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Background: Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine. Methods: This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring. Results: We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25–1.50), bipolar disorder (1.35, 1.06–1.71), and depressive disorder (1.33, 1.21–1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks. Conclusions: Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers. [ABSTRACT FROM AUTHOR]

Background: Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods: The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results: Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions: Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. Methods: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. Results: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). Conclusions: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

Background: Visual snow syndrome is a disorder characterized by the combination of typical perceptual disturbances. The clinical picture suggests an impairment of visual filtering mechanisms and might involve primary and secondary visual brain areas, as well as higher-order attentional networks. On the level of cortical oscillations, the alpha rhythm is a prominent EEG pattern that is involved in the prioritisation of visual information. It can be regarded as a correlate of inhibitory modulation within the visual network. Methods: Twenty-one patients with visual snow syndrome were compared to 21 controls matched for age, sex, and migraine. We analysed the resting-state alpha rhythm by identifying the individual alpha peak frequency using a Fast Fourier Transform and then calculating the power spectral density around the individual alpha peak (+/- 1 Hz). We anticipated a reduced power spectral density in the alpha band over the primary visual cortex in participants with visual snow syndrome. Results: There were no significant differences in the power spectral density in the alpha band over the occipital electrodes (O1 and O2), leading to the rejection of our primary hypothesis. However, the power spectral density in the alpha band was significantly reduced over temporal and parietal electrodes. There was also a trend towards increased individual alpha peak frequency in the subgroup of participants without comorbid migraine. Conclusions: Our main finding was a decreased power spectral density in the alpha band over parietal and temporal brain regions corresponding to areas of the secondary visual cortex. These findings complement previous functional and structural imaging data at a electrophysiological level. They underscore the involvement of higher-order visual brain areas, and potentially reflect a disturbance in inhibitory top-down modulation. The alpha rhythm alterations might represent a novel target for specific neuromodulation. Trial registration: we preregistered the study before preprocessing and data analysis on the platform osf.org (DOI: https://doi.org/10.17605/OSF.IO/XPQHF, date of registration: November 19th 2022). [ABSTRACT FROM AUTHOR]

Cervical arterial dissection (CAD) is an important cause of stroke in young people which may be missed because early features may mimic migraine or a musculoskeletal presentation. The study aimed to develop a diagnostic support tool for early identification of CAD. Retrospective observational study Tertiary hospital Radiologically confirmed CAD cases (n = 37), non-CAD stroke cases (n = 20), and healthy controls (n = 100). The presence of CAD is confirmed with imaging. Predictive variables included risk factors and clinical characteristics of CAD. Variables with a p-value <0.2 included in a multivariable model. Predictive utility of the model is assessed by calculating area underthe ROC curve (AUC). The model including four variables: age 40–55 years (vs < 40), trauma, recent onset headache, and > 2 neurological features, demonstrated excellent discrimination: AUC of 0.953 (95% CI: 0.916, 0.987). A predictive scoring system (total score/7) identified an optimal threshold of ≥ 3 points, with a sensitivity of 87% and specificity of 79%. The study identified a diagnostic support tool with four variables to predict increased risk of CAD. Validation in a clinical sample is needed to confirm variables and refine descriptors to enable clinicians to efficiently apply the tool. Optimum cutoff scores of ≥ 3/7 points will help identify those in whom CAD should be considered and further investigation instigated. The potential impact of the tool is to improve early recognition of CAD in those with acute headache or neck pain, thereby facilitating more timely medical intervention, preventing inappropriate treatment, and improving patient outcomes. Wordcount: 3195 [ABSTRACT FROM AUTHOR]

Background: The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. Methods: Case–control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1–3, 4–7, 8–14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables. Results: The survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1–3 MHD also increased costs by 51.3%. Conclusions: Having migraine not only causes a massive impact on patients' quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1–3 MHD. [ABSTRACT FROM AUTHOR]

Background: Migraine headache is common in older adults, often causing symptoms that may affect driving safety. This study examined associations of migraine with motor vehicle crashes (MVCs) and driving habits in older drivers and assessed modification of associations by medication use. Methods: In a multi‐site, prospective cohort study of active drivers aged 65–79 (53% female), we assessed prevalent migraine (i.e., ever had migraine, reported at enrollment), incident migraine (diagnosis first reported at a follow‐up visit), and medications typically used for migraine prophylaxis and treatment. During 2‐year follow‐up, we recorded self‐reported MVCs and measured driving habits using in‐vehicle GPS devices. Associations of prevalent migraine with driving outcomes were estimated in multivariable mixed models. Using a matched design, associations of incident migraine with MVCs in the subsequent year were estimated with conditional logistic regression. Interactions between migraine and medications were tested in all models. Results: Of 2589 drivers, 324 (12.5%) reported prevalent migraine and 34 (1.3%) incident migraine. Interactions between migraine and medications were not statistically significant in any models. Prevalent migraine was not associated with MVCs in the subsequent 2 years (adjusted OR [aOR] = 0.98; 95% CI: 0.72, 1.35), whereas incident migraine significantly increased the odds of having an MVC within 1 year (aOR = 3.27; 1.21, 8.82). Prevalent migraine was associated with small reductions in driving days and trips per month and increases in hard braking events in adjusted models. Conclusion: Our results suggest substantially increased likelihood of MVCs in the year after newly diagnosed migraine, indicating a potential need for driving safety interventions in these patients. We found little evidence for MVC risk or substantial changes in driving habits associated with prevalent migraine. Future research should examine timing, frequency, and severity of migraine diagnosis and symptoms, and use of medications specifically prescribed for migraine, in relation to driving outcomes. [ABSTRACT FROM AUTHOR]

Background: Migraine and epilepsy are two paroxysmal chronic neurological disorders affecting a high number of individuals and being responsible for a high individual and socioeconomic burden. The link between these disorders has been of interest for decades and innovations concerning diagnosing and treatment enable new insights into their relationship. Findings: Although appearing to be distinct at first glance, both diseases exhibit a noteworthy comorbidity, shared pathophysiological pathways, and significant overlaps in characteristics like clinical manifestation or prophylactic treatment. This review aims to explore the intricate relationship between these two conditions, shedding light on shared pathophysiological foundations, genetic interdependencies, common and distinct clinical features, clinically overlapping syndromes, and therapeutic similarities. There are several shared pathophysiological mechanisms, like CSD, the likely underlying cause of migraine aura, or neurotransmitters, mainly Glutamate and GABA, which represent important roles in triggering migraine attacks and seizures. The genetic interrelations between the two disorders can be observed by taking a closer look at the group of familial hemiplegic migraines, which are caused by mutations in genes like CACNA1A, ATP1A2, or SCN1A. The intricate relationship is further underlined by the high number of shared clinical features, which can be observed over the entire course of migraine attacks and epileptic seizures. While the variety of the clinical manifestation of an epileptic seizure is naturally higher than that of a migraine attack, a distinction can indeed be difficult in some cases, e.g. in occipital lobe epilepsy. Moreover, triggering factors like sleep deprivation or alcohol consumption play an important role in both diseases. In the period after the seizure or migraine attack, symptoms like speech difficulties, tiredness, and yawning occur. While the actual attack of the disease usually lasts for a limited time, research indicates that individuals suffering from migraine and/or epilepsy are highly affected in their daily life, especially regarding cognitive and social aspects, a burden that is even worsened using antiseizure medication. This medication allows us to reveal further connections, as certain antiepileptics are proven to have beneficial effects on the frequency and severity of migraine and have been used as a preventive drug for both diseases over many years. Conclusion: Migraine and epilepsy show a high number of similarities in their mechanisms and clinical presentation. A deeper understanding of the intricate relationship will positively advance patient–oriented research and clinical work. [ABSTRACT FROM AUTHOR]

