Headache is a prevalent and highly disabling neurological disorder. There are no data on its prevalence in and impact on hospitalized patients. The objective of this study was to describe the prevalence of headache in hospitalized patients, triggers associated with headaches in this population, and compliance with documentation in the electronic medical record system (EMRS).

This was a prospective, descriptive, observational, cross-sectional study. Inpatients who agreed were included.

Demographic data, admission-related data, and headache data were collected. Data were obtained from the EMRS and direct interviews with patients. Data were collected at three time points in 2021 and 2022. Statistical analysis, comprising primary and secondary data analysis, was performed with R.

Of the 403 admitted patients, 65.5% (264 of 403) participated. A total of 39% (103 of 264) had presented with headache during their hospitalization, of whom 48.5% (50 of 103) had experienced headache in the preceding 24 hours. Of these, 35.9% (37 of 103) identified stress and 26.2% (27 of 103) identified noise as the most frequent triggers and 24.3% (25 of 103) identified headache as a secondary symptom derived from the cause of admission. During the daily follow-up by the nurse, 95.5% (252 of 264) of patients indicated that they had been asked about pain in general and 11.4% (30 of 264) indicated that they had been asked specifically about headache. No records were obtained from the computer program because although some patients were asked about headache, answers were not recorded in the prespecified "headache" item in the EMRS.

Headache is a prevalent symptom in hospitalized patients. Health care professionals should ask, register, and care about headache routinely to improve patients' well-being.

The purpose of this review is to provide an update on the clinical course and management of migraine in women.

Migraine is two to three times more prevalent in women who report a longer, more severe attacks with more disability, an increased risk of recurrence, and a longer recovery period. Consequently, women use more acute and preventive medications, have more comorbid conditions and are more likely to run a chronic disease course.Real-life experience and evidence suggest that onabotulinumtoxinA and the newer generation antibody treatments against the calcitonin gene-related peptide (CGRP) ligand and its receptor are highly effective in the management of migraine in women.Pregnancy, breast feeding, and menstrual cycles should be taken into account when treating women with migraine. Topiramate and sodium valproate should be avoided in women of childbearing age (WCBA). Hormonal options can be considered in menstrual or menopausal migraines. NSAIDs and prostaglandins such as mefenamic acid can be used at onset of menstrual migraine. Venlafaxine can be effective in menopausal migraine while also treating the vasomotor symptoms. Migraine usually improves during pregnancy; however, if required nonpharmacological options should be considered.

Effectively managing migraine in women of productive and reproductive age, can reduce the socioeconomic burden of this debilitating disease.

Migraine is a prevalent neurological disorder that significantly impacts quality of life. Despite its considerable burden, the underlying pathophysiology remains poorly understood.

To identify physical-functional alterations in women with chronic migraine.

Twenty-four women (39.2 ± 7.7 years) with chronic migraine were assessed using tools selected for this study. We analyzed pain intensity and perception (Visual Analog Scale - VAS and McGill Pain Questionnaire), motion sickness (Dizziness Handicap Inventory - DHI), panic and agoraphobia (Panic and Agoraphobia Scale - PAS), postural stability (modified Clinical Test of Sensory Integration and Balance - mCTSIB and Dynamic Gait Index - DGI), and quality of life (WHOQOL-BREF).

The prevalence of pain is widely reported, with a mean intensity score of 6.7 ± 1.7, and when assessed using the McGill scale, the total pain index was 60.6 ± 14.7. The DHI showed a score with a median of 34 points, while the PAS scored with a median of 4 points. In the WHOQOL, the Physical and Psychological domains had the worst scores (53.3 ± 17.8 and 58.9 ± 18.7, respectively). The mean DGI score was 21.5 ± 2.3, where 12.5 % of the participants presented a deficit, whose score indicates gait impairment and risk of falls. In the mCTSIB, the mean score was 5.3 ± 1.1. When correlating the uni or multidimensional aspects of pain with quality of life, the pain scores by VAS are significantly associated with the score of total quality of life.

Chronic migraine can alter physical-functional conditions in women.

Migraine is a chronic neurological problem with a psychological comorbidity. However, anxiety and depression among patients with migraine have not been thoroughly investigated in Southeast Asia. Thus, we aimed to elucidate the prevalence of anxiety and depression in patients with migraine, as well as the associated factors.

This cross-sectional study was conducted between March 2022 and March 2024 at the National University of Malaysia. The participants' data were collected prior to completing two questionnaires, including the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), which were used to evaluate depression and anxiety, respectively.

A total of 246 participants who were diagnosed with migraine were recruited for this study. The mean age of the participants was 46.19 years (SD: ± 14.75). Additionally, 77.6% of the participants were female. Moreover, 27.7% of the participants had anxiety alone, 15.9% had depression alone, and 11.8% had both anxiety and depression. A younger age (p = 0.03), earlier age of migraine onset (r(246) -0.178, p < 0.01), background history of asthma (r(246) 0.161, p < 0.05), lower household income range (r(246) -0.179, p < 0.01), increased pain severity (r(246) 0.211, p < 0.01), frequency of attack (r(246) 0.139, p < 0.05), use of NSAIDs (r(246) 0.134, p < 0.05), use of pizotifen (r(246) 0.169, p < 0.01), use of propranolol (r(246) 0.286, p < 0.01), use of sodium valproate (r(246) 0.146, p < 0.05), use of topiramate (r(246) 0.178, p < 0.01), use of more than one medication (r(246) 0.240, p < 0.01), use of cold therapy (r(246) 0.223, p < 0.01) and use of acupuncture (r(246) 0.260, p < 0.01) were associated with anxiety and depression in migraine patients.

Anxiety and depression are commonly observed in patients with migraine in Asia. Routine assessments for anxiety and depression should be performed to ensure holistic management of migraine.

This review aims to summarize the current understanding of cluster headaches (CH) in children, focusing on epidemiology, pathophysiology, clinical characteristics, diagnostic challenges, treatment strategies, and future research directions.

Cluster headaches in children are infrequent, with an incidence that appears to be significantly lower than that observed in adults, highlighting the need for more comprehensive studies. Pediatric patients often present with atypical symptoms, such as shorter pain duration and less pronounced autonomic features, leading to frequent misdiagnosis or delayed diagnosis. The hypothalamus plays a central role in the pathophysiology of CH, involving circadian rhythm disturbances, trigeminal nerve-vascular activation, and autonomic dysfunction. High-flow oxygen and triptan medications are effective for acute treatment in adults, but their safety and efficacy in children require further validation. Preventive treatments, such as verapamil, are used cautiously in pediatric patients, with close monitoring for side effects. Non-pharmacological interventions, including lifestyle adjustments and psychological support, are critical for long-term management. Cluster headaches in children are a rare but debilitating condition that poses significant diagnostic and therapeutic challenges. Current diagnostic criteria, primarily based on adult data, may not fully capture the unique clinical features of pediatric patients, leading to misdiagnosis or missed diagnosis. Treatment strategies are largely extrapolated from adult studies, with limited evidence-based data for children. Future research should focus on improving diagnostic criteria, exploring pediatric-specific pathophysiological mechanisms, and validating safe and effective treatment options. Early identification and intervention are essential to improving the quality of life and long-term outcomes for pediatric patients.

