Headache-free Days Research Articles

Comparison of migraine with left- versus right-sided headache: A cross-sectional study.

The goal of this study was to clarify whether clinical differences exist between patients with migraine who experience headache that is typically left-sided ("left-migraine") versus right-sided ("right-migraine") during attacks. Migraine has been associated with unilateral headache for millennia and remains a supportive trait for the clinical diagnosis of migraine of the International Classification of Headache Disorders. It is currently unknown why headache in migraine is commonly unilateral, and whether headache-sidedness is associated with other clinical features. This is a cross-sectional study comparing left- versus right-migraine using all available intake questionnaires of new patients evaluated at an academic tertiary headache center over a 20-year period. Eligibility was based on patient written responses indicating the typical location of headache during attacks. In our analyses, the side of headache (left or right) was the predictor variable. The outcomes included various migraine characteristics and psychiatric comorbidities. We identified 6527 patients with migraine, of which 340 met study eligibility criteria. Of these, 48.8% (166/340) had left migraine, and 51.2% (174/340) had right migraine. When comparing patients with left- versus right-migraine, patients with left migraine experienced 3.6 fewer headache-free days (95% confidence interval [CI] 1.3-5.9; p = 0.002) and 2.4 more severe headache days (95% CI 0.8-4.1; p = 0.004) in the previous 4 weeks. No significant differences in age, sex, handedness, migraine characteristics, or psychiatric comorbidities were identified between the two groups. Patients with migraine with typically left-sided headache during attacks reported a higher burden of headache frequency and severity than those with typically right-sided headache during attacks. These findings may have implications for our understanding of migraine pathophysiology, treatment, and clinical trial design.

Migraine and endovascular closure of patent foramen ovale as a method of its treatment: a literature review

The literature review is devoted to the pathophysiology and clinical picture of migraine, targets of therapy and drugs used, and the connection between the pathogenesis of migraine with aura and patent foramen ovale is discussed. The results of clinical studies show a positive effect of endovascular patent foramen ovale closure on the course of migraine in the form of a decrease in the intensity, frequency of attacks and the number of headache-free days, as well as in some cases complete relief of the disease. Further study of the topic is promising, but requires careful study design and long-term follow-up of patients.

Nonsurgical Treatment of Neuralgia and Cervicogenic Headache: A Systematic Review and Meta-analysis.

Background:Extracranial compression of peripheral sensory nerves is one of many origins of chronic headaches. Identifying these patients can be difficult, and they are often diagnosed with neuralgia or cervicogenic headache. The recent literature provides the outcomes of surgical decompression in patients with these headaches. This study aimed to give an overview of the current literature on the nonsurgical treatment options and to evaluate the effectiveness of these treatments in patients with neuralgia and cervicogenic headache.Methods:Databases were searched to identify all published clinical studies investigating nonsurgical treatment outcomes in patients with neuralgia or cervicogenic headaches. Studies that reported numerical pain scores, nonnumerical pain scores, headache-free days, or the number of adverse events after nonsurgical treatment were included.Results:A total of 22 articles were included in qualitative analysis. The majority of studies included patients who received injection therapy. Treatment with oral analgesics achieved good results in only 2.5% of the patients. Better outcomes were reported in patients who received local anesthetics injection (79%) and corticosteroid injection (87%). Treatment with botulinum toxin injection yielded the highest percentage of good results (97%; 95% CI, 0.81–1.00). The duration of headache relief after injection therapy varied from 30 minutes to 5 months.Conclusions:The nonsurgical treatment of patients with neuralgia or cervicogenic headache is challenging. Injection therapy in patients with these types of headaches achieved good pain relief but only for a limited time. Surgical decompression may result in long-lasting pain relief and might be a more sustainable treatment option.

Crystal-clear days and unclear days in migraine: A population-based study.

