Background. Central sensitization (CS) is the mechanism underlying chronic migraine and other conditions combined into a group of central sensitivity syndromes. The most reliable method for assessing the severity of CS is Central Sensitization Inventory (CSI).Aim. The aim of our study is the evaluation of anti-CGRP monoclonal antibodies (erenumab, fremanezumab) effect on the central sensitization level in migraine patients.Material and methods. We recruited 90 patients over 18 years old diagnosed with episodic migraine (EM) and chronic migraine (CM) according to the International Classification of Headache Disorders, 3rd edition. All patients were from November 2020 to March 2022. Demographic data, history of migraine and previous migraine treatment were collected for each patient. All patients filled out CSI. Dynamics was followed up monthly with headache diaries.Results. After six months of treatment the level of CS in the CM group significantly decreased from the initial level of 41 (32.0, 50.5) to 36 (25.0, 39.0), which corresponds to the absence of clinically significant CS, p = 0.02*. The analysis of points of the CSI after 3 months of treatment shows a significant decrease in the prevalence of pain syndromes, cognitive impairment, asthenic disorders, hypersensitivity and affective disorders.Conclusions. The use of erenumab and fremanezumab is advisable in patients with migraine and comorbid conditions based on the CS mechanism.

Migraine is a chronic neurological disorder that is associated with considerable disadaptive effect on patients. Despite the development of pharmacotherapy strategies for migraine, only one third of patients are satisfied with their overall treatment. Many migraine patients turn to complementary and alternative medicine (CAM), which is not usually considered a part of conventional medicine and is not always evidence-based. In practise, however, they are often used to improve the effectiveness of standard therapy or to provide alternative treatment. In addition, in CAM methods, the patient is actively involved in the choice of treatment strategies, and they have good adherence. The basic principles and approaches of CAM are increasingly being introduced into clinical practise. This review discusses the principles of CAM in the treatment of migraine as a holistic approach using lifestyle strategies and selected non-pharmacological treatments that have been shown to be effective and rational.

Migraine is the most frequent and costly type of headache. The analysis of the «cost of the disease» implies an assessment of direct and indirect costs expressed in monetary units. Drastic changes have recently occurred in approaches to the treatment of the disease, in connection with which there are large differences in the structure of the economic burden «yesterday and today». «Yesterday» knowledge about the pathophysiology of migraine was insufficient and various nonspecific agents were used to treat the disease, the antimigrenous effect of which was manifested as an additional one. The relatively low prices of these ineffective drugs for relieving attacks and preventing migraines were accompanied by high indirect costs due to temporary disability of patients, frequent time off from work, decreased labor productivity, family troubles, etc. Therefore, «yesterday»: the indirect costs associated with migraine therapy outweighed the direct costs. «Today» the cost of drugs for the prevention and pathogenetic agents for the relief of migraine attacks has become significantly higher and their costs are the main part of the costs of migraine therapy, However, the effectiveness of new pathogenetic agents for the treatment of migraines helps to reduce indirect costs and improve the quality of life. Awareness of the change in the ratio of direct and indirect costs, as well as the causes of this phenomenon, will increase patient compliance, correctly allocate costs and ultimately save personal and public financial resources.