Migraine, characterized by recurrent episodes of severe headache, remains mechanistically enigmatic. While traditional theories emphasize trigeminovascular activation, the role of meningeal stromal-immune crosstalk in disease chronicity is poorly understood.

A migraine-related chronic hypersensitivity model was utilized via intermittent intraperitoneal nitroglycerin (NTG, 10 mg/kg, every other day for 9 days) and peripheral mechanical hypersensitivity was assessed using von Frey filaments. Single-cell RNA sequencing (scRNA-seq) was performed on dura tissues to construct a cellular atlas of NTG-induced remodeling. These data were then integrated with migraine genome-wide association study (GWAS) risk genes, cell-cell interaction networks, and transcriptional regulation analysis to dissect NTG-driven meningeal remodeling.

The NTG-induced migraine-related chronic hypersensitivity model demonstrated sustained mechanical allodynia, as evidenced by significantly decreased paw withdrawal thresholds (p < 0.0001). Single-cell profiling of the dura mater revealed a 2.4-fold expansion of a pro-inflammatory fibroblast subpopulation (Fibro_c5: 1.9% in Vehicle vs. 4.6% in NTG group), which exhibited marked activation of TNF-α/NF-κB signaling pathways (normalized enrichment score [NES] = 1.83). Concomitantly, we observed an 82% increase in meningeal monocytes (5.7-10.4%) that showed preferential interaction with Fibro_c5 fibroblasts through Angptl1-mediated stromal-immune crosstalk (log2 fold change = 1.41). Regulatory network analysis identified Mafk as the upstream transcriptional regulator orchestrating Angptl1 expression in this pathological communication axis.

Our study reveals that NTG reprograms meningeal fibroblasts to expand a pro-inflammatory fibroblast subtype, which drives migraine-related chronic hypersensitivity through TNF-α/NF-κB signaling and Angptl1-mediated monocyte crosstalk. The identified Mafk-Angptl1 axis presents a potential therapeutic target, though human validation remains essential.

Pediatric migraine is an increasingly recognized public health concern, with a rising prevalence among children and adolescents. Despite advances in our understanding of migraine mechanisms and treatment, major gaps and barriers persist in diagnosis, management, and awareness. This review highlights the current gaps in pediatric migraine care, including underdiagnosis, comorbidities, disparities in access to treatment, and proposes actionable strategies to improve outcomes. A structured narrative review focused on pediatric migraine prevalence, diagnosis, treatment, and comorbidities. Emphasis was placed on interdisciplinary collaboration, emerging mechanism-based therapies, and holistic approaches to managing pediatric migraine. Pediatric migraine are frequently underdiagnosed and undertreated, partly due to a lack of physician awareness, inadequate training, and outdated guidelines. Emerging mechanism-based therapies, such as CGRP-targeted treatments, hold promise but are not yet widely adopted in pediatric care and are unlikely to be accessible to all but a few patients. Holistic approaches, including lifestyle modifications and behavioral therapy, can complement traditional treatments but remain underutilized.

Addressing the current gaps and barriers in pediatric migraine care requires updated clinical guidelines, increased healthcare provider training, increased awareness of comorbidities, affordability of approved medications, and encouragement of holistic treatment options. By fostering interdisciplinary collaboration and expanding access to care, better outcomes can be achieved for children suffering from migraine.

• Pediatric migraine is a prevalent but often underdiagnosed condition, with significant impact on quality of life. • Traditional treatment approaches are frequently inadequate, and physician awareness and training remain suboptimal.

• This review identifies critical gaps in pediatric migraine care, including limited access to emerging therapies and insufficient integration of holistic approaches. • It proposes actionable strategies such as interdisciplinary collaboration, updated guidelines, and enhanced provider education to improve care outcomes.

Migraine is the most common neurological disorder and the second leading cause of disability. While the impact of migraine on daily life is often assessed by the frequency and intensity of attacks, the impairment between episodes is frequently overlooked. The four-item Migraine Interictal Burden Scale (MIBS-4) is a tool that can provide information and help in the evaluation of interictal disability.

To adapt and validate a translated version of the MIBS-4 for the Portuguese population.

A prospective, multicentric observational study was conducted between July 2023 and February 2024 in six tertiary headache centers across Portugal. The MIBS-4 was translated and back-translated to obtain a consensus version. The scale was administered to 459 patients with migraine, and its psychometric properties were assessed through correlations with established measures, including the Migraine Disability Assessment Scale (MIDAS), 12-item Short Form Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS).

A total of 459 patients were evaluated, including 430 women (93.7%), with an average age of 45.06 years. The MIBS-4 demonstrated good internal consistency with a Cronbach's alpha of 0.84 (95% confidence interval 0.81-0.86) and significant correlations with the MIDAS (r = 0.304, p < 0.001), SF-12 (r = 0.483, p < 0.001), and HADS (r = 0.211, p < 0.001), confirming its reliability and construct validity.

This analysis showed that the Portuguese version of the MIBS-4 showed identical psychometric properties to the original scale and can effectively assess interictal disability in patients with migraine in Portuguese speaking populations. Its validation provides a valuable tool for clinical practice and research, enabling improved assessment of migraine burden and contributing to better patient care in lusophone countries.

Migraine is a complex neurological disorder characterized by different signs and symptoms, often presenting with an altered pain sensitivity and cervical musculoskeletal impairments. Thus, the management of migraine patients should include the assessment and eventually a specific treatment of these characteristics.

Physiotherapists play a key role in identifying and managing cervical musculoskeletal impairments and altered pain sensitivity in migraine patients. This manuscript provides evidence-based guidance on assessment techniques and clinical reasoning strategies to help physiotherapists effectively evaluate and interpret these characteristics in clinical practice.

This manuscript serves as a practical guide for physiotherapists by: Outlining physiotherapy assessment techniques for migraine patients.Providing reference cutoff values to identify increased pain sensitivity and cervical dysfunctions.Supporting individualized clinical reasoning to understand these characteristics within each patient's overall condition.Clarifying the rationale behind physiotherapy interventions and integrating hands-on and hands-off therapeutic approaches based on patient-specific needs.

This study examined pathophysiological changes in incentive processing in migraineurs. Nineteen episodic migraine (EM) patients and 19 healthy controls (HCs) performed a monetary incentive delay task while their event-related potentials were recorded. During the incentive anticipation phase, both Cue-N2 and Cue-P3 amplitudes were responsive to incentive cues in both groups, indicating no between-group differences in the distinct anticipatory subprocesses that underly incentive cue evaluation. During the outcome phase, the feedback-related negativity amplitude, associated with performance evaluation, was larger for punishing feedback than rewarding feedback across both groups. However, the feedback-P3 amplitude, linked to attentional processing of motivational value of outcome feedback, was significantly larger for rewarding feedback than punishing feedback in HCs, but not in EM patients. Moreover, a significant negative correlation was observed between the feedback-P3 amplitude difference for rewarding minus punishing feedback and subjective pain intensity in EM patients. Finally, the feedback late-positive potential amplitude, related to affective processing of affective value of outcome feedback, was significantly larger for punishing feedback than rewarding feedback only in HCs, but not in EM patients. Our findings suggest that recurrent severe pain may relate to abnormal incentive-related brain activity during the outcome phase of incentive processing.

