Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.

Risk factors for migraine disease progression: a narrative review for a patient-centered approach.

BACKGROUND: In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk. METHODS: A group of headache expert healthcare professionals, clinicians, and researchers reviewed published evidence documenting factors associated with increased or decreased rates of migraine progression and established expert opinions for disease management recommendations. Strength of evidence was rated as good, moderate, or based solely on expert opinion, using modified criteria for causation developed by AB Hill. RESULTS: Migraine progression is commonly operationally defined as the transition from ≤ 15 to ≥ 15 monthly headache days among people with migraine; however, this does not necessarily constitute a fundamental change in migraine biology and other definitions should be considered. Established and theoretical key risk factors for migraine progression were categorized into five domains: migraine disease characteristics, treatment-related factors, comorbidities, lifestyle/exogenous factors, and demographic factors. Within these domains, good evidence supports the following risk factors: poorly optimized acute headache treatment, cutaneous allodynia, acute medication overuse, selected psychiatric symptoms, extra-cephalic chronic pain conditions, metabolism-related comorbidities, sleep disturbances, respiratory conditions, former/current high caffeine intake, physical inactivity, financial constraints, tobacco use, and personal triggers as risk factors. Protective actions that may mitigate migraine progression are sparsely investigated in published literature; our discussion of these factors is primarily based on expert opinion. CONCLUSIONS: Recognizing risk factors for migraine progression will allow healthcare providers to suggest protective actions against migraine progression (Supplementary Fig. 1). Intervention studies are needed to weight the risk factors and test the clinical benefit of hypothesized mitigation strategies that emerge from epidemiological evidence.

Evaluation and treatment of headache associated with moyamoya disease - a narrative review.

BACKGROUND: Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. METHODS: We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments.Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.

Adverse Childhood Experiences and Frequent Headache by Adolescent Self-Report.

BACKGROUND: The association between exposure to adverse childhood experiences (ACEs) and increased headache in adults has been well characterized. Childhood adversity and its effect on headache in children have not been as robustly investigated. This study examines the relationship of self-reported ACEs to frequent headache in an adolescent cohort. METHODS: We performed a retrospective cohort study using data from the National Longitudinal Study of Adolescent to Adult Health Wave I (n = 20,745) to examine self-reported ACE exposures and their relationship to frequent headache. RESULTS: The study population was composed of 20,745 participants; 50.6% male and 49.4% female. The mean age of respondents was 15.9 years (range 12 to 21 years, standard error: 0.12 years). Frequent headache was reported in 29.3% of respondents, and 45% of respondents reported one or more ACE exposures. For each increase in cumulative ACE score, odds of frequent headache increased by 1.22 (95% confidence interval [CI] 1.15 to 1.30). The ACEs that individually showed an association with frequent headache after adjusting for demographic factors were lack of maternal warmth (odds ratio [OR] 1.40, 95% CI 1.12 to 1.74, P = 0.002), lack of paternal warmth (OR 1.47, 95% CI 1.20 to 1.81, P < 0.001), paternal alcoholism (OR 1.21, 95% CI 1.05 to 1.40, P = 0.007), suicide attempt of family member (OR 1.51, 95% CI 1.22 to 1.87, P < 0.001), and living in an unsafe neighborhood (OR 1.22, 95% CI 1.06 to 1.39, P = 0.004). CONCLUSIONS: Several ACE exposures were associated with frequent headache in adolescents. An increase in cumulative ACE exposure increased the odds of having frequent headache.

Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19.

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10-12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

Efficacy of Galcanezumab for Migraine Prevention in Patients With a Medical History of Anxiety and/or Depression: A Post Hoc Analysis of the Phase 3, Randomized, Double-Blind, Placebo-Controlled REGAIN, and Pooled EVOLVE-1 and EVOLVE-2 Studies.

