Migraine, a chronic neurological disorder, imposes a significant burden on individuals and healthcare systems globally. This systematic review and meta-analysis evaluated the efficacy and safety of atogepant in preventing episodic migraine (EM) in adults. A systematic search was conducted in four major databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) up to June 2024. The inclusion criteria targeted randomized controlled trials (RCTs) comparing atogepant to placebo or standard care in patients with EM. Statistical analyses were performed using Review Manager (RevMan) software. Four RCTs with 2,018 patients receiving atogepant and 761 patients receiving placebo or standard care were included. Atogepant significantly reduced monthly migraine days compared to placebo at 10 mg daily (mean difference [MD], –1.16 days; 95% confidence interval [95% CI], –1.60 to –0.73), 30 mg daily (MD, –1.15 days; 95% CI, –1.64 to –0.66), 60 mg daily (MD, –1.48 days; 95% CI: –2.36 to –0.61 days), 30 mg twice daily (MD, –1.30 days; 95% CI, –2.17 to –0.43), and 60 mg twice daily (MD, –1.20 days; 95% CI, –1.90 to –0.50). A ≥50% reduction in migraine days was frequently significantly achieved with atogepant across all dosages. Atogepant was generally well tolerated, though it was associated with higher incidence rates of constipation and nausea compared to placebo. Atogepant is an effective and well-tolerated option for preventing EM, offering patients a noninvasive oral alternative to injectable therapies. Further research is warranted to explore its long-term safety and efficacy in diverse patient populations and refine its role in this field.
Purpose: The aim of this clinical practice guideline (CPG) from the Korean Headache Society is to provide evidence-based recommendations on the pharmacologic treatment for migraine prevention in adult migraine patients.
Methods The present CPG was developed based on the guideline adaptation methodology through a comprehensive systematic search for literature published between January 2012 and July 2020. The overall quality of the CPGs was assessed using the Korean version of the Appraisal of Guidelines for Research and Evaluation II tool. High-quality CPGs were adapted to make key recommendations in terms of strength (strong or weak) and direction (for or against).
Results The authors selected nine available high-quality guidelines throughout the process of assessment of quality. Regarding oral migraine preventive medications, propranolol, metoprolol, flunarizine, sodium divalproex, and valproic acid are recommended to adult patients with episodic migraines based on high-quality evidence (“strong for”). Topiramate can be recommended for either episodic or chronic migraine (“strong for”). For migraine prevention using calcitonin gene-related peptide monoclonal antibodies, galcanezumab, fremanezumab, erenumab, and eptinezumab are recommended for adult patients with either episodic or chronic migraine on the basis of high-quality evidence (“strong for”). OnabotulinumtoxinA is recommended for adult patients with chronic migraine based on high-quality evidence (“strong for”). Last, frovatriptan, naratriptan, and zolmitriptan are recommended for short-term prevention in women with menstrual migraine (“strong for”).
Conclusion In the present CPG, the authors provide specific, straightforward, and easy-to-implement evidence-based recommendations for pharmacologic migraine prevention. Nevertheless, these recommendations should be applied in real-world clinical practice based on optimal individualization.
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Purpose: Cognitive decline is a common complaint in young patients with migraine, especially those with depression. Independent of psychiatric factors such as depression, subjective cognitive decline (SCD) is associated with an elevated risk of progression to dementia. This study aimed to investigate patterns of subjective cognitive complaints between migraineurs with or without depression and non-depressed older adults.
Methods This retrospective study included 331 outpatients with SCD (293 from a headache clinic and 38 from a memory clinic). SCD was diagnosed as “yes” based on two questions about SCD. The Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. The SCD Questionnaire (SCD-Q) with three subdomains was analyzed to compare SCD between groups.
Results Among patients with SCD, significant differences in duration of education were found among the groups—specifically, migraineurs with depression (12.39 years) had longer education than non-depressed older adults (10.50 years) and shorter education than migraineurs without depression (14.28 years). The total MMSE and MoCA scores did not differ between migraineurs with and without depression. Regarding SCD-Q scores, migraineurs with depression showed higher scores overall and in all cognitive domains than migraineurs without depression, with no significant difference compared to non-depressed older adults.
Conclusion Although the depressed migraineurs with SCD were younger and more educated than the non-depressed older adults with SCD, both groups reported similarly high levels of SCD. Higher levels of surveillance for cognitive decline are warranted for migraineurs with depression who have SCD.
Purpose: OnabotulinumtoxinA is widely used to treat chronic migraines; however, the wear-off phenomenon before the next scheduled dose has emerged as a challenge. This study suggests a new strategy for preventing the wear-off phenomenon using bilateral greater occipital nerve block.
Methods We conducted a retrospective review of patients diagnosed with chronic migraine who were treated with onabotulinumtoxinA and bilateral greater occipital nerve block at St. Vincent Hospital from January 2023 to December 2023. Twelve chronic migraine patients with a history of the wear-off phenomenon received a greater occipital nerve block 8 weeks after the initial onabotulinumtoxinA injection for two sessions. Responses to treatment were evaluated with regular follow-ups and daily headache diaries.