To investigate crystal-clear days and unclear days in participants with migraine. Migraine affects individuals during the headache-free period. Therefore, headache-free days do not indicate migraine symptom-free days. Crystal-clear days can be characterized by days without headache and having minimal or no migraine symptoms. In contrast, days without headache, but with more than minimal migraine symptoms, can be defined as unclear days. We used the baseline respondent data set of the Circannual Change in Headache and Sleep study, a nationwide population survey on headache and sleep. This study was a cross-sectional and case-control analysis of longitudinally collected data. The number of crystal-clear days per 30 days was assessed by asking "How many days have you had crystal-clear days without headache during the previous 30 days?". We defined headache-free, but not crystal-clear days, as unclear days. The number of unclear days per 30 days was calculated as follows: 30-the number of headache days per 30 days-the number of crystal-clear days per 30 days. Of 170 participants with migraine, 165 (97.1%) had unclear days. The numbers of crystal-clear days (median [interquartile range] 20.0 [15.0-25.0] vs. 25.0 [20.0-29.0], p < 0.001) and unclears days (4.0 [0.0-8.0] vs. 1.0 [0.0-7.0], p < 0.001) per 30 days in participants with migraine were significantly lower and higher, respectively, than in those with non-migraine headache. Headache days (incident rate ratio and 95% confidence interval, 0.94 [0.90-0.97], p < 0.001) and weekly average sleep duration (0.95 [0.91-1.00], p=0.035) were significant factors for crystal-clear days. The number of crystal-clear days were different from that of headache-free days. Almost all participants with migraine had unclear days. Our findings will facilitate understanding the symptoms and burden of migraine.

Efficacy of Fremanezumab In Resistant and Refractory Chronic Migraine Patients: Real-World Data from The Hull Migraine Clinic, Uk

Background Fremanezumab is an anti-calcitonin gene-related peptide monoclonal antibody efficacious for chronic migraine prophylaxis. We evaluated real-world prophylactic efficacy of fremanezumab for refractory and resistant chronic migraine in a United Kingdom specialist headache centre (Hull Migraine Clinic). Materials and Methods 289 adult patients with resistant and refractory chronic migraine commenced fremanezumab with prospective follow-up, maintaining headache diaries for ≥1-month pre-fremanezumab initiation and continuously thereafter. Patients failed 6 median previous prophylactics. We measured monthly headache days, migraine days, headache-free days, analgesia medication days, triptan days and Headache Impact Test-6 scores at baseline and during treatment. Results All outcomes significantly improved in results of 182 patients at 4-month follow-up (p&lt;0.0001), with reduced median monthly headache days (by 9 days), migraine days (by 10 days) and Headache Impact Test-6 (by 14.5 points). 80% patients achieved ≥30% migraine reduction, whilst 68% and 42% patients achieved &gt;50% and &gt;75% reduction. 58%, 39% and 17% patients achieved ≥30%, &gt;50% and &gt;75% headache day reduction. OnabotulinumtoxinA-unresponsive patients exhibited substantial responses, with 78%, 66% and 39% patients achieving ≥30%, &gt;50% and &gt;75% migraine reduction. Medication-overuse did not affect responses. 45% patients achieved &lt;15 headache days in any month, and 65% achieved &lt;8 migraine days in any month. 37% achieved both outcomes. In multivariate analyses, baseline headache-freedom and lower Headache Impact Test-6 score associated with ≥30% migraine reduction (p&lt;0.05), whilst baseline headache-freedom and lower migraine-days associated with achieving &lt;15 headache days in any month (p&lt;0.01). Conclusion Fremanezumab demonstrates real-world efficacy at 4 months in resistant and refractorychronic migraine, including in OnabotulinumtoxinA-unresponsive patients, irrespective of medication-overuse. Baseline headache-freedom, lower migrainedays and lower Headache Impact Test-6 score heralded superior responses.

Practical Insights on the Identification and Management of Patients with Chronic Migraine.

