age 61.7 [IQR 45.5, 97.5] years, 55.4% female) to assess imaging markers of cerebral small vessel disease and brain atrophy. We used linear and logistic regression models to examine the cross-sectional association of migraine with brain volumes (total grey and white matter volumes in mL) and cerebral small vessel disease markers (white matter hyperintensity volume in mL, presence of lacunes and cerebral microbleeds). Adjustments were made for age, sex, intracranial volume and cardiovascular variables. Analyses were also stratified by sex and presence of aura., Results: The lifetime prevalence of migraine was 15.3% (752/4920). In multivariable adjusted regression models, we found no statistically significant differences between participants with and without migraine in terms of total brain volume (mean difference [MD]: 2.21 mL, 95% confidence interval [CI]: -0.38 ; 4.81), grey matter volume (MD: 0.38 mL, 95% CI: -1.98 ; 2.74), white matter volume (MD: 2.19 mL, 95% CI: -0.56 ; 4.93), log white matter hyperintensity volume (MD: -0.04 mL, 95% CI: -0.10 ; 0.02), presence of lacunes (odds ratio [OR]: 0.82, 95% CI: 0.58-1.15), and presence of cerebral microbleeds (OR: 0.95, 95% CI: 0.76-1.18)., Conclusion: In this study, we found that middle-aged and elderly participants with migraine were not more likely to have structural brain changes on magnetic resonance imaging., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The periaqueductal gray (PAG) is at the center of a powerful descending antinociceptive neuronal network, and is a key node in the descending pain regulatory system of pain. However, less is known about the altered perfusion of PAG in chronic migraine (CM)., Aim: To measure the perfusion of PAG matter, an important structure in pain modulation, in CM with magnetic resonance (MR) perfusion without contrast administration., Methods: Three-dimensional pseudocontinuous arterial spin labeling (3D-PCASL) and brain structure imaging were performed in 13 patients with CM and 15 normal subjects. The inverse deformation field generated by brain structure image segmentation was applied to the midbrain PAG template to generate individualized PAG. Then the perfusion value of the PAG area of the midbrain was extracted based on the individual PAG mask., Results: Cerebral blood flow (CBF) value of PAG in CM patients (47.98 ± 8.38 mL/100 mg min) was significantly lower than that of the control group (59.87 ± 14.24 mL/100 mg min). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.77 (95% confidence interval [CI], 0.60, 0.94), and the cutoff value for the diagnosis of CM was 54.83 mL/100 mg min with a sensitivity 84.60% and a specificity 60%., Conclusion: Imaging evidence of the impaired pain conduction pathway in CM may be related with the decreased perfusion in the PAG, which could be considered as an imaging biomarker for the diagnosis and therapy evaluation., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Abstract: Migraine headaches are a significant global health concern, frequently managed with varying levels of success. Compression of the greater occipital nerve (GON) is hypothesized to contribute to pathology in some migraine patients, making extracranial nerve decompression surgery a potential intervention for refractory cases. However, accurate methods to image the GON along its tortuous course still need to be explored. Our group has developed magnetic resonance imaging sequences to track the GON. Yet, many challenges were met, which included navigating the GON's complex anatomy, understanding anatomical variants, and designing advanced magnetic resonance imaging sequences and coils to image the posterior scalp. Addressing these hurdles is vital to capture and understand GON pathology and guide potential interventions., Competing Interests: Conflicts of Interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia., Background: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache-free intervals, leading to a compromised quality of life., Methods: This prospective, case-control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18 F-fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women)., Results: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family-wise error-corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family-wise error-corrected)., Conclusions: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine., (© 2024 American Headache Society.)