To describe evidence of migraine-associated tinnitus and hearing loss. This study was registered in PROSPERO and followed the PRISMA guidelines. The inclusion criteria were observational studies with subjects aged ≥18 years, in which the association between migraine and tinnitus and/or hearing loss was evaluated. Reviews, case reports, commentaries, letters to the editor, and studies that included individuals with some diseases were excluded. The search yielded 698 articles from electronic databases. Six studies were eligible for this review with 26,166 participants. Most studies have shown an association between migraine and tinnitus, and between migraine and hearing loss. Studies have concluded that migraine presented high odds ratio, and hazard ratio for tinnitus. Another study found a strong association between these conditions (p < 0.001), and two investigations detected the presence of migraine in 10.1 and 22.5% of tinnitus patients. Migraine presented high odds ratio and hazard ratio for hearing loss. Additionally, the studies included were of good quality, adhering to most of the requirements on the JBI Critical Appraisal Checklist. However, a limitation of this review is the small number of studies included. Associations between migraine, tinnitus, and hearing loss were observed in the included studies. [ABSTRACT FROM AUTHOR]

Objective: To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA). Background: Migraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non‐invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs). Methods: We performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30 with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions. Results: There was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (−7%, 95% confidence interval [CI] −10% to −4%; p = 0.006) and MO (−7%, 95% CI −10% to −3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI −3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye. Conclusions: These results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine. [ABSTRACT FROM AUTHOR]

Background: Individuals with bipolar disorders (BD) are at risk of premature death, mainly due to medical comorbidities. Childhood maltreatment might contribute to this medical morbidity, which remains underexplored in the literature. Methods: We assessed 2891 outpatients with BD (according to DSM-IV criteria). Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Lifetime diagnoses for medical disorders were retrospectively assessed using a systematic interview and checked against medical notes. Medical morbidity was defined by the sum of medical disorders. We investigated associations between childhood maltreatment (neglect and abuse) and medical morbidity while adjusting for potential confounders. Results: One quarter of individuals had no medical comorbidities, while almost half of them had at least two. Multivariable regression showed that childhood maltreatment (mainly abuse, but also sexual abuse) was associated with a higher medical morbidity. Medical morbidity was also associated with sex, age, body mass index, sleep disturbances, lifetime anxiety disorders and lifetime density of mood episodes. Childhood maltreatment was associated with an increased prevalence of four (i.e. migraine/headache, drug eruption, duodenal ulcer, and thyroid diseases) of the fifteen most frequent medical disorders, however with no difference in terms of age at onset. Conclusions: This large cross-sectional study confirmed a high medical morbidity in BD and its association with childhood maltreatment. The assessment of childhood maltreatment in individuals with BD should be systematically included in routine care and the potential impact on physical health of psycho-social interventions targeting childhood maltreatment and its consequences should be evaluated. [ABSTRACT FROM AUTHOR]

Objective: This observational study aimed to: (i) describe and explore preliminary psychometric properties of a multidimensional sleep health composite score in adolescent females with frequent migraine; and (ii) examine associations between the composite score, headache characteristics, and emotional health. Background: Sleep health is a multidimensional construct comprised of various dimensions of sleep and circadian functioning, including Regularity, Satisfaction, Alertness, Timing, Efficiency, and Duration (Ru‐SATED framework). The Ru‐SATED sleep health composite score may provide a holistic perspective of sleep among adolescents with frequent migraine in the context of neurobiological and psychosocial impacts on sleep unique to this developmental period. Methods: In all, 60 female adolescents (aged 12–18 years) with high‐frequency episodic or chronic migraine completed wrist‐worn actigraphy for 10 days and concurrent daily electronic surveys assessing headache, sleep, and emotional health. A sleep health composite score was derived from empirically supported "healthy" versus "unhealthy" ratings on the six Ru‐SATED sleep dimensions. Results: Half of participants (27/54 [50%]) had a composite score ≥4 (i.e., at least four of the six dimensions rated as poor). Convergent validity of the composite score was acceptable (rs = 0.30–0.56, all p < 0.05). Internal consistency among the dimensions was low (α = 0.45). Multivariate multiple regression models indicated that worse sleep health was associated with greater headache‐related disability (B = 0.71, p = 0.018) and anxiety (B = 0.59, p = 0.010), and trended toward significance for sadness (B = 0.35, p = 0.052). The composite score was not significantly associated with headache frequency or severity. Conclusions: A multidimensional sleep health composite score may provide an alternative, more comprehensive picture of sleep disturbance among adolescent females with frequent migraine. Larger studies are needed to examine psychometric properties more rigorously and further explore the composite score as a potentially unique predictor of headache outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of acceptance and mindfulness‐based interventions on migraine disability, medication use, and attack frequency. Background: Acceptance‐based approaches to headache management are those in which individuals learn to mitigate the influence of pain‐related experiences on their general functioning without controlling pain itself. Treatment approaches include acceptance and commitment therapy (ACT) and mindfulness‐based practices. Both have shown promise in improving broad functioning and disability among individuals with headache. Despite a growing body of research examining acceptance‐based interventions for headache broadly and migraine specifically, no meta‐analytic review of ACT interventions for headache exists, and two meta‐analytic reviews of mindfulness‐based practices yielded conflicting results. Methods: The present study aimed to systematically and quantitatively review the literature related to the efficacy of acceptance‐based interventions among adults with migraine. A multi‐database search (PubMed/MEDLINE, Scopus, PsycINFO, and the Cochrane Central Register of Controlled Trials) identified clinical trials among individuals with migraine that compared structured ACT or mindfulness‐based interventions to control treatment. Random‐effects meta‐analyses were performed using RevMan 5.4 meta‐analytic software, and standardized mean differences (SMD) with 95% confidence intervals (CIs) quantified effect sizes on outcomes of disability, medication use, and headache frequency. Heterogeneity was quantified via I2 index and explored via subgroup analyses. Results: Acceptance‐based interventions yielded significant improvements in disability (SMD = −0.38, 95% CI = −0.56 to −0.20; I2 = 25%, p = 0.20) but not in medication use (SMD = −0.25, 95% CI: −0.57 to 0.06; I2 = 0%, p = 0.82) or headache frequency (SMD = −0.16, 95% CI = −0.37 to 0.05; I2 = 0%, p = 0.73). Conclusion: Results suggest that acceptance‐based interventions are effective in improving disability among adults with migraine and are a viable non‐pharmacological treatment option, in addition to well‐established behavioral migraine management approaches, for patients seeking functional improvement. [ABSTRACT FROM AUTHOR]