Asari Radix et Rhizoma (ARR), a traditional Chinese medicine, has been used for centuries to treat various diseases, including migraine, rheumatic pain, and toothache. Valued for its capacity to warm the meridians and promote dispersion, ARR is regarded as an essential herb for releasing the exterior, dispelling cold, and alleviating pain. Alkamides, represented by N-isobutyl-2E,4E,8Z,10E/Z-dodecatetraenamide (DDA-E/Z), were considered closely related to traditional properties of ARR and exhibited diverse biological activities. However, their underlying anti-migraine mechanisms remain unclear.

This study aimed to identify the active constituents of ARR and investigate the pharmacological effects and mechanisms of ARR-derived alkamides DDA-E and DDA-Z in migraine models through integrated network pharmacology and experimental validation.

The chemical profile and blood entry components of ARR were analyzed by ultra-high performance liquid chromatography-quadruple time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). Network pharmacology was used to identify potential targets and pathways associated with the prototypical plasma components in migraine. Analgesic and anti-inflammatory activities of the key active ingredients, DDA-E, DDA-Z and their combinations, were assessed using behavioral tests and periorbital mechanical pain thresholds. Hematoxylin and eosin, immunofluorescence analysis, enzyme-linked immunosorbent assay, Westen blot, and real-time quantitative reverse transcription PCR were conducted to explore underlying mechanisms. Functional assay and molecular docking studies investigated the ability of DDA-E and DDA-Z to activate CB1/CB2 receptors.

A total of 35 components were identified in ARR, with 10 of them entering the blood as prototypes. Network pharmacology revealed 209 potential targets of ARR-derived prototypical blood-entry components in migraine. DDA-E and DDA-Z showed high plasma exposure and the highest degree values in the network analysis, indicating their roles as important active ingredients of ARR for migraine. The in vitro and in vivo experiments suggested that the potential targets of DDA-E were CGRP, ERK, and AKT, which mainly acted through cAMP and PI3K-Akt pathways, while DDA-Z targeted COX-2, MAPK, and AKT through MAPK and PI3K-Akt pathways. Immunofluorescence, functional assays, and molecular docking results confirmed that DDA-E and DDA-Z tend to selectively activate CB1/CB2 receptors.

In this study, serum pharmacochemistry combined with network pharmacology identified DDA-E and DDA-Z as the key active constituents of ARR. Subsequent experimental validation elucidated their potential anti-migraine mechanisms, highlighting their selective activation of cannabinoid receptors and providing a foundation for further research and therapeutic application.

Migraine is a complex neurological disorder frequently associated with hypothalamic dysfunction. This brain region is essential for maintaining homeostasis due to its regulation of autonomic, endocrine, and circadian systems. While the pathophysiology of migraine remains incompletely understood, clinical features such as the cyclic nature of attacks and symptoms, including nausea, vomiting, yawning, irritability, and sensitivity to light, indicate a significant role for the hypothalamus. Further, potential triggers of migraine, such as stress and disruption to feeding habits, also impact hypothalamic mechanisms. The higher prevalence of migraine in women compared to men suggests a link to hormonal fluctuations involving estrogen, progesterone, and prolactin. These hormones interact with the hypothalamus, potentially influencing the onset and severity of migraine episodes. Additionally, the hypothalamus synthesizes neuropeptides such as orexins, neuropeptide Y, PACAP, oxytocin, and vasopressin, which are all implicated in migraine mechanisms. Understanding the interplay between the hypothalamus, sex hormones, and neuropeptides offers valuable opportunities for endogenous targeted migraine therapies. In this review we discuss hypothalamic contributions to migraine pathophysiology, highlighting the mechanisms affected by hypothalamic connections, neuropeptides, and hormones, and their role as migraine triggers, particularly focusing on factors like stress, fasting, and changes in sleep patterns.

PRODROME was a phase 3, placebo-controlled, double-blind crossover trial evaluating whether ubrogepant 100 mg, a calcitonin gene-related peptide receptor antagonist, dosed during the premonitory (prodromal) phase of migraine, prevented development of headache and resolved prodromal symptoms. Qualifying prodromal events were defined as attacks with symptoms in which the participant was confident headache would follow within 1-6 h. Of 1,087 screened participants, 477 formed the efficacy analysis population. Outcomes were collected across 48 h showing, for example, at 2 h post-dose, absence of photophobia in 19.5% and 12.5% of ubrogepant- and placebo-treated events, respectively (odds ratio (OR) = 1.72 (95% confidence interval (CI) = 1.13-2.61)); at 3 h post-dose, absence of fatigue occurred in 27.3% and 16.8% (OR = 1.85 (95% CI = 1.17-2.92)) and absence of neck pain in 28.9% and 15.9% (OR = 2.04 (95% CI = 1.25-3.32)) of events; at 4 h post-dose, absence of phonophobia in 50.7% and 35.8% (OR = 1.97 (95% CI = 1.38-2.80)) of events; and at 24 h post-dose, absence of dizziness in 88.5% and 82.3% (OR = 1.82 (95% CI = 1.00-3.30)) of events. At 1 h and 6 h post-dose, respectively, absence of difficulty concentrating occurred in 8.7% and 2.1% (OR = 4.26 (95% CI = 1.17-15.54)) and absence of difficulty thinking occurred in 56.9% and 41.8% (OR = 2.05 (95% CI = 1.14-3.71)) of events. Treatment with ubrogepant during the prodromal phase may ameliorate common prodromal symptoms, with improvements possibly as early as 1 h post-dose.

Headaches and migraines are disabling, costly conditions. While physical activity shows benefits, specific exercise patterns' effects on headaches in the U.S. remain underexplored. This study aims to examine the cross-sectional relationship between different exercise patterns and the occurrence of severe headaches or migraines in adults using data from a nationally representative U.S. sample. Data from the National Health and Nutrition Examination Survey (NHANES) cycles 1999-2004 were analyzed. The study included adults aged 20-65 years who reported their exercise habits and severe headache or migraine status. Logistic regression models were used to assess the predictive relationships between vigorous, moderate, and muscle-strengthening exercise, as well as combinations of these activities, and the occurrence of migraines. The final sample comprised 2011 participants representing a weighted population of about 32 million U.S. adults. Combining vigorous and muscle-strengthening activities showed the most significant reduction in headache/migraine occurrence (OR: .48, 95% CI: 0.26-0.90), indicating a 52% reduction. Other exercise combinations were also associated with lower odds ratios compared to no exercise, but they were not statistically significant in the fully adjusted model. Regular physical activity, especially the combination of vigorous and muscle-strengthening exercise, is linked to a lower risk of severe headaches/migraines.

In many countries, patients with headache disorders such as migraine remain under-recognized and under-diagnosed. Patients affected by these disorders are often unaware of the seriousness of their conditions, as headaches are neither fatal nor contagious. In many cases, patients with migraine are often misdiagnosed as regular headaches.

In this article, we present a study on migraine, covering known triggers, different phases, classification of migraine into different types based on clinical studies, and the use of various machine learning algorithms such as logistic regression (LR), support vector machine (SVM), random forest (RF), and artificial neural network (ANN) to learn and classify different migraine types. This study will only consider using these methods for diagnostic purposes. Models based on these algorithms are then trained using the dataset, which includes a compilation of the types of migraine experienced by various patients. These models are then used to classify the types of migraines, and the results are analyzed.