Aim: to assess the efficacy and safety of the new Russian generic rizatriptan 10 mg tablet in alleviating migraine episodes in a real clinical practice. Patients and Methods: an open-label comparative study was conducted involving 30 patients diagnosed with migraine. Each participant was instructed to treat four migraine episodes (totaling 120 seizures) using rizatriptan 10 mg, administered at the onset of a headache, and to maintain self-monitoring diaries. If the headache recurred after initial relief, but not sooner than two hours after the first dose, a second tablet was advised. In cases where rizatriptan provided insufficient analgesic effect, the use of common analgesics was permitted. The study focused on evaluating both the drug's efficacy and safety profiles. Results: a total of 102 migraine episodes were successfully treated, while some patients opted out due to perceived insufficient efficacy. Pain relief or reduction was reported in 86% of episodes two hours post-dose, and in 87% after 24 hours. Complete pain absence was noted in 45% of episodes two hours after drug administration, and in 68% after 24 hours. A response rate was observed in 63% of participants. Non-responders, identified as those showing no improvement in at least three episodes, exhibited more severe associated symptoms such as photophobia and phonophobia, and a marked increase in headache intensity following physical activity. Mild adverse events were reported in 25% of the episodes, resolving spontaneously without the need for additional therapy. Conclusion: the Russian generic rizatriptan 10 mg tablet was demonstrated to be an effective and safe treatment option for mitigating migraine episodes. KEYWORDS: headache, migraine, triptans, relief of migraine episode, rizatriptan, real clinical practice. FOR CITATION: Filatova E.G., Latysheva N.V., Kadymova N.B., Berdnikova A.V. Relonova in the relief of migraine episodes. Russian Medical Inquiry. 2024;8(10):560–567 (in Russ.). DOI: 10.32364/2587-6821-2024-8-10-3

OBJECTIVE:To identify changes in the microbiome of saliva and to compare it with the microbiome of the oropharynx of patients with migraine.MATERIAL AND METHODS:Sixty patients with migraine (21-56 years old), were examined using a headache diary, MIDAS and VAS. A microbiological examination of saliva and smear from the mucosa of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with the determination of 57 microorganisms was performed. All patients had comorbid chronic diseases of the gastrointestinal tract and upper respiratory tract (URT), according to anamnestic data and examination by specialists.RESULTS:A significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of URT (strepto- and staphylococci); markers of transient microorganisms characteristic of intestinal microflora (clostridia, gram-negative rods, anaerobes) that are normally absent; viral markers of cytomegaloviruses and herpes groups; a decrease in the content of fungi were identified in saliva. A comparative analysis of the microbiome of saliva and oropharynx showed: 1) a significant decrease in the concentration of coccal flora Enterococcus spp., Streptococcus mutans, Staphylococcus aureus, anaerobic bacteria Clostridium difficile and Clostridium perfringens in saliva; enterobacteria Helicobacter pylori; gram-negative rods Kingella spp., fungi and Epstein-Barr virus; 2) an increase in salivary concentrations of Staphylococcus epidermidis, anaerobic Clostridium ramosum and Fusobacterium spp./Haemophilus spp. and gram-negative bacilli Porphyromonas spp.CONCLUSION:A comparative assessment of the microbiota of a smear from the posterior wall of the oropharynx and saliva using MMSM showed the presence of dysbiosis both in the oropharynx and in the saliva of patients with migraine. However, there were fewer deviations from the norm in saliva, therefore, for diagnostic purposes, a smear from the posterior wall of the oropharynx is more significant as a biomarker for patients with migraine.

OBJECTIVE:To determine the features of fibromyalgia (FM) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS:Seventy-six patients participated in the study. The patients were divided into 2 groups: RA+FM (n=55), FM (n=21). Anamnesis of life and disease was carefully collected in all patients. The intensity (according to VAS) and phenotype (Pain DETECT, DN4) of pain syndrome (PS), the presence of symptoms of central sensitization (CSI), fatigue (FSS), signs of anxiety and depression (HADS), sleep quality (PSQI), cognitive functions (DSST) and quality of life (QoL) (EQ-5D, FIQR) were also evaluated. RESULTS:The average age of patients in the FM group was significantly lower (42 [35; 53] vs. 50 [42.5; 59], p=0.042). Patients with «pure» FM without RA were more often divorced and had no children (p=0.045 and p=0.02, respectively). The duration of PS in the groups did not differ (11 [7; 17] vs. 8 [5; 13] years, p=0.429), however, patients with «pure» FM waited longer for diagnosis (115 [40; 198] vs. 20 [5.5; 59] months, p<0.001), and they also were less likely to be recognized as disabled (p=0.003). Patients of both groups had equally severe fatigue, anxiety, depression, sleep disorders and cognitive functions compared to the norms. Patients of the FM group noted a lower QoL (according to EQ-5D, p=0.041) then in RA+FM group, despite the comparable severity of FM and the intensity of the PS in both groups. CONCLUSION:FM in patients with RA develops at a later age compared to «pure» FM. The clinical picture of FM with and without RA does not differ in the main manifestations, however, the QoL of patients with «pure» FM is lower. Accounting for fibromyalgia in the treatment of rheumatoid diseases can significantly improve the QoL of patients.

