Efficacy and Safety of Galcanezumab as a Preventive Treatment for Episodic Migraine in South Korean Patients: A Post-Hoc Analysis of a Phase 3 Clinical Trial

Background@#and Purpose The estimated prevalence of migraines in South Korea is 6.0%, with affected patients having unmet needs. The efficacy, safety, and tolerability of galcanezumab, a humanized monoclonal antibody, for episodic migraine (EM) prevention was evaluated in South Korean patients. @*Methods@#During the double-blind period of the EVOLVE-2 phase 3 trial, patients with EM were randomized into placebo, 120 mg-galcanezumab, and 240-mg galcanezumab treatment groups. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days during the 6-month double-blind period. We conducted a post-hoc analysis of the South Korean cohort in EVOLVE-2. @*Results@#Among 98 South Korean patients in the intent-to-treat population, significant changes from baseline were observed in the number of monthly migraine headache days in the 240-mg galcanezumab group compared with the placebo group (-2.64, p=0.013), in the percentage of patients with ≥50% reduction in the number of monthly migraine headache days (120 mg: odds ratio=2.43, p=0.030; 240 mg: odds ratio=2.60, p=0.019), in the number of monthly migraine headache days with acute medication use (120 mg: -2.22, p=0.006; 240 mg: -2.23, p=0.005), and in the Migraine-Specific Quality-of-Life Role Function-Restrictive (120 mg: 8.34, p=0.040). Numerical improvements from baseline were observed relative to the placebo group in at least one galcanezumab group for: the percentage of patients with ≥75% reduction in the number of monthly migraine headache days functional impairment, and disease severity. The most common treatment-emergent adverse event in the combined galcanezumab group was injection site reaction, which led to treatment discontinuation for one patient. @*Conclusions@#Galcanezumab treatment demonstrated efficacy and a favorable safety and tolerability profile in South Korean patients with EM.

Suicidality and Its Risk Factor in Migraine Patients

Background@#Migraine patients have a higher frequency of suicidality than people without migraine. The aim of this study was to identify suicidality and its risk factors in migraine patients. @*Methods@#We enrolled 358 migraine patients from 11 hospitals. We collected data regarding their clinical characteristics and the patients completes the questionnaires. We also interviewed patients with the Mini International Neuropsychiatric Interview (MINI)plus version 5.0.0 to identify their suicidality. The International Classification of Headache Disorders, third edition, beta version was used in headache diagnosis. @*Results@#The frequency of suicidality in migraine patients was 118 (33.0%). Migraine patients with suicidality were more likely to have a major depressive disorder or generalized anxiety disorder than those without suicidality. Among variables, risk factors for suicidality in migraine patients were female (odds ratio [OR], 4.110; 95% confidence interval [CI], 1.55310.878; p=0.004), attack duration (OR, 2.559; 95% CI, 1.2105.413; p=0.011), Patient Health Questionnaire9 (OR, 1.111; 95% CI, 1.0381.189; p=0.002), and Generalized Anxiety Disorder7 (OR, 1.194; 95% CI, 1.1011.294; p<0.001). @*Conclusions@#Suicidality in migraine patients is common. Therefore, clinicians who take care of migraine patients should be concerned about suicidality and its risk factors such as female gender, attack duration, depression or anxiety.

Smoking History and Clinical Features of Cluster Headache:Results from the Korean Cluster Headache Registry

Background@#and Purpose Epidemiologic data suggest that cluster headache (CH) is significantly associated with cigarette smoking. The aim of this study was to determine differences in features between patients with a smoking history and those who are never-smokers, using data from a prospective multicenter registry. @*Methods@#Data used in this study were obtained from the Korean Cluster Headache Registry that collected data from consecutive patients diagnosed with CH. We compared clinical and demographic features between ever-smokers (current or former smokers) and never-smokers. @*Results@#This study enrolled 250 patients who were diagnosed with CH, of which 152 (60.8%) were ever-smokers and 98 (39.2%) were never-smokers. The age at CH onset was significantly lower in the never-smoker group than in the ever-smoker group [27.1±12.9 years vs. 30.6± 10.9 years (mean±standard deviation), p=0.024]. Seasonal rhythmicity (58.1% vs. 44.7%, p= 0.038) and triptan responsiveness (100% vs. 85.1%, p=0.001) were higher in never-smokers, while other clinical features such as pain severity, duration, attack frequency, and associated autonomic symptoms did not differ significantly between the groups. The male-to-female ratio was markedly higher in ever-smokers (29.4:1) than in never-smokers (1.7:1). @*Conclusions@#Most of the clinical features did not differ significantly between patients with a smoking history and never-smokers. However, the age at CH onset, sex ratio, and seasonal rhythmicity were significantly associated with smoking history.

