PURPOSE OF REVIEW: The purpose of this study was to review the literature on the relationship between migraine, anxiety and related disorders, anxious symptomology and related behaviors. RECENT FINDINGS: Generalized anxiety, other anxious disorders and migraine are comorbid. In addition, anxious symptomology and behaviors are common in people with migraine even if they do not meet diagnostic criteria or threshold. Anxiety including diagnosed disorders such as generalized anxiety, phobias, panic disorder, as well as behaviors such as catastrophizing, avoidance behaviors, and higher fear of headache/migraine or anxiety sensitivity are comorbid and/or common in migraine. Anxiety is associated with negative outcomes such as migraine progression, medication overuse, stigma and migraine-related disability. The association between migraine, anxiety, and fear and avoidance behaviors has an extensive empirical basis. Awareness of the high prevalence of comorbidity and symptomology as well as the negative outcomes associated with anxiety and related symptoms and behaviors is important in the comprehensive management of people with migraine. Better understanding the relationship between migraine and anxiety symptoms and behaviors and their effects on outcomes is essential to provide more effective treatment for people with migraine. The review emphasizes the necessity of screening and more comprehensive evaluation in patients with migraine using psychological diagnostic tools. Thus, prevention and management of anxiety, fear, and anxiety-related behaviors in the context of migraine management may be considered an essential treatment goal and strategies may include non-pharmacological and pharmacological approaches.

• Klíčová slova
• Anxiety, Anxiety sensitivity, Avoidance, Cephalalgiaphobia, Cogniphobia, Fear, Generalized anxiety disorder, Migraine, Phobias,
• MeSH
• komorbidita MeSH
• lidé MeSH
• migréna * epidemiologie   psychologie   MeSH
• prevalence MeSH
• strach psychologie   MeSH
• úzkost * epidemiologie   psychologie   MeSH
• úzkostné poruchy * epidemiologie   psychologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

IMPORTANCE: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. OBJECTIVE: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. DESIGN, SETTING, AND PARTICIPANTS: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. INTERVENTIONS: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. RESULTS: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03927144.

• MeSH
• adherence k farmakoterapii MeSH
• antagonisté CGRP receptorů aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• migréna * farmakoterapie   prevence a kontrola   MeSH
• prospektivní studie MeSH
• spokojenost pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté CGRP receptorů MeSH
• erenumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH

BACKGROUND: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed. METHODS: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed. FINDINGS: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group. INTERPRETATION: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population. FUNDING: Allergan (now AbbVie).

• MeSH
• běloši MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• Evropané MeSH
• lidé středního věku MeSH
• lidé MeSH
• migréna * farmakoterapie   prevence a kontrola   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• piperidiny * MeSH
• pyridiny * MeSH
• pyrroly * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Severoameričané MeSH
• spirosloučeniny * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH
• Názvy látek
• atogepant MeSH Prohlížeč
• monoklonální protilátky * MeSH
• piperidiny * MeSH
• pyridiny * MeSH
• pyrroly * MeSH
• spirosloučeniny * MeSH

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

• Klíčová slova
• CGRP, Cerebrospinal fluid, Cortical spreading depression, DTI-ALPS, Glymphatic system, Headache, Migraine, Neurological disorders, Perivascular space,
• MeSH
• bolesti hlavy metabolismus   MeSH
• glymfatický systém * diagnostické zobrazování   metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• migréna * diagnostické zobrazování   metabolismus   MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• nemoci nervového systému * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Migraine is a disabling neurovascular disorder among people of all ages, with the highest prevalence in the fertile years, and in women. Migraine impacts the quality of life of affected individuals tremendously and, in addition, it is associated with highly prevalent metabolic diseases, such as obesity, diabetes mellitus and thyroid dysfunction. Also, the clinical response to drugs might be affected in patients with metabolic disease due to body composition and metabolic change. Therefore, the efficacy of antimigraine drugs could be altered in patients with both migraine and metabolic disease. However, knowledge of the pharmacology and the related clinical effects of antimigraine drugs in patients with metabolic disease are limited. Therefore, and given the clinical relevance, this article provides a comprehensive overview of the current research and hypotheses related to the influence of metabolic state and body composition on the action of antimigraine drugs. In addition, the influence of antimigraine drugs on metabolic functioning and, vice versa, the influence of metabolic diseases and its hormonal modulating medication on migraine activity is outlined. Future exploration on personalizing migraine treatment to individual characteristics is necessary to enhance therapeutic strategies, especially given its increasing significance in recent decades.

