Migraine Research Articles

A novel technique to identify and thermally ablate the greater occipital nerve for patients with occipital neuralgia: a retrospective study with cadaveric and ex-vivo validation.

This manuscript presents the challenges of treating various forms of headaches and the potential of interventional techniques targeting the greater occipital nerve (GON) to alleviate the burden on patients. Occipital neuralgia, characterized by stabbing or shooting pain in the base of the skull, is often associated with primary, cervicogenic, or migraine headaches. While occipital nerve blocks offer temporary relief, durable treatment options are limited. Pulsed radiofrequency (PRF) and thermal radiofrequency ablation (TRFA) have shown promise as minimally invasive procedures for long-term treatment. However, GON is not easily identified using ultrasound or fluoroscopic analysis; thereby, minimizing success of proper ablation. Here, the authors provide a percutaneous strategy to localize the GON and maximize lesion performance. We intend to provide an ex-vivo description of staggered bipolar radiofrequency (RF) lesioning and include the use of staggered bipolar lesioning of the GON and stimulation of the semispinalis capitis. We also analyzed the effectiveness and side effects from this ablation, retrospectively. Patients with chronic refractory GON neuralgia were selected for GON TRFA. A novel double needle technique of sequential electrical stimulation was used to localize the GON and approximate needle to nerve distance. Once the needles were positioned adjacent to the GON, TRFA was performed using a bipolar staggered technique. Twenty-two patients with GON were treated with TRFA using a novel double needle technique. Seventy-two percent of these patients reported greater than 50% pain relief at both 1 and 6 months following the procedure. The results of our ex-vivo study demonstrate that performing TRFA using the parallel needle bipolar approach separated 8 mm apart produced the most desirable lesion dimensions that may correlate with effective ablation of the GON. This study demonstrates a new localization and ablation technique to treat refractory headaches. However, larger studies are needed to confirm our findings.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An invivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague-Dawley rats were imaged with [11C]UCB-J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB-J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB-J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof-of-concept study shows for the first time that acute taVNS for 30 min can modulate invivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.

Evaluation of the efficacy of preventive therapy in chronic migraine with or without medication overuse headache: data from a prospective study

Chronic migraine (CM) affects three out of every hundred people. As the frequency of attacks increases, so does the frequency of painkillers usage, and 85% of patients with CM are also diagnosed with medication overuse headache (MOH).Objective: to investigate the efficacy of preventive therapy of CM with or without MOH.Material and methods. The study involved 117 patients with CM and MOH (group 1) and 23 patients with CM without MOH (group 2), patients were examined at the initial visit and after 3 and 9 months of follow-up. All patients in the 1st group (CM+MOH) received a 7-day "detoxification" therapy. Patients in both groups were given an educational and information session on the type of their diagnosis, treatment methods and lifestyle correction. The choice of a preventive treatment in both groups was based on the current clinical recommendations, algorithms of modern international guidelines, concomitant pathology, the presence of contraindications in a particular patient, tolerability, as well as territorial and economic factors.Results. A positive effect was found in both groups, regardless of the presence of MOH. The lack of significant differences between the groups of CM with/without MOH is probably due to the use of "detoxification" therapy and the cessation/restriction of the use of the drug of abuse in all patients with CM and MOH, although a more pronounced positive dynamics is observed in patients of the 2nd group (CM without MOH), which in turn emphasizes the severity of the disease, the greater disability and the poorer prognosis for response to preventive treatment in the presence of MOH. It was found that one third of patients in the study favored monoclonal antibodies (mAbs) due to convenience, rapid onset of action and tolerability. In the group of patients with MOH, the best results were obtained when using injection methods of treatment (anti-CGRP mAbs, botulinum therapy) or when using combined therapy compared to monotherapy with venlafaxine or topiramate.Conclusion. All first-line drugs for the CM prophylactic treatment according to the clinical guidelines of the Ministry of Health of Russia are clearly effective, including cases with both CM and MOH. The use of combined therapy in CM with/without MOH can be effective even with a low initial response to one of the monotherapies.