To investigate neurovascular changes; including macular vascular density (VD), thickness of the ganglion cell layer (GCL) and optic nerve head (ONH) parameters in episodic migraine patients. 80 eyes of 40 episodic migraine patients were recruited. Thirty patients having a dominant side of migraine headache were statistically analyzed (5 male and 25 female; mean age 31.67 ± 9.54 years) and compared to 25 eyes of 25 healthy volunteers (5 male and 20 female; mean age of 34.4 ± 12.11 years, p = 0.361). The posterior segment was imaged with Topcon DRI optical coherence tomography (OCT) (Triton Swept source OCT Topcon, Japan), and OCT angiography (OCTA). Comparing the dominant side of migraine patients to controls we found a significant decrease of the VD in the central zone of the superficial and deep capillary plexus (SCP, p = 0.01; DCP, p = 0.004) and an enlarged foveal avascular zone (FAZ, p = 0.054). The GCL thickness was significantly reduced in the central ring (GCL + p = 0.042, GCL +  + p = 0.029), as well as the retinal nerve fiber layer (RNFL) thickness in the temporal quadrant (p = 0.021) and border tissue of Elschnig diameter (BTE, p = 0.035). The duration of migraine showed an inverse correlation with SCP in the nasal quadrant (p = 0.016, r = - 0.445) and with all DCP regions [DCP superior (p = 0.004, r = - 0.519), DCP inferior (p = 0.004, r = - 0.519), DCP nasal (p = 0.006, r = - 0.496), DCP temporal (p = 0.005, r = - 0.508), DCP CSF (p < 0.001, r = - 0.634)]. The dominant side compared to the non-dominant side showed a significant deterioration of the VD in the inferior (p = 0.04) and temporal quadrants (p = 0.023); furthermore, a significant decrease in the GCL +  + inner ring thickness (p = 0.046). Microvascular damage and consequent structural alterations of the retina and optic nerve head occur in the eyes of episodic migraine patient in association with the lateralization of the headache., (© 2024. The Author(s).)

Background: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets., Methods: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST., Results: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05)., Conclusions: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022. Out of 236 initial articles, 20 remained after filtering, encompassing data from 1155 subjects in total. Cross-sectional studies in adults showed inconsistent results, while longitudinal studies demonstrated that cerebral perfusion changes over the migraine cycle can be tracked using ASL. The most consistent findings were observed in ictal states among pediatric migraine patients, where studies showed hypoperfusion matching aura symptoms during early imaging followed by hyperperfusion. Overall, ASL is a useful but currently underutilized modality for evaluating cerebral perfusion in patients with migraine. The generalizability of results is currently limited by heterogeneities regarding study design and documentation of clinical variables (e.g., relation of attacks to scanning timepoint, migraine subtypes). Future MRI studies should consider augmenting imaging protocols with ASL to further elucidate perfusion dynamics in migraine., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine., Methods: The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables., Results: There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables., Conclusions: DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function., (© 2024. The Author(s).)

Background: Migraine has been associated with functional brain changes including altered connectivity and activity both during and between headache attacks. Recent studies established that the variability of the blood-oxygen-level-dependent (BOLD) signal is an important attribute of brain activity, which has so far been understudied in migraine. In this study, we investigate how time-varying measures of BOLD variability change interictally in episodic migraine patients., Methods: Two independent resting state functional MRI datasets acquired on 3T (discovery cohort) and 1.5T MRI scanners (replication cohort) including 99 episodic migraine patients (n 3T  = 42, n 1.5T =57) and 78 healthy controls (n 3T  = 46, n 1.5T =32) were analyzed in this cross-sectional study. A framework using time-varying measures of BOLD variability was applied to derive BOLD variability states. Descriptors of BOLD variability states such as dwell time and fractional occupancy were calculated, then compared between migraine patients and healthy controls using Mann-Whitney U-tests. Spearman's rank correlation was calculated to test associations with clinical parameters., Results: Resting-state activity was characterized by states of high and low BOLD signal variability. Migraine patients in the discovery cohort spent more time in the low variability state (mean dwell time: p = 0.014, median dwell time: p = 0.022, maximum dwell time: p = 0.013, fractional occupancy: p = 0.013) and less time in the high variability state (mean dwell time: p = 0.021, median dwell time: p = 0.021, maximum dwell time: p = 0.025, fractional occupancy: p = 0.013). Higher uptime of the low variability state was associated with greater disability as measured by MIDAS scores (maximum dwell time: R = 0.45, p = 0.007; fractional occupancy: R = 0.36, p = 0.035). Similar results were observed in the replication cohort., Conclusion: Episodic migraine patients spend more time in a state of low BOLD variability during rest in headache-free periods, which is associated with greater disability. BOLD variability states show potential as a replicable functional imaging marker in episodic migraine., (© 2024. The Author(s).)