OBJECTIVE: This post hoc analysis evaluated the efficacy of galcanezumab for the prevention of migraine in patients with and without comorbid anxiety and/or depression. BACKGROUND: Patients with migraine have a higher risk of anxiety and/or depression. Given the high prevalence of psychiatric symptoms and their potential negative prognostic impact, determining the efficacy of migraine treatments in patients with these comorbidities is important. METHODS: The results of 2 phase 3 episodic migraine studies of patients with 4-14 migraine headache days (MHD) per month were pooled. A third chronic migraine study, which was evaluated separately, enrolled patients with ≥15 headache days per month, of which ≥8 had migraine-like features. Patients in all 3 studies were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. The efficacy of galcanezumab on migraine was measured in subgroups of patients with anxiety and/or depression (current or past) and patients without. A repeated measures model was used to compare treatment groups within each subgroup and to test for consistency of treatment effect across the anxiety/depression subgroups (subgroup-by-treatment interaction) during the double-blind treatment phases. RESULTS: Among 1773 intent-to-treat patients with episodic migraine, both doses of galcanezumab demonstrated statistically significant improvements relative to placebo in overall number of MHD for the subgroups of patients with anxiety and/or depression (mean change difference from placebo [95% CI]: -2.07 [-2.81, -1.33] for galcanezumab 120 mg [P < .001], -1.91 [-2.78, -1.04] for 240 mg [P < .001]) and without anxiety and/or depression (mean change difference from placebo [95% CI]: -1.92 [-2.36, -1.47] for 120 mg [P < .001], -1.77 [-2.20, -1.33] for 240 mg [P < .001]), as was observed for the secondary outcomes of MHD with acute medication use and functional impairment. Among 1113 intent-to-treat patients with chronic migraine, those with anxiety and/or depression had significant reductions in overall MHD frequency with the 240-mg dose (mean change difference from placebo [95% CI]: -1.92 [-3.52, -0.33]; P = .018), whereas significant reductions were observed at both the 120-mg (mean change difference from placebo [95% CI]: -2.29 [-3.26, -1.31]; P < .001) and 240-mg (-1.85 [-2.83, -0.87]; P < .001) doses in patients without anxiety and/or depressions. Significant reductions (P < .01) in MHD with acute medication use were observed at both doses within both anxiety/depression subgroups and for overall functional impairment for patients without anxiety and/or depression, though neither dose significantly reduced overall functional impairment beyond placebo in the subgroup with anxiety and/or depression. In the episodic and chronic migraine studies, the subgroup-by-treatment interaction was not statistically significant for MHD, MHD with acute medication use, or functional impairment (chronic study only), suggesting a lack of evidence of differential effect between subgroups. Furthermore, differences between subgroups in the mean change differences from placebo, as well as overlapping 95% confidence intervals for the subgroups, indicated lack of a clinical or statistical difference between subgroups for these outcome variables. There was a significantly higher percentage of patients with episodic migraine attaining ≥50%, ≥75%, and 100% reductions, and a higher percentage of patients with chronic migraine attaining ≥50% and ≥75% reductions from baseline with galcanezumab compared with placebo, regardless of medical history of anxiety and/or depression. CONCLUSIONS: A medical history of anxiety and/or depression does not seem to interfere with response to galcanezumab among patients with episodic migraine, and both doses of galcanezumab appear efficacious for these individuals regardless of this psychiatric history. Among patients with chronic migraine and comorbid anxiety and/or depression, the 240-mg dose, but not the 120-mg dose, significantly decreased overall MHD, but neither dose resulted in significantly greater functional improvement. Patients with migraine and comorbid anxiety and/or depression often require additional interventions, and this may be more important in chronic migraine.

Migraine and Ischemic Stroke in Women. A Narrative Review.

