ß-Adrenoceptors (ß-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three ß-ARs, ß1-AR, ß2-AR, ß3-AR are localized to the human heart. Activation of ß1-AR and ß2-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of ß1-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of ß1-AR is critical in the pathogenesis of cardiac arrhythmias while activation of ß2-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of ß2-AR in cardiovascular disease, particularly arrhythmia generation. All ß-blockers used therapeutically to treat cardiovascular disease block ß1-AR with variable blockade of ß2-AR depending on relative affinity for ß1-AR vs ß2-AR. Since the introduction of ß-blockers into clinical practice in 1965, ß-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. ß-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. ß-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The ß-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other ß-blockers and is used successfully in the treatment of heart failure. The discovery of ß3-AR in human heart created interest in the role of ß3-AR in heart failure but has not resulted in therapeutics at this stage.
Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad range of entities. Therefore, any attempt at treatment must first start with determining the etiology. In this current perspective, we focus specifically on the diagnosis of and treatment of vestibular migraine, which is common and overlaps clinically with a variety of other diagnoses. We discuss the traditional treatments for vestibular migraine in addition to the recent explosion of novel migraine therapeutics. Because vestibular migraine can mimic, or co-exist with, a variety of other vestibular diseases, we discuss several of these disorders including persistent postural-perceptual dizziness, benign paroxysmal positional vertigo, post-concussive syndrome, Ménière's disease, and cerebrovascular etiologies. We discuss the diagnosis of each, as well as overlapping and distinguishing clinical features of which the reader should be aware. Finally, we conclude with evidence based as well as expert commentary on management, with a particular emphasis on vestibular migraine.
This study aims to investigate the effects of oral and non-oral migraine prophylaxis on subjective sleep quality in migraine patients with sleep problems. A bidirectional relationship between migraine and sleep is presumed, although this relationship is not fully clarified. Possibly, prophylactic treatment of migraine aiming at a reduction of migraine attack frequency can also positively affect the quality of sleep for patients with migraine with sleep problems. PubMed, Cochrane, Embase and CINAHL databases were searched in March 2022 for studies evaluating prophylactic treatment of migraine and the impact on perceived sleep quality (Pittsburgh Sleep Quality Index or Insomnia Severity Index). A systematic review using the McMaster Tool and a random-effects meta-analysis (effect size Cohen's d) were conducted. Seven studies were identified, including 989 participants, of which 844/989 (85.3%) female, with a mean (SD) age of 41.3 (12.1) years. In 6/7 (85.7%) studies, monthly migraine days improved (p < 0.002). Five out of six (83.3%) studies presented a relevant improvement in quality of sleep (p < 0.05), and one study reported a clinically meaningful improvement in the treatment group (Insomnia Severity Index change >7, in >50% of participants). The meta-analysis showed a large effect size of 1.09 (95% confidence interval 0.57-1.62; overall p < 0.001; Cochran's Q < 0.0001) for migraine prophylaxis on improving sleep quality. In conclusion, prophylactic migraine treatment improves sleep quality in patients with migraine and sleep problems, as measured with self-reported questionnaires Pittsburgh Sleep Quality Index and Insomnia Severity Index. Unfortunately, some included studies used prophylactic treatment that is not in current (international) guidelines. The evidence for this improvement in quality of sleep is strong, and seems a generic effect of migraine prophylaxis.
BACKGROUND: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far. METHODS: The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia). RESULTS: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan. CONCLUSION: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.
BACKGROUND: Migraine, a neurological disorder with a significant female predilection, is the leading cause of disability-adjusted life years (DALYs) in women of childbearing age (WCBA). There is currently a lack of comprehensive literature analysis on the overall global burden and changing trends of migraines in WCBA. METHODS: This study extracted three main indicators, including prevalence, incidence, and DALYs, related to migraine in WCBA from the Global Burden of Disease(GBD) database from 1990 to 2021. Our study presented point estimates with 95% uncertainty intervals (UIs). It evaluated the changing trends in the burden of migraine in WCBA using the estimated annual percentage change (EAPC) and percentage change. RESULTS: In 2021, the global prevalence, incidence, and DALYs cases of migraine among WCBA were 493.94 million, 33.33 million, and 18.25 million, respectively, with percentage changes of 48%, 43%, and 47% compared to 1990. Over the past 32 years, global prevalence rates and DALYs rates globally have increased, with an EAPC of 0.03 (95% UI: 0.02 to 0.05) and 0.04 (95% UI: 0.03 to 0.05), while incidence rates have decreased with an EAPC of -0.07 (95% UI: -0.08 to -0.05). Among the 5 Socio-Demographic Index (SDI) regions, in 2021, the middle SDI region recorded the highest cases of prevalence, incidence, and DALYs of migraine among WCBA, estimated at 157.1 million, 10.56 million, and 5.81 million, respectively, approximately one-third of the global total. In terms of age, in 2021, the global incidence cases for the age group 15-19 years were 5942.5 thousand, with an incidence rate per 100,000 population of 1957.02, the highest among all age groups. The total number of migraine cases and incidence rate among WCBA show an increasing trend with age, particularly in the 45-49 age group. CONCLUSIONS: Overall, the burden of migraine among WCBA has significantly increased globally over the past 32 years, particularly within the middle SDI and the 45-49 age group. Research findings emphasize the importance of customized interventions aimed at addressing the issue of migraines in WCBA, thus contributing to the attainment of Sustainable Development Goal 3 set by the World Health Organization.