Background: There is a clinical association between migraine and multiple sclerosis. Main body: Migraine and MS patients share similar demographics, with the highest incidence among young, female and otherwise healthy patients. The same hormonal constellations/changes trigger disease exacerbation in both entities. Migraine prevalence is increased in MS patients, which is further enhanced by disease-modifying treatment. Clinical data show that onset of migraine typically starts years before the clinical diagnosis of MS, suggesting that there is either a unidirectional relationship with migraine predisposing to MS, and/or a "shared factor" underlying both conditions. Brain imaging studies show white matter lesions in both MS and migraine patients. Neuroinflammatory mechanisms likely play a key role, at least as a shared downstream pathway. In this review article, we provide an overview of the literature about 1) the clinical association between migraine and MS as well as 2) brain MRI studies that help us better understand the mechanistic relationship between both diseases with implications on their underlying pathophysiology. Conclusion: Studies suggest a migraine history predisposes patients to develop MS. Advanced brain MR imaging may shed light on shared and distinct features, while helping us better understand mechanisms underlying both disease entities. [ABSTRACT FROM AUTHOR]

Background: Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. Methods: Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. Results: The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31–1.39 and adjusted HR = 1.31, 95% CI = 1.26–1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95–1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. Conclusions: Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities. Objective: In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship. Discussion: Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications. Conclusions: There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified. Key points : • There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. • Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. • Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. [ABSTRACT FROM AUTHOR]

Objective: Our objectives were to examine cross‐sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. Background: Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache‐related disability as measured by the Migraine Disability Assessment (MIDAS). Methods: We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS‐25), Patient Health Questionnaire‐9 (PHQ‐9), Generalized Anxiety Disorder‐7 (GAD‐7), and WHO‐5 Well‐Being Index. Results: The CDRS‐25 score was negatively correlated with the total MIDAS (r = −0.21, p = 0.009), GAD‐7 (r = −0.56, p < 0.001), and PHQ‐9 scores (r = −0.34, p < 0.001). Well‐being inversely correlated with disability (r = −0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS‐25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS‐25 score did not significantly moderate the association between headache days and disability. Conclusion: Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache. [ABSTRACT FROM AUTHOR]

Objective: To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. Background: CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. Methods: We conducted a case‐control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18–55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 μg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n = 635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. Results: Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p = 0.011). Stroke risk was higher with ≥30‐μg EE doses compared to those using a <30‐μg dose (OR, 1.52; CI 1.02, 2.26; p = 0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p = 0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p = 0.004). Conclusions: Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 μg EE are preferred. Shared decision‐making should include discussions about ischemic stroke risks in patients with migraine, even those without aura. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH). Background: Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance. Methods: We investigated patients with IIH from the Vienna‐IIH‐database and differentiated migraine (IIH‐MIG) from non‐migraine headache (IIH‐nonMIG) and without headache (IIH‐noHA). Using multivariable models, we analyzed the impact of IIH‐MIG on headache and visual outcomes 12 months after diagnosis. Results: Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m2, median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH‐MIG, 37% to IIH‐nonMIG (11% tension‐type, 26% unclassifiable), and 17% to IIH‐noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH‐MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH‐nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH‐nonMIG and 63% in IIH‐noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow‐up. In contrast, visual worsening was significantly less common in IIH‐MIG (9% vs. 28% in IIH‐nonMIG and 31% in IIH‐noHA, p = 0.045). In multivariable models, IIH‐MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40–0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12–0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04–0.82, p < 0.001). Conclusions: In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome. [ABSTRACT FROM AUTHOR]

Background: Migraine is a prevalent disorder with significant socioeconomic impact. The impairment of metabolic homeostasis in migraine warrants further investigation. Changes in serum levels of Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15) are characteristic of some metabolic and mitochondrial diseases. This study aimed to assess whether the presence of migraine affects serum levels of FGF-21 and GDF-15, and taking metabolic disorders into account as potential confounding factors. Methods: We collected serum samples from 221 migraine patients (153 episodic migraineurs and 68 chronic migraineurs) and 124 healthy controls. The serum concentrations of FGF-21 and GDF-15 were measured using an enzyme-linked immunosorbent assay (ELISA) based approach. Clinical variables, including monthly headache days, peak headache pain intensity, the 6-item Headache Impact Test (HIT-6), and the Migraine Disability Assessment (MIDAS), were also addressed. The associations between the clinical variables of migraine patients and serum levels of FGF-21 and GDF-15 were studied. Results: In the multiple regression that corrected for age, we found that the serum levels of FGF-21 and GDF-15 were significantly higher in migraine sufferers than in healthy controls. A significant elevation in serum concentration of FGF-21, but not GDF-15, was observed in patients with chronic migraine (CM) compared to those with episodic migraine (EM). Regarding migraine-related disability, higher scores on the HIT-6 and MIDAS were associated with higher levels of FGF-21 and GDF-15. For the receiver operating characteristic (ROC) analysis, the diagnosis of migraine using GDF-15 showed that the area under the ROC curve (AUC) was 0.801 and the AUC of chronic migraine was 0.880. Conclusion: Serum GDF-15 and FGF-21 levels are increased in patients with migraine and associated with the severity of migraine-related disability. [ABSTRACT FROM AUTHOR]

Purpose: Previous functional magnetic resonance imaging studies have substantiated changes in multiple brain regions of functional activity in patients with vestibular migraine. However, few studies have assessed functional connectivity within and between specific brain networks in vestibular migraine. Methods: Our study subjects included 37 patients with vestibular migraine and 35 healthy controls, and the quality of magnetic resonance images of all subjects met the requirements. Independent component analysis was performed to identify resting-state networks, and we investigated changes in functional connectivity patterns within and between brain networks. We also used Pearson correlation analysis to assess the relationship between changes in functional connectivity and the clinical features of patients with vestibular migraine. Results: A total of 14 independent components were identified. Compared to healthy controls, patients with vestibular migraine exhibited decreased intra-network functional connectivity in the executive control network and weakened functional connectivity between the anterior default mode network and the ventral attention network, between the anterior default mode network and the salience network, and between the right frontoparietal network and the auditory network. Moreover, the functional connectivity between the salience network and the dorsal attention network was increased. However, the functional connectivity of networks and clinical characteristics of vestibular migraine patients did not demonstrate any significant correlation. Conclusion: In conclusion, our study suggested that patients with vestibular migraine also have abnormal multisensory integration during the interictal period and that the attention network is involved. Changing within- and between-network functional connectivity may indicate that vestibular cortex areas are in a sensitive state. [ABSTRACT FROM AUTHOR]

Objectives: To capture patients' perspectives on migraine‐related cognitive symptoms during pre‐headache, headache, post‐headache, and interictal periods. Background: Migraine‐related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient‐centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine‐related cognitive symptoms and their perceived impact on quality of life and disability. Methods: Forty individuals with self‐reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi‐structured qualitative interviews conducted using audio‐only web conferencing. Thematic content analysis was performed to identify key concepts around migraine‐related cognitive symptoms. Recruitment continued until concept saturation was achieved. Results: Participants described symptoms consistent with migraine‐related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre‐headache (36/40 [90%] reported ≥1 cognitive feature), headache (35/40 [88%] reported ≥1 cognitive feature), post‐headache (27/40 [68%] reported ≥1 cognitive feature), and interictal periods (13/40 [33%] reported ≥1 cognitive feature). Among participants reporting cognitive symptoms during pre‐headache, 32/40 (81%) endorsed 2–5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision‐making. Memory issues were reported across all phases of the migraine attack. Conclusions: This patient‐level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre‐headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems. [ABSTRACT FROM AUTHOR]