Chronic migraine (CM) is one of the most disabling diseases, and it is commonly misdiagnosed and mistreated. Despite the importance of a timely and accurate diagnosis for the effective management of CM, recent surveys have shown that only 20–25% of individuals with CM receive a correct diagnosis. The obvious consequences of misdiagnosed CM are prolongation of symptoms and their associated effects on disability and health-related quality of life. Additionally, mistreatment of CM can lead to acute medication overuse headache with escalation of headache and end organ damage. Ideally, a diagnosis of CM should be made in the primary care setting, based on a thorough medical history including detailed descriptions of headaches occurring earlier in life as well as current headaches, and the range of headaches (not just the worst headaches). In our experience, it is often equally informative to ask the patient about the number of headache-free days (HFDs) and no accompanying symptoms (i.e., crystal-clear days) to quantify headache days and accurately estimate headache frequency/impact. Headache frequency is important, as this count is one key means of diagnosing CM, which requires ≥ 15 headache days/month, noting that these do not need to be migraine days. A headache day is defined as more than 4 h a day of headache. Comorbidities are common in CM and may affect the treatment choice and increase disability. Every CM patient should be offered a preventive migraine treatment. In this commentary, we provide practical insights and tips for diagnosing CM and cover issues of medication overuse, patient communication, diagnostic testing, and when to make a referral. Our key message to physicians for a patient who comes to the clinic with frequent disabling headaches having features of migraine is to assume CM until proven otherwise.

The burden and health care use of patients with migraine and tension-type headache in post-conflict area of Serbia.

The aim of the present study was to assess the burden and health care use of adult patients with migraine and tension type headache in a post-conflict area of Serbia. This cross-sectional study was conducted on a representative sample of adults, living in predominantly Serb communities on the Kosovo and Metohija territory. The required data was obtained through a survey, utilizing a culturally-adapted questionnaire. The study sample comprised of 1,062 adults. In the year preceding the study, 49.7% of included subjects suffering from migraines and 27.5% of those experiencing tension type headache sought medical assistance for their condition. The majority (88.5%) of the respondents utilized non steroid antiinfammatory drugs as analgesic, while 14.2% used prophylactic treatment. Migraine sufferers reported losing on average 11.1 days in a 3-month period, while those experiencing tension type headache lost 4.7 days (p < 0.001) due to headaches, preventing them from partaking in professional, family and social activities. On headache-free days, 24.5% of the respondents were anxious or tense in anticipation of a headache onset, while 30% did not feel that the headache had completely resolved. Moreover, 11.5% of the sample reported never or rarely feeling in control of the headache, while 20% of the respondents were of view that their headaches were not taken seriously by their employer and co-workers and rarely discuss them. Adverse effect of headaches on education is more frequently noted by migraine sufferers than those experiencing tension type headache (p = 0.001), and this disparity persists in relation to career (p < 0.001) and family planning (p = 0.001). In Kosovo and Metohija, primary headaches exert a profound influence on the affected individuals and their community, and thus require recognition as one of the priorities of social initiatives aimed at the enhancement of public health.

CGRP antibody therapy in patients with drug resistant migraine and chronic daily headache: a real-world experience

BackgroundCalcitonin gene-related peptide (CGRP) (receptor) antibodies (erenumab, fremanezumab and galcanezumab) are increasingly used in prophylactic treatment of migraine. In the approval studies, severely affected patients with migraine and chronic daily headache without any headache free days were excluded. Thus, less is known about the effectiveness of CGRP antibody treatment in this cohort.MethodsClinical routine data of 32 patients with migraine and daily headache were analysed after three months of treatment with a CGRP antibody (16 erenumab, 7 galcanezumab, 9 fremanezumab), including changes of monthly headache days (MHD) monthly migraine days (MMD) and monthly acute medication intake (AMD) as well as migraine characteristics. Statistical analysis was performed with the Wilcoxon-Test. Migraine characteristics were analysed descriptively.ResultsThe number of MHD was significantly reduced (mean reduction (standard error), p-value): (-4.2 (1.3), p = 0.009) as well as MMD (-4.3 (1.6), p = 0.033). Four patients (13 %) reached a 50 % reduction regarding MHD and 8 patients (25 %) regarding MMD, migraine duration and intensity improved under therapy.ConclusionsDespite the low responder rate, CGRP antibodies can be effective at least in a few cases of severely affected patients with drug resistant migraine and chronic daily headache.Trial registrationRetrospective registered.