The results of the machine learning models trained on the dataset are verified for their performance. The results are further evaluated by selective sampling and tuning, and improved performance is observed. The precision and accuracy obtained by the support vector machine and artificial neural network are 91% compared to logistic regression (90%) and random forest (87%). These models are run with the dataset without optimal tuning across the entire dataset for different migraine types; which is further improved with selective sampling and optimal tuning. These results indicate that the discussed models are relatively good and can be used with high precision and accuracy for diagnosing different types of migraine.

Our study presents a realistic assessment of promising models that are dependable in aiding physicians. The study shows the performance of various models based on the classification metrics computed for each model. It is evident from the results that the artificial neural network (ANN) performs better, irrespective of the sampling techniques used. With these machine learning models, types of migraines can be classified with high accuracy and reliability, enabling physicians to make timely clinical diagnoses of patients.

Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) levels alongside normal free thyroxine (T4) and triiodothyronine (T3) levels. Emerging evidence suggests a link between SCH and migraine disorders, including both episodic and chronic migraine. Given this association, researchers have explored whether correcting mild thyroid dysfunction with low-dose levothyroxine could alleviate migraine symptoms in affected individuals. This study investigates the potential efficacy of low-dose thyroid replacement therapy in reducing migraine frequency and severity among patients with comorbid SCH and migraine.

A search was conducted on Cochrane Central, Medline, Embase, Web of Science Core Collection, and Scopus to identify randomized clinical trials (RCTs), case-control studies, and cohort research studies evaluating the use of low-dose thyroxine in patients with subclinical hypothyroidism (SCH).

This review analyzed four studies, two of which qualified for meta-analysis. The findings suggest a potential association between (SCH) and migraine. Notably, levothyroxine treatment in hypothyroid patients appeared to correlate with reduced migraine frequency and headache severity. However, while the meta-analysis showed a trend toward migraine reduction with thyroxine therapy, the results did not reach statistical significance - likely due to the limited study sample included in the analysis.

The study highlights the importance of thyroid screening in migraine management, due to the link between hypothyroidism and migraines. It recommends routine thyroid function assessments for migraine patients and suggests personalized treatment approaches. Early intervention can minimize migraine episodes and improve quality of life. Adherence to low dose levothyroxine regimens can reduce migraine frequency. Further research is required to elucidate the underlying mechanisms, optimize treatment protocols, and explore potential comorbidities.

Neuropsychiatric disorders such as bipolar disorder, migraine, major depressive disorder, epilepsy, attention-deficit/hyperactivity disorder, autism spectrum disorder and schizophrenia, are a huge burden on global health, impacting millions of individuals worldwide and posing significant barriers to effective treatment. Despite advancements in medication and psychotherapy, many patients continue to suffer from severe symptoms and receive little alleviation. All of these conditions are quite frequent, yet they affect people in a way that is exceedingly detrimental. The increasing evidence suggests the connection between these disorders and inflammation. Therefore, the use of anti-inflammatory agents, namely cyclooxygenase-2 (COX-2) inhibitors, offers a new approach to prevent and treat neuropsychiatric disorders. This review discusses about the COX pathway and the role of COX-2 in the neuroinflammation. Furthermore, this review highlights the COX-2 inhibitors as a promising therapeutic agent in these neuropsychiatric disorders, however, further studies are required to assess appropriate illness stage-related indication.

The relationship between adipose-muscle distribution and its effect on migraine remains unclear. This study examines the association between muscle mass and migraine prevalence and evaluates potential mediation by systemic inflammatory biomarkers.

Using a cross-sectional design, we analyzed data from 10,400 participants in the National Health and Nutrition Examination Survey (NHANES) (1999-2004). The association between appendicular lean mass normalized to body mass index (ALM/BMI) and migraine prevalence was evaluated through weighted logistic regression and subgroup analyses. Mediation analyses were conducted to examine the potential mediating roles of inflammatory markers, including C-reactive protein (CRP), white blood cell count (WBC), and neutrophils, in the relationship between ALM/BMI and migraine prevalence. Genetic causality was investigated via two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data.

20% of total participants reported migraines. A higher ALM/BMI ratio was inversely associated with migraine after full adjustment (OR = 0.243; 95% CI: 0.122-0.487, p < 0.001). Vigorous activity reduced migraine susceptibility by 24% (OR = 0.760; 95% CI: 0.663-0.872, p < 0.001). CRP, WBC and neutrophils mediated 2.0% (p = 0.024), 3.1% (p = 0.011), and 2.8% (p = 0.019) of the ALM/BMI-migraine association, respectively. The inverse-variance weighted approach (IVW) in MR analysis indicated that higher basal metabolic rate (BMR) reduced migraine risk (OR = 0.996, 95% CI: 0.992-0.998, p = 0.004) and headache risk (OR = 0.998, 95% CI: 0.997-1.000, p = 0.018). Fat-free mass also exhibited protective effects on migraines (OR = 0.997, 95% CI: 0.994-1.000, p = 0.045).

Increased muscle mass is associated with reduced migraine risk, partially mediated by attenuating systemic inflammation. These findings provide us with an approach of health management to prevent migraines.

Plasma glial fibrillary acidic protein (pGFAP) and plasma neurofilament light chain (pNfL) levels reflect astrocyte activation and neuronal damage, respectively. Whether these phenomena play a role in migraine is unknown. This study aimed to compare pGFAP and pNfL levels in patients with chronic migraine (CM) and age-matched controls and to analyze their relation with clinical features.

The study evaluated two independent cohorts of patients, including in total 58 CM and 69 controls. pGFAP and pNfL were quantified with single molecule array (Simoa) technology. Demographic and clinical data were collected for each subject; differences in NfL/GFAP levels between CM and controls were evaluated in analyses adjusted for the effect of age and sex; clinical characteristics associated with NfL/GFAP levels were separately evaluated in the two cohorts.

In both cohorts, we did not find a significant difference in pGFAP or pNFL levels between CM and matched controls. The study did not find any correlation between pGFAP or pNfL levels and any migraine characteristics (namely presence of migraine aura, attack frequency, migraine intensity, years of disease).

Our negative results support the assumption that migraine represents a benign condition, characterized by transient functional brain alterations and not by the accumulation over time of neuroaxonal damage and/or associated astrocyte activation detectable by neurodegeneration marker proteins.

We conducted the current systematic review to investigate the association between dietary inflammatory index (DII) and severe headaches or migraine among adults via synthesizing observational evidence.

We conducted a systematic literature search of observational studies through PubMed, Scopus, and Web of Science databases from inception until July 2024. The PECO framework was implemented to select eligible studies as follows: Population (adults with severe headache or migraine), Exposure (individuals with the highest adherence to a pro-inflammatory diet), Comparison (individuals with the lowest adherence to a pro-inflammatory diet), Outcome (risk of developing severe headache or migraine, headaches frequency, duration, severity, and migraine-related disability).