Results All patients who had previously experienced the wear-off phenomenon with conventional onabotulinumtoxinA treatment did not experience the wear-off phenomenon during two sessions with an additional greater occipital nerve block administered 8 weeks after each onabolulinumtoxinA injection.
Conclusion Bilateral greater occipital nerve block administered 8 weeks after the initial onabotulinumtoxinA injection effectively prevents the wear-off phenomenon, enabling sustained therapeutic benefits in chronic migraine patients. Further research is needed to confirm these findings in larger cohorts.
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The glymphatic system is a brain-wide perivascular pathway that functions similarly to the lymphatic system in the periphery of the body, playing a crucial role in removing waste from the brain. Although impaired glymphatic function has a well-known relationship with neurodegenerative diseases through abnormal protein accumulation, it is also associated with migraine. While still in its nascent phase, research on the glymphatic system in migraine patients is gradually increasing. This systematic literature review focuses on studies investigating the glymphatic system in migraineurs. Furthermore, it examines the methods used to evaluate the glymphatic system in these studies and their main findings.
Since botulinum toxin (BoNT) was approved by the US Food and Drug Administration as a prophylactic treatment for chronic migraines in 2010, subsequent studies have shown that BoNT is effective in the management of chronic migraines due to its pain-relieving effects. Therefore, neurologists are increasingly utilizing BoNT as a therapeutic tool for chronic migraine. It is crucial to thoroughly understand the functional anatomy in the head, face, and neck regions to successfully administer BoNT injections in these areas. This review describes the complexity of muscles and their associated target nerves in the frontal, temporal, and occipital areas and serves as a resource for essential functional anatomy, with the goal of providing clinicians with a practical perspective on utilizing BoNT injections.
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The term “menstrual migraine” is commonly used to describe migraines that occur in association with menstruation, as distinct from other migraine types. A significant proportion of women of reproductive age experience migraine attacks related to their menstrual cycle. Menstrual migraine is characterized by migraine attacks occurring on day 1±2 (i.e., days −2 to +3) of menstruation in at least two out of three menstrual cycles. Although the reported prevalence of menstrual migraine varies considerably, population-based studies have found that menstrual migraine affects up to 60% of women with migraines. Several hypotheses have been proposed to explain the etiology of menstrual migraine, among which the estrogen withdrawal hypothesis is the most widely accepted. Women who experience menstrual migraines often face considerable disability due to perimenstrual attacks. Studies have reported that perimenstrual attacks are more severe and more difficult to manage. The principles of acute managing perimenstrual attacks are the same as those for managing nonmenstrual attacks. Short-term preventive therapy is needed to prevent menstrual migraines before they occur during the perimenstrual period. This review summarizes the prevalence, distinct clinical features, pathophysiological mechanisms, and management of menstrual migraine.
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Migraine is a representative type of primary headache and a common chronic neurological disease that accounts for a large proportion of headaches in children, adolescents, and adults. Unlike migraine in adulthood, pediatric migraine occurs when brain development is not yet complete. This characteristic may require a new perspective for the treatment and management of pediatric migraine. Dietary therapies, mainly the ketogenic diet and its variants, can have positive effects on pediatric migraine. Several recent studies have revealed that dietary therapies, such as the classic ketogenic diet, modified Atkins diet, and low glycemic index diet, improve various neurological diseases by improving dysbiosis of microbiota, reducing proinflammatory cytokines, and increasing mitochondrial function. Nonetheless, the mechanism through which active dietary therapy affects pediatric migraine requires further research. To achieve this, an important role is played by the neuro-nutritional team, which can develop and manage tolerable diets for pediatric migraine patients through mutual collaboration among pediatric neurologists, nurses, and nutritionists.
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Migraine, a prevalent neurological disorder, is more common in women than in men. This sex difference is more pronounced after menarche and diminishes after menopause. Migraines in women are influenced by the menstrual cycle, pregnancy, and lactation, suggesting a connection to sex hormones, known as the estrogen withdrawal theory. Beyond endogenous hormonal changes accompanying reproductive events, exogenous hormonal factors such as contraceptives or hormone replacement therapy may also affect migraines. The hormonal influence cannot be explained simply by serum estrogen levels; instead, it involves a complex interplay of various factors. Here, we delineate aspects of migraines associated with endogenous and exogenous hormonal changes over the course of a woman’s life, exploring the mechanisms and contributing factors through which sex hormones influence migraines.
