Headache and Pain Research

Editorial

Migraine in Women: Inescapable Femaleness?: Soo-Kyoung Kim; Headache Pain Res. 2024;25(1):1-2. Published online April 24, 2024; DOI: https://doi.org/10.62087/hpr.2024.0010

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Review Articles

Update on Cluster Headaches: From Genetic to Novel Therapeutic Approaches: Myun Kim, Je Kook Yu, Yoo Hwan Kim; Headache Pain Res. 2024;25(1):42-53. Published online April 22, 2024; DOI: https://doi.org/10.62087/hpr.2024.0009

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Abstract PDF: 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.

Menstrual Migraine: A Review of Current Research and Clinical Challenges: Jong-Geun Seo; Headache Pain Res. 2024;25(1):16-23. Published online April 22, 2024; DOI: https://doi.org/10.62087/hpr.2024.0004

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Abstract PDF

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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Citations to this article as recorded by

Migraine in Women: Inescapable Femaleness?
Soo-Kyoung Kim
Headache and Pain Research.2024; 25(1): 1. CrossRef

Application and Effectiveness of Dietary Therapies for Pediatric Migraine: Ji-Hoon Na; Headache Pain Res. 2024;25(1):34-41. Published online April 17, 2024; DOI: https://doi.org/10.62087/hpr.2024.0007

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Abstract PDF: 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.

Original Article

Cluster Headache Characteristics and the Severity of Obstructive Sleep Apnea: Insights from Polysomnography Analysis: Yooha Hong, Mi-Kyoung Kang, Min Kyung Chu, Soo-Jin Cho, Hee-Jin Im; Headache Pain Res. 2024;25(1):63-71. Published online April 16, 2024; DOI: https://doi.org/10.62087/hpr.2024.0001

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Abstract PDF: 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.

Review Articles

Migraines in Women: A Focus on Reproductive Events and Hormonal Milestones: Seonghoon Kim, Jeong Wook Park; Headache Pain Res. 2024;25(1):3-15. Published online April 5, 2024; DOI: https://doi.org/10.62087/hpr.2024.0003

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Abstract PDF

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.

Citations

Citations to this article as recorded by

Migraine in Women: Inescapable Femaleness?
Soo-Kyoung Kim
Headache and Pain Research.2024; 25(1): 1. CrossRef

COVID-19 Infection-related Headache: A Narrative Review: Yoonkyung Chang, Tae-Jin Song; Headache Pain Res. 2024;25(1):24-33. Published online April 2, 2024; DOI: https://doi.org/10.62087/hpr.2024.0008

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Abstract PDF: 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.

Original Article

Associations of Migraine and Tension-type Headache with Glaucoma: Jong-Ho Kim, Young-Suk Kwon, Sang-Hwa Lee, Jong-Hee Sohn; Headache Pain Res. 2024;25(1):54-62. Published online March 29, 2024; DOI: https://doi.org/10.62087/hpr.2024.0002

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Abstract PDF: 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.

Neuroimage

Invasive Aspergillosis Manifesting as Painful Ophthalmoplegia: Sorae Lee, Sumin Kim, Sanggyu Han, So-Ei Ann, Pil-Wook Chung, Bum Chun Suh, Jun-Sang Sunwoo; Korean J Headache. 2023;24(2):84-86. Published online December 31, 2023

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Review Article

New Targeted Drugs for Acute Treatment of Migraine: Heui-Soo Moon, Pil-Wook Chung, Byung-Kun Kim; Korean J Headache. 2023;24(2):56-65. Published online December 31, 2023

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Abstract PDF: 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-HT_1F receptors. Lasmiditan, an agonist at the 5-HT_1F 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.

Case Report

Unilateral Retro-orbital Headache Secondary to Septic Cavernous Sinus Thrombosis: A Case Report: Sumin Kim, Sorae Lee, Jun-Sang Sunwoo; Korean J Headache. 2023;24(2):80-83. Published online December 31, 2023

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Abstract PDF: Septic cavernous sinus thrombosis (SCST) is a rare but fatal central nervous system infectious disease affecting the cavernous sinuses. Here, we report a case of 51-year-old woman presenting with new-onset unilateral retro-orbital headache lasting for 3 weeks and subsequent ipsilateral abducens nerve palsy. Brain magnetic resonance imaging revealed enlargement of the cavernous sinus with dural enhancement and ring-enhancing abscess in the adjacent temporal lobe. Although blood and cerebrospinal fluid cultures were negative, the patient was successfully treated with empirical antibiotic therapy. Although SCST is a possible cause of painful ophthalmoplegia, it should be kept in mind that in the early stage it may present only with headache without ocular symptoms.

