Abstract
Migraine is a common and disabling disorder with a 1-year prevalence of 4.5–6% in men and 14.5–18% in women. The diagnosis of migraine is usually made according to the second edition of the International Classification of Headache Disorders (ICHD-2) criteria; however, not all physicians are familiar with the diagnostic criteria. Underdiagnosis remains a major issue in general practice, resulting in inadequate treatment. Several instruments are designed to improve the diagnosis of migraine, to identify the comorbid psychological disturbances, to measure the burden and disability, and to access any reduction in quality of life (QoL) that occurs due to migraine attacks with good reliability and validity. Furthermore, the disability and QoL measured by certain instruments serve as surrogate targets when treating migraines. In this review, we examine the instruments that are in common use in daily practice and current research on migraines, focusing on the purpose of each instrument, clinical applications, pitfalls in interpretation, and, if any, minimally clinically important difference(s) (MCID).
In general, a structured intake form and a headache diary are recommended in approaching patients with headache. In addition, ID-Migraine, a three-item screening test, has been validated in primary care settings as a way to improve the rapid diagnosis of migraine. The Visual Aura Rating Scale (VARS) is helpful for the diagnosis of migraine with aura. In addition, migraine is commonly associated with psychiatric comorbidities, which can be assessed by the Beck Depression Inventory (BDI), 9-item Patient Health Questionnaire (PHQ-9), and Hospital Anxiety and Depression Scale (HADS). To evaluate the impact of migraines, disability can be assessed using the Migraine Disability Assessment Questionnaire (MIDAS). Reduction in QoL can be evaluated using the Migraine-Specific Quality of Life Survey (MSQ 2.1), European Quality of Life-Five Dimensions (EQ-5D), or Short-Form 36 (SF-36). Despite all these instruments, proper selection and interpretation of each instrument remain crucial.
Keywords
migraine disorders; disability evaluation; quality of life; headache;
1. Introduction
Migraine is the most common headache disorder, with a 1-year prevalence rate of around 10% overall, ranging from 4.5–6% in men and 14.5–18% in women.1, 2, 3 Our previous population-based study showed a similar prevalence rate in Taiwan (4.5% and 14.4% for men and women, respectively).4 Among women in their 30s, the prevalence can be as high as 25%.5 The diagnosis of migraine relies on the criteria proposed by the second edition of the International Classification of Headache Disorders (ICHD-2)6 (Table 1); however, fewer than half of all patients with migraine are properly diagnosed.7 Underdiagnosis leads to unmet treatment needs. Only one-third of patients with migraine are properly treated, resulting in high levels of headache-related disability and poor health-related quality of life (HRQoL).8, 9 Furthermore, migraine is often associated with psychiatric disorders, including depression10, 11 and anxiety.12 Psychiatric comorbidity is the major determinant of poor HRQoL in patients with migraines13; thus, proper treatment of comorbid psychiatric disorders is crucial to the adequate treatment of migraines.
Migraine is the leading diagnosis following visit to neurological clinics in the United States14, 15 and in Taiwan.16 However, the majority of patients first seek assistance through general practitioners (GPs). Thus, GPs play a crucial role in the diagnosis and treatment of migraines. Several screening instruments have been developed to improve the diagnosis of migraine17, 18, 19, 20; however, due to the different clinical settings of the general population and referral patients, the global application of these instruments for primary care physicians is of uncertain validity, and some of the screening instruments are too complicated for use in primary care settings.17, 18 In addition, comorbid psychiatric diseases do affect the outcome of HRQoL when treating migraine.13 The integration of the screening items of common comorbid psychological disturbances might play a pivotal role in treatment. Reviews of the pathology, symptomology, and treatment of migraine are numerous; thus, in this review, our focus is on the commonly used screening items that facilitate diagnosis, identify the comorbid diseases, and evaluate disability and HRQoL.
2. Structured intake form for headaches
Except for specific instruments, certain clinics and hospitals have developed structured intake forms for patients who present with headaches. Though the details of the questionnaire might differ, a structured intake form generally consists of sociodemographic features, past medical history, family history of headache, and headache profile. The questions on the headache profile are generally designed in accordance with the ICHD-2 criteria, thereby including the features of common headache disorders, e.g., migraines, and tension-type headaches.6 Generally, the headache profile includes the presence or absence of aura, duration, frequency, quality (e.g., stabbing, pulsatile, band-like), lateralization, location and severity of the headache, and its relationship with physical activities (worsening or improving). In addition, associated symptoms (e.g., nausea, vomiting, photophobia, phonophobia) and cranial autonomic symptoms (e.g., conjunctival injection, lacrimation, eyelid edema, ptosis, sweating, nasal symptoms) are commonly included. Last, previous response to acute and preventive medications and the frequency of analgesic use are also queried.
