Implications of therapy interruption on monthly migraine days and modified migraine disability assessment in patients treated with erenumab for chronic and episodic migraine: SQUARE study interim results.

BACKGROUND: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life. OBJECTIVE: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland. FINDINGS: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months. CONCLUSIONS: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart.

Prevalence and Burden of Migraine in Switzerland: Cross-Sectional Study in ten Specialised Headache Centres from the BECOME Study.

INTRODUCTION: There is limited real-world evidence on the burden of migraine among patients with prior preventive treatment failure (PPTF). In the BECOME Swiss subanalysis, we aimed to assess current prevalence of PPTF in patients with migraine seen at specialised headache centres in Switzerland and burden of migraine in these patients. Furthermore, we assessed this burden in subgroups stratified by monthly migraine days (MMDs) and number of PPTFs. METHODS: BECOME was a prospective, multicentre, non-interventional two-part study conducted in 17 countries across Europe and Israel. This subanalysis includes patients visiting ten headache specialist centres in Switzerland. In part 1, patients visiting the centres over 3 months were screened by physicians for frequency of PPTF, MMD and other migraine characteristics. Patients with ≥ 1 PPTF and ≥ 4 MMDs were invited to take part in part 2. The primary endpoint was the proportion of patients with ≥ 1 PPTF (part 1). Other endpoints included proportion of patients specified by number of PPTF and MMD (part 1, part 2), and impact of migraine on patient-reported outcomes (PROs; part 2). RESULTS: Patients (1677) from ten Swiss centres were included in part 1, of which 855 (51.0%) reported ≥ 1 PPTF. One hundred fifty-five patients were included in part 2: 6.5% reported ≥ 4 PPTFs and 43.2% reported ≥ 15 MMDs. Mean EuroQoL 5 and EuroQoL visual analogue scale (EQ-VAS) were 0.8 ± 0.2 and 69.6 ± 20.2, respectively, suggesting a mild level of impairment in the daily functioning and self-reported health of the patients. Mean six-item Headache Impact Test (HIT-6) and modified Migraine Disability Assessment (mMIDAS) scores were 63.3 ± 6.5 and 22.7 ± 21.8, respectively, corresponding to severe migraine burden. Patients also reported impairment in work-related productivity and general activities (48.6 ± 22.8) but no associations of anxiety (7.2 ± 4.4) or depression (6.0 ± 4.4) with migraine were noted. Burden of migraine increased with increasing frequency of PPTF and MMD. CONCLUSIONS: Migraine-related quality of life, as well as work productivity are significantly affected in Swiss patients with migraine. Increasing migraine burden is associated with increasing migraine frequency and prior treatment failures.

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND: The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS: An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS: In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS: Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION: BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS).

Impact on monthly migraine days of discontinuing anti-CGRP antibodies after one year of treatment - a real-life cohort study.

OBJECTIVE: This study aims to analyse the effect of the discontinuation of anti-calcitonin gene-related peptide antibodies on monthly migraine days after 12 treatment months. BACKGROUND: Anti-calcitonin gene-related peptide antibodies have been a game changer in migraine prophylaxis. However, high treatment costs warrant reducing treatment duration to the essential minimum. METHODS: We collected data of patients with migraine who had received anti-calcitonin gene-related peptide antibodies and had received treatment for 12 months. RESULTS: We included 52 patients. The average number of monthly migraine days was 16 ± 7 days at baseline, 6 ± 6 in the third, and 5 ± 4 in the 12th treatment month. After treatment interruption, the number of monthly migraine days was 6 ± 4 days in the first month, 9 ± 4 days in the second, and 11 ± 5 days in the third month. Most patients (88.9%) restarted treatment. CONCLUSION: Only little of the therapeutic effect of anti-calcitonin gene-related peptide antibodies outlasts their pharmacological effect. After treatment interruption, migraine frequency rose in most patients, and prophylaxis was required again in most cases.Limiting treatment to benefitting patients and confirming the need for prophylaxis periodically is reasonable. However, our data does not support the need for prescheduled treatment discontinuation after 12 months and a fixed duration of the treatment interruption of 3 months.