OBJECTIVE/BACKGROUND: Migraine is associated with ischemic stroke. Women are 3-fold as likely as men to have migraine, and high estrogen states increase the risk of migraine with aura (MWA), venous thromboembolism (VTE), and of stroke. We review the epidemiological and mechanistic evidence of the migraine-stroke relationship and its risk factors, with a focus on women and conditions that exclusively or predominantly affect them.  METHODS: We performed a search of MEDLINE/PubMed database, then a narrative review of the epidemiological evidence of the migraine-stroke relationship as well as the evidence for arterial, thrombophilic, and cardiac mechanisms to explain this connection. We examine the implications of this evidence for the diagnostic evaluation and treatment of MWA. RESULTS: MWA is associated with multiple stroke risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, atrial fibrillation, and patent foramen ovale. In women, MWA is also associated with biomarkers of endothelial activation, hormonal contraceptive use, pregnancy, and VTE. This suggests that a subset of auras may be secondary, that is, induced by ischemia related to microemboli or in situ thrombosis. MWA-associated ischemic stroke is more common in young (<45 years old) women with high frequency of migraine attacks, hormonal contraception use, and with pregnancy and preeclampsia. There is increasing evidence that cardioembolism, often in conjunction with thrombophilia, plays a prominent role in MWA-associated cerebral infarction. CONCLUSION: The commonality of factors associated with MWA and with MWA-associated stroke suggest that persons with secondary, ischemia-induced aura may be at elevated risk of stroke. Although further research is needed, we recommend consideration of a diagnostic evaluation of MWA that mirrors the evaluation of transient ischemic attack, given that prophylactic treatment targeting the ischemic origin of secondary aura may prevent migraine as well as stroke.

The prevalence of hypnic headache in Iceland.

OBJECTIVE: To determine the prevalence of hypnic headache. BACKGROUND: The exact prevalence of hypnic headache is unknown since there are no published population-based prevalence studies. METHODS: This study was a pilot for the SAGA cohort study, a population-based study on life stressors and various indices of health. Of 1398 invited adults, 921 (66%) participated; 402 men (average age 45.6 years, SD 13.2) and 519 women (52.6 years, SD 11.1). Subjects answered a headache questionnaire including a screening question for hypnic headache. "Do you have a headache that occurs only during sleep and causes wakening?". Diagnosis of hypnic headache was made by clinical interview using ICHD-3 criteria. RESULTS: Among 921 participants, six screened positive for hypnic headache, of those two 0.22% (95% CI 0.06-0.79%) had probable hypnic headache and none had definite hypnic headache. CONCLUSION: Confirming that hypnic headache is rare, these data suggest a 0.22% prevalence of probable hypnic headache.

Long-term implementation of a prehospital severity scale for EMS triage of acute stroke: a real-world experience.

BACKGROUND: Data on the implementation of prehospital large vessel occlusion (LVO) scales to identify and triage patients with acute ischemic stroke (AIS) in the field are limited, with the majority of studies occurring outside the USA. OBJECTIVE: To report our long-term experience of a US countywide emergency medical services (EMS) acute stroke triage protocol using the Rapid Arterial oCclusion Evaluation (RACE) score. METHODS: Our prospective database was used to identify all consecutive patients triaged within Lucas County, Ohio by the EMS with (1) a RACE score ≥5, taken directly to an endovascular capable center (ECC) as RACE-alerts (RA) and (2) a RACE score <5, taken to the nearest hospital as stroke-alerts (SA). Baseline demographics, RACE score, time metrics, final diagnosis, treatments, and clinical and angiographic outcomes were captured. The sensitivity and specificity for patients with a RACE score ≥5 with LVO, eligible for mechanical thrombectomy (MT), were calculated. RESULTS: Between July 2015 and June 2018, 492 RA and 1147 SA were triaged within our five-hospital network. Of the RA, 37% had AIS secondary to LVOs. Of the 492 RA and 1147 SA, 125 (25.4%) and 38 (3.3%), respectively, underwent MT (OR=9.9; 95% CI 6.8 to 14.6; p<0.0001). Median times from onset-to-ECC arrival (74 vs 167 min, p=0.03) and dispatch-to-ECC arrival (31 vs 46 min, p=0.0002) were shorter in the RA-MT than in the SA-MT cohort. A RACE cut-off point ≥5 showed a sensitivity and specificity of 0.77 and 0.75 for detection of patients with LVO eligible for MT, respectively. CONCLUSIONS: We have demonstrated the long-term feasibility of a countywide EMS-based prehospital triage protocol using the RACE Scale within our hospital network.

