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      Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

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          Abstract

          Objectives

          The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs.

          Background

          The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials.

          Methods

          Respondents (n = 95,821) in the cross‐sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)‐3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache‐related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6‐month follow‐up assessment that included questions about their most bothersome headache symptom.

          Results

          A total of 7518 respondents completed the 6‐month follow‐up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura.

          Conclusion

          Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

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          Most cited references39

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          Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain.

          Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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            Cutaneous allodynia in the migraine population.

            To develop and validate a questionnaire for assessing cutaneous allodynia (CA), and to estimate the prevalence and severity of CA in the migraine population. Migraineurs (n = 11,388) completed the Allodynia Symptom Checklist, assessing the frequency of allodynia symptoms during headache. Response options were never (0), rarely (0), less than 50% of the time (1), > or = 50% of the time (2), and none (0). We used item response theory to explore how well each item discriminated CA. The relations of CA to headache features were examined. All 12 questions had excellent item properties. The greatest discrimination occurred with CA during "taking a shower" (discrimination = 2.54), wearing a necklace (2.39) or ring (2.31), and exposure to heat (2.1) or cold (2.0). The factor analysis demonstrated three factors: thermal, mechanical static, and mechanical dynamic. Based on the psychometrics, we developed a scale distinguishing no CA (scores 0-2), mild (3-5), moderate (6-8), and severe (> or = 9). The prevalence of allodynia among migraineurs was 63.2%. Severe CA occurred in 20.4% of migraineurs. CA was associated with migraine defining features (eg, unilateral pain: odds ratio, 2.3; 95% confidence interval, 2.0-2.4; throbbing pain: odds ratio, 2.3; 95% confidence interval, 2.1-2.6; nausea: odds ratio, 2.3; 95% confidence interval, 2.1-2.6), as well as illness duration, attack frequency, and disability. The Allodynia Symptom Checklist measures overall allodynia and subtypes. CA affects 63% of migraineurs in the population and is associated with frequency, severity, disability, and associated symptoms of migraine. CA maps onto migraine biology.
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              Prevalence and burden of migraine in the United States: data from the American Migraine Study II.

              To describe the prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population-based study employing identical methods. A validated, self-administered questionnaire was mailed to a sample of 20 000 households in the United States. Each household member with severe headache was asked to respond to questions about symptoms, frequency, and severity of headaches and about headache-related disability. Diagnostic criteria for migraine were based on those of the International Headache Society. This report is restricted to individuals 12 years and older. Of the 43 527 age-eligible individuals, 29 727 responded to the questionnaire for a 68.3% response rate. The prevalence of migraine was 18.2% among females and 6.5% among males. Approximately 23% of households contained at least one member suffering from migraine. Migraine prevalence was higher in whites than in blacks and was inversely related to household income. Prevalence increased from aged 12 years to about aged 40 years and declined thereafter in both sexes. Fifty-three percent of respondents reported that their severe headaches caused substantial impairment in activities or required bed rest. Approximately 31% missed at least 1 day of work or school in the previous 3 months because of migraine; 51% reported that work or school productivity was reduced by at least 50%. Two methodologically identical national surveys in the United States conducted 10 years apart show that the prevalence and distribution of migraine have remained stable over the last decade. Migraine-associated disability remains substantial and pervasive. The number of migraineurs has increased from 23.6 million in 1989 to 27.9 million in 1999 commensurate with the growth of the population. Migraine is an important target for public health interventions because it is highly prevalent and disabling.
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                Author and article information

                Contributors
                smunjal@drreddys.com
                Journal
                Headache
                Headache
                10.1111/(ISSN)1526-4610
                HEAD
                Headache
                John Wiley and Sons Inc. (Hoboken )
                0017-8748
                1526-4610
                14 December 2019
                February 2020
                : 60
                : 2 ( doiID: 10.1111/head.v60.2 )
                : 416-429
                Affiliations
                [ 1 ] Promius Pharma Princeton NJ USA
                [ 2 ] Vedanta Research Chapel Hill NC USA
                [ 3 ] Mayo Clinic Scottsdale AZ USA
                [ 4 ] Albert Einstein College of Medicine Bronx NY USA
                Author notes
                [*] [* ] Address all correspondence to S. Munjal, Promius Pharma, 107 College Road East, Princeton, NJ 08540, USA, email: smunjal@ 123456drreddys.com

                Article
                HEAD13708
                10.1111/head.13708
                7027490
                31837007
                ddc60a0e-dea2-4ce6-a253-ce396e93473d
                © 2019 Promius Pharma. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc., on behalf of American Headache Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 29 October 2019
                Page count
                Figures: 0, Tables: 4, Pages: 14, Words: 18856
                Categories
                Research Submissions
                Research Submissions
                Custom metadata
                2.0
                February 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:18.02.2020

                migraine,epidemiology,coprimary endpoints,most bothersome symptom

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