Diagnosis of chronic migraine and comorbid neurological disorders in real-life clinical practice

Chronic migraine (CM) is a neurological disorder whose diagnosis requires not only knowledge of its diagnostic criteria, but also the physician's ability to differentiate between various forms of primary and secondary headache (HA), as well as to recognize comorbid neurological disorders that aggravate the course of CM. Timely and correct diagnosis of CM and comorbid disorders allows to prescribe effective treatment to a patient and convert the migraine from a chronic to an episodic form. The diagnostics of CM and comorbid neurological disorders has not been sufficiently investigated in our country, which formed the basis for this study.Objective: to evaluate the quality of diagnostics of CM and comorbid neurological disorders in real-life neurological practice.Material and methods. The study included 200 patients with CM (63 men and 137 women, mean age 33.1±7.1 years) admitted to A.Ya. Kozhevnikov Clinic of Nervous Diseases (CND) of Sechenov University, complaining of frequent headaches. They had previously been examined and treated by neurologists in other medical institutions on an outpatient and/or inpatient basis. A clinical interview was conducted with all patients to establish a diagnosis and analyze their previous treatment, and a psychometric test was performed to assess symptoms of anxiety and depression.Results. Only 6% of patients had been previously diagnosed with CM, the remaining 94% were incorrectly diagnosed with secondary HA. All patients had previously been prescribed additional examinations, mainly neuroimaging of the brain and ultrasound of the cerebral vessels, although there were no "red flags". None of the patients had been previously assessed for their emotional state, while almost all patients had high situational anxiety (n=190; 95%) and high personal anxiety (n = 180; 90%), there were symptoms of depression (n=190; 95%) of varying severity. Comorbid neurological disorders (medication overuse HA), insomnia, musculoskeletal pain etc.) were diagnosed in 91.5% of patients in CND and in only in 8% of patients in other medical centers.Conclusion. In real-life clinical practice, CM and comorbid neurological disorders are inadequately diagnosed and excessive and unjustified additional examinations are prescribed.

Clinical and psychoemotional characteristics of patients with medication overuse headache

The available data indicate the important role of personality profile, psychoemotional disorders and psychosocial aspects in the development and maintenance of medication overuse headache (MOH). It is therefore important to identify predictors for the development and factors that influence the course and prognosis of treatment for this disorder.Objective: to analyze the clinical and psychological profile of patients and to identify predictors of the course of MOH in order to develop a prognostic model.Material and methods. We performed a comparative analysis of the characteristics of 117 patients with MOH (group 1) and 23 patients with chronic migraine (CM) without MOH (group 2) using clinical data and questionnaire data to determine the neuropsychological profile (PCS, Spielberger-Khanin Anxiety Scale, PHQ-9, BIS-11, TAS-26, SAGE test, Leeds Dependence Questionnaire – LDQ) at the time of admission to hospital and 9 months after the start of treatment.Results. The study showed that 100% of patients with CM and MOH had various psychoemotional disorders. At the same time, the pre-therapy baseline indicators for the level of personal anxiety, pain catastrophizing scales, impulsive behavior, alexithymia and LDQ parameters were significantly higher in the group of patients with CM and MOH than in the group with CM without excessive analgesic use. Using multiple linear regression, it was found that an increase in the severity of depression by 1 point is significantly associated with an increase in the number of days with headache (HA) by 0.33 days per month. In addition, a significant direct correlation was found between the degree of addiction according to LDQ and the extent of pain catastrophizing and situational anxiety, as well as the level of cognitive functions (according to the SAGE questionnaire) in an inverse relationship. At the same time, the frequency of analgesics use per day in the group of patients with CM and MOH is significantly related to the level of pain catastrophizing, depression and personal anxiety.Conclusion. The results obtained confirm the biobehavioral concept of MOH development. Effective therapy of the primary form of HA (in our study – CM) is significantly associated with a decrease in the severity of anxiety, depression, catastrophizing and the frequency of taking analgesics. Personality traits, especially the tendency to impulsive behavior, remain unchanged against the background of chronic HA treatment. The presented results emphasize the need for complex treatment of patients with CM and MOH.