The Relationship Between Migraine or Severe Headache and Chronic Health Conditions: A Cross-Sectional Study from the National Health Interview Survey 2013-2015.

OBJECTIVE: To estimate the prevalence of having at least one or two or more chronic health conditions among US adults with self-reported migraine or severe headaches. DESIGN: Cross-sectional study. METHODS: Using data collected from the 2013-2015 National Health Interview Survey, we examined adults with and without migraine or severe headache and associations with chronic obstructive pulmonary disease, cancer, heart disease, stroke, diabetes, and hypertension. We calculated point estimates, variances, and 95% confidence intervals and conducted bivariate and multivariable logistic regression modeling to examine the relationships between migraine or severe headache and each of the chronic health conditions, as well as multinomial modeling, to examine the relationship between migraine or severe headache and having one or more chronic health conditions. RESULTS: A total of 104,926 people were in the study. Adults aged 18 to 44 years (18.2%), women (20.1%), and those with some college education (17.6%) had the greatest proportion with migraine or severe headache (P < 0.0001). Using multinomial modeling with the number of chronic health conditions as the dependent variable, adults reporting migraine had an increased odds of reporting a single chronic health condition (adjusted odds ratio [aOR] = 1.7, 95% confidence interval [CI] = 1.6-1.8) and more than double the odds of reporting two or more chronic health conditions (aOR = 2.5, 95% CI = 2.3-2.8) compared with adults who did not have migraine or severe headache. CONCLUSIONS: Our study confirms observed relationships between migraine or severe headache and chronic health conditions and supports the need for further research to uncover the shared biological pathways.

Monitored Anesthesia Care by Sedation-Trained Providers in Acute Stroke Thrombectomy.

Background: Mechanical thrombectomy (MT) for ischemic stroke can be performed under local anesthesia (LA), conscious sedation (CS), or general anesthesia (GA). The need for monitoring by anesthesia providers may be resource intensive. We sought to determine differences in outcomes of MT when sedation is performed by an anesthesia team compared to sedation-trained providers. Methods: We performed a retrospective analysis on patients who were screened by a pre-hospital stroke severity screening tool and underwent MT at two stroke centers. Baseline characteristics, time metrics, sedatives, peri-procedural intubation, complications, and outcomes were recorded. Good outcome was defined as modified Rankin score of ≤2. Results: We analyzed 104 patients (sedation-trained provider = 63, anesthesia team = 41) between July 2015 and December 2017. In the sedation-trained provider group, four patients required intervention by an anesthesia team. There were no differences in patients receiving LA (sedation-trained provider 24% vs. anesthesia team 27% p = 0.82), CS (70 vs. 63%, p = 0.53), or GA (6 vs. 10%, p = 0.71) between groups. Sedation-trained providers were more likely to use only one drug during the procedure (62 vs. 34%, p = 0.009). The rate of procedural complications (9.5 vs. 4.5%, p = 0.48), good outcome (56 vs. 39%, p = 0.11), and mortality (22 vs. 24%, p = 0.82) was similar between groups. Sedation by provider type did not predict functional outcome or mortality at 3 months. Conclusions: Sedation-trained providers are capable of delivering appropriate sedation without compromising patient safety. The use of "as needed" anesthesia teams for MT may have considerable effect on resource allocation and cost.

Ischemic Stroke After Plasmapheresis.