Changes in the gene expression profile during spontaneous migraine attacks

Migraine attacks are delimited, allowing investigation of changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore, we hypothesized that changes in RNA expression during and outside a spontaneous migraine attack exist which are specific to migraine. Twenty-seven migraine patients were assessed during a spontaneous migraine attack, including headache characteristics and treatment effect. Blood samples were taken during attack, two hours after treatment, on a headache-free day and after a cold pressor test. RNA-Sequencing, genotyping, and steroid profiling were performed. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and genomic and transcriptomic data were integrated. We found 29 differentially expressed genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specific genes, that were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed mechanisms affected by changes in gene interactions, e.g. ‘ion transmembrane transport’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’. In conclusion, we uniquely investigated intra-individual changes in gene expression during a migraine attack. We revealed both genes and pathways potentially involved in the pathophysiology of migraine and/or migraine treatment.

Introduction of a smartphone based behavioral intervention for migraine in the emergency department

ObjectiveTo determine whether a smartphone application (app) with an electronic headache diary and a progressive muscle relaxation (PMR) intervention is feasible and acceptable to people presenting to the Emergency Department (ED) with migraine. MethodsThis single arm prospective study assessed feasibility by actual use of the app and acceptability by satisfaction with the app. We report preliminary data on change in migraine disability and headache days. ResultsThe 51 participants completed PMR sessions on a mean of 13 ± 19 (0,82) days for the 90-day study period, lasting a median of 11 min (IQR 6.5, 17) each. Median number of days of diary use was 34 (IQR 10, 77). Diaries were completed at least twice a week in half of study weeks (337/663). Participants were likely (≥4/5 on a 5-point Likert scale) to recommend both the app (85%) and PMR (91%). MIDAS scores significantly decreased by a mean of 38 points/participant (p < 0.0001). More frequent PMR use was associated with a higher odds of headache free days (p = 0.0148). ConclusionSmartphone-based PMR introduced to patients who present to the ED for migraine is feasible and acceptable. More frequent users have more headache free days. Future work should focus on intervention engagement.

Green Flags and headache: A concept study using the Delphi method.

The aim of this study was to collect and rate Green Flags, that is, symptoms or pieces of information indicating that a patient is more likely to suffer from a primary than from a secondary headache. When assessing headaches, a central question to be answered is whether the pain is primary or secondary to another disorder. To maximize the likelihood of a correct diagnosis, relevant signs and symptoms must be sought, identified, and weighed against each other. The project was designed as a Delphi study. In the first round, an expert panel proposed green flags that were rated anonymously in two subsequent rounds. Proposals with an average rating of 4.0 and higher on a scale from 0 to 5 reached consensus. Five Green Flags reached consensus: (i) "The current headache has already been present during childhood"; (ii) "The headache occurs in temporal relationship with the menstrual cycle"; (iii) "The patient has headache-free days"; (iv) "Close family members have the same headache phenotype"; and (v) "Headache occurred or stopped more than one week ago." We propose five Green Flags for primary headache disorders. None being a pathognomonic sign, we recommend searching for both Green Flags and Red Flags. If both are present, a secondary headache should be suspected. Overall, the application of the Green Flag concept in clinical practice is likely to increase diagnostic accuracy and improve diagnostic resource allocation. Prospective studies in clinical populations should be conducted to validate these Green Flags.

Effect of Headache-Free Days on Disability, Productivity, Quality of Life, and Costs Among Individuals with Migraine.

