Real-life experiences with galcanezumab and predictors for treatment response in Turkey.

BACKGROUND: The complexity of clinical practice extends far beyond the controlled settings of trials, and there is a need for real-world studies aimed at identifying which patients will respond to anti-CGRP monoclonal antibodies in different countries. This study aimed to investigate the efficacy and safety of galcanezumab in treating migraine in a real-life setting in Turkey, as well as identify predictors of treatment response. METHODS: A total of 476 patients who diagnosed with migraine according to ICHD-3 criteria and treated with galcanezumab by headache specialists were voluntarily participated in this cross-sectional study. Galcanezumab is indicated for the prevention of migraine in adults who have at least 4 monthly migraine days in Turkey. All patients filled out a survey on Google Form that comprised 54 questions, addressing various aspects such as demographics, migraine characteristics, previous use of acute symptomatic medication, failures with preventive drug classes, comorbidities, most bothersome symptoms, as well as the interictal burden of migraine. RESULTS: Among the participants, 89.3% reported that galcanezumab treatment was beneficial for them. A decrease in the frequency (80.0%), severity (85.7%), and acute medication usage for migraine attacks (71.4%) was reported with galcanezumab treatment. An adverse effect related to galcanezumab was reported in 16.3% of cases, but no serious adverse reactions were observed. Remarkably, 14.3% of participants reported no longer experiencing any headaches, and 18.9% did not require any acute treatment while receiving galcanezumab treatment. A logistic regression model showed that male gender, lack of ictal nausea, and previous failure of more than 2 prophylactic agents may predict the non-responders. CONCLUSIONS: The first large series from Turkey showed that galcanezumab treatment is safe and effective in most of the patients diagnosed with migraine by headache experts in the real-life setting. Patients reported a significant decrease in both ictal and interictal burden of migraine and expressed satisfaction with this treatment.

COVID-19 vaccination-related headache showed two different clusters in the long-term course: a prospective multicenter follow-up study (COVA-Head Study).

BACKGROUND: Although acute headache following COVID-19 vaccination is widely acknowledged, the long-term progression of these headaches remains poorly understood. Our objective was to identify various phenotypes of prolonged or worsened headaches associated with COVID-19 vaccination and document any changes in these phenotypes over an extended period. Additionally, we aimed to document the diverse headache presentations among patients with pre-existing primary headaches. METHODS: A multinational, prospective observational study was conducted to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires assessing COVID-19 vaccination-related headaches at three time points (initial visit, 3rd month follow-up, and 6th month follow-up) were developed for the study. Headache specialists/clinicians evaluated patients using these questionnaires in a prospective manner. Repeated K-means cluster analysis was performed to identify patient profiles with prolonged or worsened headaches related to COVID-19 vaccination. RESULTS: Among the 174 patients included in the study, there was a female-to-male ratio of 128 (73.6%) to 46 (26.4%). The mean age of the patient group was 45.2 ± 13.3 years, and 107 patients (61.5%) had a pre-existing history of primary headaches. Through the analysis, two major clusters were identified based on headache characteristics at each visit. During the first visit (n = 174), Cluster 1 primarily comprised patients with a history of primary headaches, frontal localization of pain, throbbing pain type, more severe headaches accompanied by symptoms such as nausea, phonophobia, photophobia, and osmophobia, and worsened by physical activity. In contrast, Cluster 2 consisted of patients with longer headache durations (over one month) and a stabbing/pressing quality of pain. Patients in Cluster 1 had a higher prevalence of migraine as the pre-existing primary headache disorder compared to Cluster 2 (90.48% vs. 68.18%, respectively; p = 0.005). CONCLUSION: The identification of two distinct phenotypes of prolonged or worsened headaches related to COVID-19 vaccination can provide valuable clinical insights. Having an awareness of the potential worsening of headaches following COVID-19 vaccination, particularly in patients with a primary headache disorder such as migraine, can help clinicians and headache experts anticipate and adjust their treatment strategies accordingly. This knowledge can aid in preplanning treatment modifications and optimize patient care.

The characteristics of COVID-19 vaccine-related headache: Clues gathered from the healthcare personnel in the pandemic.