Objective: This study aimed to construct and validate a nomogram model that predicts the remission of migraine attacks by screening factors that affect the prognosis of migraine patients with patent foramen ovale (PFO) after closure., Method: Retrospective analysis was conducted in migraine patients with PFO who underwent PFO closure in the Department of Cardiology of Jiangsu Province Hospital from September 2020 to April 2023. Based on the Migraine Disability Assessment (MIDAS) scores from the 1-year follow-up after PFO closure, all patients who met the inclusion criteria were categorized into a remission group and a non-remission group. The primary efficacy endpoint was remission of migraine headache. After collecting clinical data, transcranial doppler sonography (TCD) results and MIDAS scores, LASSO (least absolute shrinkage and selection operator) regression and multivariable logistic regression analysis were used to filter variables predictive to migraine remission and construct the nomogram model. The Nomogram's accuracy and consistency were respectively assessed through Receiver Operating Characteristic (ROC) curves and calibration curves. Additionally, an analysis of decision curves (DCA) was conducted to evaluate the clinical utility of this newly developed model., Result: A total of 241 consecutive patients were included in the study. The remission group included 21 males and 93 females, with a median age of 39 (30.25,50) years. The non-remission group included 26 males and 101 females, with a median age of 35 (25.5,47.5) years. All Patients were randomly divided into a training cohort and a validation cohort. Multivariable logistic regression analysis showed that 5 independent predictors, including MIDAS before closure (p = 0.0002), mitigating factors (p = 0.0057), number of attacks/month (p = 0.0058), TCD (p = 0.0093) and Platelet Crit (PCT) (p = 0.0351), played a significant role in the prediction of remission of migraine patients with PFO after closure. Based on these independent predictors, the predictive nomogram model of migraine remission in PFO patients was constructed. The application of the nomogram in the training cohort exhibited good discrimination (area under the ROC curve was 0.7763[95% CI 0.7108-0.8418]), which was confirmed in the validation cohort (AUC was 0.704[95% CI 0.5533-0.8547]). The calibration curve showed that the nomogram model demonstrated good calibration performance. Additionally, the decision curve analysis indicated the clinical utility of the nomogram model., Conclusion: The construction of the nomogram model had a considerable predictive accuracy for migraine remission in patients after PFO closure, which may provide constructive guidance for clinical decision making., Competing Interests: Declaration of competing interest We certify that there is no actual or potential conflict of interest in relation to this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recently, interest in sarcopenia has been increasing in patients with various neurological diseases. Thus, we investigated the presence of sarcopenia in patients with episodic migraine (EM) based on temporal muscle thickness (TMT). This was a retrospectively observational study following STROBE guidelines. We enrolled patients with EM and healthy controls. Both groups underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We calculated the TMT using T1-weighted imaging, which is a marker for sarcopenia. We compared TMT between patients with EM and healthy controls, and analyzed it according to presence of migraine aura. We retrospectively enrolled 82 patients with EM and 53 healthy controls. TMT was not different between patients with EM and healthy controls (10.804 ± 2.045 mm in patients with EM vs 10.721 ± 1.547 mm in healthy controls, P = .801). Furthermore, TMT was not different according to presence of migraine aura in patients with EM (10.994 ± 2.016 mm in patients with migraine aura vs 10.716 ± 2.071 mm in those without, P = .569). There were no correlations between TMT and clinical characteristics in patients with EM, including age, age of onset, duration of migraine, headache intensity, and headache frequency. This study found no statistical difference in TMT between patients with EM and healthy controls or between patients with EM with and without aura. These findings suggest that there is no evidence of sarcopenia in patients with EM., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment., Methods: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine., Results: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders., Conclusions: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy., (© 2024. The Author(s).)

Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance imaging (MRI) is a powerful tool for investigating whole-brain connectivity patterns; however, systematic assessment of structural connectome organization has rarely been performed. In the present study, we aimed to examine the changes in structural connectivity in patients with episodic migraines using diffusion MRI. First, we computed structural connectivity using diffusion MRI tractography, after which we applied dimensionality reduction techniques to the structural connectivity and generated three low-dimensional eigenvectors. We subsequently calculated the manifold eccentricity, defined as the Euclidean distance between each data point and the center of the data in the manifold space. We then compared the manifold eccentricity between patients with migraines and healthy controls, revealing significant between-group differences in the orbitofrontal cortex, temporal pole, and sensory/motor regions. Between-group differences in subcortico-cortical connectivity further revealed significant changes in the amygdala, accumbens, and caudate nuclei. Finally, supervised machine learning effectively classified patients with migraines and healthy controls using cortical and subcortical structural connectivity features, highlighting the importance of the orbitofrontal and sensory cortices, in addition to the caudate, in distinguishing between the groups. Our findings confirmed that episodic migraine is related to the structural connectome changes in the limbic and sensory systems, suggesting its potential utility as a diagnostic marker for migraine., (© 2024. The Author(s).)

Background and Purpose: Concentrations of calcitonin gene-related peptide, a neuropeptide and potent endogenous vasodilator, are reportedly higher in patients with migraine than in healthy subjects, both during and between migraine attacks, reflecting ongoing activation of the trigeminal nervous system. In this prospective study, we measured CBF during the interictal period of patients with migraine after considering insomnia and depression and examined the effects of ongoing activation of the trigeminal nervous system, including during the interictal period, on CBF., Materials and Methods: In a total of 242 patient with migraine (age range, 18-75 years), CBF was measured by MR imaging arterial spin-labeling during the interictal period and was compared with results from 26 healthy volunteers younger than 45 years of age as control subjects (age range, 22-45 years). Cortical hyperperfusion was defined as identification of ≥2 cerebral cortical regions with regional CBF values at least 2 SDs above the mean regional CBF in control subjects., Results: The overall frequency of cortical hyperperfusion was significantly higher in patients with migraine (115 of 242, 48%) than in control subjects (1 of 26, 4%). Multivariable analysis revealed the 18- to 40-year age group and patients with migraine without insomnia as significant positive clinical factors associated with cortical hyperperfusion. Among patients with migraine without insomnia, the frequency of cortical hyperperfusion was >92% (89 of 97). One-way ANOVA showed that in all ROIs of the cortex, regional CBF was significantly higher in patients with migraine without insomnia than in patients with migraine with insomnia or control subjects. In patients with migraine without insomnia, cortical hyperperfusion findings showed a sensitivity of 0.918 and a specificity of 0.962 for migraine in the interictal period, representing excellent accuracy. In contrast, among patients with migraine with insomnia, sensitivity was only 0.179 but specificity was 0.962., Conclusions: Patients with migraine without insomnia may have cortical hyperperfusion during the interictal period; however, the findings of the present study need to be prospectively validated on a larger scale before clinical applicability can be considered., (© 2024 by American Journal of Neuroradiology.)

Background: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR)., Methods: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis., Results: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10 - 4 ). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm 2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10 - 4 ) and thalamic volume (-9.507 cm 3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10 - 3 ). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10 - 9 ) and accelerated annual atrophy of the total cortical surface area (-31.401 cm 2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10 - 6 ). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect., Discussion: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients., (© 2024. The Author(s).)

Objectives: The primary objective of this study was to evaluate the prevalence of white matter hyperintensities (WMHs) in patients who experience migraine and compare findings between adult male and female patients. Specific symptoms and comorbidities also were analyzed to determine whether they were associated with WMH prevalence or the sex of patients with migraine. We hypothesized that females would have a higher prevalence of WMHs, experience more frequent and more severe migraine headaches, and be more likely to have certain comorbidities associated with migraine than males., Background: An increased prevalence of WMHs in patients with migraine has been proposed, although this relation is not well-supported by data from population-based MRI studies. The difference in brain morphology between males and females is of research interest, and females in the general population appear to have a higher prevalence of WMHs. Sex differences and various comorbidities in patients with migraine relative to the number of WMHs on brain imaging have not been fully investigated., Methods: This was a cross-sectional study of 177 patients aged 18 years and older with a diagnosis of migraine who were seen in the Lehigh Valley Fleming Neuroscience Institute's Headache Center between January 1, 2000, and January 1, 2017. Patients' baseline characteristics were extracted from electronic medical records, including demographics, review of systems documentation, and brain imaging from MRI. Variables including headache severity, frequency of head pain, insomnia, and comorbidities (anxiety, depression, diabetes, hyperlipidemia, hypertension, and neck pain) also were analyzed for associations with the presence of WMHs., Results: Females were found to have a significantly higher number of WMHs than males (median 3 [IQR: 0-7] vs. 0 [IQR: 0-3], p = 0.023). Patients with WMHs were significantly more likely than those without WMHs to have hypertension (39.8% of patients with WMHs vs. 20.3% without WMHs, p = 0.011), constipation (20.9% vs. 8.3%, p = 0.034), and sleep disorder (55.7% vs. 37.3%, p = 0.022). Females with migraine were significantly more likely to experience constipation than males (20.0% vs. 2.9%, p = 0.015). None of the migraine characteristics studied (frequency, severity, presence of aura) were different between sexes, nor were they significantly associated with the presence of WMHs., Conclusion: This study suggests that females with migraine may be more likely to have WMHs and experience constipation than males with migraine. Migraine frequency and severity were not different between sexes, nor were they significantly associated with the presence of WMHs. The findings of this study do not support a specific etiology of WMH development in individuals with migraine that differs from findings in the general population. Further studies are warranted., (© 2024 American Headache Society.)