The functional impairment associated with migraine can cause physical, emotional, and economic ramifications that can affect occupational, academic, social, and family life. Understanding the relationship between headache-free days (HFDs) and the disease burden of migraine may help with decisions regarding treatment and management of migraine. To determine the relationship between burden of disease measures and HFDs among individuals with migraine experiencing ≥ 4 headache days in the previous 30 days. The 2016 U.S. National Health and Wellness Survey (N = 97,503) was self-administered to a nationally representative sample of adults. Respondents with a migraine diagnosis who reported ≥ 4 headache days a month were included in the analysis. The primary independent variable was the number of HFDs assessed as both a continuous (HFDs in the previous 30 days) and categorical (0-10, 11-20, and 21-26 HFDs) measure. HFDs were used to predict outcomes using separate generalized linear models. Outcomes included effect on functional status and well-being, measured by the 6-item Headache Impact Test (HIT-6) score; number of days of work and/or household activities missed due to migraine; annualized indirect costs due to work productivity loss (assessed via the Work Productivity and Activity Impairment questionnaire); and annualized direct costs due to health care resource use (health care provider visits, emergency room visits, and hospitalizations). The survey included 372 respondents with diagnosed migraine and ≥ 4 headache days per month. Using HFDs as a continuous variable, each additional HFD was associated with a 0.15-point reduction in HIT-6 scores, a 5% reduction in both number of work days and household activities missed, and a 4% reduction in indirect costs; thus, a 5-day increase in HFDs would lead to a 0.75-point reduction in HIT-6 scores, 25% reduction in days of work or household activities missed, and 20% reduction in indirect costs. Analyzing HFDs as a categorical variable, respondents experiencing 21-26 HFDs had lower HIT-6 total scores than those with 0-10 HFDs (adjusted means: 66.59 vs. 63.91; P = 0.001) or those with 11-20 HFDs (65.66 vs. 63.91, P = 0.015). Respondents experiencing 21-26 HFDs missed fewer work days than those with 0-10 HFDs (4.44 vs. 1.46, P = 0.002) or those with 11-20 HFDs (3.36 vs. 1.46, P = 0.009). Similarly, respondents with 11-20 HFDs (22.99 vs. 9.72, P < 0.001) and those with 21-26 HFDs (22.99 vs. 7.34, P = 0.001) were associated with fewer days of household activities missed due to migraine compared with respondents with 0-10 HFDs. Respondents with 21-26 HFDs per month had significantly lower indirect costs ($16,975 vs. $6,919, P = 0.025) than those with 0-10 HFDs. A higher number of HFDs is associated with decreased headache-related disability among those with migraine. Interventions that increase the total number of HFDs may reduce the burden and cost associated with migraine. This study was funded by Teva Pharmaceutical Industries (Petach Tikva, Israel). Cohen is an employee of Teva Branded Pharmaceutical Products R&D (USA); Bell was employed by Teva Pharmaceutical Industries at the time of this study and has stock/stock options in Teva Pharmaceutical Industries. Lee is employed by Kantar, which received payment from Teva Pharmaceutical Industries for data analyses performed for this study. Lipton has received research support from the NIH, the Migraine Research Foundation, and the National Headache Foundation. He has reviewed for the NIA and NINDS; holds stock options in eNeura Therapeutics and Biohaven Holdings; and serves as consultant, advisory board member, or has received honoraria from the American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy's, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, and Vedanta. Saikali serves on the advisory board and as speaker for Allergan, Amgen, Promius, Supernus, and Teva Pharmaceuticals. He serves as a speaker for Assertio, Avanir, Cefaly, Egalet, Eli Lilly, Gammacore, and Pernix. This study has been presented as a poster at the American Academy of Neurology 2018 Annual Meeting, April 21-27, 2018, in Los Angeles, CA; Headache Update 2017, July 13-16, 2017, in Lake Buena Vista, FL; and the American Headache Society 2017 Annual Meeting, June 8-11, 2017, in Boston, MA.

Sustained response to onabotulinumtoxin A in patients with chronic migraine: real-life data

BackgroundTreatment with onabotulinumtoxin A (BT-A) is safe and effective for chronic migraine (CM). Several studies assessed possible predictors of response to treatment with BT-A, but there is little knowledge on the frequency and predictors of sustained response. The aim of this study was to evaluate sustained response to BT-A in patients with CM.Main bodyIn this prospective open-label study, 115 patients with CM and treated with BT-A were consecutively enrolled in two Italian headache centers and followed up for 15 months. Anytime responders were defined as those patients who achieved a ≥ 50% reduction in headache days during any three-month treatment cycle compared with the 3 months prior to initiation of BT-A treatment. Sustained responders were defined as those who achieved a ≥ 50% reduction in headache days within the third treatment cycle and maintained response until the end of follow-up. Non-responders were defined as those patients who never achieved a ≥ 50% reduction in headache days during the follow-up. Headache characteristics prior to BT-A treatment were assessed in order to evaluate their ability in predicting treatment response.The 115 enrolled patients (84.3% female; median age 50 years) had a median migraine duration of 30 years (interquartile range 22–38). At the end of follow-up, 66 patients (57.4%) were classified as anytime responders. Among the 51 patients who achieved a clinical response within the third month of treatment, 33 (64.7%) were sustained responders. Patients with sustained response had a lower CM duration (median 31 vs 65 months; P = 0.030) and a lower number of headache days (median 25 vs 30; P = 0.013) at baseline compared with non-responders.ConclusionsAbout two thirds of patients who gain ≥50% response to BT-A within the third cycle of treatment maintain this positive response over time. More recent onset of CM and more headache-free days at baseline are associated with sustained response. We suggest not to delay preventive treatment of CM with BT-A, in order to increase the likelihood to achieve sustained clinical response.