Background and Objective: Dysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test. Methods: A total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light‐emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack. Results: The VTDT of each visual field in both attack (mean [SD] 102.3 [38.4] ms for the right visual field and 106.3 [52.2] ms for the left) and the interictal periods (mean [SD] 75.2 [27.9] ms for the right and 78.2 [27.9] ms for the left) were significantly higher than in the control group (mean [SD] 45.3 [9.9] ms for the right and 48.2 [11.9] ms for the left) (p < 0.001, p < 0.001, p = 0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8 [53.8] vs. 78 [19.6] ms, p = 0.025) and the contralateral threshold during the attack (mean [SD] 143.8 [53.8] vs. 71.9 [14.1] ms, p = 0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r = 0.894, p < 0.001) and frequency of the attacks (r = 0.696, p = 0.004), but not correlated with photophobia. Conclusion: The VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical correlates of visual symptoms in patients with migraine.Method: Patients with migraine that attended our headache clinics were enrolled. Headache profiles, disability, and comorbidities were acquired with structured questionnaires. A semi-structured visual phenomenon questionnaire was also used to assess the characteristics of visual symptoms, including visual aura in patients with migraine with aura and transient visual disturbance in patients with migraine without aura. Headache specialists interviewed with the participants for the ascertainment of diagnosis and verification of the questionnaires.Result: Migraine with aura patients with visual aura (n = 743, female/male = 2.3, mean age: 34.7 ± 12.2 years) and migraine without aura patients with non-aura transient visual disturbance (n = 1,808, female/male = 4.4, mean age: 39.4 ± 12.6 years) were enrolled. Patients with transient visual disturbance had higher headache-related disability and more psychiatric comorbidities. Chronic migraine was more common in migraine without aura than migraine with aura patients (41.9% vs. 11.8%, OR = 5.48 [95% CI: 4.33-7.02], p < 0.001). The associations remained after adjusting confounding factors.Conclusion: Presence of non-aura transient visual disturbance may suggest a higher migraine-related disability and is linked to higher risk of chronic migraine than typical migraine aura in migraine patients. Further studies are needed to elucidate the potential mechanism. [ABSTRACT FROM AUTHOR]

Background: The migraine attack is classically divided into the prodromal, aura, headache and postdromal phase. Previous studies have highlighted non-headache symptoms associated with migraine occurring during the prodromal or postdromal phase. This study aimed to track the evolution of non-headache symptoms throughout all phases of the migraine attack. We also wished to delineate the phenotype of patients with more symptomatic migraine episodes and explore the association between non-painful symptoms and migraine disease activity and patients' disability. Methods: Two-hundred and twenty-five migraine patients were enrolled and were asked to recall retrospectively whether non-headache symptoms occurred during the prodromal, headache and postdromal phase of their attacks. The occurrence of symptoms during the different migraine phases was tested using the Cochran's Q tests, Cohen's and Fleiss' kappa. Differences between groups according to the presence of non-headache symptoms through the entire migraine attack and correlations between the frequency of non-headache symptoms experienced during all phases and patients' disease activity and disability were also assessed. Results: Ninety-nine percent of patients reported having at least one non-headache symptom in one phase of the migraine attack and 54% of patients had at least one non-headache symptom occurring during all phases of migraine. The occurrence of non-headache symptoms was different throughout the three phases of migraine, being higher during the headache phase than during the prodromal and postdromal phases. Symptoms with the highest co-occurrence throughout all migraine phases were neck stiffness, thirst and abdominal pain. Patients who experienced non-headache symptoms during all three phases of migraine were more frequently females, had a higher disability, were suffering from chronic migraine and had more frequently medication overuse headache. Conclusion: Migraine is a complex neurological disorder with a wide constellation of non-headache symptoms that can affect the burden of the disease. A better characterization of the evolution of non-headache symptoms through the different phases of migraine can enrich our knowledge on migraine pathophysiology and improve the management of the disease. [ABSTRACT FROM AUTHOR]

Background: Migraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL). Methods: We evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning–based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA). Results: In comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively. Conclusion: In this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making. [ABSTRACT FROM AUTHOR]

Background: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate lesions on diffusion-weighted imaging (hippocampal punctate diffusion lesion, HPDL). The recent literature suggests that TGA may be triggered by acute neurological conditions.Objective: To study patients with TGA triggered by an acute neurological disease.Methods: We retrospectively reviewed patients from two neurology centres with TGA (with or without HPDL) in whom an acute neurological condition could be identified as trigger. We also performed a systematic review of the literature of this situation using predefined search terms.Results: We identified 38 patients (median age 62 years, 55.3% female): 6 from our centres and 32 from the literature. Acute neurovascular diseases that preceded or were associated with TGA included ischemic and haemorrhagic strokes, convexity subarachnoid haemorrhage, and reversible cerebral vasoconstriction syndrome. As non-vascular acute neurological diseases, we identified migraine and peripheral-origin vertigo. The clinical manifestation of the neurological trigger showed a variable temporal relation with TGA onset; in some cases preceding and in others co-occurring with TGA manifestation. In some cases, presumed neurological triggers were asymptomatic and diagnosed from the neuroimaging done for the TGA.Conclusions: Acute vascular and non-vascular neurological events may trigger TGAs or may occur simultaneously. In the first case, such an acute neurological disease may activate direct pathways within the nervous systems leading to TGA, or alternatively elicit a bodily sympathetic overactivity cascade. In the second case, both neurological events may be the result of a common external stressor. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic Helicobacter pylori (HP) infection and headache has been discussed for long; nevertheless, the results of the studies are still contrasting.Objective: This cross-sectional study is aimed to investigate a possible association between HP and headache, mainly migraine.Methods: We screened, by a self-administered questionnaire, the subjects undergoing a breath test or an esophagogastroduodenoscopy. Migraine was diagnosed according to the international criteria.Results: A total of 3914 patients underwent a breath test and 2200 an esophagogastroduodenoscopy at two hospitals, in Piedmont (Italy), in a 5-year period; a total of 1362 questionnaires were included in the study. The mean age of the subjects was 53 years; there were 777 women (57%). HP was detected in 364 (27%) subjects. A total of 702 (51%) subjects suffered from headache: migraine with aura was diagnosed in 176 subjects (176/702, i.e., 25% of the headache group; 176/1362, i.e., 13% of the total population); migraine without aura in 98 subjects (98/702, i.e., 14% of the headache group; 98/1362, i.e., 7% of the total). The logistic regression model did not detect any significant association between HP infection and headache, while a significant association between HP and headache frequency (p =0.009) was found, independently of age, gender, comorbidity, and diagnostic category.Conclusion: Our study does not reveal an association between chronic HP infection and migraine. However, since HP is significantly associated with higher headache frequency, a role for HP as a risk factor for headache chronification, possibly underlain by inflammatory mechanisms, may be supposed. [ABSTRACT FROM AUTHOR]