3. Headache diary
In order to eliminate recall bias, patients who visit headache clinics are asked to keep a headache diary for at least 1 month.21 The headache diary is used to consolidate the diagnosis by recording the headache frequency, severity, features, and relevant precipitating factors, including diet, stress, and relation of the headache to the menstrual cycle. In addition, the frequency of analgesic use is recorded, thus responses to treatment and the presence of medication overuse, according the ICHD-2 revised criteria,22 could be revealed. The use of headache diary for headache diagnosis has also been validated in a recent study.23 Thus, a headache diary is not only helpful for improving the diagnosis but also for tailoring headache treatments as well.
4. Specific instruments for different purposes
There are several commonly used instruments that facilitate the diagnosis of migraine, identify comorbid conditions, and evaluate clinical outcomes, including disability, HRQoL, and health-care burdens. Here, we list the commonly used instruments for further exposition.
5. ID-Migraine: assisting the diagnosis of migraine by GPs and physicians
A GP or physician might not be familiar with the details of the ICHD-2 criteria, so a fast screening instrument might be more helpful during diagnosis. ID-Migraine, a three-item migraine screener regarding headache disability, nausea, and photophobia to a binary response, has been proven as fast and effective for use by GPs.24 If the patient is positive for two or all of the three items, the sensitivity and specificity for migraine diagnosis are high (0.82 and 0.75, respectively). Furthermore, the use of ID-Migraine has been validated for use in primary care facilities instead of tertiary headache centers.24 However, the global application of ID Migraine needs further validation due to the different prevalences of migraine symptoms in different regions and racial groups. For example, Asian studies have reported a lower prevalence of photophobia (35–60%) compared with Western studies (70–99.2%),25 but osmophobia (sensitivity to odor) was more prevalent in Asian migraine patients (57–71%).26 Thus, validation or modification might be necessary when applying a screening instrument in different regions.
In our previous series, the three most common symptoms of any ICHD-2-confirmed migraine were moderate or severe headache (88.2%), nausea (85.1%), and pulsatile characteristics (73.8%).27 Furthermore, a combination of two or all of the three items (nausea/vomiting, photophobia, and moderate or severe headache) gives a similar prediction of migraine diagnosis as ID-Migraine, while the item of moderate or severe headache replaces headache disability on ID-Migraine.27 Thus, proper validation is required before adapting an instrument to a different group of patients.
6. Migraine aura
Migraine aura is a transient neurological symptom that most commonly involves the visual fields and occurs before the headache phase. Migraine with aura accounts for 10.7–46.6% of migraine patients.4, 28, 29, 30, 31 Patients with migraine often develop visual disturbances during a migraine attack; however, not all of the visual symptoms are migraine aura.32 The migraine aura is clearly defined by ICHD-2 (Table 2). In order to better recognize migraine aura, the Visual Aura Rating Scale (VARS) was developed. The VARS score is comprised of five major symptoms that are individually weighted: 1) duration: 5–60 minutes (3 points); 2) gradual development ≥ 5 minutes (2 points); presence of scotoma (2 points); presence of zig-zag lines (2 points); and unilateral presentation (1 point). A summation score ≥ 5 demonstrates a sensitivity of 91–96% and a specificity of 96–98% for migraine aura.33 Moreover, migraine with aura is associated with increased vascular events, including ischemic stroke, hemorrhagic stroke, and myocardial infarction.34, 35, 36 Thus, properly identifying migraine aura and reducing additional cardiovascular risk factors (e.g., smoking, oral contraceptive use, weight control) in this specific group of migraine patients is crucial.
7. Evaluation of comorbid psychiatric disorders
Migraine is known to be associated with a variety of psychiatric disorders. Roughly 10% migraineurs fits the diagnostic criteria of general anxiety disorder (GAD),37 and a bidirectional association between migraine and major depression, as well as panic disorder, has been consistently confirmed.10, 38, 39, 40 In addition, certain personality traits are associated with a higher prevalence of migraine,41 especially chronic migraine and medication overuse.42 The Minnesota Multiphasic Personality Inventory (MMPI), which was designed to identify personality structure and psychopathology, is widely used to identify the personality traits of patients with various diseases.43 MMPI consists of ten different scales that are used to identify nine major different personality traits, including hypochondriasis, depression, hysteria, psychopathic deviation, masculinity/femininity, paranoia, psychasthenia, schizophrenia, hypomania, and social introversion. MMPI (original edition)43 and MMPI-2 (revised in 1989)44 are commonly used in headache studies. Patients with primary headache disorders are prone to have a higher incidence of the neurotic triad of hypochondriasis, depression, and hysteria, but are still within two standard deviations compared with the control group.45 In later series, migraine has been associated with a significantly higher incidence of neurotic triad compared with the norm46; however, to a lesser extent, elevated incidence of the neurotic triad is still common in other headache disorders.45, 47 Moreover, in some studies, normalization of the MMPI score is common in migraineurs after therapeutic intervention,48, 49 raising the issue that the personality changes measured by MMPI might be secondary to headache symptoms instead of being a predisposing factor.