Pharmaceutically treated comorbidities and associated healthcare costs among triptan users in Switzerland: A pharmacoepidemiological study from a nationwide health insurance database.

PURPOSE: In course of the new migraine drug development on the global market it is important to quantify the current burden of migraine medication. This study aimed to estimate the comorbidity burden and its relation to healthcare costs in patients using triptans in Switzerland by analyzing a large population-based database. METHODS: This retrospective cohort study was based on Swiss health insurance claims data (2015/2016). The study sample comprised adult patients with ≥1 triptan prescription in 2015. We evaluated pharmaceutically treated comorbid conditions (CCs) and costs (12 months after index prescription) of patients using triptan. Multivariable linear regression models with log-transformed outcomes were performed to identify the factors related to healthcare costs. RESULTS: From a total of 749 092, we identified 10,090 patients using triptans (1-year prevalence of 1.35%), whereas 58.9% had ≥2 CCs. The most frequent CCs were pain- and rheumatologic-related diseases and psychological disorders. Among triptan users, the mean total healthcare costs were highest in older patients with ≥2 CCs (>64 years: migraine with ≥2 CC "12 331 SFr"). Multivariate regression analyses showed that psychological disorders had the strongest impact on healthcare costs (Coefficient: 1.29; 95%-CI: 1.27-1.31). CONCLUSIONS: The present study provides an overview of comorbidities and its related costs in migraine patients, which helps to quantify the current burden of migraine. This is relevant as the recently licensed CGRP antagonists are likely to change current treatment schemes for migraine, which strongly depends also on the comorbidities. The present study might therefore be helpful for the future development of treatment guidelines.

Treatment patterns in patients using triptan and prophylactic medication: an analysis of clinical practice prior to the introduction of CGRP antagonists.

PURPOSE: The newly developed calcitonin gene-related peptide (CGRP) antagonists were recently launched on the US and European market, with Switzerland as the second country worldwide. To enable forthcoming comparisons with established migraine therapy, the aim of this study was to provide a comprehensive picture of migraine (prophylactic) treatment patterns. Recent data in daily clinical practice are lacking. PATIENTS AND METHODS: This population-based cohort study included enrollees from a Swiss Healthcare Insurance Database with at least one triptan prescription in 2015. Treatment patterns were defined by assessing subsequent triptan and prophylactic medication use (after index prescription for triptan) within the following year, divided into four quarters. RESULTS: Triptans were used by 10,090 patients (1.3%) in 2015. Most of them used triptan only (82.6%), 12.9% changed the treatment between triptan and prophylactics, and 4.5% received both in combination within 1year. Among triptan users with ≥1 prophylactic prescription in the first quarter, 48.6% used beta-blockers (BB), 40.7% "other prophylactics than BB (eg, topiramate)", and 10.7% "a combination of both". Most patients who received both BB and other prophylactics in the first quarter used this drug combination continuously over all four quarters. CONCLUSION: This study provides comprehensive data on treatment patterns prior to the introduction of a new drug class in migraine therapy. The majority of triptan users had no prophylactic medication therapy; however, a small, but relevant group used BB and other prophylactics concurrently in all quarters. Findings quantify the population in potential need for optimized migraine therapy, ie, the potential target population of the novel CGRP-targeted drugs.

Migraine Burden of Disease: From the Patient's Experience to a Socio-Economic View.

Migraine is one of the most common diseases worldwide and, importantly, a major cause of disability. This translates into a huge clinical and economic burden to individuals and society. Despite existing data on how migraine affects populations, the disease continues to be underdiagnosed and therefore undertreated, so the scale of the public health problem may be underestimated. The impact on the daily lives of patients and their families has also been underappreciated. Clinical and regulatory guidelines are encouraging the use of patient-reported outcome tools (PROs), as these may help in disease management and facilitate physician-patient interactions. In clinical trials in migraine, PRO data are key to evaluating the effects of new therapies on patients, such as disability assessment, productivity, quality of life, and emotional and physical functioning. Digital technologies have enabled the development of ePRO tools, which may play a growing role in the collection of PRO data in the future. Here, we will consider the current view of the burden imposed by migraine on patients and society, illustrate this with two patient case studies, and examine the initiatives underway to use our knowledge to improve our management approaches for the disease.