Smoking History and Clinical Features of Cluster Headache:Results from the Korean Cluster Headache Registry

Background@#and Purpose Epidemiologic data suggest that cluster headache (CH) is significantly associated with cigarette smoking. The aim of this study was to determine differences in features between patients with a smoking history and those who are never-smokers, using data from a prospective multicenter registry. @*Methods@#Data used in this study were obtained from the Korean Cluster Headache Registry that collected data from consecutive patients diagnosed with CH. We compared clinical and demographic features between ever-smokers (current or former smokers) and never-smokers. @*Results@#This study enrolled 250 patients who were diagnosed with CH, of which 152 (60.8%) were ever-smokers and 98 (39.2%) were never-smokers. The age at CH onset was significantly lower in the never-smoker group than in the ever-smoker group [27.1±12.9 years vs. 30.6± 10.9 years (mean±standard deviation), p=0.024]. Seasonal rhythmicity (58.1% vs. 44.7%, p= 0.038) and triptan responsiveness (100% vs. 85.1%, p=0.001) were higher in never-smokers, while other clinical features such as pain severity, duration, attack frequency, and associated autonomic symptoms did not differ significantly between the groups. The male-to-female ratio was markedly higher in ever-smokers (29.4:1) than in never-smokers (1.7:1). @*Conclusions@#Most of the clinical features did not differ significantly between patients with a smoking history and never-smokers. However, the age at CH onset, sex ratio, and seasonal rhythmicity were significantly associated with smoking history.

An Update On Migraine Treatment

Globally, migraine is the third most common disease affecting 1.3 billion people worldwide and the second leading cause of disability. With the recent advances in new drugs and device technology for the treatment of migraine, the Korean Headache Society (KHS) and American Headache Society (AHS) released a new practice guideline on the treatment of migraine in 2019, respectively. They developed their consensus statement after reviewing existing guidelines and recent clinical trials and having discussions with stakeholders. The KHS guideline addresses best practice for preventing migraine with oral treatments including start and stopping strategies. The AHS statement dealt with newer treatments, such as onabotulinumtoxinA, and the recently approved calcitonin gene-related peptide targeting agents, and nonpharmacological treatments such as neuromodulation and biobehavioral therapy for both preventive and acute treatment. In this paper, we will review and summarize updated guideline for migraine treatment.

Exploratory Study of the Effectiveness of Oxygen Therapy Using Home Oxygen Concentrators for Cluster Headache

Cluster headache attacks can be successfully treated with oxygen. We report four patients with episodic cluster headache were treated with oxygen therapy from one or two oxygen concentrators. Oxygen therapy with two oxygen concentrators seems to be effective in reduction or cessation of pain of cluster headaches. Patients expressed excellent satisfaction to oxygen therapy with two oxygen concentrators. Oxygen concentrators can be considered as an effective and safe alternative of oxygen cylinder for patients with cluster headache.

Factors Associated with Incidental Neuroimaging Abnormalities in New Primary Headache Patients

Background@#and PurposeDeciding whether or not to perform neuroimaging in primary headache is a dilemma for headache physicians. The aim of this study was to identify clinical predictors of incidental neuroimaging abnormalities in new patients with primary headache disorders. @*Methods@#This cross-sectional study was based on a prospective multicenter headache registry, and it classified 1,627 consecutive first-visit headache patients according to the third edition (beta version) of the International Classification of Headache Disorders (ICHD-3β). Primary headache patients who underwent neuroimaging were finally enrolled in the analysis. Serious intracranial pathology was defined as serious neuroimaging abnormalities with a high degree of medical urgency. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with incidental neuroimaging abnormalities. @*Results@#Neuroimaging abnormalities were present in 170 (18.3%) of 927 eligible patients. In multivariable analysis, age ≥40 years [multivariable-adjusted odds ratio (aOR)=3.37, 95% CI=2.07–6.83], male sex (aOR=1.61, 95% CI=1.12–2.32), and age ≥50 years at headache onset (aOR=1.86, 95% CI=1.24–2.78) were associated with neuroimaging abnormalities. In univariable analyses, age ≥40 years was the only independent variable associated with serious neuroimaging abnormalities (OR=3.37, 95% CI=1.17–9.66), which were found in 34 patients (3.6%). These associations did not change after further adjustment for neuroimaging modality. @*Conclusions@#Incidental neuroimaging abnormalities were common and varied in a primary headache diagnosis. A small proportion of the patients incidentally had serious neuroimaging abnormalities, and they were predicted by age ≥40 years. These findings can be used to guide the performing of neuroimaging in primary headache disorders.