For physicians other than psychiatrists, in order to provide better screening and treatment of depression, several quantitative batteries for anxiety and depression have been established, at least three of which are well validated and generally used in headache studies: Hospital Anxiety and Depression Scale (HADS),50 Beck Depression Inventory (BDI; both the original BDI51 and the second edition, BDI-II52), and the 9-item Patient Health Questionnaire (PHQ-9).53 Each measurement slightly varies depending on the original design and purpose. HADS is designed for screening patients with potential anxiety and depression rather than grading the severity of the anxiety and depression. There are 14 items on the HADS questionnaire, seven of which measure anxiety (HADS-A) and seven of which measure depression (HADS-D). Each item is scored in a scale of 0–3, resulting in an overall score of 0–21 for both HADS-A and HADS-D. In previous series, the cut-off value of the anxiety and depression subscales on HADS varied from study to study. A subscale of 3–9 on HADS-A yields a sensitivity of 0.66–0.86 and a specificity of 0.83–0.93 for anxiety, whereas a subscale of 7–9 on HADS-D yields a sensitivity of 0.66–0.91 and a specificity of 0.87–0.97 for depression.54, 55, 56 The HADS questionnaire has also been validated for use in Taiwan. In our previous study, a total HADS score ≥ 10 predicted depressive disorders with a sensitivity of 0.86 and a specificity of 0.33, while a total HADS score of ≥ 13 predicted anxiety disorders with a sensitivity of 0.84 and a specificity of 0.42.57 Of note, no somatic symptoms are queried on HADS, which are valuable for assessing the cognitive components of anxiety and depression.
While HADS is used for the screening of depression and anxiety, BDI is commonly used as a tool to grade depression. BDI consists of 21 questions, each scored on a scale of 0–3. The questions covers most of the diagnostic criteria of the major depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), including hypochondriasis, perception of body image, and changes in sleep, appetite, etc. Some of the items on body image, hypochondriasis, and difficulty working were replaced in BDI-II, and most of the items were modified or reworded. While both the first edition of BDI and BDI-II use a 21-item questionnaire, the cut-off value for depression on BDI-II is different from BDI. On BDI, a score of 0–9 indicates minimal depression, 10–18 indicates mild depression, 19–29 indicates moderate depression, and ≥ 30 indicates severe depression,51 whereas, on BDI-II, a score of 0–13 indicates minimal depression, 14–19 indicates mild depression, 20–28 indicates moderate depression, and ≥ 29 indicates severe depression.52 Corresponding to BDI, the Beck Anxiety Inventory (BAI) is designed to grade anxiety and has been widely used in American studies.58
PHQ-9, a 9-item questionnaire with each item corresponding to one criterion of the DSM-IV diagnostic criteria of major depressive disorder, serves as both a screening tool and a grading instrument for depression.53 Each of the nine items is scored on a scale of 0–3 depending on the frequency of symptoms. An overall score ≥ 10 provides a sensitivity of 88% and specificity of 88%.59 Furthermore, PHQ-4, a simplified edition of PHQ-9, has been developed to rapidly screen depression and anxiety.60
Despite all these instruments, one issue that remains is that the severity of depression or anxiety is sometimes inconsistent depending on the instrument one chooses; thus, an interpretation of studies covering different instruments must be prudent. Lastly, all of these instruments are designed to provide preliminary information on the presence of depression or anxiety symptoms, and an evaluation by a psychiatrist is always needed to reach a final diagnosis.