Addiction to analgesics in patients with chronic migraine and medication-overuse headache

Patients with medication-overuse headache (MOH) and chronic migraine (CM) have varying degrees of addiction to painkillers (PK), which complicates treatment and leads to relapses. Development of addiction to PK is associated with various clinical and psychological characteristics and disorders in patients with MOH.Objective: to investigate the relationship between PK addiction and individual clinical and psychological characteristics in patients with CM and MOH.Material and methods. The study included 156 patients with CM and MOH (61 men and 95 women, mean age 34.1±8.9 years). Clinical and psychological characteristics were assessed in all patients using a clinical interview, tests and headache diaries. The relationship between PK addiction (according to the Leeds Dependence Questionnaire – LDQ) and clinical and psychological characteristics (duration of migraine and CM, frequency and intensity of headaches, duration of MOH, frequency of PK use, number of PK doses, personal and situational anxiety, depression, pain catastrophizing, beliefs about the body and health, coping strategies for stressful situations, daily activities during headache, insomnia) was investigated using regression analysis.Results. All patients had misconceptions and wrong behavior regarding PK. The majority (59%) of patients had moderate degree of PK addiction according to the LDQ. Twenty six percent of patients had other forms of addictive behavior (smoking, excessive alcohol consumption, overeating, excessive use of sleeping pills), and 52.6% of patients had relatives with addictive behavior. There was a statistically significantly positive correlation (R≥0.45; p<0.05) between PK addiction and smoking, alcohol consumption, use of sleeping pills, body mass index (BMI), frequency of PK use, attitudes towards pain, body and health (pain catastrophizing, hopelessness about pain, intolerance of body sensations, overestimation of symptom severity, catastrophizing in the interpretation of body symptoms), depression, personal anxiety and avoidance (maladaptive coping behavior). Adequate treatment of CM and MOH was provided in only 7.7% of patients.Conclusion: A positive association was found between PK addiction and smoking, alcohol consumption, use of sleeping pills, BMI, frequency of PK usage, attitudes towards pain, body and health, depression, personal anxiety and avoidance behavior.

Typical clinical practice of treating patients with chronic migraine

Currently, effective methods for the treatment of chronic migraine (CM) have been developed, but it remains unclear how they are used in real clinical practice and how often. The typical practice of treating patients with CM in our country has not been sufficiently investigated, which formed the basis for conducting this study.Objective: to evaluate the quality of treatment of patients with CM in real-life neurological practice.Material and methods. The study included 200 patients with CM (63 men and 137 women, mean age – 33.1±7.1 years) admitted to A.Ya. Kozhevnikov Clinic of Nervous Diseases (CND) of Sechenov University for frequent headaches, who were previously treated by neurologists in other medical institutions on an outpatient and/or inpatient basis. All patients were clinically interviewed to establish a diagnosis and analyze their previous treatment.Results. All patients had an experience of incorrect or inadequate treatment, including ineffective drug and non-drug methods. All patients were taking painkillers to relieve migraine, but less than half of them was satisfied with their effectiveness. Only 12 (8.5%) patients with medication overuse headache had previously received treatment for drug overuse. None of the patients who were admitted to CND had previously received cognitive-behavioral therapy and treatment with an interdisciplinary approach that included not only pharmacotherapy but also psychological and behavioral methods and kinesiotherapy.Conclusion. In real-life clinical practice, ineffective methods are often used to treat migraine, and an interdisciplinary approach that includes effective pharmacotherapy and non-pharmacological methods is lacking.