Global Burden of Disease , Global Health , Migraine Disorders , Humans , Migraine Disorders/epidemiology , Female , Global Burden of Disease/trends , Adult , Global Health/statistics & numerical data , Prevalence , Incidence , Disability-Adjusted Life Years/trends , Young Adult , Middle Aged , Adolescent
BACKGROUND: The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks. METHODS: We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search. RESULTS: Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-ß and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed. CONCLUSIONS: Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.
Migraine Disorders , Humans , Migraine Disorders/immunology , Cytokines/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology
PURPOSE: To evaluate the relative contributions of objective and subjective indicators of dry eye disease (DED) in individuals with chronic pain conditions compared with controls. METHODS: A systematic review and meta-analysis was conducted of studies that reported the signs and symptoms of DED and/or their prevalence in individuals with chronic pain compared with controls. International Association for the Study of Pain (IASP) International Classification of Diseases (ICD)-11 codes for chronic pain conditions were applied, and outcomes defined as DED signs and symptoms. A search strategy utilised the EMBASE, Web of Science, Cochrane Library and MEDLINE databases. Risk of bias assessment was performed with the Newcastle-Ottawa scale. Random effects meta-analysis calculated mean differences (MD) and odds ratios (OR), while subgroup analysis of different chronic pain conditions explored their relative association with the signs and symptoms of DED. Evidence certainty was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). RESULTS: Fourteen observational studies comprising 3,281,882 individuals were included. Meta-analysis found high quality evidence that individuals with chronic pain were more likely to experience symptoms of DED than controls (OR = 3.51 [95 %CI: 3.45,3.57]). These symptoms were more severe (MD = 18.53 [95 %CI: 11.90, 25.15]) than controls with a clinically meaningful effect size. Individuals with chronic pain had more rapid tear film disruption (MD = -2.45 [95 %CI: -4.20, -0.70]) and reduced tear production (MD = -5.57 [95 %CI: -9.56, -1.57]) compared with controls (with moderate evidence quality). High quality evidence revealed individuals with chronic pain had lower basal tear production (anaesthetised) than controls (MD = -2.59 [95 %CI: -3.60, -1.58]). Tear film osmolarity showed no significant differences between the chronic pain and pain-free groups. Group differences for DED signs were not considered clinically meaningful. CONCLUSION: More severe, clinically meaningful symptoms of DED were reported in individuals with chronic pain than controls, however group differences for the signs of DED were typically of limited or questionable clinical relevance. This ocular phenotype where DED is felt more than it is seen in chronic pain may reflect underlying sensory hypersensitivity, shared by both conditions and contributing to their frequent comorbidity. Advancing understanding of this potential pathophysiological mechanism may guide clinical management.
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established. METHODS: This longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA. RESULTS: A total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0-41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p < 0.001) and headache absence (F(2,524) = 84.79; p < 0.001) throughout the observation period, explaining 14.7% of the variance in pCGRP levels. CGRP measurements showed strong intraindividual agreement in IIH (ICC 0.993, 95% CI 0.987-0.996, p < 0.001). No association was found between pCGRP levels and ophthalmological parameters. CONCLUSIONS: Although interindividual heterogeneity of pCGRP levels is generally high, migraine-like headache seems to be associated with higher pCGRP levels. CGRP may play a role in the headache pathophysiology at least in a subgroup of IIH.