Patients profiling for Botox® (onabotulinum toxin A) treatment for migraine: a look at white matter lesions in the MRI as a potential marker.

BACKGROUND: To evaluate if white matter lesions (WML) on MRI can be a potential marker for onabotulinum toxin A (Botox®) treatment success in migraine, given the limited response rate and high costs per treatment. METHODS: Retrospective data base and MRI analysis of 529 migraineurs who received Botox® between 2002 and 2009. Responders were defined as patients who underwent three or more treatments, whereas non-responders had only one or two treatments. MRIs were analysed on axial T2 and coronar FLAIR (fluid attenuated inversion recovery) sequences for the presence of WML. Statistical analysis was done with the Chi-Square-Test and the Mann-Whitney-U-Test. RESULTS: Of 529 Botox® treated migraineurs, 111 patients had a MRI. Of these 111 patients, 47 were responders, 64 non-responders to Botox®. Response rate to Botox® in migraineurs with WML was 55.3%, in migraineurs without WML 44.7%. In the investigated items "age", "age at onset", "gender", "attack duration", "frequency", "aura", "WML", "size of WML", we found no statistical significant difference between the two groups. 55% of the responders and 50% of the non-responders showed WML. All WML were located supratentorially, anteriorly, mostly of small size (3-5 mm). CONCLUSION: WML on MRIs cannot serve as a marker to predict a positive response to Botox®.

Desogestrel-only contraception may reduce headache frequency and improve quality of life in women suffering from migraine.

OBJECTIVE: To analyse the effects of a three-month course of progestogen-only contraception with desogestrel 75 µg on disability, headache frequency and headache intensity in migraineurs. MATERIALS AND METHODS: Migraine disability headache questionnaires (MIDAS) were collected from 37 migraineurs during counselling, and at the end of three months treatment with desogestrel. Another ten women initiated but did not complete treatment. They are included in the overall evaluations of the effect of the regimen on migraine status. RESULTS: Desogestrel was associated with significant reductions in headache days and intensity (p < 0.001; p < 0.006), and a significant improvement in quality of life. Days missed at work and days missing leisure activities diminished (p < 0.001; p < 0.001). The MIDAS migraine disability score improved significantly (from 27.4 to 11.1 points) (p < 0.001). While 25 of the 37 women (68%) experienced a decrease of at least one grade, this level of benefit cannot be extrapolated to all initiators. When dropouts are considered, MIDAS grades decrease in 53% (25/47) of the cases. CONCLUSION: The majority of migraineurs experienced a clinically significant reduction in headache frequency and improvement of quality of life with use of desogestrel. Prospective randomised controlled trials are needed to substantiate our results.

Self-reported headache among the employees of a Swiss university hospital: prevalence, disability, current treatment, and economic impact.

BACKGROUND: The objectives of this cross-sectional, observational study were to determine the prevalence of self-reported headache among the employees of the large Swiss university hospital, to measure the impact of headache using the MIDAS questionnaire, to assess current treatment and to estimate economic burden of headache considering indirect costs. METHODS: A self-administered questionnaire was distributed internally to 2000 randomly selected employees of the University Hospital Zurich. RESULTS: 1210 employees (60.5%) responded. Of the 1192 (98.5%) employees who provided sufficiently complete information, 723 (61%) reported at least one headache type in the last three months. The prevalence of migraine, and tension-type headache was 20% and 50%, respectively. Regarding the occupational groups, there was a trend that healthcare staff, administration employees, and medical technicians suffered more from headaches than physicians, correcting for age and sex. The economic consequences of lost productivity were calculated to amount to approximately 14 million Swiss Francs (9.5 million EUR), representing 3.2% of the overall annual expenditure of the hospital for personnel. CONCLUSION: Headache is highly prevalent among university hospital employees, with significant economic impact.

Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe paraparesis--case report and review.

Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.

Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. METHODS: 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. FINDINGS: 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p<0.0001) than in the topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups -1.09, -1.75 to -0.43; p=0.0011) [corrected] Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. INTERPRETATION: Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.