Comparative analysis of the efficacy of different treatment strategies in medication overuse headache: an open-label prospective trial

Medication overuse headache (MOH) is a common form of chronic headache with a high risk of relapse after therapy. Excessive use of analgesics most frequently leads to the development of MOH in migraine patients.Objective: to analyze the short- and long-term efficacy of MOH therapy in patients with chronic migraine (CM) using different programs to discontinue the abused drug and a detoxification regimen.Material and methods. The study included 44 patients with MOH and CM who were divided into two groups. Group A comprised 18 patients who discontinued the drug that triggered MOH and were simultaneously prescribed preventive treatment for migraine without undergoing "detoxification" therapy". Group B comprised 26 patients who received a multimodal therapeutic strategy including "detoxification treatment".Results. The strategy of complex therapy with a "detoxification treatment" was significantly more effective during the 12-month observation period. In group B, a significant (p<0.01) decrease in the number of days with migraine per month was observed (before therapy – 22.6±7.4 days, after 3 months – 15.1±8.9 days, after 6 months – 12.7±9.1 days and after 12 months – 10.2±8.7 days). In the first 6 months, a similar dynamic was observed in group A, whereby the frequency of migraine increased in the 12th month of observation. Twelve months after the start of therapy, migraine occurred in episodes in the majority (84%) of patients in group B, which is significantly more than in group A (58.9%; p<0.01).Conclusion. A comprehensive approach in the treatment of patients with CM and MOH with "detoxification" therapy" showed high efficacy in terms of reducing the number of headache days per month and converting CM to episodic migraine.

Demographic and comorbid factors associated with the development of medication overuse headache

Objective: to conduct a comparative analysis of factors associated with the development of medication overuse headache (MOH), considering demographic characteristics of patients and comorbid pathology.Material and methods. A prospective study was conducted at "Europe–Asia" International Medical Center. The main group comprised patients with primary headache (HA) aged 18 years and older with MOH, and the control group comprised patients with primary HA without MOH of comparable gender and age. A semi-structured interview was conducted with the patients and additional examinations were performed, including MRI of the brain if indicated. The study included 171 patients with MOH (mean age 43.3 years, 82% women) and 173 patients without MOH (mean age 41.4 years, 75% women).Results. Chronic migraine occurred more frequently in the MOH group (53 and 16%, respectively; p<0.001; OR 5.9; 95% CI 3.6–9.8). One third of patients in both groups suffered from chronic tension-type headache (CTH). Episodic migraine and episodic CTH occurred more frequently in patients without MOH (p<0.001). Patients in the MOH group were more frequently divorced (11.7 and 2.9%, respectively; p=0.002; OR 4.5; 95% CI 1.6–12.2). The majority of patients (76%) in both groups were employed, had a higher education (65% with MOH and 74% without MOH) and were married (63% with MOH and 72% without MOH).The analysis of more than 20 comorbid diseases revealed that three factors were most frequently associated with the development of MOH: chronic insomnia (60.2 and 47.4% respectively; p=0.02; OR 1.7; 95% CI 1.1–2.6), restless legs syndrome (37.4 and 22% respectively; p=0.002; OR 2.1; 95% CI 1.3–3.4) and subjective cognitive impairment (76 and 53.2% respectively; p<0.001; OR 2.8; 95% CI 1.8–4.8).Conclusion. Sleep disturbance, subjective cognitive impairment and marital status of patients are most frequently associated with MOH, indicating the great importance of these factors in the development of MOH and opening new opportunities for its prevention.

Influence of greater occipital nerve block on the relief of acute migraine: A meta-analysis.