Background: In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment. Methods: In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70–140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13th injection (RespondersT13). Results: Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as RespondersT13. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDASRes) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMDRes). MIDASRes and MMDRes patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDASRes (MIDASRes: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDASRes: T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMDRes (MMDRes: T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMDRes: T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of RespondersT13 did not differ between MIDASRes (74.4%) and NON-MIDASRes (52.9%) patients (p = 0.058), while the percentage of RespondersT13 was higher in the MMDRes group (83.3%) when compared to NON-MMDRes (42.9%) (p = 0.001). MMDRes predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDASRes did not. Treatment discontinuation based on MIDASRes would have early excluded 36.0% of RespondersT13. Discontinuation based on "either MIDASResor MMDRes" would have excluded a lower percentage (16%) of RespondersT13. Conclusion: MIDASRes only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option. Trial registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT05442008). CGRP: Calcitonin Gene Related Peptide. MIDAS: MIgraine Disability Assessment. MMDs: monthly migraine days. MIDASRes: Patients with a MIDAS score reduction of at least 50% at T3. MMDRes: Patients with a MMDs reduction of at least 50% at T3. ResponderT13: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T0: First erenumab administration. T3, T6, T9, T12: Follow-up visits at three, six, nine, and twelve months after first erenumab administration. T13: Last visit of the protocol. [ABSTRACT FROM AUTHOR]

Abstract: Meta-analysis suggests that migraine patients are no more sensitive to experimentally evoked pain than healthy control subjects. At the same time, studies have linked some migraine symptoms to quantitative sensory testing (QST) profiles. Unfortunately, previous studies associating migraine symptoms and QST have important methodological shortcomings, stemming from small sample sizes, and frequent use of univariate statistics for multivariate research questions. In the current study, we seek to address these limitations by using a large sample of episodic migraine patients (n = 103) and a multivariate analysis that associates pain ratings from many thermal intensities simultaneously with 12 clinical measures ranging from headache frequency to sleep abnormalities. We identified a single dimension of association between thermal QST and migraine symptoms that relates to pain ratings for all stimulus intensities and a subset of migraine symptoms relating to disability (Headache Impact Test 6 and Brief Pain Inventory interference), catastrophizing (Pain Catastrophizing Scale), and pain severity (average headache pain, Brief Pain Inventory severity, and Short-Form McGill Pain Questionnaire 2). Headache frequency, allodynia, affect, and sleep disturbances were unrelated to this dimension. Consistent with previous research, we did not observe any difference in QST ratings between migraine patients and healthy control subjects. Additionally, we found that the linear combination of symptoms related to QST was modified by the mind-body therapy enhanced mindfulness-based stress reduction (MBSR+). These results suggest that QST has a selective relationship with pain symptoms even in the absence of between-subjects differences between chronic pain patients and healthy control subjects. [ABSTRACT FROM AUTHOR]

Objective: To compare the artificial intelligence‐enabled electrocardiogram (AI‐ECG) atrial fibrillation (AF) prediction model output in patients with migraine with aura (MwA) and migraine without aura (MwoA). Background: MwA is associated with an approximately twofold risk of ischemic stroke. Longitudinal cohort studies showed that patients with MwA have a higher incidence of developing AF compared to those with MwoA. The Mayo Clinic Cardiology team developed an AI‐ECG algorithm that calculates the probability of concurrent paroxysmal or impending AF in ECGs with normal sinus rhythm (NSR). Methods: Adult patients with an MwA or MwoA diagnosis and at least one NSR ECG within the past 20 years at Mayo Clinic were identified. Patients with an ECG‐confirmed diagnosis of AF were excluded. For each patient, the ECG with the highest AF prediction model output was used as the index ECG. Comparisons between MwA and MwoA were conducted in the overall group (including men and women of all ages), women only, and men only in each age range (18 to <35, 35 to <55, 55 to <75, ≥75 years), and adjusted for age, sex, and six common vascular comorbidities that increase risk for AF. Results: The final analysis of our cross‐sectional study included 40,002 patients (17,840 with MwA, 22,162 with MwoA). The mean (SD) age at the index ECG was 48.2 (16.0) years for MwA and 45.9 (15.0) years for MwoA (p < 0.001). The AF prediction model output was significantly higher in the MwA group compared to MwoA (mean [SD] 7.3% [15.0%] vs. 5.6% [12.4%], mean difference [95% CI] 1.7% [1.5%, 2.0%], p < 0.001). After adjusting for vascular comorbidities, the difference between MwA and MwoA remained significant in the overall group (least square means of difference [95% CI] 0.7% [0.4%, 0.9%], p < 0.001), 18 to <35 (0.4% [0.1%, 0.7%], p = 0.022), and 35 to <55 (0.5% [0.2%, 0.8%], p < 0.001), women of all ages (0.6% [0.3%, 0.8%], p < 0.001), men of all ages (1.0% [0.4%, 1.6%], p = 0.002), women 35 to <55 (0.6% [0.3%, 0.9%], p < 0.001), and men 18 to <35 (1.2% [0.3%, 2.1%], p = 0.008). Conclusions: Utilizing a novel AI‐ECG algorithm on a large group of patients, we demonstrated that patients with MwA have a significantly higher AF prediction model output, implying a higher probability of concurrent paroxysmal or impending AF, compared to MwoA in both women and men. Our results suggest that MwA is an independent risk factor for AF, especially in patients <55 years old, and that AF‐mediated cardioembolism may play a role in the migraine–stroke association for some patients. [ABSTRACT FROM AUTHOR]