Background. Headache and orofacial pain (OFP) are widespread at specialized pain centers. However, reliable data on their prevalence and co-occurrence are lacking, and prevalence of OFP in headache patients seems to be underestimated. The aim of this study was to evaluate the types of headache in patients with OFP and types of OFP in patients with headache. Methods. We enrolled patients presenting with headache and/or OFP. Patients were examined by an experienced headache and pain specialist who questioned the patients about the presence of OFP. Depression was assessed with the Beck Depression Inventory (BDI-II), anxiety – with the Beck Anxiety Inventory (BAI). Bruxism was evaluated based on subject self-report. Results. We recruited 310 patients: 177 (57%) patients with headache, 28 (9%) patients with OFP and 105 (34%) patients presenting with both types of pain. The prevalence of OFP in headache patients was 37.2%. Migraine was the most prevalent type of headache, while painful temporomandibular disorder (TMD) – the most prevalent form of OFP. Patients with PFP presented with a high prevalence of sleep and awake bruxism. Conclusion. Migraine and pain-related TMD are the most prevalent diagnoses in a specialized pain center. OKI and OKI ACT are soluble forms of ketoprofen and reach peak concentration in 15 minutes. This enables faster onset of action compared to conventional NSAIDs and better tolerability. OKI and OKI ACT are recommended in the acute treatment of migraine with comorbid painful TMD.

OBJECTIVE:To determine a role of changes in the oropharyngeal microbiome in the development and clinical manifestations of migraine.MATERIAL AND METHODS:Seventy patients with migraine, aged 21-56 years, and 15 healthy subjects matched for age and sex were examined using headache diary, MIDAS and VAS, the Gastrointestinal Symptom Rating Scale (GSRS), microbiological smear examination from the mucous membrane of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with determination of 57 microorganisms.RESULTS:The following changes in the oropharynx of individuals with migraine compared with the group of healthy individuals (control group) were found: a) a significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of the upper respiratory tract (strepto- and staphylococci); b) the appearance of markers of transient microorganisms normally absent, characteristic of the intestinal microflora (clostridia, gram-negative rods, enterobacteria, anaerobes); c) the appearance of viral markers of cytomegaloviruses, Herpes group, Epstein-Barr; d) a significant decrease in the content of bifidobacteria and lactobacilli). All people with migraine had a history or were found on examination to have chronic diseases of the upper respiratory tract (sinusitis in 48%, pharyngitis in 43%, tonsillitis in 25% of people), and gastrointestinal diseases. Dyspepsia was the most frequent and pronounced of the gastrointestinal syndromes on the GSRS in people with migraine (87%). This corresponds to the data on the extremely frequent occurrence of IBS (70% of patients) and other gastrointestinal pathology obtained from the patient history.CONCLUSION:In our work, the microbiota of the oropharynx in patients with migraine was studied for the first time using a new MSMM method. Disturbance of the oropharyngeal microbiome compared to the norm was detected in 100% of people with migraine. The changes characteristic of most patients included a significant decrease in the content of normal flora, an increase in the concentration of conditionally pathogenic microorganisms and the appearance of pathogenic microflora characteristic of chronic diseases of the upper respiratory tract and gastrointestinal tract, which may indicate their role in the pathogenesis of migraine.