After reviewing six studies involving 31,958 individuals, we found that following an anti-inflammatory diet is associated with a lower frequency and severity of migraine headaches. Additionally, our research revealed that individuals with migraines tend to have lower adherence to an anti-inflammatory diet when compared to people without migraines. Surprisingly, adherence to a pro-inflammatory diet was linked to a reduced risk of chronic daily headaches.

Present findings imply a negative link between an inflammatory diet and severe headaches or migraine. However, further well-designed longitudinal studies are needed to interpret the causality and shed light on the underlying mechanisms.

The Headache Impact Test (HIT-6) questionnaire is commonly utilized to assess the impact of headaches in both clinical settings and research. To date, no validated Spanish version of this tool has been published.

This study seeks to evaluate the psychometric properties of the Spanish version of the HIT-6 questionnaire for use in patients experiencing episodic migraine.

We conducted a cross-sectional study aimed at validating this measurement instrument. A total of 100 subjects, both male and female, aged 18 to 65 years, diagnosed with episodic migraine, were included in the analysis. Construct validity was assessed using principal component analysis, test-retest reliability via the intraclass correlation coefficient (ICC), internal consistency, and convergent validity against the 12-Item Short Form Health Survey and the Migraine Disability Assessment.

The principal component analysis revealed a two-component structure. The overall HIT-6 scale demonstrated strong test-retest reliability ([ICC = 0.89; 95% CI = 0.83-0.92]), with high reliability for the indirect subscale [(ICC = 0.87; 95% CI = 0.81-0.91)] and excellent reliability for the direct subscale [(ICC = 0.90; 95% CI = 0.85-0.93)]. Internal consistency was also robust (Cronbach's α = 0.834), and the questionnaire showed a significant correlation with MIDAS (r = 0.512; p < 0.001), as well as a moderate correlation with the physical (r = -0.326; p < 0.05) and mental factors (r = -0.429; p < 0.001) of the SF-12.

The Spanish adaptation of the HIT-6 questionnaire is a reliable and valid tool for evaluating the impact of episodic migraine on patients' quality of life, confirming the validity of both subscales.

Primary cultures of brainstem tissue can be used to investigate cellular and molecular mechanisms involved in disease pathology and to identify novel therapeutic targets that modulate neuron and glial cell activities. However, preparation of primary cultures from rodent embryos or neonatal animals is labor-intensive, and it can be difficult to produce high-quality consistent cultures. To overcome these issues, cryopreservation can be used to obtain standardized, high-quality stocks of brainstem neuronal and glial cells. We present a simplified cryopreservation method for establishing primary cell cultures of pons and medulla oblongata tissue from Sprague-Dawley neonates, using a 90:10 (v/v) fetal bovine serum/dimethyl sulfoxide cell freezing medium. Cryopreserved brainstem cells stored for up to one year in liquid nitrogen exhibited similar neuronal and glial cell morphology, cell ratios, and viability when compared to fresh cultures. The expression of proteins in neurons and glial cells implicated in pain signaling and central sensitization agreed with their reported subcellular localization. Elevated intracellular calcium levels were observed in neurons and glia in response to ATP. This method for the preparation and cryopreservation of brainstem cells for establishing primary neuron-glia cultures similar to fresh preparations, is straightforward, can be utilized for biochemical, cellular, and molecular studies, increases reproducibility, requires no special equipment or reagents, saves laboratory resources including time and money, reduces the number of animals used in research, and increases flexibility in study design.

Here, we review the available evidence implicating amylin in migraine, its relationship with calcitonin gene-related peptide (CGRP) and its potential utility as a therapeutic target. The pathophysiology of migraine is currently better understood and the role of CGRP is key. Treatments targeting this pathway have been successful and migraine is a complex disorder, with so many molecules being implicated. Amylin, as for CGRP, is part of the calcitonin/CGRP peptide family. Some therapies intended to block the CGRP pathway can also target amylin receptors. Similar to CGRP, amylin can trigger migraine attacks in a provocation study. Amylin plasma levels have been highlighted as a potential migraine biomarker in one study in migraine patients. Moreover, some preclinical studies in rodents have also discussed sex differences. Comprehending the distinct and overlapping mechanisms between amylin and CGRP signalling could develop further our understanding of migraine pathophysiology. In summary, this review reveals, through initial studies, that targeting the amylin pathway may have a potential role as a novel treatment option for those who may not respond to other treatments, or as a better alternative.

To evaluate factors associated with new-onset migraine (NOM) after transcatheter atrial septal defect (ASD) closure and predictors of unremitting NOM. The pathogenic role of migraine biomarkers such as calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were also assessed.

New-onset migraine has been observed after transcatheter ASD closure. Neuropeptides like CGRP and NPY stored both in the brain and heart are implicated in migraine pathophysiology. The potential role of those migraine biomarkers in NOM, as well as the risk factors and long-term outcomes of NOM, remain largely unknown.

We enrolled patients without previous migraine who underwent successful transcatheter ASD closure between 2001 and 2013. The parameters of transthoracic echocardiography, and plasma CGRP and NPY levels measured by enzyme-linked immunosorbent assay, were collected prospectively before and after ASD closure, and compared between patients with NOM and those without. Predictors of NOM were assessed. Telephone interviews were performed in 2022 to assess migraine status. Clinical and procedural characteristics were compared between patients with unremitting migraine and those with transient migraine that remitted within 1 year.

Of the 212 patients (median age, 21 years; 75.9% female), 43 (20.3%) had NOM. Potential predictors of NOM included a young age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.96-0.99; p = 0.040), large ASD size (aOR 1.07, 95% CI 1.01-1.14; p = 0.022), and transient residual shunting after closure (aOR 2.78, 95% CI 1.05-7.36; p = 0.039). Post-closure plasma CGRP levels, but not NPY levels, were significantly higher than pre-closure levels (47.9 vs. 38.0 pg/mL, p = 0.023) among patients with NOM. Of the 27 patients with migraine who reported their migraine status at a median 14-year follow-up, 13 (48.1%) had unremitting migraine. Patients with unremitting migraine were more likely to have a smaller device-to-ASD size ratio (1.21 vs. 1.33, p = 0.039) and a larger pulmonary flow-to-systemic flow ratio (2.9 vs. 2.3, p = 0.012) than those with transient migraine.

Calcitonin gene-related peptide may play a pathogenic role in NOM after transcatheter ASD closure. A young age, large ASD size, and transient residual shunting potentially predict migraine occurrence after ASD closure. NOM not reaching remission for years may result from a significant shunt before closure.

As an adjunct or alternative to conventional pharmacotherapy, vagus nerve stimulation (VNS) which is FDA-approved has arisen as a novel means for various neurological disorders.

We searched multiple databases (through 2024) for randomised trials and observational studies of VNS (invasive and transcutaneous) and pharmacological treatments (e.g. cholinergic agents, antiepileptics, antidepressants) across several neurological disorders. Prior to comparing between VNS and pharmacological treatments, subgroup analyses of VNS studies were performed for disorder type, patient demographics, VNS stimulation parameters, and treatment duration to illustrate whether VNS itself can be effective to a satisfactory extent to be compared against the conventional method. Efficacy and adverse effects were evaluated, based on the proportion of patients achieving more than 50 % symptom reduction or equivalent clinical improvement, or all-cause mortality where applicable. Evaluation between VNS and pharmacological treatments was performed through network meta-analysis, followed by assessment of heterogeneity (I2) and meta-regression. Risk of bias was evaluated with Cochrane criteria, and all studies (including those with high risk of bias) were included in the primary analysis (with sensitivity analyses excluding high-bias studies).