Background: Studies investigating the association between migraine and dementia have reported inconsistent findings. This study aimed to evaluate whether patients with migraine have an increased risk of dementia compared to individuals without migraine. Methods: We obtained data from the 2002–2019 Korean National Health Insurance Health Screening Cohort. Non-migraine controls were selected using a 1:1 risk-set matching with a time-dependent propensity score. The main outcome was the development of all-cause dementia, and the secondary outcome was the development of each cause of dementia (Alzheimer's, vascular, mixed or other specified, and unspecified dementia). The incidence rate of dementia was calculated using Poisson regression, and the association between migraine and dementia was evaluated using Cox proportional hazards regression. Results: Among 88,390 participants, 66.1% were female, and the mean baseline age was 55.3 ± 9.4 years. During the study period, dementia cases were identified in 4,800 of the 44,195 patients with migraine and 3,757 of the 44,915 matched controls. The incidence rate of dementia was 139.6 (95% confidence interval [CI], 135.7–143.5) and 107.7 (95% CI, 104.3–111.1) cases per 10,000 person-years in patients with migraine and matched controls, respectively. Patients with migraine had a 1.30 (hazard ratio [HR], 1.30; 95% CI, 1.25–1.35), 1.29 (HR, 1.29; 95% CI, 1.23–1.35), 1.35 (HR, 1.35; 95% CI, 1.19–1.54), 1.36 (HR, 1.36; 95% CI, 1.00–1.83), and 1.30 (HR, 1.30; 95% CI, 1.17–1.45) times higher risk of developing all-cause dementia, Alzheimer's dementia, vascular dementia, mixed or other specified dementias, and unspecified dementia than their matched controls, respectively. Conclusion: Our results suggest that migraine is associated with an increased risk of subsequent dementia. Further research is warranted to confirm these findings and to reveal the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have demonstrated galcanezumab as safe and effective in migraine prevention. However, real-life data are still lacking and overlook the impact of galcanezumab on those different migraine facets strongly contributing to migraine burden. Herein we report the clinical experience from an Italian real-world setting using galcanezumab in patients with migraine experiencing previous unsuccessful preventive treatments. Methods: Forty-three patients with migraine and failure of at least 3 migraine preventive medication classes received monthly galcanezumab 120 mg s.c. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity. Furthermore, validated questionnaires were administered to explore migraine-related disability, impact, and quality of life as well as symptoms of depression or anxiety, pain catastrophizing, sleep quality and the ictal cutaneous allodynia. Results: After the third and the sixth administration of monthly galcanezumab 120 mg s.c., headache attacks frequency reduced from 20.56 to 7.44 and 6.37 headache days per month, respectively. Moreover, a significant improvement in headache pain intensity (from 8.95 to 6.84 and 6.21) and duration (from 9.03 to 3.75 and 2.38) as well as in scores assessing migraine related disability and impact, depressive and anxious symptoms, and pain catastrophizing was observed. Furthermore, we demonstrated a significant reduction in the values of "whole pain burden", a composite score derived from the product of the average of headache frequency, intensity, and duration in the last three months. Conclusion: Real-world data support monthly galcanezumab 120 mg s.c. as a safe and effective preventive treatment in reducing headache frequency, intensity, and duration as well as comorbid depressive or anxious symptoms, pain catastrophizing and quality of life in both episodic and chronic migraine patients with previous unsuccessful preventive treatments. Furthermore, we demonstrated that monthly galcanezumab 120 mg s.c. is able to induce a significant improvement in the scores of "whole pain burden". The latter is a reliable and easy-to-handle tool to be employed in clinical setting to evaluate the effectiveness of preventive drugs (in this case, galcanezumab) or when the decision of continuing the treatment with anti-CGRP mAbs is mandatory. [ABSTRACT FROM AUTHOR]

Objective/background: Despite the prevalence of concussions in young athletes, the impact of headaches on neurocognitive function at baseline is poorly understood. We analyze the effects of a history of headache treatment on baseline ImPACT composite scores in young athletes. Methods: A total of 11,563 baseline ImPACT tests taken by 7,453 student-athletes ages 12-22 between 2009 and 2019 were reviewed. The first baseline test was included. There were 960 subjects who reported a history of treatment for headache and/or migraine (HA) and 5,715 controls (CT). The HA cohort included all subjects who self-reported a history of treatment for migraine or other type of headache on the standardized questionnaire. Chi-squared tests were used to compare demographic differences. Univariate and multivariate regression analyses were used to assess differences in baseline composite scores between cohorts while controlling for demographic differences and symptom burden. Results: Unadjusted analyses demonstrated that HA was associated with increased symptoms (β=2.30, 95% CI: 2.18-2.41, p<.0001), decreased visual memory (β=-1.35, 95% CI: -2.62 to -0.43, p=.004), and increased visual motor speed (β=0.71, 95% CI: 0.23-1.19, p=.004) composite scores. Baseline scores for verbal memory, reaction time, and impulse control were not significantly different between cohorts. Adjusted analyses demonstrated similar results with HA patients having greater symptom burden (β=1.40, 95% CI: 1.10-1.70, p<.0001), lower visual memory (β=-1.25, 95% CI: -2.22 to -0.27, p=.01), and enhanced visual motor speed (β=0.60, 95% CI: 0.11-1.10, p=.02) scores. Conclusion: HA affected symptom, visual motor speed, and visual memory ImPACT composite scores. Visual memory scores and symptom burden were significantly worse in the HA group while visual motor speed scores were better, which may have been due to higher stimulant use in the HA group. The effects of HA on visual motor speed and visual memory scores were independent of the effects of the increased symptom burden. [ABSTRACT FROM AUTHOR]

Objective The Neck Disability Index (NDI) is a self-rated disability tool originally developed for whiplash-associated disorders and validated in cervical musculoskeletal conditions. It is now commonly used to assess neck disability in migraine, but it is unknown whether NDI scores relate to migraine and hypersensitivity, cervical musculoskeletal dysfunction, or both. This single-blinded observational study aimed to determine whether the presence of cervical musculoskeletal dysfunction, migraine features, and hypersensitivity predict NDI scores and whether alternate versions of the NDI (NDI-physical, NDI-8, NDI-5) relate more to cervical musculoskeletal dysfunction. Methods Migraine and neck pain features, the Headache Impact Test (HIT-6), NDI, Allodynia Symptom Checklist (ASC12), and pressure pain thresholds were assessed in 104 participants with migraine and neck pain, 45 previously identified with cervical musculoskeletal dysfunction and 59 without. The NDI score was regressed on the presence or absence of cervical dysfunction, migraine features, HIT-6, total pressure pain threshold, and ASC12 while accounting for neck pain features. The presence of cervical dysfunction was regressed on the scores of NDI versions. Results The ASC12 (standardized ß = 0.20) and HIT-6 (standardized ß = 0.18) were significantly predictive of total NDI score, as were neck pain intensity (standardized ß = 0.32) and frequency (standardized ß = 0.44). No scores from alternate NDI versions related to cervical dysfunction. Conclusion The NDI score is a complex measure of neck disability influenced by migraine disability and hypersensitivity beyond the presence of cervical musculoskeletal dysfunction. This has implications for the clinical interpretation of NDI scores in patients with migraine. Impact Many patients with migraine and neck pain report neck disability; therefore, it is important to understand if migraine impacts neck disability. The results of this study indicate that clinicians need to consider migraine-related disability and hypersensitivity when managing neck disability in this population. [ABSTRACT FROM AUTHOR]

Background It is important to implement disease-specific precautions to develop quality of life in migraine. The effect of osmophobia, which is one of the specific symptoms of migraine that might help to differentiate migraine from other headache disorders, on quality of life is unknown. The aim of the present study was to develop a practicable and reliable scale that assesses the effect of osmophobia on quality of life in migraine. Methods This cross-sectional study was carried out with 163 patients with migraine and 110 healthy individuals for control group. The scale items were constructed based on after literature review, expert opinions, and preliminary trial stage. A semi-structured interview was conducted with the patients by the Neurologist to evaluate the presence of osmophobia retrospectively. Migraine osmophobia-related quality of life assessment (MORA) consisted of 6 items including personal care, eating or cooking, house cleaning, close relationship, social life and traveling. Results The Cronbach's α coefficient was 0.86; and the Guttman split-half coefficient was 0.83. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95%) confidence interval [CI] = 0.902–0.984), a cutoff score of >9.5, a sensitivity of 91.6%, a specificity of 85.7%. Mean scores of the MORA differed between people with migraine (with and without osmophobia) and healthy controls (<0.001). Conclusion MORA is a valid and reliable self-report questionnaire that assesses the effect of osmophobia on quality of life in migraine. This questionnaire appears to be a practicable diagnostic instrument in clinical practice and research. [ABSTRACT FROM AUTHOR]