Calcitonin Gene-Related Peptide , Migraine Disorders , Pseudotumor Cerebri , Humans , Female , Male , Adult , Calcitonin Gene-Related Peptide/blood , Pseudotumor Cerebri/blood , Migraine Disorders/blood , Longitudinal Studies , Young Adult , Biomarkers/blood
Background: Migraines affect one billion individuals globally, with a higher occurrence among young adults and women. A significant survey in the United States indicated that 17.1% of women and 5.6% of men suffer from migraines. This study seeks to investigate the potential connection between NLRP3 and MMP9 in migraine pathology. Methods: The research involved searching databases such as PubMed, Scopus, Science Direct, Google Scholar, and Proquest, with the search concluding on March 31, 2024. Following PRISMA guidelines, PICO data were collected, focusing exclusively on animal models induced by Nitroglycerine (10 mg/kg), while excluding clinical studies. Results: The study, originally registered in Prospero Reg. No. CRD42022355893, conducted bias analysis using SYRCLE's RoB tool and evaluated author consensus using GraphPad v9.5.1. Out of 7,359 search results, 22 papers met the inclusion criteria. Inter-rater reliability among reviewers was assessed using Cohen's kappa statistics. Conclusion: This review summarizes 22 preclinical studies on Nitroglycerin (NTG), NLRP3, MMP9, and related biomarkers in migraine. They reveal that NTG, especially at 10 mg/kg, consistently induces migraine-like symptoms in rodents by activating NLRP3 inflammasome and stimulating proinflammatory molecule production. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42022355893.
BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.
BACKGROUND: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). METHODS: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. RESULTS: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10- 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10- 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10- 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10- 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10- 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. DISCUSSION: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.
Atrophy , Brain , Dementia , Genome-Wide Association Study , Mendelian Randomization Analysis , Migraine Disorders , Humans , Atrophy/pathology , Migraine Disorders/genetics , Migraine Disorders/pathology , Migraine Disorders/diagnostic imaging , Migraine Disorders/complications , Migraine Disorders/epidemiology , Brain/pathology , Brain/diagnostic imaging , Dementia/genetics , Dementia/epidemiology , Dementia/pathology , Dementia/etiology , Female , Longitudinal Studies , Male
BACKGROUND: Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. METHODS: The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. RESULTS: We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. CONCLUSION: Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.
Genetic Predisposition to Disease , Genome-Wide Association Study , Migraine Disorders , Transcriptome , Humans , Migraine Disorders/genetics , Genetic Predisposition to Disease/genetics , Transcriptome/genetics , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide/genetics
Background: Central sensitization is one of the pivotal pathological mechanisms in chronic migraine (CM). Silent information regulator 1 (SIRT1) was shown to be involved in CM, but its specific mechanism is unclear. Reactive oxygen species (ROS) are increasingly regarded as important signaling molecules in several models of pain. However, studies about the role of ROS in the central sensitization of CM model are rare. We thus explored the specific process of SIRT1 involvement in the central sensitization of CM, focusing on the ROS pathway. Methods: Inflammatory soup was repeatedly administered to male Sprague-Dawley rats to establish a CM model. The SIRT1 expression level in trigeminal nucleus caudalis (TNC) tissues was assessed by qRT-PCR and Western blotting analysis. The levels of ROS were detected by a Tissue Reactive Oxygen Detection Kit, DHE staining, and the fluorescence signal intensity of 8-OHdG. A ROS scavenger (tempol), a SIRT1 activator (SRT1720), a SIRT1 inhibitor (EX527), and a mitochondrial fission inhibitor (Mdivi-1) were used to investigate the specific molecular mechanisms involved. NMDAR2B, CGRP, ERK, and mitochondrial fission-related protein were evaluated by Western blotting, and the CGRP level in frozen sections of the TNC was detected via immunofluorescence staining. Results: After repeated inflammatory soup infusion and successful establishment of the CM rat model, SIRT1 expression was found to be significantly reduced, accompanied by elevated ROS levels. Treatment with Tempol, SRT1720, or Mdivi-1 alleviated allodynia and reduced the increase in NMDAR2B phosphorylation and CGRP and ERK phosphorylation in the CM rat. In contrast, EX527 had the opposite effect in CM rat. SRT1720 and EX527 decreased and increased ROS levels, respectively, in CM rats, and tempol reversed the aggravating effect of EX527 in CM rats. Furthermore, the regulatory effect of SIRT1 on ROS may include the involvement of the mitochondrial fission protein DRP1. Conclusion: The results indicate the importance of SIRT1 in CM may be due to its role in regulating the production of ROS, which are involved in modulating central sensitization in CM. These findings could lead to new ideas for CM treatment with the use of SIRT1 agonists and antioxidants.