OBJECTIVE:To assess the effect of food allergies on the course of migraine.MATERIAL AND METHODS:Seventy patients with migraine, aged 21-56 years old, were examined using headache diary, MIDAS and VAS, studies of specific antibodies of the IgG4 class (delayed type food allergy) by immuno-enzyme analysis (ELISA), microbiological examination of a smear from the mucous membrane of the posterior wall of the oropharynx with mass spectrometry of microbial markers (MSMM) with the identification of 57 microorganisms.RESULTS:We found an increase in specific IgG4 for a number of food allergens in most patients with migraine, of which 48.5% had a pronounced increase in IgG4 (>150 kEd/l) for at least one allergen (cow's milk - 13% patients, wheat flour - 5%, egg white - 47% or yolk - 26%, quail egg - 15%, sweet pepper - 6%), in 29% of people to several food allergens at once (all of them had chicken egg protein as one of the allergens). There was the association of IgG4 titers to wheat allergen with the severity of headache according to VAS (r-S=0.7; p=0.0046) in patients with the most severe, chronic migraine (17 people) and with an imbalance of the oropharyngeal microbiota, namely, concentration of pathological viruses Herpes spp. (rs=0.29; p=0.02), Epstein-Barr (rs=0.46; p=0.0002) and microscopic fungi (rs=0.39; p=0.0016), detected in these patients.CONCLUSION:We show for the first time the relationship between delayed-type food allergy and redistribution in the microbiome of the oropharynx of patients with migraine and once again confirm the role of delayed-type food allergy as a clinically significant factor influencing the course of migraine (its intensity and chronicity).

OBJECTIVE:To access the effect of Relatox, the first Russian botulinum toxin type A, in patients with chronic migraine (CM) and medication overuse (MO).MATERIAL AND METHODS:In phase IIIb single-blind randomized multicenter active-controlled parallel-group study, patients with CM were randomized to once intramuscular injections of Relatox (n=101) or onabotulinumtoxin A injections - Botox (n=108). This subgroup analysis evaluated the percentage of patients who transition from medication overuse to non overuse status from baseline; mean changes in the number of headache days, migraine headache days, acute headache medication intakes days, headache intensity, proportion of patients who had a ≥50% reduction in headache days, proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score in a 28-day periods in each treatment among patients with baseline acute medication overuse via repeated measures.RESULTS:Of 209 patients with CM, 100% met medication overuse criteria. Relatox and Botox demonstrated significant improvement for overall least squares mean change in headache days, migraine headache days, headache intensity; and headache-related disability and quality of life in CM patients with baseline MO, without differences between the groups. 75% and 70% patients in the Relatox and Botox groups, respectively, achieved ≥50% reduction in headache days from baseline (OR 1.58, CI 95% 0.84; 3.02, p=0.155). Furthermore, Relatox and Botox significant reduced average medication overuse rates in patient with CM and MO at baseline. 62% of patients in the Relatox group and 48% of patients in the Botox group transitioned from medication overuse to non overuse status compared from baseline (OR 2.07, CI 95% 0.91; 4.62, p=0.044). Relatox group had greater reductions than the Botox group in the percentage of patients with acute migraine-specific medication (triptan) overuse (p=0.050).CONCLUSION:The results demonstrate highly prevalent of medication overuse among individuals with CM. This analysis provides evidence that the Russian botulinum toxin type A Relatox significantly improves measures of headache symptoms, quality of life and headache-related disability, and also significantly greater, compared to Botox, reduces migraine-specific medication consumption in patients with chronic migraine who overuse acute medications.

On December 24, 2022, in Moscow an interdisciplinary Council of Headache Experts, held under the auspice of the interregional public organization “Russian Society for the Study of Headache”, discussed the key problems of effective treatment of a migraine attack and the possibilities of a specific drug Kaporiza® (rizatriptan). Despite the development of strategies for the relief of migraine attacks and the effectiveness of triptans as first-line therapy, the choice of a specific drug in accordance with the individual clinical profile of the patient is difficult due to the existence of drugs in various forms (standard tablets, oral dispersible forms, injections, nasal sprays, rectal suppositories). Rizatriptan in the form of an orally dispersible tablet (ODT) has a number of advantages: high bioavailability, fast onset of action, and ease of use. Therefore, Kaporiza® (rizatriptan ODT) may be recommended as a priority therapy for all migraine patients who prefer the dispersible tablet form and who experience symptoms of nausea and vomiting, as well as for patients who have experience of poor efficacy and/or poor tolerability of other triptans. The Expert Council recommends to include rizatriptan ODT in the next edition of the clinical guidelines for the diagnosis and treatment of migraine as a first-line agent with Level A evidence.