Development and Validation of the Cluster Headache Screening Questionnaire

BACKGROUND AND PURPOSE: Cluster headache (CH) is frequently either not diagnosed or the diagnosis is delayed. We addressed this issue by developing the self-administered Cluster Headache Screening Questionnaire (CHSQ). METHODS: Experts selected items from the diagnostic criteria of CH and the characteristics of migraine. The questionnaire was administered to first-visit headache patients at nine headache clinics. The finally developed CHSQ included items based on the differences in responses between CH and non-CH patients, and the accuracy and reliability of the scoring model were assessed. RESULTS: Forty-two patients with CH, 207 migraineurs, 73 with tension-type headache, and 18 with primary stabbing headache were enrolled. The CHSQ item were scored as follows: 3 points for ipsilateral eye symptoms, agitation, and duration; 2 points for clustering patterns; and 1 point for the male sex, unilateral pain, disability, ipsilateral nasal symptoms, and frequency. The total score of the CHSQ ranged from 0 to 16. The mean score was higher in patients with CH than in non-CH patients (12.9 vs. 3.4, p 8 points, the CHSQ had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.2%, 96%, 76.9%, and 99.3%, respectively. CONCLUSIONS: The CHSQ is a reliable screening tool for the rapid identification of CH.

Clinical Reasoning: A 51-Year-Old Woman Presenting with Unilateral Severe Headache

No abstract available.

Differences in Characteristics and Comorbidity of Cluster Headache According to the Presence of Migraine

BACKGROUND AND PURPOSE: Cluster headache (CH) can present with migrainous symptoms such as nausea, photophobia, and phonophobia. In addition, an overlap between CH and migraine has been reported. This study aimed to determine the differences in the characteristics of CH according to the presence of comorbid migraine. METHODS: This study was performed using data from a prospective multicenter registry study of CH involving 16 headache clinics. CH and migraine were diagnosed by headache specialists at each hospital based on third edition of the International Classification of Headache Disorders (ICHD-3). We interviewed patients with comorbid migraine to obtain detailed information about migraine. The characteristics and psychological comorbidities of CH were compared between patients with and without comorbid migraine. RESULTS: Thirty (15.6%) of 192 patients with CH had comorbid migraine, comprising 18 with migraine without aura, 1 with migraine with aura, 3 with chronic migraine, and 8 with probable migraine. Compared to patients with CH without migraine, patients with CH with comorbid migraine had a shorter duration of CH after the first episode [5.4±7.4 vs. 9.0±8.2 years (mean±standard deviation), p=0.008], a lower frequency of episodic CH (50.0% vs. 73.5%, p=0.010), and a higher frequency of chronic CH (13.3% vs. 3.7%, p=0.033). Psychiatric comorbidities did not differ between patients with and without comorbid migraine. The headaches experienced by patients could be distinguished based on their trigeminal autonomic symptoms, pulsating character, severity, and pain location. CONCLUSIONS: Distinct characteristics of CH remained unchanged in patients with comorbid migraine with the exception of an increased frequency of chronic CH. The most appropriate management of CH requires clinicians to check the history of preceding migraine, particularly in cases of chronic CH.

Comprehensive review and update on chronic migraine

Chronic migraine (CM) is a common and disabling neurologic disorder. CM is defined as more than 15 days a month over a 3-month period, including at least 8 days per month on which their headaches and associated symptoms meet diagnostic criteria for migraine. Quality of life is highly compromised in patients with this condition, and comorbidities are more frequent than with episodic migraine. The diagnosis requires a carefully-conducted patient interview and neurologic examination, sometimes combined with additional diagnostic tests, to differentiate CM from secondary headache disorders and other primary chronic headaches. CM typically develops from episodic migraine over months to years. Several factors are associated with an increased risk of episodic migraine developing into CM, including the frequent use of abortive migraine drugs. Through identification of risk factors for progression to CM, clinicians can educate patients about modifiable risk factors and can begin appropriate individualized preventive therapy. There is a high frequency of medication overuse in CM. The first step in the management of CM complicated by medication overuse is withdrawal of the overused drugs and detoxification treatment. This article provides an overview of CM, including its epidemiology, risk factors for its development, and information on its pathophysiology, diagnosis, and management.

