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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Cluster headaches affect 0.1% of the population and are four times more common in males than in females. Patients with this condition present with severe unilateral head pain localized in the frontotemporal lobe, accompanied by ipsilateral lacrimation, conjunctival injection, nasal congestion, diaphoresis, miosis, and eyelid edema. Recently, the first genome-wide association study of cluster headaches was conducted with the goal of aggregating data for meta-analyses, identifying genetic risk variants, and gaining biological insights. Although little is known about the pathophysiology of cluster headaches, the trigeminovascular and trigeminal autonomic reflexes and hypothalamic pathways are involved. Among anti-calcitonin gene-related peptide monoclonal antibodies, galcanezumab has been reported to be effective in preventing episodic cluster headaches.
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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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Understanding the Connection between the Glymphatic System and Migraine: A Systematic Review Myoung-Jin Cha, Kyung Wook Kang, Jung-won Shin, Hosung Kim, Jiyoung Kim Headache and Pain Research.2024; 25(2): 86. CrossRef
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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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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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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Primary stabbing headache (PSH), characterized by sudden, localized stabbing headache pain, is a recognized primary headache disorder with evolving diagnostic criteria. Epidemiological studies show a wide range of prevalence, influenced by various factors. PSH is more common in females, frequently occurring in conjunction with migraine, and can manifest in children. Recent diagnostic criteria have changed the definition of sharp stabbing pain, which is no longer restricted to the first division of the trigeminal nerve. In addition, the criterion of “no accompanying symptoms” has been refined to “no cranial autonomic symptoms” specifically. These changes have increased the sensitivity for capturing PSH. Although it is generally considered benign, stabbing headache can be associated with secondary causes. Clinical red flag signs can be helpful in distinguishing secondary headaches from PSH. A recent prospective study has proposed the monophasic, intermittent, and chronic patterns as subtypes, and this division may be helpful for predicting the prognosis. Pharmacological treatment is typically not required for PSH, although indomethacin and other alternating agents can be used. The treatment should be selected based on individual clinical features and comorbidities. This review aims to highlight the necessity of recognizing the distinctive clinical profile of PSH and of tailoring treatment approaches to patients’ individual needs.
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Purpose: Cluster headache (CH) is characterized by circadian rhythmicity of the attacks, and it is known to respond exceptionally well to oxygen therapy. Furthermore, obstructive sleep apnea (OSA) frequently co-occurs with CH, and both conditions may be parallel outcomes of hypothalamic dysfunction rather than being causally related. The aim of this study was to analyze the association between CH characteristics and polysomnographic factors stratified by the severity of OSA in patients diagnosed with CH and OSA.
Methods We retrospectively analyzed the data of OSA patients with CH who were enrolled in the Korean Cluster Headache Registry and underwent polysomnography due to clinical suspicion of OSA. Basic demographic data, headache-related parameters, and polysomnographic parameters were analyzed according to the severity of OSA (apnea-hypopnea index: <15 or ≥15 per hour).
Results Twelve CH patients with OSA were evaluated. The onset age of CH was higher (38.5 years vs. 19.0 years, p=0.010), and the maximal duration of cluster bouts was longer (156.5 days vs. 47.0 days, p=0.037) in the moderate-to-severe OSA group than in the mild OSA group. Unlike other polysomnographic parameters, the apnea-hypopnea index and respiratory arousal index during rapid eye movement (REM) sleep were comparable across different OSA severity levels.
Conclusion The onset age and duration of cluster bouts were associated with the severity of OSA in CH patients. Additionally, the relatively high susceptibility to hypoxia during REM sleep in patients with mild OSA implies that interventions may be potentially advantageous, even in CH patients with mild OSA.
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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.
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Tension-Type Headache and Primary Stabbing Headache: Primary Headaches Beyond Migraine Mi-Kyoung Kang Headache and Pain Research.2025; 26(2): 89. CrossRef
Tension-type headache (TTH) is the most common type of headache, characterized by mild to moderate intensity, bilateral, with a pressing or tightening (non-pulsating) quality. Migraine and TTH can occur in the same person, and their risk factors and treatments can overlap. However, TTH receives less attention than migraine. Furthermore, despite the expanding market for migraine treatments targeting calcitonin gene-related peptide (CGRP) mechanisms, the lack of evidence regarding mechanisms related to CGRP-related mechanisms in TTH continues to be neglected. There remains a need to develop effective preventive treatments for chronic TTH, which imposes a very high burden of disease. From this perspective, this review aims to provide the latest evidence on TTH.
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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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Persistent genital arousal disorder (PGAD) is characterized by unwanted and distressing genital sensations that are not associated with concomitant sexual interest or thoughts. Several etiologies have been proposed, but the underlying mechanism of the condition remains unclear. In this report, we describe a case of PGAD presenting with primary headache associated with sexual activity (PHASA). A 57-year-old female with no history of headache experienced recurrent, unwanted episodes of genital arousal lasting 3 to 5 days for 4 years. One day, she began to experience intense genital arousal that she had never experienced before. On the fourth day of arousal, while attempting intercourse with her partner, she experienced an abrupt explosive headache, which was repeated during another session of intercourse a week later. The patient underwent laboratory tests, as well as brain magnetic resonance imaging (MRI) and magnetic resonance angiography, all of which showed normal findings. She was referred to a sexual medicine specialist and prescribed amitriptyline, escitalopram, and propranolol with a diagnosis of PGAD. Her sexual arousal gradually diminished, and when she stopped all medications 3 months later, all symptoms had disappeared. On further investigation, spinal MRI revealed a Tarlov cyst. She has been in remission for three years. This case illustrates the co-occurrence of PHASA and PGAD and suggests a possible common pathophysiology shared between these two rare disorders.
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