This study aimed to assess the frontal sinus volume (FSV) on computed tomography (CT) scans in migraine patients. Cranial and paranasal CT images from 75 migraine patients (mean age: 39.14±13.63 y) and 23 control cases (mean age: 38.78±13.32 y) were analyzed retrospectively. Three-dimensionally reconstructed images of frontal sinuses were generated. Total FSV, anterolateral, and transverse diameters of the head were measured. The presence/absence and nature of supraorbital foramen and notches were evaluated. The total FSV was 8.02±5.97 cm 3 in the migraine group and 8.38±4.83 cm 3 in the control group, with no significant differences between them. Mean FSV values showed no statistically significant difference between females (7.79±5.85 cm 3 ) and males (9.12±6.66 cm 3 ) within and between the groups. Single notch was the most observed structure in both groups, with bilateral presence being the most common. Double foramen and notch were observed only in the migraine group, and the coexistence of both structures was higher in the migraine patients than in controls. There was no statistical difference in FSV between migraine and control groups, nor based on sex. Overall, the frontal region anatomy, particularly the exit locations of the supraorbital or supratrochlear foramen/notches, may be influenced by hyperplasia/hypoplasia of FSV. Therefore, assessing FSV using CT may be crucial for surgical planning in migraine patients undergoing open or endoscopic approaches to the frontal region., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Purpose: Vestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients., Methods: We searched literature measuring resting-state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size-signed differential mapping (AES-SDM) to conduct a whole-brain voxel-wise meta-analysis to identify the convergence of FC alterations in VM patients., Results: Nine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta-regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test-6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri., Conclusions: The study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background and Purposes: Numerous studies demonstrate a link between cerebrovascular alterations and migraine pathogenesis. We investigated the association between migraine and vertebral artery dominance (VAD), basilar artery (BA) curvature, and elongation., Materials and Methods: This cross-sectional MRI study included 74 migraine patients and 74 control subjects aged between 18 and 55 years. Diameters of the intracranial part of the vertebral artery (VA) and BA, height of the BA bifurcation, and total lateral displacement of the BA were measured. In addition, we investigated the directional relationship between VAD and BA curvature., Results: There were no statistically significant differences between the groups regarding VA and BA diameters and total lateral displacement of the BA. The height of the BA bifurcation was found to be significantly higher in migraine patients compared to controls ( p = 0.002). The left-side VAD was more frequent in migraine patients compared to control subjects (60.8% (45/74) vs 41.9% (31/74), p = 0.001). In migraine patients, particularly those with aura (MwA) patients, with left-side VAD, the rate of BA displacement to the right side is significantly higher than those with right-side VAD or non-VAD ( p = 0.022). Also, we found that total lateral displacement of the BA is correlated with VA asymmetry in patients with MwA (r = 0.538, p = 0.007)., Conclusion: VAD and its opposite-directional relationship with the lateral displacement of the BA may be associated with migraine pathophysiology. Together with aging, this association may contribute to changes in the vertebrobasilar system (VBS) geometry which may result in increased risk for posterior circulation infarction (PCI) in migraineurs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The etiology of migraine can be complex and multifactorial but not clear, also, intracranial pressure has been already associated with migraine attacks. This study aimed to monitor intracranial pressure during migraine attack to understand the possible relations with disease and severity., Methods: A prospective randomized study was designed. Patients with a definitive diagnosis of migraine underwent ultrasonography for optic nerve sheath diameter (ONSD) measurement before treatment and were re-measured after the attack was resolved. The severity of the migraine was assessed with Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaire before the treatment and after the symptoms regressed. ONSD values and scores from the questionnaires were compared before and after the migraine attack., Results: The study included 11 (52.4%) women and 10 (47.6%) men, and 42 eyes were evaluated. ONSD was detected as 4.23 ± 0.26 mm in the right eye and 4.10 ± 0.32 mm in the left eye during the migraine attack and decreased to 3.65 ± 0.41 mm in the right eye and 3.50 ± 0.33 mm in the left eye after the attack was treated (p < 0.001, both). A similar statistical improvement was found in HIT-6 and MIDAS scores with ONSD after treatment (p < 0.001). A significant positive correlation was found between the ONSD value in both eyes and HIT-6/MIDAS scores during the migraine attack, and also, after the migraine attack., Conclusion: A subjective increase of ONSD values during the migraine attack decreased after the disease resolved, also changes in ONSD values were significantly correlated with the severity of symptoms., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects., Methods: A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL)., Results: The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score., Conclusions: Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases., Competing Interests: The authors declare that they have no competing interests., (© 2024 Udomwech et al.)