Greater occipital nerve (GON) block may help relieve acute migraine, and this meta-analysis aimed to investigate the influence of GON block on pain relief of acute migraine. We systematically searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases, and included randomized controlled trials (RCTs) assessing the efficacy of GON block for acute migraine. Meta-analysis was performed using the random-effect model regardless of the heterogeneity. Four RCTs and 224 patients were included in the meta-analysis. Compared with control intervention in acute migraine, GON block intervention could significantly reduce pain scores at 45 to 60 minutes (MD = -2.31; 95% CI = -3.08 to -1.53; P < .00001) and pain scores at 30 minutes (MD = -1.95; 95% CI = -2.61 to -1.29; P < .00001), but demonstrated no impact on pain scores at 0 to 15 minutes (MD = -0.46; 95% CI = -1.00 to 0.08; P = .09), sustained headache relief (OR = 1.46; 95% CI = 0.06-36.66; P = .82) or rescue medication (OR = 0.32; 95% CI = 0.01-19.16; P = .59). GON block intervention may be able to alleviate pain intensity for acute migraine patients.

Internalizing disorders rather than ADHD are risk factors for chronicity in pediatric migraine patients.

Migraine is a prevalent neurological disorder that can lead to disability in children and adolescents. It is frequently accompanied by psychiatric comorbidities, both internalizing and externalizing disorders. While the relationship between migraine and internalizing disorders has been studied, there is limited research on the link between migraine and attention deficit hyperactivity disorder (ADHD). A total of 280 pediatric headache patients, 107 with externalizing (ADHD) and 173 with internalizing disorders (depression and/or anxiety), were included. The dataset was composed using the Turkish headache database, Mersin Branch. Pain characteristics, associated symptoms, and accompanying comorbidities were evaluated retrospectively. Two hundred four patients were followed up with episodic migraine (EM) and 76 patients with chronic migraine (CM). One hundred forty-six boys and 134 girls were evaluated, and internalizing disorders were more common in the girls (p < 0.001). It was a much more prominent accompaniment in chronic migraine internalizing disorders (p = 0.038). EM, on the other hand, was more frequent in ADHD. Pain intensity and frequency were greater in those with internalizing disorders (p = 0.007), while photophobia was more prevalent in those with ADHD (OR; 0.555, p = 0.044). Moreover, we observed that individuals with internalizing disorders were predominantly female (p = 0.003) and had a higher mean age (p < 0.001) than those with externalizing disorders. Internalizing disorders seem to be a risk factor for migraine chronification in pediatric migraine. ADHD is a prototypic externalizing disorder more associated with EM. This outcome provides an opportunity to follow our patients in terms of prognosis and offers us the chance for a better evaluation. Identifying factors that contribute to the chronicity of migraine may lead to better management and reduced disability for migraine sufferers.

The potential to prevent unnecessary emergency department visits by timely diagnosis of migraine-A prospective observational study.

Successful acute migraine treatment potentially prevents emergency room (ER) consultations but requires that the diagnosis of migraine was given earlier. The aim of this study is to quantify the problem of missed migraine diagnosis prior to ER visits. Inclusion criterion for this single-center prospective study was the presentation at the ER for acute headache. Patients with acute migraine attacks were assessed for previous migraine attacks, and whether they were given a diagnosis of migraine in the past. Of 137 patients with migraine diagnosis at discharge, 108 (79%) had previous headache attacks fulfilling the criteria for migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3). Of those, 54 (50%) received the diagnosis for the first time. Half of the migraine patients (50%) presenting in the ER for headache could have been diagnosed earlier. This highlights the need for better detection and treatment of migraine by pre-hospital healthcare providers, as earlier diagnosis and specific acute treatment could have prevented the ER visit.

The Role of Plastic Surgery in Management of Migraine Headaches: A Literature Review

The Role of Plastic Surgery in Management of Migraine Headaches: A Literature Review

Efficacy and Tolerability of Erenumab and Topiramate for Prevention of Chronic Migraine: A Retrospective Cohort Study

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals’ quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations.

Decoding Visual Responses: Insights into Chronic Migraine and Medication Overuse Headache with Electrophysiological Analysis.

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analysing the amplitude of the first block (100 sweeps) and to evaluate habituation by measuring the amplitude response decrement after six blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEP parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication withdrawal. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli.