Neuroimaging Findings of First-Visit Headache Patients

BACKGROUND: Neuroimaging can play a crucial role in discovering potential abnormalities to cause secondary headache. There has been a progress in the fields of headache diagnosis and neuroimaging in the past two decades. We sought to investigate neuroimaging findings according to headache disorders, age, sex, and imaging modalities in first-visit headache patients. METHODS: We used data of consecutive first-visit headache patients from 9 university and 2 general referral hospitals. The International Classification of Headache Disorders, third edition, beta version was used in headache diagnosis. We finally enrolled 1,080 patients undertook neuroimaging in this study. RESULTS: Among 1,080 patients (mean age: 47.7±14.3, female: 60.8%), proportions of headache diagnosis were as follows: primary headaches, n=926 (85.7%); secondary headaches, n=110 (10.2%); and cranial neuropathies and other headaches, n=43 (4.1%). Of them, 591 patients (54.7%) received magnetic resonance imaging (MRI). Neuroimaging abnormalities were found in 232 patients (21.5%), and their proportions were higher in older age groups and male sex. Chronic cerebral ischemia was the most common finding (n=88, 8.1%), whereas 76 patients (7.0%) were found to have clinically significant abnormalities such as primary brain tumor, cancer metastasis, and headache-relevant cerebrovascular disease. Patients underwent MRI were four times more likely to have neuroimaging abnormalities than those underwent computed tomography (33.3% vs. 7.2%, p <0.001). CONCLUSIONS: In this study, the findings of neuroimaging differed according to headache disorders, age, sex, and imaging modalities. MRI can be a preferable neuroimaging modality to identify potential causes of headache.

Clinical Reasoning: A 21-year-old Man Presenting with Thunderclap Headache

No abstract available.

Anti-N-methyl-D-aspartate Receptor Encephalitis after Herpes Simplex Virus Infection

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has clinical features of psychiatric symptoms, loss of memory, seizure, dyskinesia and autonomic dysfunction. While Anti-NMDA receptor encephalitis was initially reported in young women with ovarian teratoma, viral infections can trigger anti-NMDA receptor encephalitis as well. Among them, herpes virus is the most common. We report a patient who developed the anti-NMDA receptor encephalitis 47 days after herpes virus encephalitis, which is, to our knowledge, the first case in Korea.

Comprehensive review and update on chronic migraine

Chronic migraine (CM) is a common and disabling neurologic disorder. CM is defined as more than 15 days a month over a 3-month period, including at least 8 days per month on which their headaches and associated symptoms meet diagnostic criteria for migraine. Quality of life is highly compromised in patients with this condition, and comorbidities are more frequent than with episodic migraine. The diagnosis requires a carefully-conducted patient interview and neurologic examination, sometimes combined with additional diagnostic tests, to differentiate CM from secondary headache disorders and other primary chronic headaches. CM typically develops from episodic migraine over months to years. Several factors are associated with an increased risk of episodic migraine developing into CM, including the frequent use of abortive migraine drugs. Through identification of risk factors for progression to CM, clinicians can educate patients about modifiable risk factors and can begin appropriate individualized preventive therapy. There is a high frequency of medication overuse in CM. The first step in the management of CM complicated by medication overuse is withdrawal of the overused drugs and detoxification treatment. This article provides an overview of CM, including its epidemiology, risk factors for its development, and information on its pathophysiology, diagnosis, and management.

Severe Right Internal Carotid Artery Stenosis Mimicking Behavioral Variant Frontotemporal Dementia

Many kinds of degenerative, psychiatric, and cerebrovascular diseases can mimic behavioral variant frontotemporal dementia. We present a 73-year-old woman who presented with apathy, inappropriate social behavior, and persecutory delusion. A neuropsychological examination revealed frontal/executive dysfunction with relative sparing of episodic memory. Magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography produced normal findings. However, magnetic resonance angiography revealed severe right internal carotid stenosis. After carotid stenting, her behavioral symptoms disappeared and did not recur during an 18-month follow-up.

Clinical Features of Cluster Headache Patients in Korea

Cluster headache (CH) is a rare underdiagnosed primary headache disorder with very severe unilateral pain and autonomic symptoms. Clinical characteristics of Korean patients with CH have not yet been reported. We analyzed the clinical features of CH patients from 11 university hospitals in Korea. Among a total of 200 patients with CH, only 1 patient had chronic CH. The average age of CH patients was 38.1 ± 8.9 years (range 19–60 years) and the average age of onset was 30.7 ± 10.3 years (range 10–57 years). The male-to-female ratio was 7:1 (2.9:1 among teen-onset and 11.7:1 among twenties-onset). Pain was very severe at 9.3 ± 1.0 on the visual analogue scale. The average duration of each attack was 100.6 ± 55.6 minutes and a bout of CH lasted 6.5 ± 4.5 weeks. Autonomic symptoms were present in 93.5% and restlessness or agitation was present in 43.5% of patients. Patients suffered 3.0 ± 3.5 (range 1–25) bouts over 7.3 ± 6.7 (range 1–30) years. Diurnal periodicity and season propensity were present in 68.5% and 44.0% of patients, respectively. There were no sex differences in associated symptoms or diurnal and seasonal periodicity. Korean CH patients had a high male-to-female ratio, relatively short bout duration, and low proportion of chronic CH, unlike CH patients in Western countries.

Spontaneous Thrombosis of Posterior Inferior Cerebellar Artery Aneurysm Presenting as Cerebellar Infarction

Ischemic stroke caused by spontaneous thrombosis of posterior inferior cerebellar artery (PICA) aneurysm has been rarely reported. A 52-year-old man presented with sudden headache, dizziness, and gait disturbance. Diffusion-weighted MRI showed acute infarction in left PICA territory. A saccular aneurysm with internal thrombus at the distal PICA was detected by CT angiography and conventional angiography. The thrombus resolved spontaneously at 2 months after stroke onset with aspirin medication. At that time, endovascular coiling was underwent successfully to prevent aneurysmal rupture.

Comprehensive Application of the International Classification of Headache Disorders Third Edition, Beta Version

The purpose of this study was to test the feasibility and usefulness of the International Classification of Headache Disorders, third edition, beta version (ICHD-3beta), and compare the differences with the International Classification of Headache Disorders, second edition (ICHD-2). Consecutive first-visit patients were recruited from 11 headache clinics in Korea. Headache classification was performed in accordance with ICHD-3beta. The characteristics of headaches were analyzed and the feasibility and usefulness of this version was assessed by the proportion of unclassified headache disorders compared with ICHD-2. A total of 1,627 patients were enrolled (mean age, 47.4±14.7 yr; 62.8% female). Classification by ICHD-3beta was achieved in 97.8% of headache patients, whereas 90.0% could be classified by ICHD-2. Primary headaches (n=1,429, 87.8%) were classified as follows: 697 migraines, 445 tension-type headaches, 22 cluster headaches, and 265 other primary headache disorders. Secondary headache or painful cranial neuropathies/other facial pains were diagnosed in 163 patients (10.0%). Only 2.2% were not classified by ICHD-3beta. The main reasons for missing classifications were insufficient information (1.6%) or absence of suitable classification (0.6%). The diagnoses differed from those using ICHD-2 in 243 patients (14.9%). Among them, 165 patients were newly classified from unclassified with ICHD-2 because of the relaxation of the previous strict criteria or the introduction of a new diagnostic category. ICHD-3beta would yield a higher classification rate than its previous version, ICHD-2. ICHD-3beta is applicable in clinical practice for first-visit headache patients of a referral hospital.

Chronic Daily Headache and Medication Overuse Headache in First-Visit Headache Patients in Korea: A Multicenter Clinic-Based Study

BACKGROUND AND PURPOSE: Chronic daily headache (CDH) is defined as a headache disorder in which headaches occur on a daily or near-daily basis (at least 15 days/month) for more than 3 months. Chronic migraine (CM) and medication overuse headache (MOH) are very disabling headaches that remain underdiagnosed. The aim of this study was to establish the frequency of CDH and its various subtypes, and examine the associations with MOH among first-visit headache patients presenting at neurology outpatient clinics in Korea. METHODS: Eleven neurologists enrolled first-visit patients with complaints of headaches into outpatient clinics for further assessment. Headache disorders were classified according to the International Classification of Headache Disorder (third edition beta version) by each investigator. RESULTS: Primary CDH was present in 248 (15.2%) of the 1,627 included patients, comprising CM (143, 8.8%), chronic tension-type headache (CTTH) (98, 6%), and definite new daily persistent headache (NDPH) (7, 0.4%). MOH was associated with headache in 81 patients (5%). The association with MOH was stronger among CM patients (34.5%) than patients with CTTH (13.3%) or NDPH (14.3%) (p=0.001). The frequency of CDH did not differ between secondary and tertiary referral hospitals. CONCLUSIONS: The frequencies of CDH and MOH diagnoses were 15.2% and 5%, respectively in first-visit headache patients presented at secondary or tertiary referral hospitals in Korea. CM was the most common subtype of CDH and was most frequently associated with MOH.