Migraine and estrogen.

PURPOSE OF REVIEW: The aim is to systematically and critically review the relationship between migraine and estrogen, the predominant female sex hormone, with a focus on studies published in the last 18 months. RECENT FINDINGS: Recent functional MRI (fMRI) studies of the brain support the existence of anatomical and functional differences between men and women, as well as between participants with migraine and healthy controls. In addition to the naturally occurring changes in endogenous sex hormones over the lifespan (e.g. puberty and menopause), exogenous sex hormones (e.g. hormonal contraception or hormone therapy) also may modulate migraine. Recent data support the historical view of an elevated risk of migraine with significant drops in estrogen levels. In addition, several lines of research support that reducing the magnitude of decline in estrogen concentrations prevents menstrually related migraine (MRM) and migraine aura frequency. SUMMARY: Current literature has consistently demonstrated that headache, in particular migraine, is more prevalent in women as compared with men, specifically during reproductive years. Recent studies have found differences in headache characteristics, central nervous system anatomy, as well as functional activation by fMRI between the sexes in migraine patients. Although the cause underlying these differences is likely multifactorial, considerable evidence supports an important role for sex hormones. Recent studies continue to support that MRM is precipitated by drops in estrogen concentrations, and minimizing this decline may prevent these headaches. Limited data also suggest that specific regimens of combined hormone contraceptive use in MRM and migraine with aura may decrease both headache frequency and aura.

Migraine and psychiatric comorbidities among sub-saharan african adults.

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 2151 employed adults in sub-Saharan Africa. A standardized questionnaire was used to identify sociodemographic, headache, and lifestyle characteristics of participants. Migraine classification was based on the International Classification of Headache Disorders-2 diagnostic criteria. Depressive, anxiety, and stress symptoms were ascertained with the Patient Health Questionnaire and the Depression Anxiety Stress Scale, respectively. Multivariable logistic regression models were used to estimate adjusted odds ratio (OR) and 95% confidence intervals (CIs). 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 with 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 with 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.

Post-traumatic stress disorder, drug abuse and migraine: new findings from the National Comorbidity Survey Replication (NCS-R).

BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to be associated with migraine and drug abuse. METHODS: This was an analysis of data from the National Comorbidity Survey Replication (NCS-R) to evaluate the association of PTSD in those with episodic migraine (EM) and chronic daily headache (CDH). RESULTS: Our sample consisted of 5,692 participants. Lifetime and 12-month prevalence rates of PTSD were increased in those with EM and CDH. After adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11; women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the association between migraine with depression or anxiety. The lifetime OR of PTSD was also increased in CDH sufferers. The OR of illicit drug abuse was not increased in those with EM or CDH unless co-occurring with PTSD or depression. CONCLUSION: The lifetime and 12-month OR of PTSD is increased in those with migraine or CDH, and is greater in men than women with migraine. The lifetime and 12-month OR of illicit drug abuse is not increased in those with migraine or CDH unless co-occurring with PTSD or depression.

Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

OBJECTIVE: To evaluate in a headache clinic population the relationship of childhood maltreatment on the prevalence of pain conditions comorbid with migraine. BACKGROUND: Childhood maltreatment is highly prevalent and has been frequently associated with recurrent headache. The relationship of maltreatment and pain has, however, been a subject of some debate. METHODS: Cross-sectional data on self-reported physician-diagnosed pain conditions were electronically collected from persons with migraine (diagnosed according to International Classification of Headache Disorders-2), seeking treatment in headache clinics at 11 centers across the US and Canada. These included irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), interstitial cystitis (IC), arthritis, endometriosis, and uterine fibroids. Other information included demographics, migraine characteristics (frequency, headache-related disability), remote and current depression (The Patient Health Questionnaire-9), and remote and current anxiety (The Beck Anxiety Inventory). Patients also completed the Childhood Trauma Questionnaire regarding sexual, emotional, and physical abuse, and emotional and physical neglect under the age of 18 years old. Statistical analyses accounted for the survey design and appropriate procedures in SAS such as surveymeans, surveyfreq, and surveylogistic were applied to the weighted data. RESULTS: A total of 1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine fibroids by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was associated with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids. Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI: 1.22-2.46) were independently associated with an increased number of pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34-2.68) with an increased number of pain comorbidities. CONCLUSION: The association of childhood maltreatment and pain was stronger in those reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in migraineurs childhood maltreatment may be a risk factor for development of comorbid pain disorders.

Migraine and obesity: epidemiology, mechanisms, and implications.

Adipose tissue is a dynamic neuroendocrine organ that is involved in multiple physiological and pathological processes, and when excessive, results in obesity. Clinical and population-based data suggest that migraine and chronic daily headache are associated with obesity, as estimated by anthropometric indices. In addition, translational and basic science research shows multiple areas of overlap between migraine pathophysiology and the central and peripheral pathways regulating feeding. Specifically, neurotransmittors such as serotonin, peptides such as orexin, and adipocytokines such as adiponectin and leptin have been suggested to have roles in both feeding and migraine. In this article, we first review the definition and ascertainment of obesity. This is followed by a review of the clinical and population-based studies evaluating the associations between obesity and chronic daily headache and migraine. We then discuss the central and peripheral pathways involved in the regulation of feeding, where it overlaps with migraine pathophysiology, and where future research may be headed in light of these data.

Allodynia in migraine: association with comorbid pain conditions.

BACKGROUND: Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. METHODS: Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. RESULTS: A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. CONCLUSION: Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.

The associations between migraine, unipolar psychiatric comorbidities, and stress-related disorders and the role of estrogen.

Migraine is a common and often disabling neurovascular disorder. It has been linked with several psychiatric disorders, such as depression and anxiety, and to stress-related disorders, such as abuse and posttraumatic stress disorder (PTSD). Epidemiological data have consistently shown a higher prevalence of migraine, depression, anxiety, abuse, and PTSD in women as compared with men. The increased vulnerability of women to migraine and psychiatric disorders often occurs during periods of marked hormonal fluctuations of ovarian hormones. One consequence of these associations is the hypothesis that estrogens have a role in the pathophysiology of both disorders. This article offers an in-depth review of several studies linking psychiatric disorders and stress-related disorders with migraine. We also discuss the role of estrogen in the pathophysiologic overlap between these disorders. Finally, we briefly touch on where future research may be headed, in light of these data.

Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels.

The utility of muscle biopsy in patients with modest elevations of serum creatine kinase (CK) level but normal neurological examinations and nondiagnostic electrodiagnostic studies is uncertain. We performed systematic, extensive studies on muscle biopsies of 20 such patients. A definitive diagnosis was arrived at in only 1 by histochemical studies, although 4 others demonstrated minor myopathic changes. Biochemical evaluation led to a diagnosis in an additional 5. Muscle biopsy is useful for evaluating such patients, but extensive studies of the muscle are necessary.

Use of intravenous immunoglobulin in Lambert-Eaton myasthenic syndrome.

The authors report a case of a 65-year-old woman with small cell lung cancer who had profound, progressive lower extremity weakness, intermittent blurred vision, a dry mouth, and orthostatic hypotension. Results of laboratory and electrodiagnostic studies were consistent with the diagnosis of Lambert-Eaton myasthenic syndrome. The patient was treated with one course of intravenous immunoglobulin and had significant improvement.