Associations between migraine attacks and nightly sleep characteristics among adults with episodic migraine: a prospective cohort study.

Given the unknown immediate impact of migraine on nighttime sleep, we prospectively examined whether migraine headaches were associated with subsequent shorter sleep duration, higher fragmentation, and poorer quality in a cohort of 98 adults with episodic migraine. Participants completed twice-daily electronic diaries and wore actigraphs continuously for 6 weeks. We examined whether days with headaches were associated with changes in that night's sleep characteristics compared with headache-free days, using adjusted multivariable linear mixed models with subject-specific intercepts. Participants were 35 ± 12 years old, 88% women, with an average of five migraine headaches per month. Over 4,406 days, we observed 1,077 headache days, representing 823 discrete headaches. Average nightly objective sleep duration was 7.3 ± 1.2 hr, efficiency 89.5 ± 3.3%, and wake after sleep onset (WASO) 44.8 ± 17.0 min. Objective sleep duration was 7.3 min (95% CI: 1.5, 13.0) longer on nights following a headache day compared with nights on a headache-free day. Objective sleep efficiency, WASO, and reported sleep quality were not significantly different on headache days compared with headache-free days (sleep efficiency: -0.06 min, 95% CI: -0.3, 0.2; WASO 1.5 min, 95% CI: 0.0, 3.0; sleep quality: 1.0, 95% CI: 0.8, 1.3). Sleep periods immediately following migraine headaches are not associated with shorter duration, higher disruption, or poorer sleep quality in patients with episodic migraine. These results suggest that clinical evaluation of sleep disturbance in patients with episodic migraine should be approached independently of their migraine status.

Cathodal Transcranial Direct Current Stimulation of the Occipital cortex in Episodic Migraine: A Randomized Sham-Controlled Crossover Study.

Summary: Three consecutive daily sessions of cathodal transcranial direct current stimulation (tDCS) was sufficient to show a significant decrease in headache duration and intensity as well as tablets consumption, in patients suffering from episodic migraine. Background: Migraine prophylaxis is recommended in patients with frequent and/or intense headaches, but poor tolerability and lack of efficacy of preventive drugs are common in clinical practice. Hence, new prophylactic strategies are needed. Objective: The aim of this study was to evaluate the efficacy of tDCS in terms of migraine prophylaxis. Methods: This was a double blind and sham-controlled trial. Forty-two migraine patients were randomly assigned in a crossover design to receive three consecutive daily sessions of both sham and cathodal tDCS stimulation (2.0 mA, 20 min) over the occipital cortex of the dominant side of the migraine pain (O1/O2). Migraine duration and intensity, number of analgesic tablets, and number of headache-free days (where no headache abortive medications are taken) were recorded one week before and two weeks after treatment. A washout period of one week was allowed before crossing to the other treatment arm. Results: Relative to sham, cathodal stimulation was associated with a significant reduction in the number of headache days, tablets consumption, and pain intensity; and a significant increase in the number of headache-free days. These beneficial effects were sustained over two weeks. No serious side effects were observed, and the procedure was well tolerated. Conclusion: Based on these findings, cathodal tDCS applied to the occipital cortex seems to be an effective and well tolerated alternative to pharmacotherapy in patients with episodic migraine.

Associations Between Headache-Free Days and Patient-Reported Outcomes Among Migraine Patients: A Cross-Sectional Analysis of Survey Data in Europe.