Plasmapheresis involves the separation of all cellular elements of blood with the help of an extracorporeal semipermeable membrane. Even though plasmapheresis is generally considered safe, there have been anecdotal reports of thrombosis related to this exchange. We present 2 cases of healthy young males developing ischemic strokes within 24 hours of plasmapheresis. Patient A was a 24-year-old man with a family history of Factor V Leiden mutation presented with right-sided weakness 1 hour after donating plasma. A hypercoagulable work-up revealed elevations in Factor II. Patient B was a 42-year-old man who presented with a right facial droop, expressive aphasia and right arm weakness. He had donated plasma 18 hours before his presentation. A hypercoagulable work-up revealed elevated levels of von Willebrand factor antigen and high sensitivity C-reactive protein. A procoagulant state induced by plasmapheresis likely increases the risk for symptomatic thrombosis when an underlying thrombophilic state is present in the donor.

Mechanical Thrombectomy in Elderly Stroke Patients with Mild-to-Moderate Baseline Disability.

BACKGROUND: The number of elderly patients suffering from ischemic stroke is rising. Randomized trials of mechanical thrombectomy (MT) generally exclude patients over the age of 80 years with baseline disability. The aim of this study was to understand the efficacy and safety of MT in elderly patients, many of whom may have baseline impairment. METHODS: Between January 2015 and April 2017, 96 patients ≥80 years old who underwent MT for stroke were selected for a chart review. The data included baseline characteristics, time to treatment, the rate of revascularization, procedural complications, mortality, and 90-day good outcome defined as a modified Rankin Scale (mRS) score of 0-2 or return to baseline. RESULTS: Of the 96 patients, 50 had mild baseline disability (mRS score 0-1) and 46 had moderate disability (mRS score 2-4). Recanalization was achieved in 84% of the patients, and the rate of symptomatic hemorrhage was 6%. At 90 days, 34% of the patients had a good outcome. There were no significant differences in good outcome between those with mild and those with moderate baseline disability (43 vs. 24%, p = 0.08), between those aged ≤85 and those aged > 85 years (40.8 vs. 26.1%, p = 0.19), and between those treated within and those treated beyond 8 h (39 vs. 20%, p = 0.1). The mortality rate was 38.5% at 90 days. The Alberta Stroke Program Early CT Score (ASPECTS) and the National Institutes of Health Stroke Scale (NIHSS) predicted good outcome regardless of baseline disability (p < 0.001 and p = 0.009, respectively). CONCLUSION: Advanced age, baseline disability, and delayed treatment are associated with sub-optimal outcomes after MT. However, redefining good outcome to include return to baseline functioning demonstrates that one-third of this patient population benefits from MT, suggesting the real-life utility of this treatment.

Emergent carotid endarterectomy versus stenting in acute stroke patients with tandem occlusion.

OBJECTIVE: Acute stroke due to tandem cervical internal carotid artery (ICA) and intracranial large-vessel occlusion (ILVO) has a high rate of morbidity and mortality. The most appropriate treatment strategy for the extracranial culprit lesion remains unclear. In this study, we report our institutional outcomes with two approaches: emergent carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: Patients with tandem ICA-ILVO were identified in a prospective mechanical thrombectomy (MT) database between July 2012 and April 2016. Patients had a concomitant complete ICA origin occlusion and occlusion of the intracranial ICA or M1 or M2 middle cerebral artery segment. Baseline characteristics, procedural data, and treatment times were reviewed. End points included good recanalization of both ICA and ILVO, symptomatic intracerebral hemorrhage (defined by clinical decline of >4 points on the National Institutes of Health Stroke Scale), and functional outcome at 90 days. RESULTS: Forty-five patients had tandem ICA-ILVO occlusion; 27 patients underwent emergent CAS and 12 patients underwent emergent CEA after MT. Successful Thrombolysis in Cerebral Infarction grade 2B/3 recanalization was achieved in 92% of the CEA and 96% of the CAS patients (P = .53). Three CAS patients (11%) and none of the CEA patients had symptomatic intracerebral hemorrhage (P = .54). At 90 days, 75% (9/12) of the CEA patients were functionally independent compared with 70% (19/27) in the CAS group (P = 1.0). No deaths were noted in the CEA group compared with five (18.5%) in the CAS arm (P = .30). CONCLUSIONS: Our study indicates that early recanalization with MT followed by emergent CEA is safe and feasible, which suggests that both CAS and CEA should be considered in the emergent treatment of patients with tandem occlusion.

