The burdens attributable to primary headache disorders in children and adolescents in Iran: estimates from a schools-based study.

BACKGROUND: We recently found headache disorders to be highly prevalent among children (aged 6-11 years) and adolescents (aged 12-17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study. METHODS: In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country's diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains. RESULTS: The analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores reflected these measures of burden. CONCLUSIONS: Headache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran.

The burden attributable to primary headache disorders in children and adolescents in Ethiopia: estimates from a national schools-based study.

BACKGROUND: We previously reported high prevalences of headache disorders among children (6-11 years) and adolescents (12-17 years) in Ethiopia. Here we provide data on headache-attributed burden collected contemporaneously from the same study participants. Part of the global schools-based programme within the Global Campaign against Headache, the study is the first to present such data from sub-Saharan Africa. METHODS: A cross-sectional survey following the generic protocol for the global study was conducted in six schools (urban and rural), in Addis Ababa city and three regions of Ethiopia. The child or adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaires were self-completed under supervision by pupils in class. Headache diagnostic questions were based on ICHD-3 beta but for the inclusion of undifferentiated headache (UdH). RESULTS: Of 2,349 eligible participants, 2,344 completed the questionnaires (1,011 children [43.1%], 1,333 adolescents [56.9%]; 1,157 males [49.4%], 1,187 females [50.6%]; participating proportion 99.8%). Gender- and age-adjusted 1-year prevalence of headache, reported previously, was 72.8% (migraine: 38.6%; tension-type headache [TTH]: 19.9%; UdH: 12.3%; headache on ≥ 15 days/month (H15+): 1.2%). Mean headache frequency was 2.6 days/4 weeks but, with mean duration of 2.7 h, mean proportion of time with headache was only 1.0% (migraine: 1.4%; TTH: 0.7%; H15+: 9.1%). Mean intensity was 1.8 on a scale of 1-3. Symptomatic medication was consumed on about one third of headache days across headache types. Lost school time reportedly averaged 0.7 days over the preceding 4 weeks, representing 3.5% of school time, but was 2.4 days/4 weeks (12.0%) in the important small minority with H15+. However, actual absences with headache the day before indicated averages overall of 9.7% of school time lost, and 13.3% among those with migraine. Emotional impact and quality-of-life scores reflected other measures of burden, with clear adverse impact gradients (H15 + > migraine > TTH > UdH). CONCLUSIONS: The high prevalence of headache among children and adolescents in Ethiopia, who represent half its population, is associated with substantial burden. Lost school time is probably the most important consequence. Estimates suggest a quite deleterious effect, likely to be reflected in both individual prospects and the prosperity of society.

Secondary headache disorders in Turkey, the Middle East, Asia, and Africa: A cross-sectional, multicenter study.

BACKGROUND: This multicenter cross-sectional study aimed to determine the frequency and characteristics of secondary headaches in different geographic regions, including Turkey, the Middle East, Asia, and Africa. METHODS: Patients were admitted to the study on a particular day each week for five consecutive weeks between 1 April and 16 May 2022. Before the study, all researchers underwent a constructed briefing about the use and code of the ICHD-3 criteria. The study was conducted in two stages. In the first stage, data on secondary headaches were compared between the regions. In the second stage, the sub-diagnoses of secondary headaches were analyzed only in Turkey. RESULTS: A total of 4144 (30.0%) of the 13,794 patients reported headaches as the main symptoms at admission. A total of 422 patients were excluded from the study. In total, 1249 (33.4%) of 3722 patients were diagnosed as having secondary headaches (Turkey [n = 1039], Middle East [n = 80], Asia [n = 51], Africa [n = 79]). The frequency of secondary headaches (Turkey 33.6%, Africa 30.1%, Middle East 35.5%, Asia 35.4%) did not differ significantly between the regions (p > 0.05). The most common subtype of secondary headaches was headache attributed to substances or their withdrawal in all the studied regions. There was a female predominance in all regions, but it was lower in Africa than in Turkey. The severity and density of headaches differed significantly between the regions, with patients from Africa reporting milder pain than patients from other regions. In Turkey, the most common sub-diagnoses of secondary headaches were medication overuse headache, idiopathic intracranial hypertension, and cervicogenic headache. CONCLUSION: In the present study, one in three patients with a headache had a secondary headache. Headache attributed to substances or their withdrawal was the most common subtype of secondary headaches in all the studied regions. The female predominance of secondary headaches was lower in Africa than in Turkey. The severity and density of headaches differed significantly between regions, with patients from Africa reporting milder pain.

Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) associated with pregnancy and puerperium has long been recognized, with poor information in terms of functional outcomes. Our objective was to analyze risk factors, clinical, imaging, and laboratory variables to predict functional outcome and death in this population. METHODS: CVT registries from three referral centers from Pakistan, Turkey, and Mexico, recruiting prospective cases, were combined for CVT associated with pregnancy or puerperium. Datasets and variables were standardized. Demographic characteristics, presentation, risk factors, and functional outcomes in pregnancy/puerperium-related CVT were analyzed. Binary logistic regression was used to assess predictors of outcome. The main outcome was modified Rankin score >2 at 30 days and mortality at 30 days. RESULTS: Five hundred fifty-three cases (median age 28 years [IQR 23-34]) of CVT associated with pregnancy and puerperium were included; 439 cases (79.4%) happened in the puerperium and 20.6% during pregnancy (53.5% occurred during the first trimester). Anemia (36.7%) and dehydration (22.9%) were the commonest obstetric risk factors identified. Predictors of poor outcome (mRS >2) were encephalopathy (OR 12.8, p < 0.001), cases from Mexican origin (OR 3.1, p = 0.004), fever/puerperal infection (OR 2.7, p = 0.02), and anemia (OR 2.2, p = 0.01). Cases from Mexican origin (OR 12.0, p = 0.003) and Encephalopathy (OR 7.7, p < 0.001), presented with the highest mortality association in the final adjusted model. DISCUSSION/CONCLUSION: In CVT associated with pregnancy and puerperium, encephalopathy, fever/puerperal infection, and anemia are associated with bad functional outcomes, meanwhile encephalopathy and cases from Mexican origin with higher mortality in the acute (30-days) of CVT onset. Anemia and infection are potential reversible predictors of poor outcome that clinicians should be aware of in order to prevent poor outcomes in these patients.

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.

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis.

OBJECTIVE: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach. RESULTS: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events. CONCLUSIONS: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 2: flunarizine.

OBJECTIVE: Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis. METHODS: A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation. RESULTS: Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06). CONCLUSIONS: Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 1: amitriptyline.

OBJECTIVE: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis. METHODS: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach. RESULTS: Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more). CONCLUSIONS: Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention.

European Headache Federation (EHF) critical reappraisal and meta-analysis of oral drugs in migraine prevention - part 3: topiramate.

OBJECTIVE: Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate. METHODS: A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework. RESULTS: Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)]. CONCLUSIONS: There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.

The prevalence of headache disorders in children and adolescents in Iran: a schools-based study.

BACKGROUND: While the Global Burden of Disease study reports headache disorders as the third-highest cause of disability worldwide, the headache data in this study largely come from adults. This national study in Iran, the first of its type in the Eastern Mediterranean Region, was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (6-11 years) and adolescents (12-17 years). METHODS: We followed the generic protocol for the global study. In a cross-sectional survey, self-completed structured questionnaires were administered to pupils within their classes in 121 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache. RESULTS: Of 3,357 potential participants, 3,244 (children 1,308 [40.3%], adolescents 1,936 [59.7%]; males 1,531 [47.2%], females 1,713 [52.8%]) satisfactorily completed the questionnaire. Children and males were therefore somewhat under-represented, with a participating proportion of 96.6%. Gender- and age-adjusted 1-year prevalence of any headache was 65.4%, of migraine 25.2%, of tension-type headache 12.7%, of undifferentiated headache 22.1%, of all headache on ≥15 days/month 4.1%, and of probable medication-overuse headache 1.1%. All headache types except undifferentiated headache were more prevalent among adolescents than children; probable medication-overuse headache increased five-fold between childhood and adolescence. CONCLUSIONS: Headache disorders are common in children and adolescents in Iran, with undifferentiated headache accounting for over one third of cases. The increasing prevalence of probable medication-overuse headache with age is concerning. These findings are of importance to health and educational policies in Iran.

Burden of headache in a HIV-positive population of sub-Saharan Africa.