IntroductionMigraine imposes a substantial burden on patients, society, and healthcare systems. This study aimed to assess the associations between the number of headache-free days (HFDs) and health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU) in patients with migraine in the EU5 (France, Germany, Italy, Spain, and the United Kingdom).MethodsThis retrospective cross-sectional study collected survey responses from adults aged ≥ 18 years from the 2017 National Health and Wellness Survey (N = 62,000). Migraine patients with a physician’s diagnosis of migraine and who had experienced at least 4 monthly headache days in the prior month were included (N = 1569). Number of HFDs was compared with Short-Form 12-Item Survey Instrument, version 2 (SF-12v2) physical and mental component summary scores (PCS and MCS), Short-Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) scores, WPAI, and HRU in migraine patients. Correlation analyses were conducted to test the bivariate associations, whereas generalized linear models were used for multivariable analyses.ResultsAn increase of 1 HFD was associated with average increases of 0.171, 0.306, 0.003, and 0.008 points for MCS, PCS, SF-6D utility score, and EQ-5D index score, respectively (p < 0.001 for all). Extrapolating the results to a tenfold increase in monthly HFDs corresponded to clinically meaningful increases in PCS and EQ-5D scores. An increase of 1 HFD was associated with expected average decreases in absenteeism of 3.9% and presenteeism of 2.1%. Further, an increase of 1 HFD was associated with expected decreases in HCP visits and neurologist visits of 1.0% and 4.7%, respectively.ConclusionAn increase in the number of HFDs was associated with better health-related outcomes in patients suffering from migraine. Further, the results demonstrate a need for more effective treatments that can reduce migraine frequency and thus improve HRQoL, increase work productivity, and reduce both activity impairment and HRU.FundingNovartis Pharma AG, Switzerland.

“No Pain, More Gain”? Affect and Adherence to Exercise in Migraine Patients: A Prospective Cohort Study

Objectives: To compare the affective and perceptual responses to a standardized exercise session between episodic migraine patients and nonheadache persons, and its influence on adherence to an 12-week exercise training program. Methods: In a secondary analyses of a prospective cohort enrolled in a clinical trial, we assessed the affective response at rest, at 15th minof exercise, and immediately after an acute 40-min exercise session previously the training program. All measurements were undertaken in headache-free days. Participants were subsequently randomly assigned to a 12-week aerobic exercise-training program, or to a waitlist. In a multiple linear regression model, variables tested as possible predictors of adherence were body massindex, cardiorespiratory fitness, and the perceived exertion and affect scores elicited in the previous exercise session. Results: Fifty-four participants were analyzed for acute exercise session data (mean±SD age: 37.37±11.5; mean±SD BMI: 26.7±4.5). Patients (N=28) and controls (N=26) showed no differences in anthropometric characteristics and cardiorespiratory fitness. Compared to controls, migraine patients showed reduced affective response during and after exercise, but showed no differences in perceived exertion. Twentyfive participants (patients: N=13; controls: N=13) concluded the 12-week exercise-training program. Adherence was lower in migraine group (p = 0.1, d = 0.641). Multiple linear regression analysis showed post-exercise affect score as the only predictor variable of adherence to the exercise-training program (β =0.405, p = 0.040). Conclusions: This study indicates that migraine patientshave lower affective response to exercise, which was associated with adherence to the training program.

Anandamide Is Related to Clinical and Cardiorespiratory Benefits of Aerobic Exercise Training in Migraine Patients: A Randomized Controlled Clinical Trial.

Introduction: Since endocannabinoids have been implicated in migraine pathophysiology, we conducted a randomized, controlled clinical trial to test the effects of a 12-week aerobic exercise intervention on plasma anandamide (AEA) and its relation with clinical, psychological, and cardiorespiratory outcomes. Materials and Methods: Episodic migraine patients taking no preventive drugs and nonheadache individuals were recruited from Hospital São Paulo and a tertiary headache clinic between March 2012 and March 2015. Participants were randomly assigned to receive aerobic exercise or enter the waitlist. Primary outcome was changes in plasma AEA; secondary outcome was number of days with migraine/month; and other clinical variables, mood scores, and cardiorespiratory fitness were chosen as tertiary outcomes. Measurements were taken on headache-free days. Data were analyzed by generalized linear models. Discussion: Fifty participants concluded the study (mean±SD age=36.2±10.9, and BMI=26.5±4.5). The plasma AEA reduced in migraine exercise (p<0.05) and control exercise groups (p<0.01). The number of days with migraine (p<0.01), migraine attacks (p<0.05), and abortive medication used (p<0.05) reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups (both p<0.05). Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group (p<0.05 for all). Significant correlations between reduction in abortive medication used and cardiorespiratory fitness (r=-0.81 p<0.001), and reduced AEA (r=0.68 p<0.05) were found. Conclusions: This study suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients. Trials registration: #NCT01972607.