Effects of probiotic and vitamin D co-supplementation on clinical symptoms, mental health, and inflammation in adult patients with migraine headache: a randomized, triple-blinded, placebo-controlled trial

BackgroundMigraine headache is a major public health problem. Routine medications for migraine treatment are not useful in treating all patients and may have some side effects. The present study aimed to investigate the effect of vitamin D and probiotic co-supplementation on clinical characteristics of migraine, daily functioning, mental health outcomes, and serum levels of high-sensitivity C-reactive protein (hs-CRP).MethodsIn this randomized, triple-blinded, placebo-controlled trial, patients aged 18 to 55 years diagnosed with migraine based on the International Classification of Headache Disorders-3 (ICHD-3) were randomized to either vitamin D (50,000 IU every 2 weeks) plus probiotic (4.5 × 1011 CFU per day) or placebo for 12 weeks. The Headache Impact Test (HIT-6) and Depression, Anxiety, and Stress Scale (DASS) questionnaires were administered to patients at baseline and after 12 weeks. In addition, the frequency, duration, and severity of migraine headaches per month were assessed using a self-administered 30-day headache diary at baseline and the end of the intervention. Anthropometric indices, blood pressure, and serum levels of 25-hydroxy vitamin D and hs-CRP were also examined at first and the end of the study.ResultsSeventy-two migraine patients with a mean age of 37.46 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 8.32 years were included in this trial. Probiotic and vitamin D co-supplementation compared to placebo resulted in a significant increase in serum levels of vitamin D (+ 12.86 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 1.64 vs. + 1.12 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 0.80 ng/mL, P < 0.001). The between-group analysis in the adjusted model showed a significantly greater reduction in migraine headache frequency (− 3.17 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 0.84 vs. − 1.25 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 0.34; P = 0.031) and severity (− 1.55 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 0.35 vs. + 0.67 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 0.29; P = 0.017) in the probiotic and vitamin D group than the placebo group. No significant difference was found between the two arms of the intervention regarding the change in headache duration, hs-CRP, scores of DASS, and HIT-6 questionnaires (P > 0.05).ConclusionsThis trial showed that probiotic and vitamin D co-supplementation for 12 weeks has beneficial effects on migraine headache characteristics. Further research is needed to confirm this finding.

Association Between Migraine and Open-Angle Glaucoma: A Twelve-Year Nationwide Retrospective Korean Cohort Study.

Previous studies have reported that migraine headaches may be one of the possible risk factors for open-angle glaucoma (OAG); however, a consensus has not been reached regarding the association between OAG and migraine. In this study, we examined the risk of developing OAG in migraine patients using a 12-year nationwide cohort. In this study, data from the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2015 was used to perform a retrospective cohort study. The study included 1,103,302 subjects, out of which 41,148 were diagnosed with migraine during 2003-2008 and were categorized as the migraine group, while 205,741 patients were selected as controls through propensity score matching at a 1:5 ratio. Subjects with migraine or OAG was ascertained based on KCD code. Multivariate Cox regression analysis was used to evaluate the hazard rate of OAG onset in the migraine group, and subgroup analysis was performed to identify any differences based on sex and age. Multivariate Cox regression analysis showed that the incidence of OAG was significantly greater among patients with migraine than among patients in the comparison group (hazard ratio [HR] 1.238; 95% confidence interval [CI] 1.160-1.132, P < 0.001). Moreover, the risk of developing OAG compared to subjects without migraine did not differ according to the presence of an aura (migraine with aura: HR 1.235; 95% CI 1.137-1.342, P < 0.001; migraine without aura: HR 1.248; 95% CI 1.143-1.363, P < 0.001). In subgroup analyses, the patients with migraine under 40-year-old were found to have a greater hazard rate (HR 1.576, 95% CI: 1.268-1.957) of developing OAG in contrast with patients with migraine and over 40-year-old (HR 1.167, 95%CI: 1.089-1.250) when compared to the corresponding non-migraine patients. This study showed that migraine is a significant risk factor for OAG onset in Korean population, and the presence of aura did not affect the hazard rate of OAG development. Patients with migraine showed significantly increased risk of developing OAG in Korean population, without significant differences according to the presence of aura. Our results suggest presence of migraine as a possible risk factor for OAG.