We included 56 VNS-related studies (n = 5773 participants) and 29 pharmacological drug-based studies (n = 14827 participants) from spanning epilepsy, depression, migraine/headache, Alzheimer's disease, inflammatory disorders, and heart failure. A network meta-analysis directly comparing VNS to pharmacological drugs yielded an overall advantage for VNS (summary SMD = 0.27 favouring VNS, 95 % CI 0.19-0.35). However, the high heterogeneity and risk of bias have been assessed, indicating potential issues with the VNS studies.

Overall, VNS was shown to be a viable therapeutic modality across diverse neurological disorders, superior to standard pharmacological treatments with a distinct adverse effect profile. It appears particularly beneficial in conditions where conventional drugs have limited success (e.g. refractory epilepsy, depression), although patient-specific factors influence outcomes. Further high-quality trials are anticipated to optimise stimulation parameters, confirm long-term benefits, and manage patient selection for VNS.

Headache is a symptom of the long-COVID syndrome. The incidence and characteristics of de novo post-COVID headaches remain unclear. Our aim was to characterize new-onset headaches in a population-based prospective cohort of COVID-19 patients from the first pandemic wave.

This study followed a prospective cohort of 732 COVID-19 patients consecutively diagnosed between March and June 2020. Neurological follow-up was performed face-to-face or by phone at 3, 12, and 24 months. A structured clinical questionnaire was used to characterize headaches before infection and 24 months postinfection.

Overall, 448 patients completed the 24-month follow-up, with a mean age of 51.6 years at SARS-CoV-2 infection; 272 (60.7%) were women. A prior history of headaches was reported by 115 (25.7%). Patients with either pre-existing or de novo persistent headaches were younger, more often women, and exhibited hyposmia, hypogeusia, and headache during the acute phase of infection. De novo persistent headaches occurred in 54 of 333 (16.2%) headache-naïve patients. Of these, 35 (64.8%) fulfilled migraine-like headache (MLH) criteria (mean age of 49.1 years at 24-month follow-up), with a cumulative incidence of 42/1000/year.

De novo persistent headaches are common 2 years after COVID-19, with MLH being the most frequent type. MLH incidence after COVID-19 is elevated and de novo "migraineurs-like" tend to be older compared to the general population. This is an important finding with potential implications for healthcare and quality of life, considering the high number of COVID-19 cases and the global burden of migraine.

Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets-now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions.

A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on "MIGRAINE AND (neurogenic inflammation)" (2019-15 April 2025), followed by expanded searches from 1950 onward using terms such as "MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)", and "MIGRAINE AND (diet, dietary, nutrition, nutritional)". A specific search also targeted "(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)". Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available.

Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization.

The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes.

Calcitonin gene-related peptide (CGRP) inhibitors have been FDA-approved for migraine prophylaxis and relief. However, their safety profile remains uncertain. This study analyzes adverse events (AEs) and signals of disproportionate reporting (SDRs) using the FDA Adverse Event Reporting System (FAERS).

We analyzed FAERS reports from approval through Q2 2023, standardizing terms using preferred terminology and system organ class (SOCs) classifications. Disproportionality analyses (ROR, PRR, IC) identified SDRs and inclusion in FDA prescribing information was reviewed. Additional analyses included comparisons with other migraine drugs, indication-based sensitivity analyses and causality assessment using the Bradford Hill framework.

Galcanezumab showed strong signals for underdose (ROR 47.4; 95% CI 43.79-51.3), alopecia (5.72; 5.09-6.43), and constipation (6.01; 5.35-6.75), while fremanezumab exhibited notable associations with alopecia (6.9; 5.72-8.33) and weight increased (6.34; 5.18-7.76). Among gepants, rimegepant was linked to somnolence (4.52; 3.57-5.73) and dizziness (3.73; 3.15-4.42) and atogepant showed a strong signal for therapy interruption (16.58; 12.86-21.38).

This study highlights CGRP inhibitor-associated AEs, underscoring the need for clinical monitoring and risk identification. Early detection of AEs and SDRs can inform protective measures to enhance patient safety.

Several innovative treatment modalities for dry eye disease have emerged over the past decade. This systematic review aims to explore botulinum toxin A as a novel treatment modality for dry eye symptoms. PubMed, Cochrane Library, Medline (Ovid), and SCOPUS databases were searched with medical subject headings (MeSH). MeSH terms 'Dry eye' and 'Botulinum Toxin A' were used in combination with one or more of the following phrases 'Disease Management', 'Therapy', or 'prevention'. Following the preferred reporting items for systematic reviews and meta-analyses, these studies were evaluated by two independent reviewers for inclusion criteria and exclusion criteria. Subsequently, the included studies were evaluated via Oxford centre for evidence-based medicine level of evidence and the risk of biases were assessed by using the Cochrane handbook for systematic reviews. The subjective and objective measurements of dry eye from the included studies were summarised. Consistent measurements of interest were analysed through the review mananager software. The objective outcome measures were Schirmer's test and tear break-up time, while ocular surface disease index was the subjective measure. Eighteen studies were included, where number of eyes for each assessment ranged from 131 to 241 in the final analysis. The tear break-up time was increased after botulinum toxin A injection, by a standardised mean difference (SSMD) of 1.33 (95% CI 1.12 to 1.54, p < 0.01). Schirmer's test findings were improved by a SSMD of 0.69 (95% CI 0.45 to 0.93, p < 0.01). An improvement in the widely used dry eye questionnaire, Ocular surface disease index, was noted in the scores with a SSMD of -8.72 (95% CI -10.77 to -6.67, p < 0.01). Botulinum toxin A injection has the potential to be a useful treatment for dry eye symptoms. Different methods and locations of botulinum toxin A injections may alter the dry eye treatment response.

Vagus nerve stimulation (VNS) has emerged as a promising therapeutic intervention across various neurological and psychiatric conditions, including epilepsy, depression, and stroke rehabilitation; however, its mechanisms of action on neural circuits remain incompletely understood. Here, we present a novel theoretical framework based on predictive coding that conceptualizes VNS effects through differential modulation of feedforward and feedback neural circuits. Based on recent evidence, we propose that VNS shifts the balance between feedforward and feedback processing through multiple neuromodulatory systems, resulting in enhanced feedforward signal transmission. This framework integrates anatomical pathways, receptor distributions, and physiological responses to explain the influence of the VNS on neural dynamics across different spatial and temporal scales. Vagus nerve stimulation may facilitate neural plasticity and adaptive behavior through acetylcholine and noradrenaline (norepinephrine), which differentially modulate feedforward and feedback signaling. This mechanistic understanding serves as a basis for interpreting the cognitive and therapeutic outcomes across different clinical conditions. Our perspective provides a unified theoretical framework for understanding circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.

This study aimed to identify cerebral radiomic features related to migraine diagnosis and subtyping into migraine with aura (MwA) and migraine without aura (MwoA) and to develop predictive models based on these markers.

