Societal and economic burden of migraine in Spain: results from the 2020 National Health and Wellness Survey.

BACKGROUND: The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. METHODS: Case-control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1-3, 4-7, 8-14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables. RESULTS: The survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1-3 MHD also increased costs by 51.3%. CONCLUSIONS: Having migraine not only causes a massive impact on patients' quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1-3 MHD.

Pathophysiology of migraine aura.

Migraine aura occurs in about a third of patients with migraine and consists of a group of transient focal neurological symptoms that appear from 5 to 60min and then resolve prior to or in the early phase of a migraine headache attack. Migraine auras may consist of visual, language, unilateral sensory, or motor symptoms. There has been considerable debate as to the origins of the migrainous aura. Investigations during physiologically induced visual auras suggest that the phenomenon of cortical spreading depression or its human equivalent underpins the migraine aura. Single gene defects have been linked to relatively rare forms of the motor subtypes of aura known as familial hemiplegic migraine (FHM). These include CACNA1A (FHM1), ATP1A2 (FHM2), and SCN1A (FHM3). In the familial hemiplegic forms of migraine, the more typical forms of aura are almost always also present. Despite ample epidemiological evidence of increased heritability of migraine with aura compared to migraine without aura, identification of the specific variants driving susceptibility to the more common forms of aura has been problematic thus far. In the first genome-wide association study (GWAS) that focused migraine with aura, a single SNP rs835740 reached genome-wide significance. Unfortunately, the SNP did show statistical significance in a later meta-analysis which included GWAS data from subsequent studies. Here, we review the clinical features, pathophysiological theories, and currently available potential evidence for the genetic basis of migraine aura.

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.

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.

The 5-HT1F receptor as the target of ditans in migraine - from bench to bedside.

Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans - a group of selective serotonin 5-HT1F receptor agonists - has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.

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 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) 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.

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.

The impact of a digital platform on migraine patient-centered outcome research. Evaluation of midolordecabeza.org, a headache website in Spanish.

OBJECTIVE: This internet survey aimed to analyze the activity of midolordecabeza.org, a specialized website for headache stakeholders. BACKGROUND: eHealth tools, such as websites, can be educational for stakeholders of a specific disease, such as patients. This is particularly helpful in chronic disorders such as migraine. eHealth also enhances patient-centered outcome research. The website midolordecabeza.org has the stated aim of organizing key information on headache making it accessible and useful for all stakeholders, and, eventually promoting patient participation. METHODS: We analyzed Google Analytics (GA) data to study the web's activity, traffic source, geographical distribution of access, registered-user behavior, electronic device performance, and temporary references with greater web activity. RESULTS: From January 2015 until December 2020, the website registered 1,121,585 visitors, 1,775,953 sessions, and a total of 3,833,144 views with an average time per session of nearly 2 min. Higher data traffic has been registered in Spanish-speaking countries such as Spain (33.3%; 591,256/1,775,953), where Spain's regions with higher views were statistically significantly correlated with the nationwide migraine prevalence (ρ = 0.505; p = 0.039). In regard to social behavior, returning users were statistically significantly associated with being a woman (84.0%; 5696/6781), and they predominantly acceded from organic searches (50.6%; 3434/6781). When answering available open surveys, 72.5% (1827/2520) described their migraine as a disabling disease with high impact on their daily tasks and 64.4% (14,016/21,764) were unaware of what their headache diagnosis is. CONCLUSIONS: Spanish-speaking patients with migraine around the world increasingly visited the headache-specialized website midolordecabeza.org using different electronic devices, showing great interest in their disease. This website allowed them to get updated information on their disease, share clinical data with physicians, and finally express their concerns.

Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm.

INTRODUCTION: Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM. METHODS: Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs. RESULTS: During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM). CONCLUSION: Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit-risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1. TRIAL REGISTRATION NUMBERS: EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257.

Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance.

BACKGROUND: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. METHODS: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. RESULTS: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. CONCLUSIONS: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

Cluster headache therapies: pharmacology and mode of action.