Exploring the Phytochemistry, Signaling Pathways, and Mechanisms of Action of Tanacetum parthenium (L.) Sch.Bip.: A Comprehensive Literature Review.

The traditional use of Tanacetum parthenium (L.) Sch.Bip., commonly known as feverfew, extends across various medical conditions, notably those associated with pain and inflammation. In alignment with the growing trend towards developing medications that target specific signaling pathways for enhanced efficacy and reduced side effects, extensive research has been conducted to investigate and validate the pharmacological effects of feverfew. Among its bioactive compounds, parthenolide stands out as the most potent, categorized as a germacranolide-type sesquiterpene lactone, and has been extensively studied in multiple investigations. Significantly, the anti-inflammatory properties of feverfew have been primarily attributed to its capacity to inhibit nuclear factor-kappa B (NF-κB), resulting in a reduction in pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α). Furthermore, the anticancer properties of feverfew have been associated with the modulation of Mitogen-Activated Protein Kinase (MAPK) and NF-κB signaling pathways. This study further delves into the neuroprotective potential of feverfew, specifically in the management of conditions such as migraine headaches, epilepsy, and neuropathic pain through various mechanisms. The core objective of this study is to elucidate the phytochemical composition of feverfew, with a particular emphasis on understanding the molecular mechanisms and examining the signaling pathways that contribute to its pharmacological and therapeutic effects. Additionally, the safety, toxicity, and potential adverse effects of feverfew are comprehensively evaluated, with an overarching goal of providing valuable insights into the plant's potential for targeted and effective treatments.

Is sexual function impaired in patients with primary headaches? A systematic review of observational studies.

Primary headaches, particularly migraine and tension-type headaches, as chronic and painful conditions, have a significant impact on individuals' health and overall quality of life, including aspects such as sexual health parameters. The aim of this study was to review observational studies and to summarize the presence of sexual dysfunction in patients with primary headache and to discern whether it is more common in patients with primary headache than in healthy control subjects. Observational studies published between January 1, 2000, and May 21, 2023 were searched in Medline (PubMed), Web of Science, Scopus, and EBSCO. This review included 23 observational studies that evaluated sexual dysfunction with or without comparison with healthy control subjects. As a result, the mean Female Sexual Function Index score, a score of <26.55 indicating sexual dysfunction, ranged from 19.25 ± 8.18 to 27.5 ± 7.5 in patients with primary headache. The prevalence of sexual dysfunction and erectile dysfunction was found to be between 10.7% and 93.75% in female patients and between 54.83% and 80% in male patients. Both migraineurs and tension-type headache sufferers had statistically significantly lower sexual function scores in females and lower erectile function scores in males compared with healthy control subjects. Sexual function is significantly affected in patients with primary headache, which is a chronic painful disorder. Therefore, it is very important to ask these patients about their sexual health and, if necessary, to seek support from a sexual health professional. Additionally, future studies may prioritize tension-type headaches and male patients due to the limited amount of research available on these subjects.

Sex and gender differences in the epidemiology, clinical features, and pathophysiology of trigeminal autonomic cephalalgias

Emerging evidence suggests that primary headaches, classified as trigeminal autonomic cephalalgias (TACs), may exhibit sex and gender differences in clinical features, mechanisms, and treatment responses. While epidemiological and clinical gender-specific differences have been widely reported for cluster headache, limited evidence is available for other TACs. In this narrative review, we have analyzed the existing data on the influence of sex and gender on cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. Given the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache, sex and gender differences in the levels and function of CGRP in preclinical models and patients are reported. Future studies are warranted to elucidate the role of sex and gender in the complex interplay of genetic and neurochemical factors in TACs.