BACKGROUND: About 26 million people are living with HIV in sub-Saharan Africa. The DREAM programme in sub-Saharan Africa provides free healthcare for HIV/AIDS and a range of chronic non-communicable diseases. HIV is a risk factor for neurological non-communicable diseases including stroke and epilepsy, which themselves are associated with headache, and HIV may be a direct risk factor for headache. We investigated the prevalence and burden of headache in a HIV+ population in sub-Saharan Africa. METHODS: At the DREAM Centre in Blantyre, Malawi, a low-income country with a population of 19 million and 9.2% HIV prevalence, a structured questionnaire was administered by a trained lay interviewer to consecutively attending HIV+ patients aged 6-65 years. All were monitored with regular viral load detection. RESULTS: Of 513 eligible patients invited, 498 were included (mean age 34.1 ± 12.8 years; 72% females; 15 declined). All were on antiretroviral treatment, with viral load undetectable in 83.9%. The 1-year prevalence of headache was 80.3% (females 83.6%, males 71.9%); 3.8% had ≥15 headache days/month, 1.4% had probable medication-overuse headache. Mean overall headache frequency was 4.4 ± 5.4 days/month. Those reporting headache lost means of 2.3% of paid workdays and 3.3% of household workdays because of headache. Only one third had sought advice for their headache. CONCLUSIONS: Headache is very prevalent among HIV+ patients in Malawi, imposing additional burden and costs on individuals and the community. Management of headache disorders should be implemented in HIV centres, as it is for other chronic non-communicable diseases.

The Global Campaign turns 18: a brief review of its activities and achievements.

The Global Campaign against Headache, as a collaborative activity with the World Health Organization (WHO), was formally launched in Copenhagen in March 2004. In the month it turns 18, we review its activities and achievements, from initial determination of its strategic objectives, through partnerships and project management, knowledge acquisition and awareness generation, to evidence-based proposals for change justified by cost-effectiveness analysis.

The prevalence of primary headache disorders in children and adolescents in Zambia: a schools-based study.

BACKGROUND: The Global Campaign against Headache collects data from children (6-11 years) and adolescents (12-17) to inform health and education policies and contribute to the Global Burden of Disease (GBD) study. This survey in Zambia, part of this global enquiry, was the second from sub-Saharan Africa (SSA). METHODS: Following the generic protocol, this was a schools-based cross-sectional survey. We used the child and adolescent versions of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, self-completed by pupils within classes, in a total of nine schools in Lusaka (urban) and Copperbelt (semi-rural). These two of Zambia's ten provinces were selected to represent the country's urban/rural divide. Headache diagnostic questions were based on ICHD-3 except for undifferentiated headache (UdH). RESULTS: Of 2,759 potential participants, 2,089 (615 children [29.4%], 1,474 adolescents [70.6%]) completed questionnaires (participating proportion 75.7%). Children were therefore under-represented (mean age 13.1 ± 2.8 years), while gender distribution (1,128 [54.0%] male, 961 [46.0%] female) was close to expectation. Observed lifetime prevalence of headache was 97.5%. Gender- and age-adjusted 1-year prevalence estimates were 85.8% for all headache, 53.2% for migraine (definite 17.5%, probable 35.7%), 12.1% for tension-type headache (TTH), 14.8% for UdH, 3.3% for all headache on ≥ 15 days/month and 0.9% for probable medication-overuse headache. Headache durations were short: only 28.6% of participants with any headache, and only 10.5% of those diagnosed as probable migraine, reported usual durations of > 2 h (the threshold for definite migraine). Of the latter, 36.6% reported < 1 h, the duration criterion for UdH. There were weak associations of migraine (definite + probable) with female gender, and of TTH and headache on ≥ 15 days/month with adolescence. Headache yesterday was reported by 22.2% of the sample, 25.5% of those with headache. CONCLUSIONS: Headache disorders among young people are prevalent in Zambia. Among them, migraine is the most common, with UdH also highly prevalent. In this study there were diagnostic uncertainties, which rested to a large extent on the distinction between migraine and UdH among the many participants reporting headache of < 2 h' duration. Similar uncertainties occurred in the first study in SSA, in Ethiopia. Because of these, we conclude only that migraine affects at least 17.5% of these age groups in Zambia, which is still a large proportion, adult prevalence in an earlier study being 22.9%. Supplementary estimates of attributed burden are needed to inform public-health and educational policies in Zambia.