BACKGROUND AND OBJECTIVES: Stroke and migraine are common neurological illnesses that cause tremendous suffering for patients. Certain diseases can mimic the clinical manifestations of an actual stroke. Migraine is one of the most commonly reported stroke mimics. The main goals of this study are to look at the prevalence of stroke mimics on the stroke pathway of Sheffield Teaching Hospitals and how many of them are migraines. MATERIALS AND METHODS: A retrospective service evaluation was conducted at the hyperacute stroke unit (HASU) of the Royal Hallamshire Hospital (RHH) in the United Kingdom. The total admissions from 2013 to 2022 were collected from the Sentinel Stroke National Audit Programme database, and the number of stroke mimics was evaluated each year. The burden of migraine stroke mimics was also evaluated. Then, a one-year sample of stroke mimics was extracted to look for the types of each mimic. RESULTS: From 2013 to 2022, 45.75% (n = 12156) of the stroke pathway patients (n = 26573) were stroke mimics, with an increment of up to 55% in the years 2021 and 2022. During these 10 years, migraine stroke mimics accounted for 10.21% of admissions (n = 1240). The three most common mimics in a one-year sample of stroke pathway patients were migraine (14.70%) (n = 373), functional neurological disorders (FNDs) (7.17%) (n = 182), and Guillain-Barré syndrome (6.66%) (n = 169). Seizures, syncope, and metabolic derangements were reported as mimics in 4.17% (n = 106), 3.14% (n = 80), and 1.77% (n = 45), respectively. CONCLUSIONS: About half of the HASU attendees were stroke mimics rather than actual strokes, and the most common mimics were migraines.
Background: Abnormalities in electrocortical parameters and persistence of afterimage after visual stimulation are known to occur in migraine patients. The results of studies on Contingent Negative Variation (CNV) and afterimage persistence in migraine patients suggest a link between these two phenomena and a connection to the pathomechanism of migraine. Objectives: To date, no studies have investigated both afterimage duration and CNV parameters in the same subjects. The aim of this study was to investigate the relationship between the early component of CNV (iCNV) and the duration of the afterimage in migraine patients. Methods: Sixty seven migraine patients from the headache center of the University of Rostock Medical Center were examined for iCNV amplitude, iCNV habituation and afterimage duration. The subjects also completed questionnaires developed for this study and the MIDAS (Migraine Disability Assessment) questionnaire. Results: Associations were found between iCNV amplitude and afterimage duration and between habituation capacity and afterimage duration. A deficit in habituation capacity correlated with a significantly prolonged afterimage duration. Increased iCNV amplitude and prolonged afterimage duration were also significantly correlated. Conclusion: Conclusions about the pathophysiology of migraine can be drawn from the results of this study. The results support the hypothesis of cortical hyperexcitability as a consequence of a low pre-activation level, which may be a possible contributory cause of migraine. Furthermore, they allow assessment of whether the afterimage examination, which is easier and quicker to perform than the CNV examination, can be used as a diagnostic tool or as a parameter to monitor the course of therapy in people with migraine.
BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. METHODS: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. RESULTS: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. CONCLUSION: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.
Antibodies, Monoclonal , Calcitonin Gene-Related Peptide , Migraine Disorders , Registries , Humans , Migraine Disorders/drug therapy , Migraine Disorders/immunology , Female , Male , Antibodies, Monoclonal/therapeutic use , Germany/epidemiology , Middle Aged , Adult , Calcitonin Gene-Related Peptide/immunology , Calcitonin Gene-Related Peptide Receptor Antagonists/therapeutic use , Calcitonin Gene-Related Peptide Receptor Antagonists/administration & dosage , Quality of Life , Drug Substitution/statistics & numerical data , Cost of Illness , Receptors, Calcitonin Gene-Related Peptide/immunology , Receptors, Calcitonin Gene-Related Peptide/metabolism
PURPOSE: Vestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients. METHODS: We searched literature measuring resting-state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size-signed differential mapping (AES-SDM) to conduct a whole-brain voxel-wise meta-analysis to identify the convergence of FC alterations in VM patients. RESULTS: Nine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta-regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test-6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri. CONCLUSIONS: The study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM.