Background: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods., Methods: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored., Results: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05)., Conclusions: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective., (© 2024. The Author(s).)

Background: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders., Methods: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders., Results: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache., Conclusions: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research., (© 2024. The Author(s).)

Nitric oxide (NO) is one of the reactive nitrogen species (RNS) that has been proposed to be a key signaling molecule in migraine. Migraine is a neurological disorder that is linked to irregular NO levels, which necessitates precise NO quantification for effective diagnosis and treatment. This work introduces a novel fluorescent probe, 2,3-diaminonaphthelene-1,4-dione (DAND), which was designed and synthesized to selectively detect NO in-vitro and in-vivo as a migraine biomarker. DAND boasts high aqueous solubility, biocompatibility, and facile synthesis, which enable highly selective and sensitive detection of NO under physiological conditions. NO reacts with diamine moieties (recognition sites) of DAND, results in the formation of a highly fluorescent product (DAND-NO) known as 1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione at λ em 450 nm. The fluorescence turn-on sensing mechanism operates through an intramolecular charge transfer (ICT) mechanism. To maximize fluorescence signal intensity, parameters including DAND concentration, reaction temperature, reaction time and pH were systematically optimized for sensitive and precise NO determination. The enhanced detection capability (LOD = 0.08 μmol L -1 ) and high selectivity of the probe make it a promising tool for NO detection in brain tissue homogenates. This demonstrates the potential diagnostic value of the probe for individuals suffering from migraine. Furthermore, this study sheds light on the potential role of zolmitriptan (ZOLM), an antimigraine medication, in modulating NO levels in the brain of rats with nitroglycerin-induced migraine, emphasizing its significant impact on reducing NO levels. The obtained results could have significant implications for understanding how ZOLM affects NO levels and may aid in the development of more targeted and effective migraine treatment strategies., Competing Interests: Declaration of competing interest The current study is new, original and not under consideration elsewhere. The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks., Methods: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days., Results: The active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment., Conclusions: M1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks., Significance: M1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to assess abnormalities in the insular cortex of individuals suffering from migraines and examine their associations with pain duration, medication usage, and clinical symptoms., Methods: We analyzed radiological data from 38 migraine patients who had undergone 3D iso T1-weighted brain MRI at our university hospital between 2019 and 2023. Structured questionnaires were used to collect information on participants' age, migraine type, disease duration, clinical symptoms, and medication use. Volumetric analysis was performed on the insular regions using Volbrain and 3DSlicer. The results were statistically analyzed., Results: Comparing groups with chronic pain to normal groups revealed significant differences in several insular regions, including the posterior insula (p = 0.034), parietal operculum (p = 0.04), and the entire insular cortex (p = 0.023). Further group comparisons (Group 1, 2, and 3) showed significant differences in specific insular regions. For instance, the anterior insula (p = 0.032) was associated with taste changes, the posterior insula (p = 0.010) with smell-related changes, and the central operculum (p = 0.046) with sensations of nausea. Additionally, significant changes were observed in the parietal operculum concerning nausea, photophobia, phonophobia, and changes in smell., Conclusion: To the best of our knowledge, there have been no studies investigating the relationship between clinical manifestations and volumetric correlation. This study provides insights into abnormalities in the insular cortex among migraine patients and their potential relevance to pain duration, severity, and