Real-world migraine burden: clinical and economic aspects

To evaluate the rationale for different approaches to preventive chronic migraine (CM) treatment by comparing clinical outcomes and financial burden of the disease in the real-world practice. Sixty-six patients with CM were enrolled at the Alexander Vein Headache Clinic (60 women and 6 men, aged 28-51). All patients were divided into 3 groups: group 1 (n=22) received oral preventative treatment with topiramate, up to 100 mg daily, for three months; group 2 (n=20) received 12 acupuncture sessions (3 sessions a week); group 3 (n=24) received 155-195 units of botulinum toxin type A (botox, BTA). The follow-up period in all groups was 3 months. Efficacy was evaluated by clinical examination, the Headache Impact Test (HIT-6) and questionnaires to assess subjective patient satisfaction and treatment tolerability. BTA demonstrated the highest efficacy in this study. Compared to the oral preventative treatment and acupuncture, BTA reduced the frequency of headache faster and more significantly facilitating CM transformation into episodic migraine (headache frequency was 16.1±0.1; 18.0±0.02; and 13.9±0.3 in groups 1, 2 and 3, respectively, after one month of treatment). BTA also improved the quality of life faster and more significantly and was better tolerated (good - 51%, 75% and 85% in groups 1, 2 and 3, respectively; satisfactory - 35%, 25% and 15% in groups 1, 2 and 3, respectively; bad 14% in the oral prevention group). In the BTA group, the majority of patients demonstrated earlier treatment satisfaction. Despite higher (compared to topiramate) direct costs in the BTA group (RUB 29 931.51 and RUB 32 085.87, respectively), the predicted cost of a headache-free day was the smallest and totaled RUB 652.15 (compared to RUB 692.86 and RUB 1017.60 in the topiramate and acupuncture groups, respectively). The data on the efficacy and costs of different CM prevention strategies would facilitate optimal treatment choice for neurologists and patients.

“No Pain, More Gain”? Resposta Afetiva e Aderência ao Exercício em Pacientes com Migrânea: Um Estudo Prospectivo

Objectives: To compare the affective and perceptual responses to a standardized exercise session between episodic migraine patients and nonheadache persons, and its influence on adherence to an 12-week exercise training program. Methods: In a secondary analyses of a prospective cohort enrolled in a clinical trial, we assessed the affective response at rest, at 15th minof exercise, and immediately after an acute 40-min exercise session previously the training program. All measurements were undertaken in headache-free days. Participants were subsequently randomly assigned to a 12-week aerobic exercise-training program, or to a waitlist. In a multiple linear regression model, variables tested as possible predictors of adherence were body massindex, cardiorespiratory fitness, and the perceived exertion and affect scores elicited in the previous exercise session. Results: Fifty-four participants were analyzed for acute exercise session data (mean±SD age: 37.37±11.5; mean±SD BMI: 26.7±4.5). Patients (N=28) and controls (N=26) showed no differences in anthropometric characteristics and cardiorespiratory fitness. Compared to controls, migraine patients showed reduced affective response during and after exercise, but showed no differences in perceived exertion. Twentyfive participants (patients: N=13; controls: N=13) concluded the 12-week exercise-training program. Adherence was lower in migraine group (p = 0.1, d = 0.641). Multiple linear regression analysis showed post-exercise affect score as the only predictor variable of adherence to the exercise-training program (β =0.405, p = 0.040). Conclusions: This study indicates that migraine patientshave lower affective response to exercise, which was associated with adherence to the training program.