INTRODUCTION: Headache is a frequent adverse event after viral vaccines. We aimed to investigate the frequency and clinical associations of COVID-19 vaccine-related headache. METHODS: The characteristics, associations of this headache, main comorbidities, headache history following the influenza vaccine and during COVID-19 were investigated using a web-based questionnaire. RESULTS: A total of 1819 healthcare personnel (mean age: 44.4 ± 13.4 years, 1222 females), vaccinated with inactivated virus, contributed to the survey; 209 (11.4%) had been infected with COVID-19. A total of 556 participants (30.6%) reported headache with significant female dominance (36.1% vs. 19.3%), 1.8 ± 3.5 (median: 1; IQR: 0-2) days following vaccination. One hundred and forty-four participants (25.9%) experienced headache lasting ≥3 days. Headache was mostly bilateral without accompanying phenomena, less severe, and shorter than COVID-19-related headache. The presence of primary headaches and migraine were significantly associated with COVID-19 vaccine-related headache (ORs = 2.16 [95% CI 1.74-2.68] and 1.65 [1.24-2.19], respectively). Headache during COVID-19 or following influenza vaccine also showed significant association with headache following COVID-19 vaccine (OR = 4.3 [95% CI 1.82-10.2] and OR = 4.84 [95% CI 2.84-8.23], respectively). Only thyroid diseases showed a significant association (OR = 1.54 [95% CI 1.15-2.08]) with vaccine-related headache among the common comorbidities. CONCLUSION: Headache is observed in 30.6% of the healthcare workers following COVID-19 vaccine and mostly experienced by females with pre-existing primary headaches, thyroid disorders, headache during COVID-19, or headache related to the influenza vaccine.

Primary headaches among gender dysphoric female-to-male individuals: A cross-sectional survey on gender transition experience.

OBJECTIVE: To investigate the frequency, attack characteristics, and treatment experiences of migraine and tension-type headache (TTH) among gender dysphoric female-to-male (FtM) participants as well as in relation to psychiatric comorbidities and real-life experience that relates to being transgender in Turkey. BACKGROUND: There are only a few publications to date on transgender individuals with headache. Further studies to understand the distinctive needs might provide better management. METHODS: A total of 88 gender dysphoric FtM individuals (mean (SD) age: 24.8 (5.7) years) were included on a voluntary basis in this cross-sectional survey. Each participant filled out the questionnaire form that elicited items on sociodemographic characteristics, Gender Identity Transition Inventory, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Headache Questionnaire. RESULTS: Overall, 32/88 (36.4%; 95% confidence interval [CI]: 27.0%-47.0%) participants were diagnosed with migraine, and 36/88 (40.9%; 95% CI: 31.5%-52.3%) participants were diagnosed with TTH. High rates of unemployment, smoking, and social drinking were observed in our sample compared with the general population in Turkey. The three-item ID migraine screener was positive in 20.5% (18/88 patients) of our population. Patients with migraine in comparison with patients with TTH had statistically significantly higher BDI [12.0 (1-50) vs. 7.0 (0-33); p = 0.013] and BAI [13 (1-48) vs. 5 (0-22); p = 0.016] scores, longer headaches in the past month [median 3 vs. 1 day; p < 0.001], higher Numerical Rating Scale scores for headache severity [7 (2-10) vs. 5 (1-9), p < 0.001], and higher likelihood of menstruation acting as a triggering factor [8/32 patients (25.0%) vs. 0/36 patients (0.0%); p = 0.001] as well as increased rates of previously given diagnosis by a physician [15/32 patients (46.9%) vs. 4/36 patients (11.1%); p < 0.001], a greater number of neuroimaging tests being performed [12/32 patients (37.5%) vs. 3/36 patients (9.1%); p = 0.012], and a higher rate of emergency room utilization [7/32 patients (21.9%) vs. 1/36 patients (2.8%); p = 0.039] for headache. CONCLUSIONS: In the FtM transgender population we investigated, migraine and TTH were quite common. The screening and early recognition of comorbid migraine, as well as the comorbid depression and anxiety, seem to be important in gender dysphoric FtM individuals. Further studies are needed to better understand the potential interaction of migraine with comorbid psychiatric disorders and the prevalence of headache types and gender-affirmative hormone treatment outcomes in the transgender population.

Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database.

The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).

The persistence versus interchangeability of migraine and tension-type headaches in a 5-year population-based validated survey.

OBJECTIVE: The aim of this population-based validated study was to determine the course of tension-type headache and migraine and to evaluate the predictors of persistence. METHODS: We evaluated the course of headache in a large population from the first assessment in 2008 through a second assessment in 2013. Then we examined the factors associated with persistent migraine and persistent tension-type headache. RESULTS: Our study in 2013 revealed that only 42.9% of definite migraineurs in 2008 received the same diagnosis again, and of the remaining migraineurs 23.3% were newly diagnosed as definite tension-type headache; 11.6% evolved into probable tension-type headache, 6.4% changed to probable migraine, and 15.8% were headache free. The 17.7% of patients with definite tension-type headache in 2008 were newly diagnosed as having probable tension-type headache, 14.7% as having definite migraine, 6.4% as having probable migraine, and 28.9% as headache free in 2013, and only 32.3% received the definite tension-type headache diagnosis again. Binary logistic regression analysis showed nausea, throbbing and severe headache were the significant parameters for persistent migraine. A multiple regression analysis model with stepwise variable selection revealed that nausea, throbbing and severe headache and osmophobia remained in the final model as predictors of migraine persistence. We found no predictive factor for persistent tension-type headache. CONCLUSION: Migraine and tension-type headache did not seem to show a simple bidirectional linear worsening from headache-free state to definite migraine or vice versa, hence the transitions between them are more chaotic, reflecting that there are still unknown modifiers and modulators. Certain headache characteristics of migraine might predict persistent migraine.

Headache characteristics in COVID-19 pandemic-a survey study.

BACKGROUND: Headache is the most common COVID-19-related neurological symptom. We aimed to reveal diagnostic clues of headache for COVID-19 infection and to investigate the course of primary headaches during the pandemic. METHODS: We developed a detailed web-based questionnaire screening the characteristics and course of headaches besides clinical COVID-19 features. The participants were grouped according to being diagnosed with COVID-19 infection or not, and having previous or new-onset headaches. The COVID-19 related headache features and their associations with other clinical features were investigated. A binary logistic regression model was performed to differentiate the characteristics of headache related to COVID-19. FINDINGS: A total of 3458 participants (2341 females;67.7%, 1495 healthcare workers;43.2%) with a mean age of 43.21 ± 11.2 years contributed to the survey. Among them, 262 participants had COVID-19 diagnosis and 126 (48.1%) were male. The rate of males in the group without COVID-19 was 31% (991 out of 3196 participants) showing significant gender difference between groups (p < 0.000). COVID-19 related headaches were more closely associated with anosmia/ageusia and gastrointestinal complaints (p < 0.000 and p < 0.000), and showed different characteristics like pulsating, pressing, and even stabbing quality. Logistic regression analyses showed that bilateral headache, duration over 72 h, analgesic resistance and having male gender were significant variables to differentiate COVID-19 positive patients from those without COVID-19 (p = 0.04 for long duration and p < 0.000 for others). A worsening of previous primary headaches due to the pandemic-related problems was not reported in the majority of patients. INTERPRETATION: Bilateral, long-lasting headaches, resistance to analgesics and having male gender were more frequent in people with COVID-19 in conjunction with anosmia/ageusia and gastrointestinal complaints. These features may be helpful for diagnosing the headache related to COVID-19 during the pandemic.

Migraine incidence in 5 years: a population-based prospective longitudinal study in Turkey.