Objective: Migraine and sleep disorders are common health problems in the community and cause loss of labor. There are studies showing that there is a relationship between migraine and sleep quality and these two conditions worsen each other. The aim of this study was to determine the relationship between migraine and sleep quality. Methods: This is a case-control type cross-sectional study consisting of a total of 454 participants, included migraine patients, patients with non-migraine headaches and patients without headache complaint admitted to Family Medicine outpatient clinics between October 2017 and March 2018. Sociodemographic data form, Identity Migraine test, International Headache Society diagnostic criteria questionnaire, Pittsburgh sleep quality scale (PSQI) and Epworth day sleepiness scale (Epw) were applied to the participants by face to face interviews. Results: The total PSQI score was 6.5 ± 3.1, and significantly different between the groups. Patients with diagnosis of migraine had a higher PSQI score and poor sleep quality rate than the control groups. There was no correlation between the frequency of migraine attacks and PSQI scores. Extreme sleepiness in day time for the migraine group (30.7%) was higher than the control groups and there was no correlation between the frequency of migraine attacks and Epw scores. Conclusions: Poor sleep quality and daytime sleepiness rates in migraine patients were higher than those with non-migraine headache patients and patients without headache complaints. This may be due to the fact that migraine is a specific problem affecting sleep or the frequency and severity of headache in the migraine patients are greater than that of the non-migraine headache patients and headache-free participants. [ABSTRACT FROM AUTHOR]

Background: Migraine is a complex and highly disabling neurological disease whose treatment remains challenging in many patients, even after the recent advent of the first specific‐preventive drugs, namely monoclonal antibodies that target calcitonin gene‐related peptide. For this reason, headache researchers are actively searching for new therapeutic targets. Cannabis has been proposed for migraine treatment, but controlled clinical studies are lacking. A major advance in cannabinoid research has been the discovery of the endocannabinoid system (ECS), which consists of receptors CB1 and CB2; their endogenous ligands, such as N‐arachidonoylethanolamine; and the enzymes that catalyze endocannabinoid biosynthesis or degradation. Preclinical and clinical findings suggest a possible role for endocannabinoids and related lipids, such as palmitoylethanolamide (PEA), in migraine‐related pain treatment. In animal models of migraine‐related pain, endocannabinoid tone modulation via inhibition of endocannabinoid‐catabolizing enzymes has been a particular focus of research. Methods: To conduct a narrative review of available data on the possible effects of cannabis, endocannabinoids, and other lipids in migraine‐related pain, relevant key words were used to search the PubMed/MEDLINE database for basic and clinical studies. Results: Endocannabinoids and PEA seem to reduce trigeminal nociception by interacting with many pathways associated with migraine, suggesting a potential synergistic or similar effect. Conclusions: Modulation of the metabolic pathways of the ECS may be a basis for new migraine treatments. The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area. Multiple molecules related to the ECS or to allosteric modulation of CB1 receptors have emerged as potential therapeutic targets in migraine‐related pain. The complexity of the ECS calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development. [ABSTRACT FROM AUTHOR]

Background: Under a typical light and sound environment context, individuals with migraine showed balance control deficits on a series of functional activities, which helps to explain why migraineurs report more falls. it isn't established, the effects of intensity light and sound in migraineurs during functional tasks.Research Question: Based on the hypersensitivity to light and sound in migraineurs, not only during the attack but also in the interictal period, does the exposure to bright light and loud sound impact motor control in this population?Methods: This cross-sectional study consisted of 51 women with migraine and 22 healthy women. They performed three walking tasks: crossing an obstacle, stepping-up and stepping-down a curb, in a control situation with ambient lighting (≅350 lux), bright light (≅1200 lux), and loud sound (≅90 dBa). For statistical analysis, a t-test, a Spearman correlation test, and a repeated measures mixed ANOVA were applied.Results: Migraineurs presented higher discomfort induced by light (p ≤ 0.0001) and sound (p = 0.001). In the obstacle task, migraineurs had greater step width than controls in the ambient light condition (p = 0.038) and participants of both groups placed their leading foot farther away from the obstacle in the light (p = 0.033) than in the ambient light condition. For the step-up task, this distance increased for both groups and limbs in the light (leading limb: p = 0.015; trailing limb: p = 0.002) and sound (leading limb: p = 0.010; trailing limb: p ≤ 0.0001) conditions compared to the ambient light condition. Step speed increased for light and sound conditions compared to ambient light condition, except for the sound condition in the step-down task.Significance: Despite the higher discomfort induced by light and sound in the migraineurs, the effects of these sensory manipulations were similar for both migraineurs and controls, except for step width. Light and sound manipulation induced a less conservative strategy to deal with uneven terrain in both groups. [ABSTRACT FROM AUTHOR]

Objective Specific pain conditions such as back pain and migraines are associated with increased risk of suicide mortality after accounting for key covariates. The purpose of the current study was to assess the associations of specific pain conditions with suicide attempts. Design Case-control Setting Veterans Health Administration (VHA) Subjects Individuals who utilized VHA services with a record of a suicide attempt (N   =   30,051) in Fiscal Years 2013 and 2014 were identified and propensity score matched with controls with no such record (N   =   30,051). Methods Data on pain condition diagnoses (back pain, arthritis, migraine, headaches, psychogenic pain, neuropathy, fibromyalgia) psychiatric diagnoses, medical comorbidity, and demographics were extracted from VHA medical record and suicide surveillance datasets. Results Unadjusted logistic regression analyses found that each of the pain conditions were associated with suicide attempts (e.g. back pain: Odds ratio [OR]=3.25, 95% Confidence Interval [CI]=3.12–3.39). After adjusting for mental health conditions, medical comorbidity, and each of the pain conditions, the effects were attenuated across pain conditions; however, remained significant for each of the pain conditions except for fibromyalgia. Specifically, back pain (OR = 1.25, 95% CI = 1.19–1.32), migraines (OR = 1.29, 95% CI = 1.14–1.46), headaches (OR = 1.33, 95% CI = 1.19–1.48), and neuropathic pain (OR = 1.52, 95% CI = 1.33–1.74) were each associated with increased odds of a suicide attempt. Fibromyalgia was the only pain condition associated with re-attempt status (OR = 1.25, 95% CI = 1.08–1.45). Conclusions Specific pain conditions are associated with increased odds of suicide attempts even after including key covariates. Limitations Limitations of the study include the retrospective study design and lack of examination into additional variables including prescription opioid use, pain intensity, and pain duration. The case-control design also limits the ability to draw causal or temporal conclusions. [ABSTRACT FROM AUTHOR]

Objective To evaluate gender differences in clinical characteristics of migraine by examining presence and severity of cutaneous allodynia, migraine-related disability, neck pain and its associated disability, passive mobility of the upper cervical spine, and performance of the deep neck flexor muscles. Design Cross-sectional study. Subjects 30 men and 30 women with migraine. Methods Participants responded to the questionnaires Migraine Disability Assessment questionnaire, 12-item Allodynia Symptom Checklist, and Neck Disability Index. The mobility of the upper cervical spine was assessed by using the Flexion-Rotation Test. Performance of the deep neck flexor muscles was evaluated by applying the Craniocervical Flexion Test. Comparison of the groups was carried out by using the Student's t -test or the χ2 test. The prevalence ratio was also calculated. Results Women showed a higher prevalence of cutaneous allodynia (P  = .001) and a 4 times greater risk of having severe cutaneous allodynia than to men (P  = 0.007). No gender differences were observed in migraine-related disability (P  = .08). Women showed higher prevalence of self-reported neck pain (P  = .03) and increased risk of having this symptom in comparison to men (Prevalence Ratio = 1.69; P  = 0.025). However, there were no gender differences in neck pain-related disability (P  = .25), mobility of the upper cervical spine (P  = .92), or performance of the deep neck flexor muscles (P  = .52). Conclusion Women with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia when compared to men. However, the two groups did not differ regarding neck pain-related disability and performance in the physical tests. [ABSTRACT FROM AUTHOR]