Migraine Disorders , Humans , Migraine Disorders/physiopathology , Migraine Disorders/diagnostic imaging , Magnetic Resonance Imaging , Vestibular Diseases/physiopathology , Functional Status , Connectome/methods , Vertigo/physiopathology , Brain/physiopathology , Brain/diagnostic imaging
BACKGROUND: The cAMP and cGMP pathways are implicated in the initiation of migraine attacks, but their interactions remain unclear. Calcitonin gene-related peptide (CGRP) triggers migraine attacks via cAMP, whereas the phosphodiesterase-5 inhibitor sildenafil induces migraine attacks via cGMP. Our objective was to investigate whether sildenafil could induce migraine attacks in individuals with migraine pre-treated with the CGRP-receptor antibody erenumab. METHODS: In this randomized, double-blind, placebo-controlled, cross-over study, adults with migraine without aura received a single subcutaneous injection of 140â mg erenumab on day 1. They were then randomized to receive sildenafil 100â mg or placebo on two experimental days, each separated by at least one week, between days 8 and 21. The primary endpoint was the difference in the incidence of migraine attacks between sildenafil and placebo during the 12-h observation period after administration. RESULTS: In total, 16 participants completed the study. Ten participants (63%) experienced a migraine attack within 12â h after sildenafil administration compared to three (19%) after placebo (p = 0.016). The median headache intensity was higher after sildenafil than after placebo (area under the curve (AUC) for the 12-h observation period, p = 0.026). Furthermore, sildenafil induced a significant decrease in mean arterial blood pressure (AUC, p = 0.026) and a simultaneous increase in heart rate (AUC, p < 0.001) during the first hour after administration compared to placebo. CONCLUSION: These findings provide evidence that migraine induction via the cGMP pathway can occur even under CGRP receptor blockade. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier NCT05889455.
Cross-Over Studies , Cyclic GMP , Migraine Disorders , Receptors, Calcitonin Gene-Related Peptide , Sildenafil Citrate , Humans , Adult , Male , Double-Blind Method , Female , Sildenafil Citrate/pharmacology , Receptors, Calcitonin Gene-Related Peptide/metabolism , Migraine Disorders/metabolism , Migraine Disorders/chemically induced , Middle Aged , Cyclic GMP/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Calcitonin Gene-Related Peptide Receptor Antagonists , Phosphodiesterase 5 Inhibitors/pharmacology , Young Adult
The support has been provided by clinical trials and guidelines for managing patent foramen ovale (PFO) in adults; however, the optimal approach is still unclear for treating PFO in pediatric patients. PFO and its associated clinical syndromes, imaging diagnosis, and management in pediatric patients were analyzed by a comprehensive analysis. Extensive research was performed using electronic databases, including PubMed, Cochrane, Web of Science, and EMBASE. This review includes the studies published until February 1st, 2024. A total of 583 articles were obtained, of which 54 were included in the comprehensive review. Numerous evidences have indicated that a right-to-left shunt through a PFO may be involved in cryptogenic stroke in children, although the connection between migraine and aura has not been substantiated by robust evidence. Children with sickle cell disease and a PFO were at higher risks of paradoxical embolization, rare syndromes caused by PFO could also occur in children such as platypnea-orthodeoxia syndrome, myocardial infarction, and decompression sickness. Contrast transthoracic echocardiography was deemed the most appropriate examination for children due to its favorable transthoracic windows, eliminating the need for anesthesia. This review suggested that the additional treatment was not needed as no evidence was provided for potential future complications linked to isolated PFO in children. For children facing unique circumstances related to PFO, a customized interdisciplinary consultation is essential prior to considering medical interventions.
OBJECTIVES: The primary objective of this proposed guideline is to update the prior 2016 guideline on parenteral pharmacotherapies for the management of adults with a migraine attack in the emergency department (ED). METHODS: We will conduct an updated systematic review and meta-analysis using the 2016 guideline methodology to provide clinical recommendations. The same search strategy will be used for studies up to 2023, with a new search strategy added to capture studies of nerve blocks and sphenopalatine blocks. Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization International Clinical Trial Registry Platform will be searched. Our inclusion criteria consist of studies involving adults with a diagnosis of migraine, utilizing medications administered intravenously, intramuscularly, or subcutaneously in a randomized controlled trial design. Two authors will perform the selection of studies based on title and abstract, followed by a full-text review. A third author will intervene in cases of disagreements. Data will be recorded in a standardized worksheet and subjected to verification. The risk of bias will be assessed using the American Academy of Neurology tool. When applicable, a meta-analysis will be conducted. The efficacy of medications will be evaluated, categorizing them as "highly likely," "likely", or "possibly effective" or "ineffective." Subsequently, clinical recommendations will be developed, considering the risk associated with the medications, following the American Academy of Neurology recommendation development process. RESULTS: The goal of this updated guideline will be to provide guidance on which injectable medications, including interventional approaches (i.e., nerve blocks, sphenopalatine ganglion), should be considered effective acute treatment for adults with migraine who present to an ED. CONCLUSIONS: The methods outlined in this protocol will be used in the design of a future systematic review and meta-analysis-informed guideline, which will then be assessed by and submitted for endorsement by the American Headache Society.