BACKGROUND: The incidence of migraine has been investigated only in a few studies worldwide and it is not known in our country. We, therefore, aimed to estimate the migraine incidence in a previously accomplished population-based prevalence study sample of 5323 individuals in the year 2008. METHODS: The former Turkish headache prevalence study has been completed as a nationwide, randomized, home-based study of face-to-face examination by physicians trained for headache diagnosis by using ICHD criteria. Five years after this study an optimized survey including 50 questions was performed to estimate the migraine incidence in migraine-free individuals in the previous study, with a 56.4 % responder rate. Two validation studies for this survey were performed prior and after the study each in 100 subjects by comparing the gold standard of expert diagnosis of headache, showing high rate of reliability (Crohnbach alpha: 0.911 and 0.706, respectively). RESULTS: Migraine incidence was estimated as 2.38 % (2.98 % in women and 1.93 % in men) per year in 2563 migraine-free individuals; if the population at risk is defined as the group without any headaches, the migraine incidence decreased to 1.99 %. The chronic migraine (CM) incidence [without medication overuse (MOH)] was 0.066 % and that of MOH was 0.259 %. We found a significant burden of the disease on the occupational functionality as well as on social and family life, even in the early years of the migraine. The family history of headaches especially in the fathers could be useful to predict new cases of migraine, besides the well-known risk factor, diagnosis of depression, whereas income and education did not seem to relate to migraine onset. CONCLUSIONS: Our study with a large population-based nation-wide sample, using ICHD-II criteria, with structured headache interviews as well as blinded re-validation of the questionnaire diagnoses showed a 2.38 % incidence rate of migraine in Turkey, higher than most of the other previous reports; a finding which could be related to genetic factors and also to the methodological differences in the study designs. Moreover the incidence of CM was found to be 0.066 %.

Efficacy and safety of 400 and 800 mg etodolac vs. 1,000 mg paracetamol in acute treatment of migraine: a randomized, double-blind, crossover, multicenter, phase III clinical trial.

AIM: We aimed to determine the efficacy and safety of etodolac, in acute migraine attacks in comparison with paracetamol (acetaminophen). METHODS: We designed a randomized, double-blind, crossover phase III clinical trial for patients diagnosed with migraine for at least 1 year, according to ICHD-II criteria. Two hundred and twenty-nine adult patients having 2 to 8 attacks monthly from 17 centers were included. The patients were instructed to use 3 attack treatment packages consisting of 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac on 3 migraine attacks of moderate-severe intensity each in a 3-month treatment period, interchangeably. RESULTS: Any pain medication was used in 1,570 migraine attacks while study treatments were used in 1,047 attacks. The results for 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac were as follows: response of headache at 2 hours 44.9%, 48.3% and 46.1%; pain-free at 2 hours 19.2%, 19.3% and 24.1%; sustained pain-free from 2 to 24 hours 34.3%, 38.3% and 41.1%; relapse rates in 2 to 24 hours 7.3%, 14.3% and 9.7%. There were no statistically significant differences between the groups regarding the headache response, pain-free, sustained pain-free, and relapse rates. Nausea, vomiting, phonophobia, or photophobia decreased similarly in all groups within 24 hours of treatment administration. Drug-related adverse events were noted in 8 patients with 1,000 mg paracetamol, in 9 patients with 400 mg etodolac and in 9 patients for 800 mg etodolac during the study. COMMENT: Our study showed that etodolac is a safe and effective alternative in acute migraine treatment and showed comparable efficacy to paracetamol 1,000 mg. Etodolac may be considered as an alternative option for acute treatment of migraine.

Prevalence and self-management of migraine among neurologists and neurology residents in Turkey: do neurologists apply effective rational prophylaxis to their migraines?

AIM: The aim of the study to determine the migraine prevalence and self-management of migraine among the neurologists and neurology residents registered to the Turkish Neurological Society. METHODS: This cross-sectional study includes 851 participants. Based on the "The International Classification of Headache Disorders, 3rd edition" and previous literature, an anonymous questionnaire was prepared and used to collect data online via Google Forms. The link to the study was posted on the website of the Turkish Neurological Society. RESULTS: Women (73.2%) and neurologists (77.4%) made up the majority of the participants. Of the participants, 37.9% met the diagnosis criteria for migraine. Being women and positive family history were associated with migraine compared to the tension-type headache (TTH) (both p values < 0.001). Comparing with the TTH sufferers, migraine significantly hindered work, social, and family life (all p values < 0.001). Participants with migraine had more magnetic resonance imaging (MRI) (47.4%) and electroencephalography (EEG) (4.3%) than those with TTH (both p values < 0.05). Participants with migraine received drug prophylaxis more frequently (20.1%) than those with TTH (2.3%) (p < 0.001), and these drugs were selective serotonin reuptake inhibitors (SSRIs) (7.1%), beta-blockers (5.9%), and serotonin-norepinephrine reuptake inhibitors (SNRIs) (5.3%) (all p values < 0.05). Participants with migraine received non-pharmacological prophylaxis for headache more frequently (25.7%) compared to those with TTH (p < 0.001). CONCLUSIONS: Migraine is common among neurologists and neurology residents. Identifying migraine self-management is important for preventing the loss of work and negative economic and social consequences that migraine may cause in these groups of physicians.

The Adaptation of 12-Item Utah Photophobia Symptom Impact Scale (UPSIS-12) in Turkish, Internal Consistency, and Reproducibility.

Introduction: The 12-item Utah Photophobia Symptom Impact Scale (UPSIS-12) is a questionnaire to assess the impact of photophobia on daily living during and outside migraine episodes. We aimed to translate UPSIS-12 and assess its usability in the Turkish cohort by analyzing internal consistency, reliability, and reproducibility. Methods: In this multicenter prospective, descriptive study, 120 patients with migraine were recruited. The patients received the diagnosis of migraine without aura (MwoA) and migraine with aura (MwA) according to the International Classification of Headache Disorders 3rd edition. The scale was translated into Turkish, and the patients were evaluated by headache experts in two visits four weeks apart from each other. Results: The questionnaire showed highly correlated test-retest reliability (r=0.828). Cronbach alpha values of internal consistency revealed good to excellent results ranging from 0.78-0.82. There was a strong and positive correlation between self and physician-administered scales at both visits (r=0.964 and 0.985, respectively). The questionnaire was considered "well understood" by 95.6% of the patients. The average UPSIS-12 score of each visit was 25.8 and 26.9 (average standard deviation of 10.4). Subjects with MwoA (25.5±10.4) had remarkably lower mean scores compared to MwoA plus MwA (29.2±8.9) and MwA (32.9±9.4) (p=0.0167). Patients with high frequency migraine presented with a higher mean UPSIS-12 score than those with low frequency (31.3±9.5 and 24.7±9.8, respectively). It was noted that the mean UPSIS-12 scores of those with severe (29.4±9.4) and moderate ictal cutaneous allodynia (CA) (28.4±10.6) were higher than those without CA (22.0±9.3)(p=0.020). Conclusion: The Turkish version of the UPSIS-12 questionnaire is a reliable tool and well-understood by the Turkish population. Patients with MwA, frequent migraine headache days and moderate to severe CA presented with higher scores. Given the independent burden of photophobia in migraineurs, the use of UPSIS-12 scale should be encouraged in Turkish population.

The analysis of allodynia in patients with idiopathic intracranial hypertension.

OBJECTIVES: Allodynia is frequently associated with migraine and other primary headaches. Our aim was to investigate the presence of allodynia and related features in idiopathic intracranial hypertension (IIH), which is a disabling secondary headache disorder. METHODS: We included 46 IIH patients and analyzed their clinical and laboratory findings retrospectively. Allodynia was assessed using the validated 12-item allodynia symptom checklist (ASC-12), in addition to examining pressure (with von Frey filaments) and brush allodynia. RESULTS: Allodynia was detected in 23 (50%) of IIH patients with ASC-12 and/or instrumental testing. The most commonly reported location was unilateral V1 distribution. The allodynic symptom profile was similar but milder when compared to 143 migraineurs with ASC-12. Only the aggravation of headache with physical activity emerged as a significant variable associated with allodynia in IIH. Among allodynic patients, only eight had previous migraine diagnosis. After onset of IIH, 20 patients reported migraine-like headache, while only three reported non-migrainous headache. In contrast, 13 of 23 non-allodynic IIH patients had non-migrainous headache features (p = 0.0045). CONCLUSION: Half of the IIH patients reported allodynia, and these allodynic patients had mostly migraine-like headache profiles. Our study suggested that IIH may trigger some common mechanisms with migraine in pain pathways causing allodynia.