Review Article

Treatment Strategies of Medication Overuse Headache: Mi-Kyoung Kang, Jong-Hee Sohn; Korean J Headache. 2023;24(2):33-38. Published online December 31, 2023

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Abstract PDF: Medication overuse headache (MOH) is a common secondary headache disorder in which chronic headaches develop or worsen due to frequent and excessive intake of medications used for acute headache treatment. While the concept of MOH is widely recognized among headache specialists, ongoing debates exist regarding its causes, diagnostic criteria, and treatment strategies. Treating MOH has traditionally been challenging, and there is currently no universal consensus on how to effectively manage patients with MOH. Furthermore, a specific treatment approach based on well-powered randomized trials is still lacking. The treatment strategy for MOH typically involves several steps: patient education and counseling, withdrawal of overused medications, preventive drug therapy, and non-pharmacological prevention. It is recommended that all patients discontinue the overused medication, which can be carried out on an outpatient or inpatient basis. Additionally, topiramate, Botox, and anti-calcitonin gene-related peptide monoclonal antibodies have shown potential in reducing headache and migraine frequency, as well as acute drug consumption, even without active drug withdrawal. However, many aspects of MOH management require further investigation through properly designed and adequately powered randomized controlled trials.

Original Articles

Secular Trend of Sex Ratio in Participants under Randomized Controlled Trials for Cluster Headache: Pil-Wook Chung, Heui-Soo Moon; Korean J Headache. 2023;24(2):70-76. Published online December 31, 2023

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Abstract PDF: Background
Although cluster headache (CH) is well known as a disorder of predominantly young males, the male to female ratio decreased from 5-7:1 before 1980s to -2:1 in the 2000s and afterward in Western observational studies. It is unclear whether this represents a true rise of CH in women or better recognition of CH in women. We sought to assess whether the sex ratio of CH were changing or not in randomized controlled trials (RCTs) over time in accordance with observational studies.
Methods
We included RCTs regarding pharmacologic medication, as well as procedural and surgical treatment, devices. Time trend of sex ratio was compared among 3 different publication era (1985-2000 vs 2001-2010 vs 2011-). Sex ratio between different cluster headache type (Episodic vs Chronic) was also compared.
Results
22 acute treatment trials and 25 preventive treatment trials were initially selected for inclusion. 5 acute treatment trials and 10 preventive treatment trials were excluded due to small sample size (n<20) and/or no demographic information. All studies were underwent in western countries. Of 32 trials finally included, 10 studies were published between 1985 to 2000 (1^st era), 8 studies from 2001 to 2010 (2^nd era), 14 studies after 2010 (3^rd era). Of the 2,476 patients, 80% were male. Secular tendency of decreasing male predominance was shown over time. 542 of 623 patients (87%) were male in 1^st era, while 83% were male in 2^nd era, and 75.3% were male in 3^rd era (p<0.001). Male to female ratio was 6.7:1 in 1^st era, 4.9:1 in 2^nd era, and 3:1 in 3^rd era. In chronic CH, 28% of subjects were female, while in episodic CH, 14.6% were female (p<0.001)
Conclusions
As suggested by observational and registry data, the population enrolled in the RCT also exhibited a decreasing trend in male predominance over time in CH.

A Survey on Headache Education Curriculum in College of Dentistry: Jin Kyu Kang, Ji-Won Ryu, Seong-Taek Kim; Korean J Headache. 2023;24(2):66-69. Published online December 31, 2023

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Abstract PDF: Background
Headache is a common pain condition encountered in clinical practice. Many patients visit a doctor or dentist complaining of headaches accompanied by toothaches or facial pain. However, it has been reported that education on headaches is insufficient in medical schools, which is believed to be a more serious problem in dental schools.
Methods
We surveyed the current status of headache education curriculum in 11 dental schools in Korea.
Results
In most dental schools, headache education was provided as part of orofacial pain course within the oral medicine program. Only two universities covered headache as an in-depth postgraduate course. Lectures were delivered by oral medicine faculty, and only one university included a neurologist as part of the team teaching. Dental textbooks still described headaches based on the 2^nd edition of the International Classification of Headache Disorders.
Conclusion
Currently, headache education in dental schools in Korea is inadequate and outdated. Considering the specificity of dentists who are in charge of pain in oral and facial region, continuous discussions and mutual cooperation with the neurology department are necessary to ensure sufficient education related to headaches during the undergraduate course.

Review Article

Diagnosis and Treatment of Hemicrania Continua, Paroxysmal Hemicrania, Short-lasting Unilateral Neuralgiform Headache Attacks: Sang-Hwa Lee, Mi-Kyoung Kang, Soo-Jin Cho; Korean J Headache. 2023;24(2):39-44. Published online December 31, 2023

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Abstract PDF: Chronic paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua are rare headache disorders characterized by severe unilateral headache accompanied by ipsilateral autonomic symptoms. Accurate diagnosis and specific treatment approaches for these conditions are crucial for appropriate management. This article covers the clinical features, diagnostic criteria, and treatment strategies of each disorder, aiming to differentiate them from other major headaches and provide targeted treatment strategies to improve patient outcomes.

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