OBJECTIVE:To access the efficacy and safety of the first Russian botulinum toxin type A (Relatox) as a headache prophylaxis in adult with chronic migraine (CM).MATERIAL AND METHODS:The randomized, one-blind, multicenter, active-controlled, parallel-group trial study involved 209 patients with CM aged from 19 to 65 years. The patients were randomized to injections of the Russian botulinum toxin type A - Relatox (n=101) or onabotulinumtoxinA injections - Botox (n=108). The duration of the study was 16 weeks, which included five visits of patients every 4 weeks. Relatox and Botox were injected once into seven muscle groups of the head and neck at a dose of 155-195 units. Primary efficacy variable was mean change from baseline in frequency of headache days after 12 weeks. Secondary efficacy variables were mean changes from the baseline to week 12 in frequency of migraine days, acute headache pain medication intakes days; headache intensity; proportion of patients achieving ≥50% reduction from baseline in headache days, the proportion of the patients with medication overuse, the proportion of the patients with severe (≥60) Headache Impact Test-6 score and with a severe (≥21) MIDAS score.RESULTS:Analyses demonstrated a large mean decrease from baseline in frequency of headache days, without statistically significant between-group differences Relatox vs Botox at week 12 (-10.89 vs -10.06; p=0.365) and at other time points. Significant differences from baseline were also observed for all secondary efficacy variables at all time points without differences between the groups. The proportion of patients achieving ≥50% reduction from baseline in headache days was 75.0% and 70% in the Relatox and Botox groups, respectively (OR, CI 95% 1.58 [0.84; 3.02], p=0.155). Adverse events (AE) occurred in 15.8% of Relatox patients and 15.7% of Botox patients (p=1.000). No unexpected AE were identified.CONCLUSION:The results demonstrate that the first Russian botulinum toxin type A (Relatox) is an effective prophylactic treatment for CM in adult patients. Relatox led to significant improvements from baseline in multiple measures of headache symptoms, headache-related disability and quality of life. For the first time, a comparative analysis of two botulinum toxin type A products in parallel groups showed no less (not inferior) efficacy and safety of Relatox relative to Botox in the treatment of CM in adults.

This consensus reviewed the main current issues of clinical application and integration into everyday practice of a new targeted preventive therapy for migraine using monoclonal antibodies (mAbs) to the calcitonin gene related peptide (CGRP) ligand or receptor. These recommendations are based on current scientific and clinical studies and an analysis of the results of several years of clinical use. The main purpose of the consensus is to assist practitioners in prescribing effective prophylactic treatment of migraine using anti-CGRP mAbs and to improve care for patients with various forms of the disease.

Thе review presents the mechanism of action of a new class of targeted drugs for the treatment of migraine with CGRP gepant receptor antagonists — gepants. Currently, two drugs — ubrogepant and rimegepant are approved by the FDA for the relief of acute migraine attacks in the United States. In the Russian Federation, none of the drugs of this new class is registered, however, this is possible in the near future. The review presents the results of RCTs that demonstrated their effectiveness in comparison with triptans and placebo, as well as good tolerability and safety. Rimegepant and ubrogepant cause minimal side effects and are safe for people with cardiovascular diseases. Gepants may provide an alternative for migraine patients who do not tolerate the side effects observed with triptans, as well as the main therapy.