INTRODUCTION: Cluster headache (CH) is the most common trigeminal autonomic cephalalgia with a significant need for novel treatment options. While the use of most of the acute CH medications is supported by clinical trials and based on a pathophysiological concept for the generation of pain, the scientific evidence for preventive CH medications is very limited. AREAS COVERED: This article reviews acute and preventive substances for the pharmacological treatment of CH with a focus on the mode of action of these drugs. We also summarized the clinical trial evidence and discuss future research directions. EXPERT OPINION: Recommendations for current pharmacological CH therapies, in particular for CH prevention, are often based on small open label studies with inconclusive results. Larger trials are missing. A shared pathophysiological mechanism of action of these preventatives does not exist. Future studies with CGRP(R) antibodies and novel substances with specific actions are needed and will thereby help to understanding the pathophysiology of CH.

European headache federation consensus on the definition of resistant and refractory migraine : Developed with the endorsement of the European Migraine & Headache Alliance (EMHA).

INTRODUCTION: Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances. MAIN BODY: Definitions were established with a consensus process using the Delphi method. Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures. Resistant migraine is defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts. Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 consecutive months. Drug failure may include lack of efficacy or lack of tolerability. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required. CONCLUSIONS: We hope, that the updated EHF definition will be able to solve the conflicts that have limited the use of definitions which have been put forward in the past. Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved. This new definition has also the aim to increase the understanding of the impact of the migraine as a disease with all of its social, legal and healthcare implications. It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

The potential of lasmiditan in migraine.

Lasmiditan, a highly selective 5-hydroxytryptamine receptor 1F (5-HT1F) agonist, is the first drug in its class and is lacking triptan-like vasoactive properties. The US Food and Drug Administration (FDA) has recently approved lasmiditan for the acute treatment of migraine in adults based on positive results of two pivotal phase III trials, which showed a significant difference to placebo in the proportion of patients achieving total migraine freedom within 2 h. More patients with lasmiditan achieved headache freedom and, in addition, freedom from the most bothersome symptom, that is, photophobia, than with placebo. Treatment-related side effects seem to be related to the rapid penetration of the drug into the brain and include dizziness, paresthesia and drowsiness, mostly of mild to moderate intensity. Interim results from an ongoing long-term phase III trial suggest a decrease in the frequency of adverse events after multiple lasmiditan use. Lasmiditan is a promising acute anti-migraine therapy, in particular for patients with cardiovascular risk factors, contraindications, or unwanted side effects to triptans.

Transcranial static magnetic field stimulation (tSMS) of the visual cortex decreases experimental photophobia.

Background Transcranial static magnetic field stimulation (tSMS) reduces cortical excitability in humans. Methods The objective of this study was to determine whether tSMS over the occipital cortex is effective in reducing experimental photophobia. In a sham-controlled double-blind crossover study, tSMS (or sham) was applied for 10 minutes with a cylindrical magnet on the occiput of 20 healthy subjects. We assessed subjective discomfort induced by low-intensity and high-intensity visual stimuli presented in a dark room before, during and after tSMS (or sham). Results Compared to sham, tSMS significantly reduced the discomfort induced by high-intensity light stimuli. Conclusions The visual cortex may contribute to visual discomfort in experimental photophobia, providing a rationale for investigating tSMS as a possible treatment for photophobia in migraine.

Errors in recognition and management are still frequent in patients with cluster headache.

OBJECTIVES: To analyze the trajectory to diagnosis and information provided in a series of cluster headache (CH) patients from five headache clinics. METHODS: CH patients were asked to fill in an ad hoc questionnaire. RESULTS: Seventy-five patients (mean age 41.5 years, 67 males) completed the questionnaire. Patients had visited during an average of 4.9 years a mean of 4.6 physicians who had obtained 2.5 neuroimaging procedures per patient before getting a diagnosis of CH. Sixty-three (84%) had received no diagnosis (21 cases; 28%), while 43 (57%) had been given an average of 2.1 alternative diagnoses. Migraine, trigeminal neuralgia and sinusitis were the most frequent mistakes. After diagnosis, 55% had subjectively received poor/very poor information on CH. Ninety-five percent had poor or incorrect information about the nature of the disease, or acute (70%) and preventive (61%) treatments. Etiology (90%), management options (36%) and potential adverse events of medications (29%) were their main information demands. CONCLUSIONS: Although CH is an invalidating and clinically clear-cut disorder suffered by around 1/1,000 people, it is still frequently unrecognized and/or mistaken for other disorders, which calls for a better knowledge and education in the diagnosis of the main primary headaches.