5HT1F- and 5HT7-receptor agonists for the treatment of migraines.

Serotonin was the first neurotransmitter believed to be involved in cephalic pain transfer forward to the cortex, but the precise mechanism was confirmed only after sumatriptan, a 5-HT(1B/1D0) high affinity agonist, was introduced in the acute treatment of migraine. Although very efficient for migraine relief, activation of 5-HT(1B) receptor may also cause vasoconstriction outside brain, within the heart arteries for example. Unlike 5-HT(1B), the 5-HT(1D) receptor is not located in vascular tissues but exclusively within neuronal, but high affinity agonists for 5-HT(1D) failed to prove clinical significance in randomized trials. The recent clone of 5-HT(1F) receptor together with data showing that sumatriptan exerts high affinity for this receptor subtype generated high expectations. Potent agonists for 5-HT(1F) receptors were effective in animal models for migraine and later clinical trials showed efficacy even in humans, introducing the first line future anti-migraine drugs. Apart from 5-HT(1F), another new cloned 5-HT subtype receptor, the 5-HT(7) also attracts attention. Recently developed and clinically tested selective 5HT(7) antagonists SB-269970-A and SB-656104-A suggest that the receptor may play a role in other CNS disorders including anxiety and cognitive disturbances, suggesting a potential role for the migraine prophylaxis. These data and speculations are discussed in details in this paper with special references.

Nosology and treatment of primary headache in a Swiss headache clinic.

We assessed demographics, diagnoses, course, severity, impact and treatment of primary headache outpatients from records in the Headache and Pain Clinic, Neurological Department, Zürich University Hospital. All outpatients seen from 1996 to 1998 for migraine, tension-type headache, and both, were included. Diagnoses, drug, physical and alternative treatments before and after referral were listed. Descriptive statistics were used for differences between the general population and this sample, the diagnoses, and treatments. The coexistence of migraine and tension-type headache, and the high frequencies of headache days would have excluded most migraine patients from typical drug trials: at best, only one third were eligible. The socioeconomic impact of combined and difficult syndromes calls for comprehensive management beyond simple treatment with instant relief drugs. The diagnostic and therapeutic practices of referring physicians exposed a deficit of information on headache, and a need for relevant education.

Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets.

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo. METHODS: These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies. RESULTS: The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.

Guidelines for the organization of headache education in Europe: the headache school.

According to its mission statement, one of the goals of the European Headache Federation (EHF) is to "educate Europe" about headache through the teaching of the key health personnel, such as young physicians and all those involved in headache management, about the seriousness of headache disorders. The countries of Europe share a close geographical proximity that facilitates international exchanges, particularly between university faculties. In recent years, this has, indeed, been the working basis of European educational endeavours in the field of headache. For a number of years, annual summer schools were organized in different European countries and a permanent Summer Headache School was set up in Cambridge (to be held every alternate year). The last summer headache school was held in Vilnius in 2002. In the past decade, a patronage scheme was also set up, which, combining two or more countries (one developed, one or more developing), allowed international exchanges of doctors and students for training purposes. In some centres, participants were also able to gain clinical practice and research experience by staying at the host institutions for extended periods of time. As a result of all this activity there have emerged, in Europe, "clusters" of people with a particular interest in headache. However, the rapid growth of insight into headache (new molecules, new headache categories, etc.) has contributed to a widening of the scientific gap between developing and developed countries. Moreover, in the past four years, due to the relative restriction of national/international drug company budgets, it has proved possible to organize only relatively inexpensive teaching courses. As a result, countries whose medical communities had been developing a "headache culture" now find themselves destined to be increasingly held back. Therefore, the EHF, in order to promote education on headache in Europe at national level, felt there was a need for guidelines for the organization of educational courses that meet uniform standards of excellence and in terms of code of conduct: guaranteed courses that will attract investors and those seeking to increase their knowledge, skills and understanding in the area of primary and secondary headache. The guidelines, presented here, specify the ideal length of a headache course, the number of lectures it should include, as well as the ideal number of participants and teachers. A sample course outline is provided, together with a checklist to help the organizers to meet the criteria for an EHF-approved headache school.