Most people who see, treat or experience migraine will be aware that its clinical manifestations exceed the symptom of head pain. However, available acute treatments so far have targeted migraine symptoms only in the context of the pain phase of an attack. The associated disability clearly involves more than just these symptoms, and the phenotype can include additional painless features, including alterations in mood, cognition and homeostasis and sensory sensitivities. Recognising these symptoms, understanding their neurobiological basis and systematically recording them prospectively in clinical therapeutic trials are likely to offer valuable pathophysiological and therapeutic insights into this complex brain disorder, ultimately helping to improve the quality of lives of sufferers. We aim to explore the multifaceted disorder that is migraine, with a particular focus on the non- painful non- aura symptoms. [ABSTRACT FROM AUTHOR]

Background: Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine. Methods: This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD. Results: Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07–1.35) for ischemic stroke and 1.02 (95%CI, 0.93–1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20–1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67–0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17–1.39) and 0.99 (0.93–1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07–1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72–0.95]), each versus those without migraine. Conclusions: Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this narrative review is to explore the relationship between visual snow syndrome (VSS), migraine, and a group of other perceptual disorders. Background: VSS is characterized by visual snow and additional visual and nonvisual disturbances. The clinical picture suggests a hypersensitivity to internal and external stimuli. Imaging and electrophysiological findings indicate a hyperexcitability of the primary and secondary visual areas of the brain possibly due to an impairment of inhibitory feedback mechanisms. Migraine is the most frequent comorbidity. Epidemiological and clinical studies indicate that other perceptual disorders, such as tinnitus, fibromyalgia, and dizziness, are associated with VSS. Clinical overlaps and parallels in pathophysiology might exist in relation to migraine. Methods: We performed a PubMed and Google Scholar search with the following terms: visual snow syndrome, entoptic phenomenon, fibromyalgia, tinnitus, migraine, dizziness, persistent postural‐perceptual dizziness (PPPD), comorbidities, symptoms, pathophysiology, thalamus, thalamocortical dysrhythmia, and salience network. Results: VSS, fibromyalgia, tinnitus, and PPPD share evidence of a central disturbance in the processing of different stimuli (visual, somatosensory/pain, acoustic, and vestibular) that might lead to hypersensitivity. Imaging and electrophysiological findings hint toward network disorders involving the sensory networks and other large‐scale networks involved in the management of attention and emotional processing. There are clinical and epidemiological overlaps between these disorders. Similarly, migraine exhibits a multisensory hypersensitivity even in the interictal state with fluctuation during the migraine cycle. All the described perceptual disorders are associated with migraine suggesting that having migraine, that is, a disorder of sensory processing, is a common link. Conclusion: VSS, PPPD, fibromyalgia, and chronic tinnitus might lie on a spectrum of perceptual disorders with similar pathophysiological mechanisms and the common risk factor migraine. Understanding the underlying network disturbances might give insights into how to improve these currently very difficult to treat conditions. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between pre-existing migraines and postconcussion symptoms and cognitive performance acutely (within 72 hours) after a suspected concussion. Design: Nested case-control study. Setting: High schools in Maine, USA. Participants: From a sample of 39161 adolescent athletes who underwent baseline preseason testing, 633 were assessed within 3 days of a suspected concussion. Of these, 59 reported a history of treatment for migraines at baseline (9.3%). These athletes were individually matched to 2 athletes who had a suspected concussion but denied preinjury migraines (total N = 177; age: M = 15.8, SD = 1.3). Assessment of Risk Factors: Self-reported history of treatment for migraines by a physician. Main Outcome Measures: Post-Concussion Symptom Scale total score, ImPACT composite scores, and individual symptom endorsement. Results: Individuals with a pre-existing migraine disorder endorsed greater symptom severity (M = 8.4, SD = 9.9) compared with controls (M = 4.5, SD = 6.5; Cohen's d = 0.47) at preinjury baseline and acutely after suspected injury (migraine: M = 26.0, SD = 25.5; controls: M = 16.7, SD = 15.4; d 5 0.44). Acutely after a suspected concussion, greater proportions of athletes with migraine disorders reported mental fogginess (49.2% vs 33.9%) and memory problems (39.0% vs 24.6%; P < 0.05). Baseline ImPACT composite scores were similar between migraine and control groups (d = 0.04-0.13). Adolescents with pre-existing migraine disorders performed worse after a suspected concussion compared with the control participants on verbal memory (F = 4.32, P = 0.041) and visual memory (F = 3.95, P = 0.049). Conclusions: Individuals with pre-existing migraine disorders may be at higher risk for worse outcomes, including greater overall burden of symptoms and worse cognitive functioning in the memory domain, in the first 72 hours after concussion. [ABSTRACT FROM AUTHOR]

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom. Results: Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time. Conclusions: This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint. Trial Registration: SAMURAI (NCT02439320); SPARTAN (NCT02605174). [ABSTRACT FROM AUTHOR]

Background: Stroke-like migraine attacks after radiation therapy – also known as SMART syndrome – constitute a rare condition characterised by headache, seizures, vision abnormalities, hemiparesis, and aphasia. The condition usually resolves within a few days or weeks with little to no residual impairment; however, recovery in some cases is protracted and incomplete. Aims: The purpose of this case report was to describe the one-year progression of language in a person, GB, with slow recovery from SMART syndrome. Methods & Procedures: GB was diagnosed with SMART syndrome at 39 years of age. Formal and informal assessments occurred at six, 11, 18, 29, and 52 weeks post-onset of SMART syndrome. Standardised assessment involved administration of portions of the Western Aphasia Battery – Revised, and informal assessment took the form of written and spoken language sample analyses. Outcomes & Results: Initial evaluation at two weeks post-onset revealed global aphasia. This evolved into severe Wernicke's aphasia by six weeks post-onset. Repeated evaluation over subsequent months revealed gradual improvement but continuing and substantial language impairment. At one-year post-onset, GB displayed anomic aphasia and persistent reading and writing deficits. Conclusions: Substantial language recovery from SMART syndrome can occur beyond the initial few months post-onset. Documentation of the nature and extent of language impairment provides a starting point for developing and refining efficacious treatment protocols. [ABSTRACT FROM AUTHOR]

The article focuses on challenging the long-standing hypothesis that migraine aura directly initiates a migraine attack, presenting evidence that common brain mechanisms are activated before both migraine with aura and without aura attacks, indicating that aura is not the primary initiator of migraines and supporting the idea that both types of migraines share common underlying mechanisms.

Background and aims: Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe. We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation. Methods: We screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis. Results: CACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1. Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy. Discussion: The variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits. These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine. [ABSTRACT FROM AUTHOR]