Photoreactivity of the occipital cortex measured by functional magnetic resonance imaging-blood oxygenation level dependent in migraine patients and healthy volunteers: pathophysiological implications.

BACKGROUND: The brain of migraineurs is hyperexcitable, particularly the occipital cortex, which is probably hypersensitive to light. Photophobia or hypersensitivity to light may be accounted for by an increased excitability of trigeminal, the visual pathways, and the occipital cortex. OBJECTIVE: To study light sensitivity and photophobia by assessing the response to light stimuli with functional magnetic resonance imaging-blood oxygenation level dependent (fMRI-BOLD) of the occipital cortex in migraineurs and in controls. Also, to try to decipher the contribution of the occipital cortex to photophobia and whether the cortical reactivity of migraineurs may be part of a constitutional (defensive) mechanism or represents an acquired (sensitization) phenomenon. METHODS: Nineteen patients with migraine (7 with aura and 12 without aura) and 19 controls were studied with fMRI-BOLD during 4 increasing light intensities. Eight axial image sections of 0.5 cm that covered the occipital cortex were acquired for each intensity. We measured the extension and the intensity of activation for every light stimuli. Photophobia was estimated according to a 0 to 3 semiquantitative scale of light discomfort. RESULTS: Migraineurs had a significantly higher number of fMRI-activated voxels at low (320.4 for migraineurs [SD = 253.9] and 164.3 for controls [SD = 102.7], P = .027) and medium-low luminance levels (501.2 for migraineurs [SD = 279.5] and 331.1 for controls [SD = 194.3], P = .034) but not at medium-high (579.5 for migraineurs [SD = 201.4] and 510.2 for controls [SD = 239.5], P = .410) and high light stimuli (496.2 for migraineurs [SD = 216.2] and 394.7 for controls [SD = 240], P = .210). No differences were found with respect to the voxel activation intensity (amplitude of the BOLD wave) between migraineurs and controls (8.98 [SD = 2.58] vs 7.99 [SD = 2.57], P = .25; 10.82 [SD = 3.27] vs 9.81 [SD = 3.19], P = .31; 11.90 [SD = 3.18] vs 11.06 [SD = 2.56], P = .62; 11.45 [SD = 2.65] vs 10.25 [SD = 2.22], P = .16). Light discomfort was higher in the group of migraineurs at all the intensities tested, but there was no correlation with the number of activated voxels in the occipital cortex and photophobia. Repetitive light stimuli failed to demonstrate a lack of habituation in migraineurs. CONCLUSIONS: Migraineurs during interictal periods showed hyperxcitability of the visual cortex with a wider photoresponsive area, the underlying mechanism probably being dual: constitutional-defensive and acquired-sensitizating.

Perimenstrual migraines and their response to preventive therapy with topiramate.

INTRODUCTION: Preventive treatment with topiramate is effective for overall reduction of migraine frequency, but there are few data regarding its efficacy on perimenstrual migraines. To determine whether topiramate can prevent perimenstrual migraines, we analyzed data from premenopausal women as a subgroup of the Prolonged Migraine Prevention with Topiramate (PROMPT) study. METHODS: In total, 198 women from the PROMPT study with menstrually related migraine (MRM) were evaluated. After a one-to-two-month prospective baseline period, patients received open-label topiramate (50-200 mg/day) for six months. RESULTS: During topiramate treatment, mean monthly migraine frequency was reduced from 7.03 at baseline to 4.36 (mean change: -2.66; p < .001, endpoint analysis). Mean percentage reductions were similar for migraines during and outside the perimenstrual period (-45.9% and -46.1%, respectively). In patients with aura, reductions in migraine days with (-48.3%) or without (-43.4%) aura were similar to those in patients without aura (-45.4%). Reductions were also similar whether women were taking combined oral contraceptives (-47.0%) or were not (-46.6%). CONCLUSIONS: Topiramate reduces the frequency, but not severity or duration, of perimenstrual migraines in women with MRM, including migraines with and without aura, and regardless of combined oral contraceptive use.