• Klíčová slova
• CGRP, Diabetes mellitus, Lifestyle, Metabolic disorders, Migraine, Obesity,
• MeSH
• kvalita života MeSH
• lidé MeSH
• metabolické nemoci * farmakoterapie   MeSH
• migréna * MeSH
• obezita MeSH
• složení těla MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and socioeconomic burden. The link between these disorders has been of interest for decades and innovations concerning diagnosing and treatment enable new insights into their relationship. FINDINGS: Although appearing to be distinct at first glance, both diseases exhibit a noteworthy comorbidity, shared pathophysiological pathways, and significant overlaps in characteristics like clinical manifestation or prophylactic treatment. This review aims to explore the intricate relationship between these two conditions, shedding light on shared pathophysiological foundations, genetic interdependencies, common and distinct clinical features, clinically overlapping syndromes, and therapeutic similarities. There are several shared pathophysiological mechanisms, like CSD, the likely underlying cause of migraine aura, or neurotransmitters, mainly Glutamate and GABA, which represent important roles in triggering migraine attacks and seizures. The genetic interrelations between the two disorders can be observed by taking a closer look at the group of familial hemiplegic migraines, which are caused by mutations in genes like CACNA1A, ATP1A2, or SCN1A. The intricate relationship is further underlined by the high number of shared clinical features, which can be observed over the entire course of migraine attacks and epileptic seizures. While the variety of the clinical manifestation of an epileptic seizure is naturally higher than that of a migraine attack, a distinction can indeed be difficult in some cases, e.g. in occipital lobe epilepsy. Moreover, triggering factors like sleep deprivation or alcohol consumption play an important role in both diseases. In the period after the seizure or migraine attack, symptoms like speech difficulties, tiredness, and yawning occur. While the actual attack of the disease usually lasts for a limited time, research indicates that individuals suffering from migraine and/or epilepsy are highly affected in their daily life, especially regarding cognitive and social aspects, a burden that is even worsened using antiseizure medication. This medication allows us to reveal further connections, as certain antiepileptics are proven to have beneficial effects on the frequency and severity of migraine and have been used as a preventive drug for both diseases over many years. CONCLUSION: Migraine and epilepsy show a high number of similarities in their mechanisms and clinical presentation. A deeper understanding of the intricate relationship will positively advance patient-oriented research and clinical work.

• Klíčová slova
• Anti-seizure medication, Epilepsy, Genetics, Hemiplegic migraine, Migraine, Migralepsy, Neurotransmitters,
• MeSH
• antikonvulziva terapeutické užití   MeSH
• epilepsie * etiologie   genetika   MeSH
• komorbidita MeSH
• lidé MeSH
• migréna s aurou * genetika   MeSH
• migréna * diagnóza   genetika   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikonvulziva MeSH

BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

• Klíčová slova
• ASICs, Headache, K2P, Mechano-neurobiology, Mechanotransduction, Migraine, NMDA, Piezo, TRP,
• MeSH
• bolest MeSH
• buněčný převod mechanických signálů * fyziologie   MeSH
• migréna * diagnóza   MeSH
• nocicepce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. METHODS: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1-12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1-12. Safety was assessed through adverse events reported. RESULTS: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1-12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. CONCLUSION: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries.Trial registration: encepp.eu: EUPAS35111.

• Klíčová slova
• Calcitonin gene-related peptide, chronic, episodic, real-world data, real-world evidence,
• MeSH
• bolesti hlavy MeSH
• dospělí MeSH
• lidé MeSH
• migréna * farmakoterapie   prevence a kontrola   MeSH
• monoklonální protilátky * MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• pozorovací studie MeSH
• Názvy látek
• fremanezumab MeSH Prohlížeč
• monoklonální protilátky * MeSH

Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development.

• Klíčová slova
• Hormones, Migraine, OTR, Oxytocin, PRLR, Pain, Prolactin, Sex differences,
• MeSH
• analgetika terapeutické užití   MeSH
• bolest farmakoterapie   MeSH
• lidé MeSH
• migréna * MeSH
• oxytocin * fyziologie   MeSH
• pohlavní steroidní hormony MeSH
• prolaktin * fyziologie   MeSH
• receptory oxytocinu MeSH
• receptory prolaktinu MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• analgetika MeSH
• oxytocin * MeSH
• pohlavní steroidní hormony MeSH
• prolaktin * MeSH
• receptory oxytocinu MeSH
• receptory prolaktinu MeSH

Migraine is a complex brain disorder explained by the interaction of genetic and environmental factors. In monogenic migraines, including familial hemiplegic migraine and migraine with aura associated with hereditary small-vessel disorders, the identified genes code for proteins expressed in neurons, glial cells, or vessels, all of which increase susceptibility to cortical spreading depression. The study of monogenic migraines has shown that the neurovascular unit plays a prominent role in migraine. Genome-wide association studies have identified numerous susceptibility variants that each result in only a small increase in overall migraine risk. The more than 180 known variants belong to several complex networks of "pro-migraine" molecular abnormalities, which are mainly neuronal or vascular. Genetics has also highlighted the importance of shared genetic factors between migraine and its major co-morbidities, including depression and high blood pressure. Further studies are still needed to map all of the susceptibility loci for migraine and then to understand how these genomic variants lead to migraine cell phenotypes.

• Klíčová slova
• Familial hemiplegic migraine, Genetics, Genome-wide association studies, Migraine, Polygenic,
• MeSH
• celogenomová asociační studie MeSH
• lidé MeSH
• migréna s aurou * MeSH
• migréna * genetika   MeSH
• šířící se kortikální deprese * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH