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1.  Association Between Intimate Partner Violence, Migraine and Probable Migraine 
Headache  2010;51(2):208-219.
Objective
Intimate partner violence (IPV) among women is a global public health problem. The association between childhood maltreatment and migraine is well established, but not the association between IPV and migraine. The aim of this cross-sectional study was to evaluate the relationship between type and severity of IPV and migraine in a large cohort of Peruvian women.
Methods
Women who delivered singleton infants (N=2,066) at the Instituto Nacional Materno Perinatal, Lima, Peru were interviewed during their post-partum hospital stay. Participants were queried about their lifetime experiences with headaches and migraine, and with physical and sexual violence. The International Classification of Headache Disorders (ICHD-2) diagnostic criteria were used to classify participants according to their migraine status. Questions on physical and sexual violence were adapted from the protocol of Demographic Health Survey Questionnaires and Modules: Domestic Violence Module and the World Health Organization (WHO) Multi-Country Study on Violence against Women. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire Depression Subset. Logistic regression was used to estimate multivariate adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Results
Compared with women without a history of violence, women with experiences of lifetime physical or sexual violence (aOR=1.44, 95% CI 1.19–1.75), physical violence only (aOR=1.36, 95% CI 1.10–1.68), sexual violence only (aOR=1.76, 95% CI 0.97–3.21) and both physical and sexual violence (aOR=1.61, 95% CI 1.12–2.31) had increased odds of any migraine after adjusting for maternal age, parity and access to basic foods. There was no gradient of increased odds of any migraine with severity of physical violence. The relationship between IPV and any migraine was strongest among women with depressive symptoms. The odds of any migraine was increased 2.25-fold (95% CI 1.75–2.28) among abused women who also had depressive symptoms compared with non-abused and non-depressed women. Associations from sensitivity analyses that segregated women according to probable migraine (ICHD-2 category 1.6.1) and migraine (ICHD-2 category 1.1) diagnoses were of similar magnitudes as those reported here for women with any migraine diagnoses. IPV, particularly sexual violence, appears to be a risk factor for migraine.
Conclusion
Our findings suggest the potential importance of considering a history of violence among migraineurs.
doi:10.1111/j.1526-4610.2010.01777.x
PMCID: PMC3662491  PMID: 20946432
2.  Anatomical Alterations of the Visual Motion Processing Network in Migraine with and without Aura 
PLoS Medicine  2006;3(10):e402.
Background
Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine.
Methods and Findings
To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing.
Conclusions
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a “silent” cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability seen in people who have migraine.
Editors' Summary
Background.
Migraine is a disabling brain disorder that affects more than one in ten people during their lifetimes. It is characterized by severe, recurrent headaches, often accompanied by nausea, vomiting, and light sensitivity. In some migraineurs (people who have migraines), the headaches are preceded by neurological disturbances known as “aura.” These usually affect vision, causing illusions of flashing lights, zig-zag lines, or blind spots. There are many triggers for migraine attacks—including some foods, stress, and bright lights—and every migraineur has to learn what triggers his or her attacks. There is no cure for migraine, although over-the-counter painkillers can ease the symptoms and doctors can prescribe stronger remedies or drugs to reduce the frequency of attacks. Exactly what causes migraine is unclear but scientists think that, for some reason, the brains of migraineurs are hyperexcitable. That is, some nerve cells in their brains overreact when they receive electrical messages from the body. This triggers a local disturbance of brain function called “cortical spreading depression,” which, in turn, causes aura, headache, and the other symptoms of migraine.
Why Was This Study Done?
Researchers need to know more about what causes migraine to find better treatments. One clue comes from the observation that motion perception is abnormal in migraineurs, even between attacks—they can be very sensitive to visually induced motion sickness, for example. Another clue is that aura are usually visual. So could brain regions that process visual information be abnormal in people who have migraines? In this study, the researchers investigated the structure of the motion processing parts of the brain in people who have migraine with aura, in people who have migraine without aura, and in unaffected individuals to see whether there were any differences that might help them understand migraine.
What Did the Researchers Do and Find?
The researchers used two forms of magnetic resonance imaging—a noninvasive way to produce pictures of internal organs—to examine the brains of migraineurs (when they weren't having a migraine) and healthy controls. They concentrated on two brain regions involved in motion processing known as the MT+ and V3A areas and first measured the cortical thickness of these areas—the cortex is the wrinkled layer of gray matter on the outside of the brain that processes information sent from the body. They found that the cortical thickness was increased in both of these areas in migraineurs when compared to healthy controls. There was no difference in cortical thickness between migraineurs who had aura and those who did not, but the area of cortical thickening in V3A corresponded to the source of cortical spreading depression previously identified in a person who had migraine with aura. The researchers also found differences between the white matter (the part of the brain that transfers information between different regions of the gray matter) immediately below the V3A and MT+ areas in the migraineurs and the controls but again not between the two groups of migraineurs.
What Do These Findings Mean?
This study provides new information about migraine. First, it identifies structural changes in the brains of people who have migraines. Until now, it has been thought that abnormal brain function causes migraine but that migraineurs have a normal brain structure. The observed structural differences might either account for or be caused by the hyperexcitability that triggers migraines. Because migraine runs in families, examining the brains of children of migraineurs as they grow up might indicate which of these options is correct, although it is possible that abnormalities in brain areas not examined here actually trigger migraines. Second, the study addresses a controversial question about migraine: Is migraine with aura the same as migraine without aura? The similar brain changes in both types of migraine suggest that they are one disorder. Third, the abnormalities in areas MT+ and V3A could help to explain why migraineurs have problems with visual processing even in between attacks. Finally, this study suggests that it might be possible to develop a noninvasive test to help doctors diagnose migraine.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030402.
The MedlinePlus encyclopedia has several pages on migraine
The US National Institute of Neurological Disorders and Stroke offers patient information on migraine and other headaches
The NHS Direct Online contains patient information on migraine from the UK National Health Service
MAGNUM provides information from The US National Migraine Association
The Migraine Trust is a UK charity that supports research and provides support for patients
The Migraine Aura Foundation is a site about aura that includes a section on art and aura
doi:10.1371/journal.pmed.0030402
PMCID: PMC1609120  PMID: 17048979
3.  Migraine and Psychiatric Comorbidities among Sub-Saharan African Adults 
Headache  2012;53(2):310-321.
Background
Despite being a highly prevalent disorder and substantial cause of disability, migraine is understudied in Africa. Moreover, no previous study has investigated the effects of stress and unipolar psychiatric comorbidities on migraine in a sub-Saharan African cohort.
Objective
To evaluate the prevalence of migraine and its association with stress and unipolar psychiatric comorbidities among a cohort of African adults.
Methods
This was a cross-sectional epidemiologic study evaluating 2,151 employed adults in sub-Saharan Africa. A standardized questionnaire was used to identify socio-demographic, headache, and lifestyle characteristics of participants. Migraine classification was based on the International Classification of Headache Disorders (ICHD)-2 diagnostic criteria. Depressive, anxiety and stress symptoms were ascertained with the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scale (DASS-21) respectively. Multivariable logistic regression models were used to estimate adjusted odds ratio (OR) and 95% confidence intervals (CI).
Results
A total of 9.8% (n=212) of study participants fulfilled criteria for migraine (9.8%; 95%CI: 8.6, 11.1) with a higher frequency among women (14.3%; 95%CI: 11.9, 16.6) than men (6.9%; 95%CI: 5.5, 8.3). Similar to predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were more likely to be younger, have a lower education and more likely to report a poor health status than non-migraineurs. However, in contrast to historical reports in predominantly Caucasian migraine cohorts, sub-Saharan African migraineurs were less likely to report smoking than non-migraineurs. Participants with moderately severe depressive symptoms had over a 3-fold increased odds of migraine (OR=3.36; 95% CI 1.30,8.70), compared with those classified as having minimal or no depressive symptoms; and the odds of migraine increased with increasing severity of depressive symptoms (p-trend <0.001). Similarly those with mild, moderate and severe anxiety symptoms had increased odds of migraine (OR=2.28; 95%CI 1.24, 4.21; OR=1.77; 95%CI 0.93, 3.35, and OR=5.39; 95%CI 2.19, 13.24, respectively). Finally, those with severe stress had a 3.57-fold increased odds of migraine (OR=3.57; 95%CI 1.35, 9.46).
Conclusion
Although historically it has been reported that migraine prevalence is greater in Caucasians than African Americans, our study demonstrates a high migraine prevalence among urban dwelling Ethiopian adults (9.9%) that is comparable to what is typically reported in predominantly Caucasian cohorts. Further, among employed sub-Saharan African adults, and similar to predominantly Caucasian populations, migraine is strongly associated with stress and unipolar psychiatric symptoms. The high burden of migraine and its association with stress and unipolar psychiatric symptoms in our study of well-educated and urban dwelling African adults has important clinical and public health implications pending confirmation in other African populations.
doi:10.1111/j.1526-4610.2012.02259.x
PMCID: PMC3556345  PMID: 23095087
Migraine; Depression; Anxiety; Stress; Comorbidities; Sub-Saharan Africa
4.  Risk of Preterm Delivery and Hypertensive Disorders of Pregnancy in Relation to Maternal Comorbid Mood and Migraine Disorders during Pregnancy 
Summary
We evaluated risks of preterm delivery and hypertensive disorders of pregnancy among pregnant women with mood and migraine disorders. We used data from a cohort study of 3,432 pregnant women. Maternal pre-gestational or early pregnancy (before 20 weeks gestational) mood disorder and pre-gestational migraine diagnoses were ascertained from in-person interview and medical record review. We fitted generalized linear models to derive risk ratios (RR) and 95% confidence intervals (CI) of preterm delivery and hypertensive disorders of pregnancy for women with isolated mood, isolated migraine, and comorbid mood-migraine disorders, respectively. Reported RRs were adjusted for maternal age, race/ethnicity, marital status, parity, smoking status, chronic hypertension or pre-existing diabetes mellitus, and pre-pregnancy body mass index. Women without mood or migraine disorders were defined as the reference group. The risks for preterm delivery and hypertensive disorders of pregnancy were more consistently elevated among women with comorbid mood-migraine disorders than among women with isolated mood or migraine disorder. Women with comorbid disorders were almost twice as likely to deliver preterm (adjusted RR=1.87, 95% CI 1.05–3.34) compared with the referent group. There was no clear evidence of increased risks of preterm delivery and its subtypes with isolated migraine disorder. Women with mood disorder had elevated risks of preeclampsia (adjusted RR=3.57, 95% CI 1.83–6.99). Our results suggest an association between isolated migraine disorder and pregnancy-induced hypertension (adjusted RR=1.42, 95% CI 1.00–2.01). This is the first study examining perinatal outcomes in women with comorbid mood-migraine disorders. Pregnant women with a history of migraine may benefit from depression screening during prenatal care, and vigilant monitoring, especially for women with comorbid mood-migraine disorders.
doi:10.1111/j.1365-3016.2010.01182.x
PMCID: PMC3756187  PMID: 21281324
Mood disorders; Migraine; Pregnant women; Preterm Delivery; Preeclampsia
5.  Risk of placental abruption in relation to migraines and headaches 
BMC Women's Health  2010;10:30.
Background
Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women.
Methods
Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders.
Results
Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20). A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75). The odds of placental abruption was 2.11 (95% CI 1.00-4.45) for migraineurs without aura; and 1.59 (95% 0.70-3.62) for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57).
Conclusions
This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.
doi:10.1186/1472-6874-10-30
PMCID: PMC2984417  PMID: 20977769
6.  The relation of sexual function to migraine-related disability, depression and anxiety in patients with migraine 
Background
Depression and anxiety are two phenomena that affect quality of life as well as sexual function. Depression and anxiety levels are reported to be high in migraine sufferers. We aimed to understand whether sexual function in women with migraine was associated to migraine-related disability and frequency of migraine attacks, and whether this relationship was modulated by depressive and anxiety symptoms.
Methods
As migraine is more commonly seen in females, a total of 50 women with migraine were included. The diagnosis of migraine with or without aura was confirmed by two specialists in Neurology, according to the second edition of International Headache Society (IHS) International Classification of Headache Disorders (ICHD-II) in 2004. Migraine disability assessment scale score, female sexual function index scores, Beck depression inventory score and Beck anxiety inventory scores.
Results
Mean MIDAS score was 19.3 ± 12.8, and mean number of migraine attacks per month were 4.3 ± 2.7. Mean Female Sexual Function Index score was 20.9 ± 5.9 and 90% of patients had sexual dysfunction. Sexual dysfunction was not related to MIDAS score or frequency and severity of attacks. No relationship between sexual function and anxiety was found, whereas severity of depressive symptoms was closely related to sexual function. Depressive symptoms affected all dimensions of sexual function, except for pain.
Conclusion
Sexual dysfunction seemed to be very common in our patients with migraine, while not related to migraine related disability, frequency of attacks and migraine severity or anxiety. The most important factor that predicted sexual function was depression, which was also independent of disease severity and migraine related disability. While future larger scale studies are needed to clarify the exact relationship, depressive and sexual problems should be properly addressed in all patients with migraine, regardless of disease severity or disability.
doi:10.1186/1129-2377-15-32
PMCID: PMC4046390  PMID: 24884652
Migraine; Sexual dysfunction; Migraine related disability; Depression; Anxiety
7.  Migraine, Headache and the Risk of Depression: Prospective Cohort Study 
Background
While cross-sectional studies have shown associations between migraine and depression, few studies have been able to evaluate the association between migraine and incident depression.
Methods
Prospective cohort study among 36,016 women without a history of depression enrolled in the Women’s Health Study who provided information about migraine and headache at baseline. Women were classified as either having non-migraine headache, migraine with aura, migraine without aura, past history of migraine or no history of headache. Cox proportional hazards models were used to evaluate the association between migraine and headache status and incident depression.
Results
At baseline, 5115 women reported a history of non-migraine headache, 1805 reported migraine with aura, 2723 reported migraine without aura and 1896 reported a past history of migraine. During 13.8 mean years of follow-up, 3833 new cases of depression occurred. The adjusted relative risks of incident depression were 1.44 (95% CI: 1.32, 1.56) for non-migraine headache, 1.53 (95% CI: 1.35, 1.74) for migraine with aura, 1.40 (95% CI: 1.25, 1.56) for migraine without aura and 1.56 (95% CI: 1.37, 1.77) for past history of migraine compared to no history of headache.
Conclusions
Middle-aged women with migraine or non-migraine headache are at increased risk of incident depression.
doi:10.1177/0333102413483930
PMCID: PMC3720737  PMID: 23588795
Migraine; depression; epidemiology
8.  Migraine may be a risk factor for the development of complex regional pain syndrome 
The aim was to assess the relative frequency of migraine and the headache characteristics of complex regional pain syndrome (CRPS) sufferers. CRPS and migraine are chronic, often disabling pain syndromes. Recent studies suggest that headache is associated with the development of CRPS. Consecutive adults fulfilling International Association for the Study of Pain criteria for CRPS at a pain clinic were included. Demographics, medical history, and pain characteristics were obtained. Headache diagnoses were made using International Classification of Headache Disorders, 2nd edn criteria. Migraine and pain characteristics were compared in those with migraine with those without. ANOVA with Tukey post hoc tests was used to determine the significance of continuous variables and Fisher’s exact or χ2 tests for categorical variables. The expected prevalence of migraine and chronic daily headache (CDH) was calculated based on age- and gender-stratified general population estimates. Standardized morbidity ratios (SMR) were calculated by dividing the observed prevalence of migraine by the expected prevalence from the general population. The sample consisted of 124 CRPS participants. The mean age was 45.5 ± 12.0 years. Age-and gender-adjusted SMRs showed that those with CRPS were 3.6 times more likely to have migraine and nearly twice as likely to have CDH as the general population. Aura was reported in 59.7% (74/124) of participants. Of those CRPS sufferers with migraine, 61.2% (41/67) reported the onset of severe headaches before the onset of CRPS symptoms Mean age of onset of CRPS was earlier in those with migraine (34.9 ± 11.1 years) and CDH (32.5 ± 13.4 years) compared with those with no headaches (46.8 ± 14.9 years) and those with tension-type headache (TTH) (39.9 ± 9.9 years), P < 0.05. More extremities were affected by CRPS in participants with migraine (median of four extremities) compared with the combined group of those CRPS sufferers with no headaches or TTH (median 2.0 extremities), P < 0.05. The presence of static, dynamic and deep joint mechanoallodynia together was reported by more CRPS participants with migraine (72.2%) than those with no headaches or TTH (46.2%), P ≤ 0.05. Migraine may be a risk factor for CRPS and the presence of migraine may be associated with a more severe form of CRPS. Specifically: (i) migraine occurs in a greater percentage of CRPS sufferers than expected in the general population; (ii) the onset of CRPS is reported earlier in those with migraine than in those without; and (iii) CRPS symptoms are present in more extremities in those CRPS sufferers with migraine compared with those without. In addition, as we also found that the presence of aura is reported in a higher percentage of those CRPS sufferers with migraine than reported in migraineurs in the general population, further evaluation of the cardiovascular risk profile of CRPS sufferers is warranted.
doi:10.1111/j.1468-2982.2009.01916.x
PMCID: PMC3979276  PMID: 19614690
Migraine; chronic daily headache; complex regional pain syndrome; allodynia; aura
9.  Are Sleep Difficulties Associated With Migraine Attributable to Anxiety and Depression? 
Headache  2008;48(10):1451-1459.
Objective
To examine whether sleep complaints reported by migraineurs can be attributed to comorbid anxiety and/or depression.
Background
A consistent association between migraine and sleep complaints has been reported in community and clinical studies. However, anxiety and depression are often comorbid with migraine. Thus, it may be possible that the increased prevalence of sleep problems in migraineurs is attributable to comorbid anxiety and depression. To our knowledge, no previous studies have demonstrated that the associations are not solely attributed to comorbid anxiety and depression.
Design and Methods
Controlled family study of anxiety disorders and substance use disorders in a community in New Haven County, CT. The sample included 221 probands (41 migraineurs) and their 261 directly interviewed first-degree relatives (39 migrainuers), including parents, siblings, and offspring over age 18. A lifetime history of migraine was obtained using the Diagnostic Interview for Headache Syndromes. A lifetime history of psychiatric disorders was obtained using the semi-structured Schedule for Affective Disorders and Schizophrenia which was modified to incorporate Diagnostic and Statistical Manual diagnostic criteria. Several sleep items on current and lifetime sleep complaints were included as a subset of the interview.
Results
There was a significant association between migraine and the number of sleep problems as well as several specific sleep symptoms among probands and their adult relatives. Adults with migraine reported having significantly more lifetime sleep problems (OR [CI] = 2.3 [1.1-4.6]), and more current sleep difficulties, specifically, inadequate sleep (2.5 [1.2-5.0]), difficulty falling asleep (3.0 [1.5-6.3]), and persistent nightmares of childhood onset (4.3 [1.8-9.9]) than those without migraine. The associations between sleep problems and migraine persisted after controlling for both lifetime and current anxiety and mood disorders.
Conclusions
The association between sleep problems and migraine that is not solely explained by comorbid anxiety disorders or depression suggests that sleep problems should be evaluated among people with migraine.
doi:10.1111/j.1526-4610.2008.01175.x
PMCID: PMC2692650  PMID: 18624714
sleep; migraine; anxiety; depression
10.  Migraine aura or transient ischemic attacks? A five-year follow-up case-control study of women with transient central nervous system disorders in pregnancy 
BMC Medicine  2007;5:19.
Background
Migraine aura may be difficult to differentiate from transient ischemic attacks and other transient neurological disorders in pregnant women. The aims of the present study were to investigate and diagnose all pregnant women with transient neurological disorders of suspected central nervous system origin, and to compare this group with a control group of pregnant women with regard to vascular risk factors and prognosis.
Methods
During a 28 month period, 41 patients were detected with transient neurological symptoms during pregnancy. These were studied in detail with thorough clinical and laboratory investigations in order to make a certain diagnosis and to evaluate whether the episodes might be of a vascular nature. For comparison, the same investigations were performed in 41 pregnant controls. To assess the prognosis, both patients and controls were followed with questionnaires every year for five years.
Results
Migraine with aura was the most common cause of symptoms during pregnancy, occurring in 34 patients, while 2 were diagnosed with stroke, 2 with carpal tunnel syndrome, 1 with partial epilepsy, 1 with multiple sclerosis and 1 with presyncope. Patients had more headache before pregnancy than controls, but the average levels of vascular risk factors were similar. None of the patients or the controls reported cerebrovascular episodes during the five-year follow-up.
Conclusion
The diagnosis of migraine aura was difficult because for many patients it was their first ever attack and headache tended to be absent or of non-migraineous type. The aura features were more complex, with several aura symptoms and a higher prevalence of sensory and dysphasic aura than usual. Gradually developing aura symptoms, or different aura symptoms occurring in succession as described in the International Classification of Headache Disorders, seem to be useful for differentiating aura from other transient disorders. A meticulous history and clinical neurological examination are more useful than routine supplementary investigations for cerebrovascular disease. The five-year follow-up clearly indicates that migraine with aura in pregnancy usually has a good prognosis with regard to cerebrovascular events.
doi:10.1186/1741-7015-5-19
PMCID: PMC1939710  PMID: 17640340
11.  Neuroimaging for the Evaluation of Chronic Headaches 
Executive Summary
Objective
The objectives of this evidence based review are:
i) To determine the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) scans in the evaluation of persons with a chronic headache and a normal neurological examination.
ii) To determine the comparative effectiveness of CT and MRI scans for detecting significant intracranial abnormalities in persons with chronic headache and a normal neurological exam.
iii) To determine the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Clinical Need: Condition and Target Population
Headaches disorders are generally classified as either primary or secondary with further sub-classifications into specific headache types. Primary headaches are those not caused by a disease or medical condition and include i) tension-type headache, ii) migraine, iii) cluster headache and, iv) other primary headaches, such as hemicrania continua and new daily persistent headache. Secondary headaches include those headaches caused by an underlying medical condition. While primary headaches disorders are far more frequent than secondary headache disorders, there is an urge to carry out neuroimaging studies (CT and/or MRI scans) out of fear of missing uncommon secondary causes and often to relieve patient anxiety.
Tension type headaches are the most common primary headache disorder and migraines are the most common severe primary headache disorder. Cluster headaches are a type of trigeminal autonomic cephalalgia and are less common than migraines and tension type headaches. Chronic headaches are defined as headaches present for at least 3 months and lasting greater than or equal to 15 days per month. The International Classification of Headache Disorders states that for most secondary headaches the characteristics of the headache are poorly described in the literature and for those headache disorders where it is well described there are few diagnostically important features.
The global prevalence of headache in general in the adult population is estimated at 46%, for tension-type headache it is 42% and 11% for migraine headache. The estimated prevalence of cluster headaches is 0.1% or 1 in 1000 persons. The prevalence of chronic daily headache is estimated at 3%.
Neuroimaging
Computed Tomography
Computed tomography (CT) is a medical imaging technique used to aid diagnosis and to guide interventional and therapeutic procedures. It allows rapid acquisition of high-resolution three-dimensional images, providing radiologists and other physicians with cross-sectional views of a person’s anatomy. CT scanning poses risk of radiation exposure. The radiation exposure from a conventional CT scanner may emit effective doses of 2-4mSv for a typical head CT.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used to aid diagnosis but unlike CT it does not use ionizing radiation. Instead, it uses a strong magnetic field to image a person’s anatomy. Compared to CT, MRI can provide increased contrast between the soft tissues of the body. Because of the persistent magnetic field, extra care is required in the magnetic resonance environment to ensure that injury or harm does not come to any personnel while in the environment.
Research Questions
What is the effectiveness of CT and MRI scanning in the evaluation of persons with a chronic headache and a normal neurological examination?
What is the comparative effectiveness of CT and MRI scanning for detecting significant intracranial abnormality in persons with chronic headache and a normal neurological exam?
What is the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Research Methods
Literature Search
Search Strategy
A literature search was performed on February 18, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January, 2005 to February, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Systematic reviews, randomized controlled trials, observational studies
Outpatient adult population with chronic headache and normal neurological exam
Studies reporting likelihood ratio of clinical variables for a significant intracranial abnormality
English language studies
2005-present
Exclusion Criteria
Studies which report outcomes for persons with seizures, focal symptoms, recent/new onset headache, change in presentation, thunderclap headache, and headache due to trauma
Persons with abnormal neurological examination
Case reports
Outcomes of Interest
Primary Outcome
Probability for intracranial abnormality
Secondary Outcome
Patient relief from anxiety
System service use
System costs
Detection rates for significant abnormalities in MRI and CT scans
Summary of Findings
Effectiveness
One systematic review, 1 small RCT, and 1 observational study met the inclusion and exclusion criteria. The systematic review completed by Detsky, et al. reported the likelihood ratios of specific clinical variables to predict significant intracranial abnormalities. The RCT completed by Howard et al., evaluated whether neuroimaging persons with chronic headache increased or reduced patient anxiety. The prospective observational study by Sempere et al., provided evidence for the pre-test probability of intracranial abnormalities in persons with chronic headache as well as minimal data on the comparative effectiveness of CT and MRI to detect intracranial abnormalities.
Outcome 1: Pre-test Probability.
The pre-test probability is usually related to the prevalence of the disease and can be adjusted depending on the characteristics of the population. The study by Sempere et al. determined the pre-test probability (prevalence) of significant intracranial abnormalities in persons with chronic headaches defined as headache experienced for at least a 4 week duration with a normal neurological exam. There is a pre-test probability of 0.9% (95% CI 0.5, 1.4) in persons with chronic headache and normal neurological exam. The highest pre-test probability of 5 found in persons with cluster headaches. The second highest, that of 3.7, was reported in persons with indeterminate type headache. There was a 0.75% rate of incidental findings.
Likelihood ratios for detecting a significant abnormality
Clinical findings from the history and physical may be used as screening test to predict abnormalities on neuroimaging. The extent to which the clinical variable may be a good predictive variable can be captured by reporting its likelihood ratio. The likelihood ratio provides an estimate of how much a test result will change the odds of having a disease or condition. The positive likelihood ratio (LR+) tells you how much the odds of having the disease increases when a test is positive. The negative likelihood ratio (LR-) tells you how much the odds of having the disease decreases when the test is negative.
Detsky et al., determined the likelihood ratio for specific clinical variable from 11 studies. There were 4 clinical variables with both statistically significant positive and negative likelihood ratios. These included: abnormal neurological exam (LR+ 5.3, LR- 0.72), undefined headache (LR+ 3.8, LR- 0.66), headache aggravated by exertion or valsalva (LR+ 2.3, LR- 0.70), and headache with vomiting (LR+ 1.8, and LR- 0.47). There were two clinical variables with a statistically significant positive likelihood ratio and non significant negative likelihood ratio. These included: cluster-type headache (LR+ 11, LR- 0.95), and headache with aura (LR+ 12.9, LR- 0.52). Finally, there were 8 clinical variables with both statistically non significant positive and negative likelihood ratios. These included: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, and migraine type headache.
Outcome 2: Relief from Anxiety
Howard et al. completed an RCT of 150 persons to determine if neuroimaging for headaches was anxiolytic or anxiogenic. Persons were randomized to receiving either an MRI scan or no scan for investigation of their headache. The study population was stratified into those persons with a Hospital Anxiety and Depression scale (HADS) > 11 (the high anxiety and depression group) and those < 11 (the low anxiety and depression) so that there were 4 groups:
Group 1: High anxiety and depression, no scan group
Group 2: High anxiety and depression, scan group
Group 3: Low anxiety and depression, no scan group
Group 4: Low anxiety and depression, scan group
Anxiety
There was no evidence for any overall reduction in anxiety at 1 year as measured by a visual analogue scale of ‘level of worry’ when analysed by whether the person received a scan or not. Similarly, there was no interaction between anxiety and depression status and whether a scan was offered or not on patient anxiety. Anxiety did not decrease at 1 year to any statistically significant degree in the high anxiety and depression group (HADS positive) compared with the low anxiety and depression group (HADS negative).
There are serious methodological limitations in this study design which may have contributed to these negative results. First, when considering the comparison of ‘scan’ vs. ‘no scan’ groups, 12 people (16%) in the ‘no scan group’ actually received a scan within the follow up year. If indeed scanning does reduce anxiety then this contamination of the ‘no scan’ group may have reduced the effect between the groups results resulting in a non significant difference in anxiety scores between the ‘scanned’ and the ‘no scan’ group. Second, there was an inadequate sample size at 1 year follow up in each of the 4 groups which may have contributed to a Type II statistical error (missing a difference when one may exist) when comparing scan vs. no scan by anxiety and depression status. Therefore, based on the results and study limitations it is inconclusive as to whether scanning reduces anxiety.
Outcome 3: System Services
Howard et al., considered services used and system costs a secondary outcome. These were determined by examining primary care case notes at 1 year for consultation rates, symptoms, further investigations, and contact with secondary and tertiary care.
System Services
The authors report that the use of neurologist and psychiatrist services was significantly higher for those persons not offered as scan, regardless of their anxiety and depression status (P<0.001 for neurologist, and P=0.033 for psychiatrist)
Outcome 4: System Costs
System Costs
There was evidence of statistically significantly lower system costs if persons with high levels of anxiety and depression (Hospital Anxiety and Depression Scale score >11) were provided with a scan (P=0.03 including inpatient costs, and 0.047 excluding inpatient costs).
Comparative Effectiveness of CT and MRI Scans
One study reported the detection rate for significant intracranial abnormalities using CT and MRI. In a cohort of 1876 persons with a non acute headache defined as any type of headache that had begun at least 4 weeks before enrolment Sempere et al. reported that the detection rate was 19/1432 (1.3%) using CT and 4/444 (0.9%) using MRI. Of 119 normal CT scans 2 (1.7%) had significant intracranial abnormality on MRI. The 2 cases were a small meningioma, and an acoustic neurinoma.
Summary
The evidence presented can be summarized as follows:
Pre-test Probability
Based on the results by Sempere et al., there is a low pre-test probability for intracranial abnormalities in persons with chronic headaches and a normal neurological exam (defined as headaches experiences for a minimum of 4 weeks). The Grade quality of evidence supporting this outcome is very low.
Likelihood Ratios
Based on the systematic review by Detsky et al., there is a statistically significant positive and negative likelihood ratio for the following clinical variables: abnormal neurological exam, undefined headache, headache aggravated by exertion or valsalva, headache with vomiting. Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al. there is a statistically significant positive likelihood ratio but non statistically significant negative likelihood ratio for the following clinical variables: cluster headache and headache with aura. The Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al., there is a non significant positive and negative likelihood ratio for the following clinical variables: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, migraine type headache. The Grade quality of evidence supporting this outcome is very low.
Relief from Anxiety
Based on the RCT by Howard et al., it is inconclusive whether neuroimaging scans in persons with a chronic headache are anxiolytic. The Grade quality of evidence supporting this outcome is low.
System Services
Based on the RCT by Howard et al. scanning persons with chronic headache regardless of their anxiety and/or depression level reduces service use. The Grade quality of evidence is low.
System Costs
Based on the RCT by Howard et al., scanning persons with a score greater than 11 on the High Anxiety and Depression Scale reduces system costs. The Grade quality of evidence is moderate.
Comparative Effectiveness of CT and MRI Scans
There is sparse evidence to determine the relative effectiveness of CT compared with MRI scanning for the detection of intracranial abnormalities. The Grade quality of evidence supporting this is very low.
Economic Analysis
Ontario Perspective
Volumes for neuroimaging of the head i.e. CT and MRI scans, from the Ontario Health Insurance Plan (OHIP) data set were used to investigate trends in the province for Fiscal Years (FY) 2004-2009.
Assumptions were made in order to investigate neuroimaging of the head for the indication of headache. From the literature, 27% of all CT and 13% of all MRI scans for the head were assumed to include an indication of headache. From that same retrospective chart review and personal communication with the author 16% of CT scans and 4% of MRI scans for the head were for the sole indication of headache. From the Ministry of Health and Long-Term Care (MOHLTC) wait times data, 73% of all CT and 93% of all MRI scans in the province, irrespective of indication were outpatient procedures.
The expenditure for each FY reflects the volume for that year and since volumes have increased in the past 6 FYs, the expenditure has also increased with a pay-out reaching 3.0M and 2.8M for CT and MRI services of the head respectively for the indication of headache and a pay-out reaching 1.8M and 0.9M for CT and MRI services of the head respectively for the indication of headache only in FY 08/09.
Cost per Abnormal Finding
The yield of abnormal finding for a CT and MRI scan of the head for the indication of headache only is 2% and 5% respectively. Based on these yield a high-level estimate of the cost per abnormal finding with neuroimaging of the head for headache only can be calculated for each FY. In FY 08/09 there were 37,434 CT and 16,197 MRI scans of the head for headache only. These volumes would generate a yield of abnormal finding of 749 and 910 with a CT scan and MRI scan respectively. The expenditure for FY 08/09 was 1.8M and 0.9M for CT and MRI services respectively. Therefore the cost per abnormal finding would be $2,409 for CT and $957 for MRI. These cost per abnormal finding estimates were limited because they did not factor in comparators or the consequences associated with an abnormal reading or FNs. The estimates only consider the cost of the neuroimaging procedure and the yield of abnormal finding with the respective procedure.
PMCID: PMC3377587  PMID: 23074404
12.  Stress and psychological factors before a migraine attack: A time-based analysis 
Background
The objective of this study is to examine the stress and mood changes of Japanese subjects over the 1–3 days before a migraine headache.
Methods
The study participants were 16 patients with migraines who consented to participate in this study. Each subject kept a headache diary four times a day for two weeks. They evaluated the number of stressful events, daily hassles, domestic and non-domestic stress, anxiety, depressive tendency and irritability by visual analog scales. The days were classified into migraine days, pre-migraine days, buffer days and control days based on the intensity of the headaches and accompanying symptoms, and a comparative study was conducted for each factor on the migraine days, pre-migraine days and control days.
Results
The stressful event value of pre-migraine days showed no significant difference compared to other days. The daily hassle value of pre-migraine days was the highest and was significantly higher than that of buffer days. In non-domestic stress, values on migraine days were significantly higher than on other days, and there was no significant difference between pre-migraine days and buffer days or between pre-migraine days and control days. There was no significant difference in the values of domestic stress between the categories. In non-domestic stress, values on migraine days were significantly higher than other days, and there was no significant difference between pre-migraine days and buffer days or between pre-migraine days and control days.
There was little difference in sleep quality on migraine and pre-migraine days, but other psychological factors were higher on migraine days than on pre-migraine days.
Conclusion
Psychosocial stress preceding the onset of migraines by several days was suggested to play an important role in the occurrence of migraines. However, stress 2–3 days before a migraine attack was not so high as it has been reported to be in the United States and Europe. There was no significant difference in the values of psychological factors between pre-migraine days and other days.
doi:10.1186/1751-0759-2-14
PMCID: PMC2556692  PMID: 18799013
13.  One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults 
The Journal of Headache and Pain  2012;13(2):147-157.
Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0414-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0414-5
PMCID: PMC3274583  PMID: 22246025
Prevalence of migraine; Prevalence of tension-type headache; Migraine; Tension-type headache; Headache
14.  One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults 
The Journal of Headache and Pain  2012;13(2):147-157.
Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0414-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0414-5
PMCID: PMC3274583  PMID: 22246025
Prevalence of migraine; Prevalence of tension-type headache; Migraine; Tension-type headache; Headache
15.  Prevalence and characteristics of allodynia in headache sufferers 
Neurology  2008;70(17):1525-1533.
Objective:
The authors estimated the prevalence and severity of cutaneous allodynia (CA) in individuals with primary headaches from the general population.
Methods:
We mailed questionnaires to a random sample of 24,000 headache sufferers previously identified from the population. The questionnaire included the validated Allodynia Symptom Checklist (ASC) as well as measures of headache features, disability, and comorbidities. We modeled allodynia as an outcome using headache diagnosis, frequency and severity of headaches, and disability as predictor variables in logistic regression. Covariates included demographic variables, comorbidities, use of preventive medication, and use of opioids.
Results:
Complete surveys were returned by 16,573 individuals. The prevalence of CA of any severity (ASC score ≥3) varied with headache type. Prevalence was significantly higher in transformed migraine (TM, 68.3%) than in episodic migraine (63.2%, p < 0.01) and significantly elevated in both of these groups compared with probable migraine (42.6%), other chronic daily headaches (36.8%), and severe episodic tension-type headache (36.7%). The prevalence of severe CA (ASC score ≥9) was also highest in TM (28.5%) followed by migraine (20.4%), probable migraine (12.3%), other chronic daily headaches (6.2%), and severe episodic tension-type headache (5.1%). In the migraine and TM groups, prevalence of CA was higher in women and increased with disability score. Among migraineurs, CA increased with headache frequency and body mass index. In all groups, ASC scores were higher in individuals with major depression.
Conclusions:
Cutaneous allodynia (CA) is more common and more severe in transformed migraine and migraine than in other primary headaches. Among migraineurs, CA is associated with female sex, headache frequency, increased body mass index, disability, and depression.
doi:10.1212/01.wnl.0000310645.31020.b1
PMCID: PMC2664547  PMID: 18427069
16.  Migraine Care Among Different Ethnicities: Do Disparities Exist? 
Headache  2006;46(5):754-765.
Objective
Evaluate whether, in a primary care setting, Caucasians (C) and African Americans (AA) with moderately to severely disabling migraines differed in regards to: utilizing the health-care system for migraine care, migraine diagnosis and treatment, level of mistrust in the health-care system, perceived communication with their physician, and perceived migraine triggers.
Background
Research has documented ethnic disparities in pain management. However, almost no research has been published concerning potential disparities in utilization, diagnosis, and/or treatment of migraine. It is also important to consider whether ethnic differences exist for trust and communication between patients and physicians, as these are essential when diagnosing and treating migraine.
Methods
Adult patients with headache (n = 313) were recruited from primary care waiting rooms. Of these, 131 (AA = 77; C = 54) had migraine, moderate to severe headache-related disability, and provided socioeconomic status (SES) data. Participants completed measures of migraine disability (MIDAS), migraine health-care utilization, diagnosis and treatment history, mistrust of the medical community, patient–physician communication (PPC), and migraine triggers. Analysis of covariance (controlling for SES and recruitment site), chi-square, and Pearson product moment correlations were conducted.
Results
African Americans were less likely to utilize the health-care setting for migraine treatment (AA = 46% vs. C = 72%, P < .001), to have been given a headache diagnosis (AA = 47% vs. C = 70%, P < .001), and to have been prescribed acute migraine medication (AA = 14% vs. C = 37%, P < .001). Migraine diagnosis was low for both groups, and <15% of all participants had been prescribed a migraine-specific medication or a migraine preventive medication despite suffering moderate to severe levels of migraine disability. African Americans had less trust in the medical community (P < .001, η2 = 0.26) and less positive PPC (P < .001, η2 = 0.11). Also, the lower the trust and communication, the less likely they were to have ever seen (or currently be seeing) a doctor for migraine care or to have been prescribed medication.
Conclusions
Migraine utilization, diagnosis, and treatment were low for both groups. However, this was especially true for African Americans, who also reported lower levels of trust and communication with doctors relative to Caucasians. The findings highlight the need for improved physician and patient education about migraine diagnosis and treatment, the importance of cultural variation in pain presentation, and the importance of communication when diagnosing and treating migraine.
doi:10.1111/j.1526-4610.2006.00453.x
PMCID: PMC2443411  PMID: 16643578
migraine; ethnicity; health-care disparities; utilization; migraine diagnosis and treatment; patient–physician communication
17.  Prevalence and risk factors for depression and anxiety among outpatient migraineurs in mainland China 
The Journal of Headache and Pain  2012;13(4):303-310.
This study aimed to investigate the prevalence and risk factors for anxiety and depression symptoms in outpatient migraineurs in mainland China. In addition, we evaluated whether the Hospital Anxiety and Depression Scale (HADS) provided sufficient validity to screen depression and anxiety. A cross-sectional study was conducted consecutively at our headache clinic. Migraine was diagnosed according to International Classification of Headache Disorders, 2nd edition (ICHD-II). Demographic characteristics and clinical features were collected by headache questionnaire. Anxiety and depression symptoms about migraineurs were assessed using HADS. Several questionnaires were simultaneously used to evaluate patients with depressive disorder including the Hamilton Depression Rating Scale-17 (HAMD), Hamilton Anxiety Rating Scale (HAMA) and HADS. Pearson correlation analysis was applied to test the validity of HADS. 176 outpatients with migraine (81.8 % female) were included. Overall, 17.6 and 38.1 % participants had depression and anxiety, respectively. Possible risk factors for depression in migraineurs included headache intensity of first onset of migraine, migraine with presymptom, migraine with family history and migraine disability. The possible risk factors for anxiety included fixed attack time of headache in one day and poor sleeping, and age represented a protective factor for anxiety. The correlation coefficient of HADS-A and HADS-D with HAMA and HAMD was 0.666 and 0.508, respectively (P < 0.01). This study demonstrates that depression and anxiety comorbidity in our mainland Chinese migraineurs are also common, and several risk factors were identified that may provide predictive value. These findings can help clinicians to identify and treat anxiety and depression in order to improve migraine management.
doi:10.1007/s10194-012-0442-9
PMCID: PMC3356469  PMID: 22466285
Anxiety; Cross-sectional study; Depression; Migraine; Risk factor
18.  Body Mass Index and Adult Weight Gain Among Reproductive Age Women with Migraine 
Headache  2011;51(4):559-569.
Objective
To evaluate the cross-sectional relationship between migraine and pre-gravid obesity; and to assess the risk of adult weight gain among women with history of a pediatric diagnosis of migraine.
Background
Obesity, comorbid with pain disorders including migraine, shares common pathophysiological characteristics including systemic inflammation, and derangements in adipose-tissue derived cytokines. Despite biochemical and epidemiological commonalities, obesity-migraine associations have been inconsistently observed.
Methods
A cohort of 3,733 women was interviewed during early pregnancy. We ascertained participants’ self-reported history of physician-diagnosed migraine and collected self-reported information about pre-gravid weight, adult height and net weight change from age 18 to the 3-monthsperiodpriorto pregnancy. Using pre-gravid body mass index, we categorized participants as follows: lean (<18.5 kg/m2); normal (18.5–24.9 kg/m2); overweight (25–29.9 kg/m2), obese (30–34.9 kg/m2), severely obese (35–39.9 kg/m2), and morbidly obese (≥ 40 kg/m2). Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Results
After adjusting for confounders, relative to normal weight women, obese women had a 1.48-fold increased odds of migraine(OR=1.48; 95%CI 1.12–1.96). Severely obese (OR=2.07; 95%CI 1.27–3.39) and morbidly obese (OR=2.75; 95%CI 1.60–4.70) had the highest odds of migraines. Women with a history of diagnosed pediatric migraine had a 1.67-fold higher odds of gaining ≥10.0 kg above their weight at age 18, as compared with non-migraineurs (OR=1.67; 95%CI 1.13–2.47).
Conclusion
These data support earlier observations of migraine-obesity association among women, and extend the literature to include evidence of adult weight gain among women with a history of pediatric migraine.
doi:10.1111/j.1526-4610.2010.01833.x
PMCID: PMC3187699  PMID: 21269300
Migraine; Obesity; Adult Weight Gain; Pediatric Migraine; Body Mass Index
19.  Relationship between insomnia and headache in community-based middle-aged Hong Kong Chinese women 
The Journal of Headache and Pain  2010;11(3):187-195.
Limited studies have investigated the prevalence of insomnia symptoms among individuals with different headache diagnoses and the association between insomnia and headache in subjects with comorbid anxiety and depression. A total of 310 community-dwelling Hong Kong Chinese women aged 40–60 years completed a self-administered questionnaire on headache, sleep difficulties, mood disturbances, and functional impairment. About 31% of the sample complained of recurrent headache unrelated to influenza and the common cold in the past 12 months. The percentages of women diagnosed to have migraine, tension-type headache (TTH), and headache unspecified were 8.4, 15.5 and 7.1%, respectively. The most frequent insomnia complaint was “problem waking up too early” (29.4%), followed by “difficulty staying asleep” (28.0%) and “difficulty falling asleep” (24.4%). Women with headaches were significantly more likely to report insomnia symptoms than those without headaches. There were no significant differences among women with migraine, TTH, and headache unspecified in the prevalence of insomnia symptoms. Logistic regression analysis showed that women with insomnia disorder as defined by an insomnia severity index total score ≥8 had 2.2-fold increased risk of reporting recurrent headache, 3.2-fold increased risk of migraine, and 2.3-fold increased risk of TTH, after adjusting for anxiety and depression. Individual insomnia symptoms were not independent predictors. The association between insomnia and headache was stronger in subjects with more frequent headaches. Our findings suggest that insomnia and the associated distress, but not insomnia symptoms alone, is an independent risk factor for recurrent headache in middle-aged women with mixed anxiety, depression and sleep disturbances.
doi:10.1007/s10194-010-0199-y
PMCID: PMC3451911  PMID: 20186559
Anxiety; Depression; Headache; Insomnia; Migraine; Tension-type headache
20.  Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study 
BMC Neurology  2014;14(1):238.
Background
Although anxiety and depression have been classified as distinct traits of affective disorders, previous studies have reported their co-occurrence in subjects with migraine. However, few reports are available on the clinical implications of this comorbidity. This study is to assess the comorbidity of anxiety and depression in subjects with migraine and its clinical implications in a population-based sample from Korea.
Methods
We selected Korean subjects aged 19–69 years by the stratified random sampling method, and evaluated them using a semi-structured interview, designed to identify headache type, anxiety, and depression. We used Goldberg Anxiety Scale questions and Patient Health Questionnnaire-9 for the diagnosis of anxiety and depression, respectively.
Results
Of the 2,762 participants who completed the interview, 147 subjects (5.4%) were classified as having a migraine during the previous year. Among these 147 subjects, 17 (11.6%) had anxiety and depression, 28 (19.0%) had anxiety alone, 9 (6.1%) had depression alone, and 93 (63.3%) had neither anxiety nor depression. Headache frequency per month was remarkably higher in subjects having migraine with anxiety and depression (median [25–75 percentile values], 8.0 [2.5–21.0]) than in those having migraine with anxiety alone (2.0 [1.0–5.0], p = 0.003), migraine with depression alone (1.0 [0.3–4.0], p = 0.001), and migraine without anxiety or depression (1.0 [0.3–3.0], p < 0.001). The migraine with anxiety alone (7.0 [6.0–8.0], p = 0.011) group and migraine with anxiety and depression (7.0 [5.0–9.0], p = 0.018) group showed higher Visual Analogue Scale scores for pain intensity compare to migraine without anxiety or depression (6.0 [5.0-7.0]) group.
Conclusions
Approximately 1/3 of migraineurs with anxiety had depression and 2/3 of migraineurs with depression had anxiety. Combination of anxiety and depression was associated with an increased headache frequency. Anxiety was associated with exacerbation of headache intensity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12883-014-0238-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12883-014-0238-4
PMCID: PMC4279894  PMID: 25494868
Migraine; Anxiety; Depression; Epidemiology; Comorbidity
21.  Sleep duration, vital exhaustion and perceived stress among pregnant migraineurs and non-migraineurs 
Background
Migraine has been associated with sleep disorders in men and non-pregnant women, but little is known about sleep complaints among pregnant migraineurs.
Methods
A cohort of 1,334 women was interviewed during early pregnancy. At the time of interview we ascertained participants' migraine diagnosis status and collected information about sleep duration before and during early pregnancy, daytime sleepiness, vital exhaustion and perceived stress during early pregnancy. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of short/long sleep duration, excessive daytime sleepiness, vital exhaustion and elevated perceived stress associated with a history of migraine.
Results
Approximately 19.4% of the cohort (n = 259) reported having a medical diagnosis of migraine prior to the study pregnancy. Compared with women without migraine, the multivariable-adjusted ORs (95% CI) among migraineurs for short sleep duration before and during early pregnancy were 1.51 (1.09-2.09), and 1.57 (1.11-2.23), respectively. The corresponding OR (95% CI) for long sleep duration before and during pregnancy were 1.33 (0.77-2.31) and 1.31 (0.94-1.83), respectively. A modest and statistically insignificant association between migraine history and excessive daytime sleepiness in early pregnancy was noted (OR = 1.46; 95% CI 0.94-2.26). Migraineurs had an increased risk of vital exhaustion (OR = 2.04; 95% CI 1.52-2.76) and elevated perceived stress (OR = 1.57; 95% CI 1.06-2.31). Observed associations were more pronounced among overweight migraineurs.
Conclusions
These data support earlier research documenting increased risks of sleep disorders among migraineurs; and extends the literature to include pregnant women. Prospective studies are needed to more thoroughly explore factors that mediate the apparent migraine-sleep comorbidity among pregnant women.
doi:10.1186/1471-2393-10-72
PMCID: PMC2987887  PMID: 21047418
22.  Associations of socioeconomic status with migraine and non-migraine headache 
Cephalalgia  2011;32(2):159-170.
Background
Migraine has been linked with several measures of socioeconomic status (SES). However, results are inconsistent and data on the association between SES and non-migraine headache, migraine subtypes and migraine frequency are sparse.
Methods
We conducted a cross-sectional study among 36,858 participants in the Women’s Health Study. As proxy for SES, we calculated an SES index using annual household income and education. Migraine, migraine aura, and non-migraine headache were self-reported with good validation rates. Multinomial logistic regression models were used to evaluate the association between SES index and the various headache forms.
Results
12,140 (32.9%) women reported any history of headache, 6,801 women (18.4%) reported any history of migraine and 5,339 (14.5%) reported non-migraine headache. Women with low SES had an increased risk for all headache forms. The multivariable-adjusted OR (95% CI) were 1.22 (1.10–1.36) for non-migraine headache, 1.40 (1.28–1.54) for any migraine, 1.44 (1.23–1.69) for migraine with aura, and 1.38 (1.21–1.58) for migraine without aura. Among active migraineurs, low SES was associated with an increased OR for ≥weekly attack frequency (1.77, 1.26–2.49).
Conclusions
In this large cohort of female health professionals, low SES was associated with an increased prevalence for all headache forms and an increased migraine attack frequency.
doi:10.1177/0333102411430854
PMCID: PMC3266434  PMID: 22174348
Migraine; non-migraine headache; migraine frequency; socioeconomic status
23.  Migraine and stroke in young women: case-control study 
BMJ : British Medical Journal  1999;318(7175):13-18.
Objective
To investigate the association between migraine and ischaemic or haemorrhagic stroke in young women.
Design
Hospital based case-control study.
Setting
Five European centres participating in the World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
Subjects
291 women aged 20-44 years with ischaemic, haemorrhagic, or unclassified arterial stroke compared with 736 age and hospital matched controls.
Intervention
Questionnaire.
Main outcome measure
Self reported history of headaches.
Results
Adjusted odds ratios associated with a personal history of migraine were 1.78 (95% confidence intervals, 1.14 to 2.77), 3.54 (1.30 to 9.61), and 1.10 (0.63 to 1.94) for all stroke, ischaemic stroke, and haemorrhagic stroke respectively. Odds ratios for ischaemic stroke were similar for classical migraine (with aura) (3.81, 1.26 to 11.5) and simple migraine (without aura) (2.97, 0.66 to 13.5). A family history of migraine, irrespective of personal history, was also associated with increased odds ratios, not only for ischaemic stroke but also haemorrhagic stroke. In migrainous women, coexistent use of oral contraceptives or a history of high blood pressure or smoking had greater than multiplicative effects on the odds ratios for ischaemic stroke associated with migraine alone. Change in the frequency or type of migraine on using oral contraceptives did not predict subsequent stroke. Between 20% and 40% of strokes in women with migraine seemed to develop directly from a migraine attack.
Conclusions
Migraine in women of childbearing age significantly increases the risk of ischaemic but not haemorrhagic stroke. The coexistence of oral contraceptive use, high blood pressure, or smoking seems to exert a greater than multiplicative effect on the risk of ischaemic stroke associated with migraine.
Key messagesA personal history of migraine was associated with increased risk of ischaemic but not haemorrhagic strokeCoexistence of risk factors—use of oral contraceptives, high blood pressure, or smoking had more than multiplicative effects on odds ratios for ischaemic stroke associated with migraine aloneA family history of migraine, irrespective of a personal migraine history, was associated with increased risk of ischaemic and haemorrhagic strokeUp to 40% of strokes in migrainous women develop directly out of a migraine attack—so called migrainous strokesA change in type or frequency of migraine with use of oral contraceptives did not predict subsequent stroke
PMCID: PMC27668  PMID: 9872876
24.  Risk of Spontaneous Preterm Birth in Relation to Maternal Depressive, Anxiety and Stress Symptoms 
Objective
To examine the risk of preterm birth (PTB) in relation to maternal psychiatric symptoms during pregnancy in Peruvian women.
Methods
This case control study included 479 PTB cases and 480 term controls. In-person interviews were conducted to assess women’s depressive, anxiety and stress symptoms using the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Results
Compared with women reporting no or minimal depressive symptoms, the aOR (95% CI) for PTB associated with consecutive severity of depressive symptoms based on the PHQ-9 assessment method were as follows: mild 2.22 (95% CI 1.64–3.00) and moderate-severe 3.67 (95% CI 2.09–6.46). The corresponding aORs for mild, moderate, and moderate- severe depressive symptoms based on the DASS-21 assessment were, 1.00 (reference), 3.82 (95% CI 1.90–7.66) and 2.90 (95% CI 1.66–5.04), respectively. A positive gradient was observed for the odds of PTB with severity of anxiety (ptrend <0.001) and stress symptoms (ptrend <0.001).
Conclusions
The odds of PTB are increased in pregnant Peruvian women with psychiatric symptoms. Efforts to screen and treat affected women may modify risks of PTB and possibly other associated disorders.
PMCID: PMC3662498  PMID: 23447915
25.  Migraine management in pregnancy 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 78.
Abstract:
Background:
Migraine and tension-type headache are primary headache disorders that occur during pregnancy. Most women with migraine improve during pregnancy. Some women have their first attack during pregnancy. Migraine can recur postpartum; it can also begin at that time. Women who have had menstrual migraine and migraine onset at menarche tend to experience no migraine during pregnancy. Not all migraines improve during pregnancy, however. Some women experience migraine for the first time during pregnancy.
Etiology:
Headaches caused by cerebral arteriovenous malformations often present as migraine with aura. Cerebral venous thrombosis (common during pregnancy and the puerperium) may manifest with migraine-like visual disturbance and headache.
Treatment:
Nondrug therapies (relaxation, sleep, massage, ice packs and biofeedback) should be tried first to treat migraine in women who are pregnant. For treatment of acute migraine attacks 1000 mg of paracetamol (acetaminophen) preferably as a suppository is considered the first choice drug treatment.
Conclusions:
Migraine has also been recently postulated as one of the major risk factors for stroke during pregnancy and the puerperium. There is thus an urgent need for prospective studies of large numbers of pregnant women to determine the real existence and extent of the risks posed by migraine during pregnancy.
Keywords:
Migraine, Pregnancy, Headache
PMCID: PMC3571604

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