Headache and Pain Research

Review Articles

Morning Headaches: An In-depth Review of Causes, Associated Disorders, and Management Strategies: Yooha Hong, Mi-Kyoung Kang, Min Seung Kim, Heejung Mo, Rebecca C. Cox, Hee-Jin Im; Received August 4, 2024 Accepted September 30, 2024 Published online January 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0023 [Epub ahead of print]

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Abstract PDF: Morning headaches, which are defined by occurrence upon or shortly after waking up in the morning, range from mild discomfort to severe pain and significantly impact an individual’s quality of life. Although morning headaches are a prevalent and potentially debilitating condition, the criteria for defining these headaches vary. The lack of universally accepted diagnostic criteria complicates understanding their etiology, associated factors, and potential interventions. The causes of morning headaches are multifaceted, including primary headache disorders like migraines and cluster headaches, and secondary causes such as sleep disorders, hypertension, abnormal intracranial pressure, and brain parenchymal diseases. Psychological factors, including anxiety and depression, as well as substance use, further complicate the clinical presentation, often requiring a multidisciplinary approach for effective diagnosis and treatment. This review provides a comprehensive overview of morning headaches, examining their various aspects and possible treatment options, with the goal of enhancing clinicians’ understanding and management of this common yet often overlooked condition.

Update on Tension-type Headache: Hye Jeong Lee, Soo-Jin Cho, Jong-Geun Seo, Henrik Winther Schytz; Received September 7, 2024 Accepted October 4, 2024 Published online December 30, 2024; DOI: https://doi.org/10.62087/hpr.2024.0025 [Epub ahead of print]

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Abstract PDF: 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.

Advances in Primary Stabbing Headache: Diagnostic Criteria, Epidemiological Insights, and Tailored Treatment Approaches: Ayush Chandra, Avinash Chandra, Soohyun Cho; Received June 8, 2024 Accepted July 3, 2024 Published online September 2, 2024; DOI: https://doi.org/10.62087/hpr.2024.0018 [Epub ahead of print]

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Abstract PDF: 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.

Case Report

Primary Headache Associated with Sexual Activity Presenting with Persistent Genital Arousal Disorder: A Case Report: Woo-Seok Ha, Hye-Kyung Baek; Headache Pain Res. 2024;25(2):117-121. Published online September 2, 2024; DOI: https://doi.org/10.62087/hpr.2024.0012

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Abstract PDF: 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.

Original Article

Side Shift of Attacks in Cluster Headache: A Prospective Single-center Study: Michelle Sojung Youn, Jun Pyo Kim, Mi Ji Lee; Headache Pain Res. 2024;25(2):96-102. Published online August 28, 2024; DOI: https://doi.org/10.62087/hpr.2024.0013

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Abstract PDF: Purpose: Although strict unilaterality is a characteristic of cluster headache (CH), side shift of attacks has been reported. We aimed to assess the prevalence and patterns of side shifts, as well as their correlations with clinical characteristics and treatment response in CH patients.
Methods
We prospectively recruited and followed up CH patients at a university hospital. Patients with two or more lifetime CH bouts were interviewed about their side shift history using a structured questionnaire. The demographics and disease characteristics were collected at baseline, and the treatment response at 2- to 4-week follow-up examinations was compared between patients with versus without side shifts.
Results
Out of 124 CH patients, 26 (21.0%) experienced side shifts. Sixteen (61.5%) experienced shifts between bouts, 13 (50.0%) within a bout, and four (15.4%) within an attack, with none (0%) reporting bilateral pain during an attack. Among patients who experienced shifts between bouts, six (37.5%) reported a single shift during the entire disease course, while 10 (62.5%) reported multiple shifts between bouts. The demographics, characteristics, and treatment response did not significantly differ according to the history of side shift.
Conclusion
In our study, the prevalence and pattern of side shifts were comparable to the results from earlier studies. The presence of side shifts did not show significant association with a specific clinical profile and their incidence did not impact the treatment response. These findings suggest that side-shifting CH is not a distinct entity or migraine variant, but rather within the spectrum of CH.

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.

Citations

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Exercise as an abortive treatment for cluster headaches: Insights from a large patient registry
Mi‐Kyoung Kang, Yooha Hong, Soo‐Jin Cho
Annals of Clinical and Translational Neurology.2025; 12(1): 149. CrossRef
Side Shift of Attacks in Cluster Headache: A Prospective Single-center Study
Michelle Sojung Youn, Jun Pyo Kim, Mi Ji Lee
Headache and Pain Research.2024; 25(2): 96. CrossRef
Reduction of neck pain severity in patients with medication-overuse headache
Yooha Hong, Hong-Kyun Park, Mi-Kyoung Kang, Sun-Young Oh, Jin-Ju Kang, Heui-Soo Moon, Tae-Jin Song, Mi Ji Lee, Min Kyung Chu, Soo-Jin Cho
The Journal of Headache and Pain.2024;[Epub] 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.

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Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea
Kyung-Hee Cho, Seol-Hee Baek, Sung-Hee Kim, Byung-Su Kim, Jong-Hee Sohn, Min Kyung Chu, Mi-Kyoung Kang, Hee Jung Mo, Sang-Hwa Lee, Hong-Kyun Park, Soohyun Cho, Sun-Young Oh, Jong-Geun Seo, Wonwoo Lee, Ju-Young Lee, Mi Ji Lee, Soo-Jin Cho
The Journal of Headache and Pain.2024;[Epub] CrossRef
Nutritional Approaches to Managing Pediatric Migraine
Hye Eun Kwon
Headache and Pain Research.2024; 25(2): 75. CrossRef
Reduction of neck pain severity in patients with medication-overuse headache
Yooha Hong, Hong-Kyun Park, Mi-Kyoung Kang, Sun-Young Oh, Jin-Ju Kang, Heui-Soo Moon, Tae-Jin Song, Mi Ji Lee, Min Kyung Chu, Soo-Jin Cho
The Journal of Headache and Pain.2024;[Epub] CrossRef

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 Article

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.

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Unclosing Clinical Criteria and the Role of Cytokines in the Pathogenesis of Persistent Post-COVID-19 Headaches: A Pilot Case-Control Study from Egypt
Ahmed Abualhasan, Shereen Fathi, Hala Gabr, Abeer Mahmoud, Diana Khedr
Clinical and Translational Neuroscience.2025; 9(1): 5. CrossRef

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.

Citations

Citations to this article as recorded by

Subjective Cognitive Decline Patterns in Patients with Migraine, with or without Depression, versus Non-depressed Older Adults
Sun Hwa Lee, Soo-Jin Cho
Headache and Pain Research.2024; 25(2): 103. CrossRef

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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