We retrospectively analyzed MR imaging from 88 migraine patients (32 MwA and 56 MwoA) and 49 healthy control subjects (HCs). Features representing the gray matter morphometry and diffusion properties were extracted from participants via histogram analysis. These features were put through an all-relevant feature selection procedure within cross-validation loops to identify features with significant discriminative power for migraine diagnosis and subtyping. Based on the selected features, the predictive ability of the random forest models constructed from the previous sample was tested in an independent sample of 30 patients (10 MwA) and 17 HCs.

No overall differences in total brain volume or gray matter volume were revealed between patients and HCs, or between MwA and MwoA (all P values > 0.05). Six features significantly differed between patients and HCs for migraine diagnosis, and four features distinguished MwA from MwoA for subtyping (all P values < 0.001). Four features were significantly correlated with headache severity score (all P values < 0.01). Based on these relevant features, the random forest models achieved accuracies of 80.9% in distinguishing patients from HCs and 76.7% in differentiating MwA from MwoA in the testing cohort.

Our findings suggest cerebral radiomic alterations in migraine patients may potentially serve as a biomarker to assist in migraine diagnosis and subtyping, contributing to personalized treatment strategy.

Not applicable.

Migraine is a common primary and often disabling neurological disorder, whose pathophysiology is still debated. It does not appear to be an isolated event of head pain but the consequence of recurrent disruption of healthy homeostasis in some brain functions. We propose a new theoretical model, focused on the existence of a "high-risk area" for migraine attacks, which can represent a potential target of non-pharmacologic treatment and prevention. We suggest that migraine arises from the combined effects of three primary factors, namely depressive or unstable mood, unrestful sleep and sympathetic-parasympathetic imbalance with parasympathetic prevalence, alongside with their temporal variability, potentially through dysfunction of homeostatic hypothalamic networks in susceptible individuals. Moreover, these three primary factors contribute to a state of low brain energy, that contains the high-risk area and represents the condition in which migraine attacks rise up. Wearable devices, self-administered questionnaires and clinical tools (i.e., polysomnography, pupillary light reflex, plasma catecholamines dosage) may be used to monitor autonomic nervous system function, mood and sleep and demonstrate the existence of the high-risk area. This will be helpful for patients to understand when they are about to enter in the high-risk area, in order to implement strategies to prevent migraine attacks. This approach would provide a significant advantage in terms of prevention and early treatment.

Migraine is a prevalent neurological disorder characterized by severe, recurrent headaches accompanied by symptoms, such as nausea, photophobia, and phonophobia, significantly affecting the quality of life of millions of people worldwide. Although the neurovascular pathway, involving blood vessel dilation and neurogenic inflammation, has been a cornerstone in understanding migraine pathophysiology. Emerging evidence suggests that immune dysregulation plays a pivotal role in the onset and progression of migraine. This review uniquely synthesizes recent advances linking immune regulatory pathways to migraine, an area that has not been widely explored in the literature. Specifically, we highlighted the involvement of CD4 + CD25 + regulatory T (Treg) cells, interleukins, and pro-inflammatory and anti-inflammatory cytokines, which have been implicated in pain signaling and immune imbalance in patients with migraine. Furthermore, genetic studies have provided compelling evidence by identifying associations between migraine susceptibility and immune-related polymorphisms, particularly in forkhead box P3 (FOXP3) and nuclear factor of activated T cells (NFAT). Moreover, the higher prevalence of migraine in individuals with comorbid autoimmune diseases further supports the hypothesis of a shared pathophysiological mechanism. Despite the growing recognition of immune involvement in migraine, its precise mechanisms remain unclear. By integrating key immune biomarkers and genetic insights, this review proposes a novel framework for understanding the immune-mediated pathways in migraine progression. Future research should focus on elucidating the specific immunological mechanisms underlying migraine, which could open new avenues for innovative, targeted therapeutic strategies.

Significant associations in the epidemiologic and clinical features between migraine and dry eye syndrome suggest that both conditions are comorbid. A potentially overlapping pathophysiological mechanism further indicates a connection between the two conditions. This study highlights the clinical implications of treating dry eye disease on migraine.

This study aimed to investigate the impact on migraine severity of treating dry eye disease in migraine patients using ocular lubricants.

A randomized, double-masked, crossover trial was conducted on 24 participants with both migraine and dry eye disease. They received either Systane Hydration UD (Alcon, Fort Worth, TX) or saline eye drops (NeilMed, Santa Rosa, CA) four times per day for 4 weeks each, with a 2-week washout period between treatments. Migraine severity was assessed using the Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment questionnaires. Dry eye disease was evaluated using the Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire 5 (DEQ-5), tear breakup time, tear osmolarity, and corneal surface integrity. Outcomes were assessed at baseline and after using the first and then second drops.

Ocular lubrication was significantly associated with reduced migraine severity and dry eye disease. The HIT-6 score was reduced from baseline when using Systane Hydration UD (mean change, ∆ = -3.0, p=0.01) and saline (∆ = -3.9, p=0.002). Dry eye disease symptoms and corneal staining were reduced when using Systane Hydration UD (OSDI ∆ = -8.3, p=0.004; DEQ-5 ∆ = -2.1, p=0.004; corneal staining ∆ = -2.2, p=0.001) and saline (OSDI ∆ = -6.4, p=0.03; DEQ-5 ∆ = -1.5, p=0.03; corneal staining ∆ = -1.5, p=0.005).

When migraine and dry eye disease coexist, successfully treating dry eye disease reduces the severity of migraine, as measured by HIT-6.

Menstrual migraine (MM) is a common subtype of migraine that greatly affects a woman's quality of life. A number of different drugs are used to treat menstrual migraine, but it is not known which is more effective.

In this study, we searched all randomized controlled trials that satisfied the inclusion and exclusion criteria up to December 2023 on PubMed, Embase and Cochrane Library using a suitable search strategy. We constructed a suitable network model for analysis after evaluating the heterogeneity among the included direct, indirect and pooled evidence. Odds ratio (OR) and corresponding 95% confidence intervals (CI) were used as valid indicators for this network meta-analysis.

In the Bayesian network model we constructed, we found that lasmiditan (vs. placebo OR, 14; 95% CI 3.1-100) was better than rizatriptan (vs. placebo OR, 1.9; 95% CI 1.2-3.3) in terms of the rate of sustained freedom from pain. There was no statistically significant difference between lasmiditan and different triptans in terms of the rate of being pain-free at 2 h (2-h pain-free) and the rate of pain relief at 2 h (2-h pain relief). Regarding safety, the probability of adverse events was significantly higher for rizatriptan (OR, 2.7; 95% CI 1.1-7.3) than for placebo.

In terms of treatment efficacy for MM, lasmiditan was not worse than different triptans and was even better than some of the triptans in the rate of sustained freedom from pain. As an emerging treatment, lasmiditan is promising for the treatment of MM. However, more research needs to be carried out because of the lack of safety analysis for lasmiditan.