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Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019 (COVID-19), which caused a global pandemic and then became an endemic condition. COVID-19 infection may be associated with clinical manifestations such as respiratory symptoms and systemic diseases, including neurological disorders, notably headaches. Headaches are a common neurological symptom in individuals infected with COVID-19. Furthermore, with the transition to endemicity, COVID-19 infection-related headaches may reportedly persist in the acute phase of COVID-19 infection and in the long term after COVID-19 infection resolves. Persistent headaches after COVID-19 infection can be a significant concern for patients, potentially leading to disability. The present review discusses the clinical characteristics and potential underlying mechanisms of COVID-19 infection-related headaches.
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Purpose: It remains unclear whether primary headaches, particularly migraine, are associated with glaucoma. We investigated potential associations between primary headaches, including migraine and tension-type headache (TTH), and primary glaucoma, including open-angle glaucoma (OAG) and closed-angle glaucoma (CAG).
Methods We used data from the Clinical Data Warehouse collected between 2008 and 2023 to investigate whether migraine and TTH influence the risk of primary glaucoma. We compared the prevalence of primary glaucoma, including OAG, CAG, other glaucoma, and total glaucoma (TG), among patients with migraine, those with TTH, and controls.
Results This study analyzed 46,904 patients with migraine, 48,116 patients with TTH, and 455,172 controls. Controls were selected based on propensity score matching (PSM). After adjustment for covariates and PSM, the fully adjusted odds ratios (ORs) for patients with migraine were 1.83 for OAG (95% confidence interval [95% CI], 1.33–2.51; p<0.004) and 1.55 for TG (95% CI, 1.26–1.91; p<0.004) compared to controls. Furthermore, in patients with TTH, the ORs for CAG were 2.20 (95% CI, 1.40–3.47; p<0.004) compared to controls. Additionally, patients with migraine had fully adjusted ORs of 1.71 for OAG (95% CI, 1.24–2.36; p<0.004) and 1.41 for TG (95% CI, 1.15–1.73; p<0.004) compared to those with TTH.
Conclusion Migraine is associated with primary glaucoma, particularly OAG.
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Acute migraine treatments primarily aim to relieve headache pain and address accompanying symptoms such as photophobia, phonophobia, and nausea. Triptans have traditionally been the first-line treatment for moderate to severe migraine attacks. Nevertheless, they have several limitations, such as causing temporary vasoconstriction of blood vessels, contraindications in patients with cardiovascular issues, and distinctive side effects like chest tightness. Medication overuse is another concern with triptans, prompting research into new antimigraine drugs targeting calcitonin gene-related peptide (CGRP) or 5-HT1F receptors. Lasmiditan, an agonist at the 5-HT1F receptor, has emerged as a safe and effective option for abortive treatment in acute migraine attacks. It lacks the vasoconstrictive effects associated with triptans, making it a safer choice for individuals with contraindications to triptans. However, it may lead to central nervous system-related adverse effects, particularly dizziness and paresthesia. Gepants, which are CGRP antagonists, offer an innovative approach by targeting CGRP receptors which is believed to be central in migraine pathophysiology. These medications have demonstrated efficacy in alleviating migraine symptoms, providing alternatives to traditional treatments like triptans and ergots. Ubrogepant and rimegepant are the first approved oral gepants for acute migraine treatment, while Zavegepant is the first approved intranasal gepant. The most common treatment-related adverse events are gastrointestinal symptoms, including nausea. No vascular or hepatic concerns have emerged to date. In this review, we delve into the development of ditans and gepants for acute migraine treatment in adults and discuss their potential advantages and disadvantages in clinical use.
The relationship between migraine and stroke is intricate and bidirectional. Migraine, a neurological disorder characterized by severe headaches and associated symptoms, exhibits some similarities in presentation with stroke. Conversely, stroke can at times mimic migraine symptoms. Migrainous infarction is directly associated with stroke. Specifically, migraine with aura has been linked to an increased risk of ischemic stroke. Migraine with aura and the frequency of headaches are considered risk factors for stroke. Moreover, migraine is associated with subclinical infarct-like brain lesions and white matter changes. Additionally, some genetic disorders predispose individuals to develop both migraine and stroke. In this review, we aim to investigate the relationship between migraine and stroke.
Headache disorders and sleep problems are common conditions with a high prevalence in the general population, and impose a considerable socio-economic burden. They show a close association with headache disorders through various relationship. The prevalence of sleep problems is elevated in individuals with headache, especially for migraine. In most headache disorders, sleep problems are accompanied by the deterioration of clinical characteristics
of headache disorders. The sharing brain structures and neurotransmitters involved in the pathogenesis of headache disorders and sleep disorders may be an explanation for the close relationship between two disorders. In this article, we briefly review the relationship of headache disorders with sleep disorders including insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders,
parasomnias, and sleep related movement disorders.
Calcitonin gene-related peptide (CGRP) is probably the most potent vasodilator in cerebral circulation. The new CGRP-targeted therapy for the treatment of acute treatment are now available for clinical practice. This review article summarized efficacy and safety of zavegepant, which is the first intranasal small molecule CGRP receptor antagonist for acute migraine treatment.