Do Personality Traits Mediate the Relationship Between Childhood Abuse and Migraine? An Exploration of the Relationships in Young Adults Using the Add Health Dataset.

BACKGROUND: Personality traits (especially neuroticism) and childhood maltreatment have been independently related to many negative health outcomes later in life, including migraine. Studies have also shown the association between childhood maltreatment and maladaptive personality traits. The mediating role of personality traits on the relationship between childhood maltreatment and depression, psychological distress, and alcohol dependence has been extensively studied. However, this type of mediation has not been studied in the case of the development of migraine. This study investigated (1) the main effects of childhood abuse on personality traits, and of personality traits on migraine, and (2) the mediating role of neuroticism, on the relationship between childhood abuse and migraine in young adults. METHOD: We analyzed retrospective, cross-sectional data from 13,493 adults aged 24-32 years in Wave 4 of the National Longitudinal Survey of Adolescent Health ("Add Health") data set. Participants were queried regarding maltreatment (emotional, physical, and sexual) during childhood, current Big Five personality traits (using mini International Personality Item Pool), current depression (using Center for Epidemiologic Studies-Depression Scale), perceived stress (Using Cohen's Perceived Stress Scale), and diagnosis of migraine by a health care provider. Linear and logistic regressions were used to assess the main effects of childhood maltreatment on the five personality traits (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism) and the main effect of the personality traits on self-reported provider diagnosis of migraine. A structural equation model (SEM) was used to examine the mediating role of neuroticism on the relationship between childhood maltreatment and migraine. RESULTS: Linear regression models showed that childhood abuse independently predicted increased neuroticism (ß = 0.338, SE=±0.05, P < .001), and increased openness to experiences (ß = 0.341, SE = ±0.06, P < .001) after adjusting for socio-demographic characteristics, current depression, and perceived stress. Logistic regression to examine the main effect of personality traits on migraine revealed that only neuroticism had a significant effect (OR = 1.07, 95%CI = 1.04-1.10) after controlling for childhood abuse, socio-demographic characteristics, current depression, and perceived stress. Our regression analyses showed that neuroticism, but not openness to experience, was a potential mediator for the relationship between childhood abuse and migraine. SEM confirmed significant mediation of the relationship between childhood abuse and migraine through neurotic personality traits (goodness of fit indices: CFI = 0.992, TLI = 0.979, RMSEA = 0.025), unadjusted for socio-demographic variables, depression, and stress. In addition to the indirect effect (ß = 0.039, P < .01) of childhood abuse on migraine through neuroticism, there was also a significant direct effect (ß = 0.143, P < .01) of childhood abuse on migraine. After adjusting for socio-demographic variables, other personality types, depression, and stress, both the direct effect (ß = 0.127; P < .01) of childhood abuse on migraine and the indirect effect (ß = 0.09; P < .01) of childhood abuse on migraine through neuroticism were attenuated, but remained significant. CONCLUSION: Childhood abuse is associated with personality and migraine. An estimated 21% of the total effect of childhood abuse on migraine could be explained by mediation through neuroticism in the unadjusted model. In the fully adjusted model, an estimated 8.7% of the total effect could be explained by mediation, although, self-reported data limit the ability to draw firm conclusions.

Migraine and vascular disease biomarkers: A population-based case-control study.

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex. Results Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II. Conclusions Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks.