Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research

Migraine is a primary headache disorder characterized by a unilateral, throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors, and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses, including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This narrative review discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

Comprehensive approach for the treatment of medication-overuse headache

Background: Medication-overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder that occurs on 15 or more days per month for more than 3 months. It is caused by overuse of medication for acute or symptomatic headache treatment. Regular and frequent use of acute or symptomatic medications can worsen headaches and lead to chronic headache or MOH. MOH is a burdensome medical condition that is difficult to treat, and the frequent recurrence of headaches may result in disability in individuals and impair socioeconomic outcomes.Current Concepts: Awareness of MOH and the education of patients, the general population, and healthcare providers are important for the first step of treatment. Scientific research regarding the treatment of MOH has been published in the past few years.Discussion and Conclusion: Physicians should educate and counsel patients to stop or at least reduce the intake of acute or symptomatic medications that can be discontinued abruptly or tapered slowly. During the period after the discontinuation of the overused medications, some withdrawal symptoms including headache might be manageable with bridging therapy. Evidence-based preventive therapies including anticonvulsants (topiramate and divalproex sodium), botulinum toxin A, and medications acting by antagonism of the calcitonin generelated peptide pathway might be helpful in patients with MOH for both avoiding the overused medication and preventing the relapse of overuse. A comprehensive and multidisciplinary approach may improve the outcomes of patients with MOH.

Neurogenic Inflammation: One of the Participants of Migraine and the Contribution of Translational Research

Migraine is a primary headache disorder characterized by unilateral throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This review article discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

Evidence That HFE H63D Variant Is a Potential Disease Modifier in Cluster Headache

Cluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have been associated with hereditary hemochromatosis (HH), an iron overload disorder. The objective of the current study was to examine the association of the more common HFE H63D variant, with the susceptibility to develop CH and diverse clinical phenotypes in a population of Southeastern European Caucasian (SEC) origin. Genomic DNA samples from 128 CH patients and 294 neurologically healthy controls were genotyped for the HFE rs1799945 (H63D) variant. H63D genotypic and allelic frequency distribution did not differ significantly between patients and controls (p > 0.05). Subgroup analysis revealed a significantly more frequent occurrence of the variant G allele in chronic compared to episodic CH patients, indicative for a possible correlation of the HFE gene with the susceptibility for disease chronification. Although homozygosity for the less prevalent H63D variant G allele was minimal in the CH cohort, the results of the present study are in accordance with previous studies in CH and migraine patients, suggesting that HFE H63D variant modifies the disease clinical characteristics. Hence, despite the absence of a per se association with CH susceptibility in the current SEC cohort, variability in HFE gene may be potentially regarded as a disease modifier genetic factor in CH.

Migraine patients in Germany - need for medical recognition and new preventive treatments: results from the PANORAMA survey

Background Migraine is a primary headache disorder characterized by recurrent attacks that may have a significant impact on patients’ daily life. Treatment options must often be re-evaluated in light of efficacy, tolerability and compliance issues. Few data on commonly applied treatment algorithms and treatment failures have existed in Germany in 2017/2018. The PANORAMA survey was designed to explore and characterize the migraine healthcare landscape and to demonstrate the medical treatment need at that time in Germany. Methods Three different questionnaires were used to assess the profile of the 119 participating centers, characterize migraine patients at centers and evaluate qualitative aspects of the current migraine healthcare situation from a physician´s professional perspective. Data were analyzed as observed and summarized by descriptive statistics. Results The results demonstrate that once referred to a migraine specialist, the majority of patients continue to be treated at a specialist. At specialized centers, 41.6 % of migraine patients receive prophylactic treatment. 45.4 % of prophylactic treatments are initiated with a beta-blocker and 28.1 % with an anti-epileptic. Pivotal factors to initiate prophylactic treatment are migraine attack frequency and intensity (58.0 %). Treatment decisions are largely based on prior / concomitant diseases and physical constitution of the patient (52.1 %). Following an inadequate treatment, most patients either switch substance class or discontinue prophylactic treatment. Conclusions PANORAMA gives a comprehensive overview of the migraine healthcare landscape in Germany in 2017/2018, elucidates a lack of common treatment algorithms and reveals a high demand for defined therapy strategies and new prophylactic treatment going forwards.

