Polymorphism of methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene and hyperhomocysteinemia in migraine

В обзоре обсуждается роль полиморфизма гена фолатного обмена метилентетрагидрофолат-редуктазы (MTHFR), ответственного за развитие гипергомоцистеинемии в патогенезе мигрени. Изложены общие данные о полиморфизме С677 гена фолатного цикла и метаболизме гомоцистеина. Представлен патогенетический механизм развития мигрени, связанный с провоспалительными, прокоагулянтными свойствами гомоцистеина, активацией процессов окислительного стресса, эндотелиальной дисфункцией и нейрогенным воспалением при повышении концентрации этой аминокислоты. Отражены перспективы и социальная значимость имплементации данных генетических исследований в клиническую практику, их роль в прогнозировании течения мигрени и оценке риска развития осложнений, а также коррекции фармакотерапевтических подходов. Методика. Для поиска данных в базах MEDLINE, SCOPUS и Web of Science использованы поисковые запросы: МТHFR, мигрень, патофизиология, гипергомоцистеинемия, таргетная терапия. The review discusses the role of polymorphism of the methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene responsible for hyperhomocysteinemia in the pathogenesis of migraine. Data on the polymorphism of the folate cycle gene C677 and homocysteine metabolism are presented. The pathogenetic mechanism of migraine associated with proinflammatory, procoagulant properties of homocysteine and with the activation of oxidative stress, endothelial dysfunction, and neurogenic inflammation related with increased concentrations of homocysteine is described. Prospects and social significance of implementing data of genetic research into clinical practice are discussed. Included is the role of genetic research in predicting the course and complications of migraine, in assessment of risk for complications, and in pharmacotherapeutic approaches to migraine treatment. Methods. MEDLINE, SCOPUS and Web of Science databases were used to search for data: MTHFR, migraine, pathophysiology, hyperhomocysteinemia, targeted therapy

Migraine in children and adolescents: modern principles of diagnostics and treatment

Migraine is a nervous system disorder that affects 7.7% of children and can debut before the age of 3 years. As they get older, the incidence of migraine increases, and among adolescents, its prevalence reaches 15%. The disease can significantly reduce the child's daily activity, school performance. Migraine is the most common cause of headache in children and adolescents, but it is not always diagnosed; it is not uncommon for patients with migraine to be misdiagnosed and given ineffective treatment. An effective approach to the diagnosis of migraine in children is presented, diagnostic criteria for migraine according to the 3rd edition of International Classification of Headache Disorders are described. Special disorders in childhood are described – episodic syndromes in children associated with migraine. Migraine treatment in children includes four main approaches: 1) lifestyle recommendations; 2) migraine attack treatment; 3) nonpharmacological treatment; 4) migraine preventive pharmacotherapy. All of the listed approaches for the treatment of migraine in childhood are discussed in detail.

Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies

Background Patients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo. Methods Cardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion. Results Cardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo. Conclusions In this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo. Trial registration NCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016

fMRI findings in cortical brain networks interactions in migraine following repetitive transcranial magnetic stimulation

Background: Repetitive transcranial magnetic stimulation (rTMS) is one of high-potential non-pharmacological methods for migraine treatment. The purpose of this study is to objectively evaluate the efficacy of rTMS in patients with migraine based on data from functional magnetic resonance imaging (fMRI). Methods: 19 patients with migraine without aura underwent a 5-day course of rTMS of the ventrolateral prefrontal cortex bilaterally, at 10Hz frequency and 60% of motor threshold response of 900 pulses. Resting-state functional MRI (1.5 T) and battery of tests were carried out for each patient to clarify their diagnosis, qualitative and quantitative characteristics of pain, and associated affective symptoms. Changes in functional connectivity (FC) in the brain’s neural networks before and after the treatment were identified through independent components analysis. Results: Over the course of therapy, we observed an increase in FC of the default mode network within it, with pain system components and with structures of the visual network. We also noted a decrease in FC of the salience network with sensorimotor and visual networks, as well as an increase in FC of the visual network. Besides, we identified 5 patients who did not have a positive response to one rTMS course, presumably because of an increased trend to depressive symptoms and neuroimaging criteria for depressive disorder. Conclusions: Our findings provide evidence of a 70% efficacy of rTMS judging by neuroimaging changes and a decrease in clinical symptoms. Moreover, we identified neuroimaging criteria for the therapy efficacy as well as possible predictors of successful/unsuccessful response to the therapy.

Chronic migraine reversal and prevention with the LIFE diet: a nutrient dense whole food plant-based diet (WFPBD)

We report a case of a 60-year-old man who struggled with frequent migraines for 12.5 years, which were refractory to all conventional therapies. Six months before initial consultation, these migraines become chronic. The patient was then advised to follow the Low Inflammatory Foods Everyday (LIFE) diet, a nutrient-dense, dark green leafy vegetable-rich, whole food plant-based diet. Within 2 months, his headache frequency declined from 18 to 24 headache days per month to 1, and he discontinued his preventive and abortive migraine medications. After 3 months, the patient had no headaches. These results far exceed the goal of migraine treatment with medication, which is to reduce migraine frequency by >50% per month. In addition, the results were durable; this patient has been migraine-free for 7.5 years. Serum beta-carotene more than tripled after the patient started the LIFE diet, consistent with its high content of dark green leafy vegetables. Weight, high-sensitivity C-reactive protein (hsCRP), complete blood count (CBC), hydration status, sodium and other electrolytes remained constant throughout the study.

P.027 Efficacy and Safety of Eptinezumab Initiated During a Migraine Attack: Results from the RELIEF Study

Background: Eptinezumab is approved for migraine prevention, with demonstrated rapid onset of preventive benefit. RELIEF evaluated the efficacy and safety of eptinezumab initiated during a migraine attack. Methods: RELIEF (NCT04152083; parallel-group, double-blind, placebo-controlled) randomized adults with migraine (4-15d/mo in 3mo prior to screening) to eptinezumab 100mg or placebo, administered IV within 1-6h of qualifying migraine onset. Co-primary efficacy endpoints were time to headache pain freedom and time to absence of most bothersome symptom (MBS). Results: Eptinezumab (n=238) compared with placebo (n=242) achieved significantly faster headache pain freedom (median 4h vs 9h; hazard ratio=1.54, P=0.0006) and absence of MBS (2h vs 3h; 1.75, P<0.0001). At 2h, 23.5% and 12.0% (P=0.0009) of eptinezumab-treated and placebo patients, respectively, reported headache pain freedom, and 55.5% and 35.8% (P<0.0001) reported absence of MBS. Significantly fewer eptinezumab-treated patients used rescue medication within 24h (31.5% vs 59.9%; P<0.0001). Treatment-emergent adverse events occurred in 10.9% eptinezumab-treated and 10.3% placebo patients; no serious adverse events occurred. Conclusions: Infusion of the preventive migraine treatment, eptinezumab, during a migraine resulted in rapid and sustained freedom from headache pain and MBS vs placebo, starting 2h post-infusion, decreasing need for acute medication within 24h post-infusion. No notable safety findings were identified.