One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults.

Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35-40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria.

Impact of sex hormonal changes on tension-type headache and migraine: a cross-sectional population-based survey in 2,600 women.

Sex hormones have some implications on headaches. The objective of the study was to investigate the effects of hormonal changes comparatively on tension-type headache (TTH) and migraine, in a population-based sample. A nationwide face-to-face prevalence study was conducted using a structured electronic questionnaire. 54.3 % of the migraineurs reported that the probability of experiencing headache during menstruation was high, whereas 3.9 % had headache only during menstruation. Forward logistic regression analysis revealed that menstruation was a significant trigger for migraine in comparison to TTH. On the other hand, nearly double the number of TTH sufferers reported "pure menstrual headache" compared to migraineurs (p = 0.02). Menstrual headaches caused significantly higher MIDAS grades. One-third of the definite migraineurs reported improvement during pregnancy and oral contraceptives significantly worsened migraine. Menopause had a slight improving effect on migraine compared to TTH. Sex hormonal changes have major impacts particularly on migraine; however, the effects of hormonal fluctuations on TTH should not be underestimated.

Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache.

Objective: To investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis. Methods: A total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences. Results: Cluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smoking (76.0 vs. 33.0%; p=0.002), higher rates of smoking at diagnosis (78.0 vs. 32.0%; p=0.006), higher rates of parental smoking/tobacco exposure during childhood (72.0 vs. 33.0%; p = 0.010), longer duration of attacks with (44.21 (34.44) min. vs. 34.51 (24.97) min; p=0.005) and without (97.50 (63.58) min. vs. (83.95 (49.07) min; p = 0.035) treatment and higher rates of emergency department visits in the last year (81.0 vs. 26.0%; p< 0.001). Conclusions: Cluster one and cluster two patients had different phenotypic features, possibly indicating different underlying genetic mechanisms. The cluster 1 phenotype may suggest a genetic or biology-based etiology, whereas the cluster two phenotype may be related to epigenetic mechanisms. Toxic exposure to cigarettes, either personally or secondarily, seems to be an important factor in the cluster two subgroup, inducing drug resistance and longer attacks. We need more studies to elaborate the causal relationship and the missing links of neurobiological pathways of cigarette smoking regarding the identified distinct phenotypic classes of patients with CH.

Living with Burden of Migraine: The Analysis of "My Migraine Voice" Survey Results in Turkey.

INTRODUCTION: Migraine is a common, chronic neurologic disease which causes serious social and economical disability at both the individual and the community level. The aim of this study was to interpret the data for Turkey from "My Migraine Voice," an online survey of individuals suffering from frequent migraine attacks (≥4 days/month with migraine headaches) who had not benefited from existing prophylactic therapies, conducted in 31 countries to investigate the burden of migraine for the individual and the society. METHODS: Based on a set of predetermined criteria (90% of the patients must have used prophylactic therapy, and 80% of them must have needed to change therapy), patients who had ≥ 4 days in a month with migraine headache in the past 3 months were asked to take an online survey of 88 questions. The study included questions aimed at determining the burden of disease during not only the headache phase, but also the prodrome and postdrome phases, as well as a questionnaire for determining the Reduction of Overall Activity and Productivity at Work ((WPAI: GH). RESULTS: A total of 237 patients from Turkey were included in the study. 62% of the patients stated that they were severely or very severely disabled in their daily activities during the headache phase of migraine, and 31% and 34% of the patients reported that they were disabled during the prodrome and postdrome phases, respectively. 28% of the patients stated they had been receiving prophylactic therapy for more than 2 years, and only 84% of these patients reported complete or partial satisfaction with their current therapies. This value was as low as ~70% in patients in whom 2 or more previous drug treatments or therapies had failed. Actively-working patients reported that they had lost 21% of their time at work due to migraine, and the overall loss of workforce was 67%. CONCLUSION: This study showed that migraine can cause disability in an individual's private and professional lives during every stage of migraine, including the prodrome and postdrome phases. This finding will be important for designing future treatments aimed at enhancing the quality of life and productivity of patients who cannot adequately benefit from existing therapies.

Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial.

INTRODUCTION: It is well-known that specific foods trigger migraine attacks in some patients. We aimed to investigate the effect of diet restriction, based on IgG antibodies against food antigens on the course of migraine attacks in this randomised, double blind, cross-over, headache-diary based trial on 30 patients diagnosed with migraine without aura. METHODS: Following a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA. Then, the patients were randomised to a 6-week diet either excluding or including specific foods with raised IgG antibodies, individually. Following a 2-week diet-free interval after the first diet period, the same patients were given the opposite 6-week diet (provocation diet following elimination diet or vice versa). Patients and their physicians were blinded to IgG test results and the type of diet (provocation or elimination). Primary parameters were number of headache days and migraine attack count. Of 30 patients, 28 were female and 2 were male, aged 19-52 years (mean, 35 +/- 10 years). RESULTS: The average count of reactions with abnormally high titre was 24 +/- 11 against 266 foods. Compared to baseline, there was a statistically significant reduction in the number of headache days (from 10.5 +/- 4.4 to 7.5 +/- 3.7; P < 0.001) and number of migraine attacks (from 9.0 +/- 4.4 to 6.2 +/- 3.8; P < 0.001) in the elimination diet period. CONCLUSION: This is the first randomised, cross-over study in migraineurs, showing that diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks.

Sex Differences of Migraine: Results of a Nationwide Home-based Study in Turkey.

INTRODUCTION: The prevalence of migraine was found to be more than three-fold higher in women as compared with men, and in addition to differences in prevalence rates, the characteristics and associated features might also differ between the sexes. The aim of this study was to compare sex-specific features of migraine and demographic parameters in a nationwide population-based study in Turkey. METHODS: Among 5323 subjects, a total of 871 patients who were diagnosed as having definite migraine according to the diagnostic criteria of the International Classification of Headache Disorders-III (ICHD-III) were included in our study. The demographic characteristics, associated features, and triggers of migraine were examined with regard to sex. RESULTS: The study group comprised 640 women (73.5%) and 231 men (26.5%), with a female to male ratio of 2.8:1. Attack duration, mean migraine disability assessment scores (MIDAS), frequencies of nausea, vomiting, osmophobia, vertigo/dizziness, and allodynia were found significantly different between women and men. When we compared these parameters between men and postmenopausal women, all these parameters were still significant except nausea. Odor was statistically more frequent as a reported trigger in women, whereas excessive sleep was a statistically more frequent triggering factor in men. The rates of depression and allergy were significantly higher in women when compared with men. CONCLUSION: Longer attack duration, higher MIDAS scores, and the frequencies of nausea, vomiting, osmophobia, vertigo/dizziness, and allodynia were more significant in women and this variance in sex persisted after menopause. Also, some trigger factors and co-morbidities differed between the sexes. These findings might result from complex genetic factors besides sociocultural influences, biologic, and sociocultural roles. Future studies should continue to explore biologic and genetic factors with respect to sex in migraine.

A Case of HaNDL with Low Cerebrospinal Fluid Level of Neurofilament Light Chain.

Diagnosis of the syndrome of headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is based on clinical features, and no diagnostic biomarkers are available. We present a case presenting with characteristic features of HaNDL and an MRI lesion in the splenium of corpus callosum. CSF neurofilament light chain (NFL) levels were assessed in this patient together with 7 additional HaNDL patients, 18 multiple sclerosis (MS) patients, and 15 primary headache patients. Both HaNDL and primary headache patients showed significantly lower NFL levels than MS patients. Our results suggest that increased CSF levels of NFL and neuroaxonal loss are not characteristic features of HaNDL. Neurological disorders mimicking HaNDL often present with increased levels of NFL, and thus CSF measurement of NFL might be useful in differential diagnosis of HaNDL.

Erratum: Evaluation of OnabotulinumtoxinA Treatment in Patients with Concomitant Chronic Migraine and Temporomandibular Disorders.

[This corrects the article on p. 330 in vol. 55, PMID: 30622389.].