migraine type. The results suggest that understanding alterations in insular regions possibly linked to pain could contribute to the development of innovative approaches to managing chronic pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: IIH is a severe form of headache that often has superimposed migraine and often it is very difficult to distinguish the two forms of headache. Intracranial hemodynamics is a relatively unexplored means of distinguishing between the two forms of headache., Objectives: We aimed to study intracranial flow dynamics using Transcranial Doppler in patients with IIH, migraine, and normal controls., Materials and Methods: It was a hospital-based observational study that included 51 people with IIH, 87 people with migraine, and 101 healthy controls and all were subjected to TCD study after detailed clinical examination., Results: Mean age of patients in three groups were similar with the mean age in IIH being 33.41 ± 10.75 (age in years ± SD). Vision loss was present in 66.67% of patients with IIH, and most common field defect was generalized constriction (27.5%). Neuroimaging was abnormal in 94.11% of patients of IIH with mean CSF pressure was 31.27±5.32 cm of water. Of all the TCD-measured velocities, mean flow velocity (MFV) showed a significant difference in all three groups with (p-value <0.001). The pulsatility index, both for middle cerebral arteries as well as ophthalmic arteries showed a significant difference in the three groups with the highest values in IIH patients (p-value<.001). The mean VMR in IIH (1.11±0.32) was lower than the mean VMR in migraine (1.34±0.43) as well as controls (1.49±0.46)., Conclusion: TCD parameters like MFV and PI are useful parameters that show considerable variation and can be used to differentiate between IIH and migraine., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Microcirculatory pathology is one of the pathophysiological theories of migraine, which may present as visually subclinical lesions. Image markers of cerebral small vessel disease (CSVD) have been investigated in elderly migraineurs. However, past studies looked at only part of image features, and the conclusions may have been hindered by confounding factors. The relationship between migraine and CSVD signs needs reliable demonstrations., Methods: We conducted a case-control study by recruiting episodic young migraineurs from a tertiary headache centre, with tension-type headache (TTH) and healthy controls. Distinct image features of microvascular damage and baseline characteristics across groups were assessed, and multivariate linear regression was performed to evaluate the risk factors for image abnormalities in migraineurs., Results: Forty-eight migraineurs, 32 TTHs and 49 healthy controls were included. The median age was 32 year-old. 58.7% of the participants were female. The Scheltens score and volume of white matter hyperintensities (WMHs) in migraineurs, and the number of Virchow-Robin spaces (VRSs) in both migraineurs and TTHs were different from those in normal controls. No lacunar infarct-like lesions (ILLs) or cerebral microbleeds (CMBs) were found. Age, education level (high level: β = -2.23, lobar WMHs), attack duration (long duration: β = 3.81, lobar WMHs) and attack frequency were independent risk factors for Scheltens score and volume of WMH in migraineurs. Migraine aura (β = -2.389), attack frequency and education level were correlated with the number of VRSs., Conclusions: Migraine was associated with WMHs and VRSs. Aura, attack duration, attack frequency, age and education level were risk factors for image abnormalities of CVSD in migraineurs., Significance: This study provides a novel and comprehensive landscape of CSVD MRI features in young migraineurs, and it fills the blank of CMBs and VRSs which received less attention, with more persuasive, more reliable and stronger evidence of the association between CSVD and migraine. Our results also imply some new feature of TTH and the possible pathophysiology of the migraine course as well as new clues for the early management of migraine in terms of visual brain damage., (© 2023 European Pain Federation - EFIC ®.)

Introduction: The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients' disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups., Patients and Methods: The study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations., Results: The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons., Conclusions: The classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients., (© 2024. The Author(s).)

Glymphatic system is an emerging pathway of removing metabolic waste products and toxic solutes from the brain tissue. It is made of a network of perivascular spaces, filled in cerebrospinal and interstitial fluid, encompassing penetrating and pial vessels and communicating with the subarachnoid space. It is separated from vessels by the blood brain barrier and from brain tissue by the endfeet of the astrocytes rich in aquaporin 4, a membrane protein which controls the water flow along the perivascular space. Animal models and magnetic resonance (MR) studies allowed to characterize the glymphatic system function and determine how its impairment could lead to numerous neurological disorders (e.g. Alzheimer's disease, stroke, sleep disturbances, migraine, idiopathic normal pressure hydrocephalus). This review aims to summarize the role of the glymphatic system in the pathophysiology of migraine in order to provide new ways of approaching to this disease and to its therapy., (© 2024. The Author(s).)

Objective: To investigate the neural correlates of working memory during a spontaneous migraine attack compared to the interictal phase, using functional magnetic resonance imaging (fMRI)., Background: Cognitive disturbances are commonly observed during migraine attacks, particularly in the headache phase. However, the neural basis of these changes remains unknown., Methods: In a fMRI within-subject test-retest design study, eleven women (32 years of age, average) with episodic migraine were evaluated twice, first during a spontaneous migraine attack, and again in a pain-free period. Each session consisted in a cognitive assessment and fMRI while performing a working memory task (N-back)., Results: Cognitive test scores were lower during the ictal session than in the pain-free session. Regions typically associated with working memory were activated during the N-back task in both sessions. A voxel wise between session comparison showed significantly greater activation in the left frontal pole and orbitofrontal cortex during the attack relative to the interictal phase., Conclusion: Migraine patients exhibited greater activation of the left frontal pole and orbitofrontal cortex while executing a verbal working memory task during a spontaneous migraine attack when compared to the interictal state. Given the association of these regions with pain processing and inhibitory control, these findings suggest that patients recruit inhibitory areas to accomplish the cognitive task during migraine attacks, a neural signature of their cognitive difficulties., (© 2023. The Author(s).)

Objective: This study was undertaken to investigate migraine glymphatic and meningeal lymphatic vessel (mLV) functions., Methods: Migraine patients and healthy controls (HCs) were prospectively recruited between 2020 and 2023. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index for glymphatics and dynamic contrast-enhanced magnetic resonance imaging parameters (time to peak [TTP]/enhancement integral [EI]/mean time to enhance [MTE]) for para-superior sagittal (paraSSS)-mLV or paratransverse sinus (paraTS)-mLV in episodic migraine (EM), chronic migraine (CM), and CM with and without medication-overuse headache (MOH) were analyzed. DTI-ALPS correlations with clinical parameters (migraine severity [numeric rating scale]/disability [Migraine Disability Assessment (MIDAS)]/bodily pain [Widespread Pain Index]/sleep quality [Pittsburgh Sleep Quality Index (PSQI)]) were examined., Results: In total, 175 subjects (112 migraine + 63 HCs) were investigated. DTI-ALPS values were lower in CM (median [interquartile range] = 0.64 [0.12]) than in EM (0.71 [0.13], p = 0.005) and HCs (0.71 [0.09], p = 0.004). CM with MOH (0.63 [0.07]) had lower DTI-ALPS values than CM without MOH (0.73 [0.12], p < 0.001). Furthermore, CM had longer TTP (paraSSS-mLV: 55.8 [12.9] vs 40.0 [7.6], p < 0.001; paraTS-mLV: 51.2 [8.1] vs 44.0 [3.3], p = 0.002), EI (paraSSS-mLV: 45.5 [42.0] vs 16.1 [9.2], p < 0.001), and MTE (paraSSS-mLV: 253.7 [6.7] vs 248.4 [13.8], p < 0.001; paraTS-mLV: 252.0 [6.2] vs 249.7 [1.2], p < 0.001) than EM patients. The MIDAS (p = 0.002) and PSQI (p = 0.002) were negatively correlated with DTI-ALPS index after Bonferroni corrections (p < q = 0.01)., Interpretation: CM patients, particularly those with MOH, have glymphatic and meningeal lymphatic dysfunctions, which are highly clinically relevant and may implicate pathogenesis for migraine chronification. ANN NEUROL 2024;95:583-595., (© 2024 American Neurological Association.)

Background: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options., Methods: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort., Results: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities., Conclusions: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described., (© 2024. The Author(s).)