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.

BACKGROUND: A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments. METHODS: The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided. RESULTS: We found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts' opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives. CONCLUSION: Monoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.

European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure.

BACKGROUND: Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder. MAIN BODY: The Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient's well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics. CONCLUSIONS: The novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care.

Does measurement of the jugular foramen diameter on MRI help to differentiate transverse sinus thrombosis from unilateral transverse sinus hypoplasia?

BACKGROUND AND PURPOSE: The transverse sinus (TS) is a frequent location of cerebral venous thrombosis. However, unilateral TS hypoplasia is a frequent variation and radiological imaging pitfall in the diagnosis because it may mimic unilateral TS thrombosis. The purpose of this study is to find a cutoff value for bilateral jugular foramen (JF) diameter ratios on magnetic resonance imaging (MRI) for differentiating TS thrombosis from TS hypoplasia. MATERIALS AND METHODS: We retrospectively reviewed magnetic resonance venography results for 174 patients with reduced unilateral TS caliber resulting from either unilateral thrombosis (80 patients) or unilateral hypoplasia (94 patients). We calculated the ratio by proportioning the diameter of the JF ipsilateral to the TS with caliber reduction to the diameter of the contralateral JF. The Mann-Whitney U test was used to compare the ratios between thrombosis and hypoplasia groups, and the cutoff value was calculated by receiver-operating characteristic curve analysis. RESULTS: The ratio of bilateral JF diameters was lower in patients with hypoplasia than those with thrombosis (P < .01). The cutoff value to determine the diagnosis of TS hypoplasia with maximum accuracy was 0.638, with a sensitivity of 91.3% and specificity of 64.9%. CONCLUSION: In equivocal cases, calculating the cutoff value by proportioning the diameter of JF ipsilateral to the TS with caliber reduction to the contralateral JF seems to be an efficient, quick, and straightforward method and valuable aid to differentiate TS thrombosis from TS hypoplasia.

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study.

BACKGROUND: We recently showed headache to be common in children (aged 7-11 years) and adolescents (aged 12-17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. METHODS: Following the generic protocol for Lifting The Burden's global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains. RESULTS: Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1-3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types. CONCLUSIONS: Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Are Migraine Patients at Increased Risk for Symptomatic Coronavirus Disease 2019 Due to Shared Comorbidities?

The coronavirus disease 2019 (COVID-19) pandemic has rapidly transformed the whole world and forced us to look through comorbid diseases and risk factors from a different perspective. COVID-19 shows some inherent risk factors like cardiovascular comorbidities independent from age, gender, and geographic location. One of the most peculiar features of the COVID-19 pandemic is that severe acute respiratory syndrome coronavirus 2 respiratory infections disproportionately impact patients with hypertension, diabetes, and other cardiovascular comorbidities rather than those with allergic respiratory diseases and immune-compromised conditions. Migraine is a complex neuro-vasculo-inflammatory disorder that is also packed frequently with certain medical conditions including vascular disorders, hypertension, allergic diseases such as asthma and systemic inflammatory disorders. Accordingly, 2 different questions arise during the pandemic: (1) Do share comorbidities of cardiovascular diseases and hypertension increase the risk of symptomatic COVID-19 for migraine patients? (2) Do comorbid allergic and atopic diseases, including asthma act as opposite influencers alongside with female gender? This paper focuses on the co-existence of comorbidities of COVID-19, in comparison with migraine, based on a wide clinical dataset and available reports. Discussed mechanisms include potential strategic roles of angiotensin-converting enzyme 2, angiotensin-II, and nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 inflammasome, playing remarkable parts in the pathogenesis of COVID-19 and migraine. There are also some clues about the importance of endothelial and pericyte dysfunction and neuroinflammation in COVID-19 infection, related to complications and survival of the patients. The large epidemiological studies as well as basic research, focusing on migraine patients with COVID-19 will clarify these vital questions during the upcoming periods.

Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.

INTRODUCTION: Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. MATERIALS AND METHODS: In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. RESULTS: CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. DISCUSSION AND CONCLUSION: CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.