Association of Migraine and Irritable Bowel Syndrome in Saudi Arabia: A Nationwide Survey.

Migraine is a primary headache disorder with a prevalence of 11.6% globally and 27% in Saudi Arabia. Irritable bowel syndrome has a prevalence of 9.2% worldwide. The prevalence of IBS has not been established nationally. However, provincial studies for both migraine and IBS have been conducted across the nation. There is a significant link between migraines and IBS globally. This identifies an association that needs to be investigated in a nationwide manner. This study aims to observe the association and the relationship between migraine and irritable bowel syndrome in Saudi Arabia. A cross-sectional study was conducted between March 2021 to June 2021 among the general population of Saudi Arabia, whose ages are 15 years old or greater. The data collection tools included MS-Q for migraine symptoms, MIGSEV scale for severity of migraine, and The IBS module of the Rome IV Diagnostic Questionnaire (R4DQ) for IBS symptoms and its subtype. With a total of 2802 participants, the majority of the study sample were males, who constituted 52.5%. Among the study's sample, the prevalence of migraine consisted of 27.4%, and the prevalence of IBS was 16.4%. The odds of having IBS in migraineurs were much higher than in those without migraines (OR 4.127; 95% CI 3.325-5.121), and the association was statistically significant (P<0.001). In conclusion, there is a strong association between migraine and irritable bowel syndrome in Saudi Arabia.

Update on Treatment of Cluster Headache

Cluster headache (CH) is characterized by severe unilateral short-lasting headache attacks, accompanying ipsilateral cranial autonomic symptoms or the sense of restlessness and agitation, or both. CH is a highly disabling primary headache disorder but often not optimally treated. High-flow oxygen and parenteral triptans are the most effective treatment to treat an acute CH attack. Transitional treatments include systemic steroid therapy and sub-occipital steroid injection. For preventive therapy, verapamil and lithium are recommended as first-line treatments. Novel treatments have appeared, such as neuromodulation and medication targeting calcitonin gene-related peptide (CGRP) or its receptor. Galcanezumab, the only anti-CGRP receptor monoclonal antibody with proven efficacy for the preventive treatment of episodic CH, represents an important advance for pharmacological treatment of CH. Neuromodulation strategies, such as the non-invasive vagus nerve stimulation and the sphenopalatine ganglion stimulation, have been proven effective in reducing the intensity and frequency of attacks, and also to be safe and well tolerated.

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (CPS1, PBRM1, and SLC25A21) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.

Diagnosis and management of migraine in ten steps

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.

A Comparative Analysis of Amytripiline, Flunnarazine and Topiramate in the treatment of Primary Headache

Introduction Primary headache disorder, characterized by recurrent headache is the most prevalent disease leading to widespread ill health and impaired quality of life. In Nepal headache is one of the most common cause of patient attending neurology clinic. Amitriptyline, Flunarizine and Topiramate are common drugs in the treatment of primary headache. We conducted this study to compare the efficacy of drugs namely Amitriptyline, Flunarizine and Topiramate in the treatment of primary headache Materials and Methods This is the retrospective data analysis of primary headache patient treated with amitriptyline, flunarizine and topiramate. On their first, second and third subsequent visits, Headache Impact Test 6 Scoring was done by a medical person. Patient were treated clinically. After third follow up data were analyzed using SPSS version 20.0. Categorical variables were compared by chi-square test, paired sample t-test, ANOVA test and Welch test. Results A total of 142 patient data was analyzed. The most common age group were between 20 to 39 years (56.34%) followed by 40 to 59 years (33.80%). Female were predominant in the group 124 (87.32%). All three medication Amitriptyline, Flunarizine and Topiramate were able to significantly lower Headache impact test -17.23 ± 6.643, -14.06 ± 7.155, -15.82 ± 5.907 respectively (P- <0.001). Amitriptyline was found to be better than other two drugs in reducing Headache Impact Test. Conclusion All three drugs namely Amitriptyline, Flunarizine and Topiramate, are significantly effective in the treatment of primary headache. Though tension type of headache is the most common type of headache, amitriptyline seems to be equally effective in treatment with other primary headaches.