Migraine with aura is a common neurological disorder. Cortical spreading depression is the hypothetical pathophysiologic correlate, but it has never been directly recorded during migraine in a human. A 32-year-old female with a history of migraine underwent a presurgical workup for comorbid epilepsy. While implanted for stereotactic electroencephalography with 94 electrode contacts across bilateral hemispheres, she experienced a typical migraine with aura. Stereotactic electroencephalography demonstrated low-voltage suppression starting in the left mesial occipital cortex and propagating anteriorly at 3 mm/min, clinically correlating with a contralateral right superior scintillating scotoma and ipsilateral headache. Intracranial stereotactic electroencephalographic recording demonstrated cortical spreading depression during migraine with aura. Our findings add to the body of evidence implicating cortical spreading depression in the pathophysiology of migraine with aura.

Migraine, a debilitating neurological disorder, is often co-occurring with sleep disturbances. This study used the Epworth Sleepiness Scale (ESS) to explore changes in sleep quality between individuals with migraine and healthy controls. Additionally, we examined associations between ESS scores and migraine frequency, severity, and demographic factors.

This cross-sectional study included 404 participants, 204 with chronic migraine (diagnosed using ICHD-3 criteria) and 200 controls without neurological disorders. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Demographic and clinical data were analyzed using Python3 and SPSS, using t-tests and ANOVA (P < 0.05).

The study analyzed demographics, clinical characteristics, and daytime sleepiness in 204 migraine participants compared with 200 controls. Individuals with chronic migraine had higher Epworth Sleepiness Scale scores, with increased sleepiness associated with higher BMI, age, and female gender. Significant differences in sleepiness levels were observed with migraine severity, highlighting the impact of migraine on sleep patterns and quality, and no significant differences were found between control and migraine groups in ESS scores, sleep duration, or physical activity. Reliability testing confirmed high ESS consistency.

This study highlights the prevalence of daytime sleepiness among individuals with chronic. Managing sleep quality emerges as an important treatment strategy. The use of standardized tools such as the Epworth Sleep Scale can guide personalized interventions, improve patient outcomes, and emphasize the role of lifestyle and overall health management.

Recurrent and intense headache is a well appreciated cardinal feature of migraine, a common and incapacitating neurological disorder. Often, there are associated canonical sensory abnormalities, such as light and sound sensitivity, as well as associated nausea. Given this phenotype of disordered sensory processing and, in a third of patients, the phenomenon called aura accompanying migraine attacks, it has been suggested that the pathophysiology of migraine is likely to involve glutamate, the main excitatory neurotransmitter in the central nervous system (CNS). Glutamate plays a role in nociception, central sensitization, and cortical spreading depression (CSD), three processes that are deemed important in migraine biology. With an emphasis on the therapeutic potential of targeting various glutamate receptors in migraine, this review will discuss the currently available literature and emerging findings on the role of targeting glutamatergic pathways for the treatment of migraine. A thorough literature review was carried out on the functions of both metabotropic glutamate receptors (mGluRs), and the ionotropic glutamate receptors (NMDA, AMPA, and kainate) in migraine pathogenesis. The ever-present need for new treatments, the role of glutamate in the migraine aura phenomenon, and the consequences of monogenic migraine mutations on mediating prolonged, complex, or permanent aura are all discussed, culminating in a suggestion that glutamatergic targeting may hold particular promise in the management of migraine aura. There are plausible roles for metabotropic receptors in regulating pain processing in important migraine-related brain structures, like the thalamus and trigeminal nucleus. Similarly, ionotropic receptors contribute to excitatory neurotransmission and neuronal hyperexcitability. Recent studies have shown preclinical and early clinical results for treatments targeting these receptors, but there are still significant issues with treatment response, including drug transport, side effects, and efficacy. With ongoing and emerging discoveries in the field, there is increasing promise of new migraine medications targeting glutamate receptors. For bench to bedside translation in this area, continued study of the molecular basis of migraine, receptor subtypes, and exploration of potential drug delivery methods are needed.

Migraine headache (MH) and cluster headache (CH) are debilitating primary headache disorders that impose a significant global burden. While they share certain clinical features, such as unilateral pain and autonomic dysfunction, their underlying pathophysiological mechanisms remain distinct. Advances in the understanding of neurophysiological features, such as neuroimaging and biomarker research, have provided critical insights into both their overlapping and divergent characteristics. Neurophysiological research has revealed differences in nociceptive processing, cortical excitability, and sensory integration, underscoring the complexity of these conditions. Neuroimaging studies reveal common activation patterns within pain-processing networks, including the trigeminal system and hypothalamus, while highlighting key differences, such as hypothalamic hyperactivity in CH and cortical alterations in MH. Additionally, biomarker research has identified shared elements, including elevated calcitonin gene-related peptide (CGRP), yet distinct variations in its regulation and genetic predispositions. Genome-wide association studies have further elucidated the genetic architecture of these disorders, uncovering susceptibility loci that reinforces their unique yet occasionally intersecting genetic foundations. These multifield advancements not only enhance the understanding of MH and CH pathophysiology but also pave the way for improved diagnostic precision, personalized therapeutic strategies, and future research.

Attention performance in chronic migraine remains unclear. The present study aimed to explore the pre-attentive detection and attention orienting ability in individuals with chronic migraine (CM) measured by mismatch negativity (MMN) and P3a components and assess their associations with migraine characteristics.

This cross-sectional observational study recruited 25 individuals with episodic migraine (EM), 25 individuals with CM and 25 healthy controls (HC) matched for age, sex, and educational level. The MMN and P3a components were measured using event-related potential (ERPs) tools with auditory oddball paradigms and migraine characteristics were collected.

Individuals with CM exhibited a longer MMN latency (p = 0.010) and a lower P3a amplitude than HC (p = 0.004) and EM (p = 0.002). Correlation analysis showed that P3a amplitude was negatively correlated with headache attack frequency and the Migraine Disability Assessment Scale (MIDAS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores.

Individuals with CM showed deficits in pre-attentive detection and attention orientation. Moreover, attention-oriented dysfunction is associated with headache attack frequency, headache-related disability, anxiety and depression.

Background/Objectives: Pediatric migraine is a prevalent neurological disorder that significantly impacts children's quality of life, academic performance, and social interactions. Unlike migraines in adults, pediatric migraines often present differently and involve unique underlying mechanisms, making diagnosis and treatment more complex. Methods: This review discusses the clinical phases of pediatric migraine, key trigger factors, sex- and age-related differences, and the role of childhood maltreatment in migraine development. We also discuss episodic syndromes such as cyclic vomiting syndrome, abdominal migraine, benign paroxysmal vertigo, and benign paroxysmal torticollis, along with comorbidities such as psychiatric disorders, sleep disturbances, and epilepsy. Results: The underlying pathophysiological mechanisms for pediatric migraines, including genetic predispositions, neuroinflammation, and gut microbiota dysbiosis, are summarized. Current therapeutic strategies, including conventional and emerging pharmacological treatments, nutraceuticals, and non-pharmacological approaches, are evaluated. Non-pharmacological strategies, particularly evidence-based lifestyle interventions such as stress management, diet, hydration, sleep, exercise, screen time moderation, and cognitive behavioral therapy, are highlighted as key components of migraine prevention and management. The long-term prognosis and follow-up of pediatric migraine patients are reviewed, emphasizing the importance of early diagnosis, and tailored multidisciplinary care to prevent chronic progression. Conclusions: Future research should focus on novel therapeutic targets and integrating gut-brain axis modulation, with a need for longitudinal studies to better understand the long-term course of pediatric migraine.