The prevalence of fibromyalgia (FM) in the general population is 2–8%, and among patients with rheumatic diseases it is 2–3 times higher. The presence of comorbid FM significantly affects the course of rheumatoid arthritis (RA).Objective: to assess the effect of FM on RA activity indicators, features of pain syndrome, and quality of life (QoL) of patients.Patients and methods. The study included patients with a confirmed diagnosis of RA. RA activity was assessed by the DAS28 index. FM was diagnosed according to the 2016 ACR criteria using the FM Diagnostic Questionnaire (FSQ). Patients also completed the central sensitization questionnaires – CS (CSI) and PainDETECT (PD). Pain intensity at rest was assessed using a visual analog scale (VAS, 10 cm), QoL was assessed using the FIQR and EQ-5D questionnaires.Results and discussion. 55 patients with RA were examined. FM was diagnosed in 24 of them (43.6%). RA activity in the presence and absence of FM (FM+ and FM- respectively) was high: the DAS28 index in the FM+ group averaged 4.58 points, and in the FM- group it was 5.14 points (p=0.227). The median pain intensity according to VAS in the FM+ and FM- groups was 6.5 and 4.0 cm, respectively (p=0.017). Symptoms of CS were more common in patients with FM than in patients without FM (p=0.004). The median score on the PD questionnaire in the FM+ and FM- groups reached 17.5 and 11.0 points, respectively (p=0.015). Patients with FM had lower QoL scores both in EQ-5D (p=0.037) and FIQR (p<0.001).Conclusion. FM is a serious burden for RA patients. The pain syndrome in the presence of FM is of greater intensity and prevalence, accompanied by neuropathic descriptors, which significantly worsens the quality of life in patients with RA.

Результаты консенсуса специалистов. Роль фиксированной комбинации напроксена и дифенгидрамина — препарата НОВЕМА НАЙТ в терапии пациентов с болевым синдромом, сопровождающимся нарушениями сна.

ЦЕЛЬ ИССЛЕДОВАНИЯ Валидизация опросника для оценки центральной сенситизации (ОЦС) при неспецифической боли в шее, сочетающейся с головными болями, — мигренью, головной болью напряжения и цервикогенной головной болью. МАТЕРИАЛ И МЕТОДЫ С участием 37 пациентов с неспецифической болью в шее и 167 пациентов с болью в шее, сочетающейся с эпизодическими и хроническими головными болями, — мигренью и головной болью напряжения, проведена оценка психометрических свойств русскоязычной версии ОЦС, таких как конструктная валидность, конвергентная валидность, надежность «тест — ретест». Проведен факторный анализ ОЦС. РЕЗУЛЬТАТЫ Валидизированная версия обладает хорошей внутренней согласованностью (α Кронбаха = 0,88) и надежностью «тест — ретест» (коэффициент внутриклассовой корреляции ICC2,1 для абсолютного согласия = 0,91). Коэффициент корреляции r Спирмена при оценке корреляции ОЦС с Госпитальной шкалой тревоги и депрессии: для субшкалы «Тревога» r=0,57, для субшкалы «Депрессия» rS=0,56 при p<0,05. Факторный анализ выявил однофакторную структуру опросника. «Эффектов пола и потолка» выявлено не было. Разница между группами «боль в шее» (32 балла) и «боль в шее, сопровождающаяся хроническими головными болями» (45 баллов) составила по ОЦС 13 баллов. Минимальные клинически значимые изменения составили 10 баллов. ВЫВОД В группе пациентов с неспецифической болью в шее, сочетающейся с эпизодическими и хроническими головными болями, валидизированная русскоязычная версия ОЦС обладает хорошими психометрическими свойствами. Необходимы дальнейшие исследования для оценки других психометрических свойств опросника.

The Russian experts’ guidelines on evaluation and treatment of medication-overuse headache are based on evidence-based medicine, the latest revision of the International Classification of Headache Disorders. Basic information about epidemiology, risk factors, pathophysiological mechanisms, evaluation, and the most effective pharmacological drug and non-pharmacological approaches to managing patients with medication-overuse headache are presented.