8. Quantification of disability
Because patients with migraines suffer from a notable loss of work, household chores, and leisure time, the reduction of pain and disability are the goals of migraine treatment. In 1999, Stewart and Lipton developed the Migraine Disability Assessment Questionnaire (MIDAS), a 5-item questionnaire designed to evaluate disability within the most recent 3 months.61 The patient needs to score the reduction in the performance, in days, of work/school, household work, and family/social activities. A score 0–270 is used to indicate the overall level of disability due to headaches based on the following grading system: grade I, little or no disability (score of 0–5); grade II, mild disability (score of 6–10); grade III, moderate disability (score of 11–20); and grade IV, severe disability (score of ≥ 21).62 Recently, in order to better characterize headache-related disability due to chronic migraines, grade IV (MIDAS ≥ 21) was further divided into grade IV-A (MIDAS 21–40) and grade IV-B (MIDAS ≥ 41).63 Due to its high internal consistency, validity, and good correlation with clinical diagnoses and treatment, MIDAS has been widely validated across countries and translated into several different languages, including Chinese for use in Taiwan.64 In addition to disability assessment, MIDAS also serves as a powerful instrument for the stratified care of patients with migraine, e.g., the early use of triptans was better than stratified care strategies (adding triptans at follow-up to those who fail to respond to the initial treatment) in patients with a high grade of disability, measured by MIDAS.65
In addition to MIDAS, the Headache Impact Test (HIT-6) is also a widely validated instrument used to measure the functional impairment of headaches. The HIT-6 comprises six items to evaluate the frequency of severe headache, limitations of daily activities (including work, school, and social), desire to lie down, fatigue, irritability, and difficulty concentrating.66 Each of the six items is scored according to frequency, generating an overall score of 36–78. The impact scores can be classified as little or no impact (grade 1: score 36–49), moderate impact (grade 2: score 50–55), substantial impact (grade 3: score 56–59), or severe impact (grade 4: score 60–78).67 The HIT-6 score is obtained at baseline and at every 4 weeks of treatment and could be used as a good surrogate marker of the response to treatment.67 A reduction of 2.3 points on the HIT-6 score following treatment indicates a clinically significant improvement in patients with chronic daily headache.68 Furthermore, in a recent study, HIT-6 was found to be useful for understanding the specific burden of chronic daily headache compared with episodic headache (i.e., chronic migraine vs. episodic migraine).69
9. Assessing HRQoL
Except for disability reduction, improvement in HRQoL also serves as a major goal during the treatment of migraines. The most commonly used instruments for assessing HRQoL are listed.
(1)Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1)
MSQ v2.1 is a 14-item questionnaire used to assess the limitations in daily performance due to migraine.70 MSQ v2.1 is composed of three domains: role function-restrictive (RR), role function-preventive (RP), and emotional function (EF). The first two of these domains are used to access the reduction and prevention of daily social- and work-related activities, while the last domain is used to evaluate emotions associated with migraine. Raw dimensional scores are computed as a sum of the item responses and rescaled to 0–100, where higher scores indicate better HRQoL. To analyze treatment responses, the within-group minimal difference score is 5.0 for RR, 5.0–7.9 for RP, and 8.0–10.6 for EF.71
(2)European Quality of Life-5 Dimensions (EQ-5D)
EQ-5D is a self-reported health status that covers five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and general health status.72 The health status of the five dimensions is presented as an index (0–1, where 1 is the best), while general health status is measured using the Visual Analogue Scale (VAS; 0–100%, where 100% is the best). EQ-5D is widely used to evaluate the HRQoL of different diseases, including psychiatric diseases, medical diseases, surgical outcomes, etc.73 In addition, in patients with migraines, EQ-5D scores are even worse during frequent attacks compared with the baseline condition of the patient.74
(3)Short-form 36 (SF-36)
SF-36 is a multidimensional questionnaire used to assess the impact of disease on eight health domains, including physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. A score of 0–100 on each subscale is generated, with higher scores indicating better HRQoL.75 When SF-36 was first developed, the authors suggested that a 5-point difference on the general health subscale be the smallest change that would be considered clincially significant, a factor that is also known as the minimally clinically improtant difference (MCID).75 However, in later studies, a variable MCID (range: 3.3–7.8) was found on different subscales of patients with osteoarthritis.76 Nontheless, a differnece of 3–5 points in terms of MCID is generally used on different subscales, but the interpretation must be cautious due to variable results in differnet studies.77 SF-36 has been widely used in pain studies, and it has also been used to analyze different headache diagnoses in our previous study.13 Migraine patients are known to have the highest reductions in scores regarding role limitations, social functioning, and bodily pain.78 In addition, in patients with chronic migraines, the reduction in scores is more pervasive over a wider range of subscales.13 Furthermore, both improvement on the pain scale and psychological well-being predicted an improvement on the SF-36,13 suggesting the crucial role of recognizing and treating comorbid psychiatric illness during the treatment of headache disorders.
10. Conclusions
The introduction of different instruments not only improves migraine diagnosis in general practice, but also serves as a screening/grading tool for comorbid psychological disturbances. In addition, instruments used for the grading of disability and HRQoL provide an objective goal for the treatment of migraine. However, different instruments are designed for different purposes; thus, the selection of instruments and the interpretation must be carried out with prudence.