Migraine Stroke Research Articles

Unravelling pharmacological mechanisms and effects of Tianma Siwu Decoction-derived compounds on ischemic stroke by multidimensional network pharmacological analysis

Ethnopharmacological relevanceIschemic stroke (IS) a complex pathological event emerging as one of the most serious threats with huge economic impact in the 21st century. Following IS, multiple cascades and pathways are stimulated, culminating in long term consequences. One of Chinese Traditional Medicine, Tianma Siwu Decoction (TSD), is known to have sedative-hypnotic, anticonvulsant and anti-inflammatory effects, which is usually used to treat migraine and ischemic stroke, but its potential pharmacological mechanism remains unclear. Aim of the studyThis study is aimed to identify the active principles from TSD that has strong pharmacological effect on the treatment of IS. Materials and MethodsBased on liquid chromatography-triple quadrupole mass spectrometry (LC-Q-MS/MS) technology, a new three-step-based approach integrating concentration parameters and Quality marker (Q-marker) with network pharmacology and bioactivity evaluation to explore the therapeutic effects and mechanisms of TSD on ischemic stroke. Ultimately, as the main herb of the TSD, high-concentration compounds from Gastrodia elata Blume (GEB) were identified and collected by LC-Q-MS/MS, and an optimized analytical model in multidimensional network pharmacology was introduced to more accurately explore the potential mechanisms by which TSD affects IS. ResultsThe results showed that 280 overlapping targets of TSD were obtained after the introduction of compound concentration parameters into the multidimensional network pharmacology analysis. Additionally, TSD might regulate IS through the AGE-RAGE and Rap1 signaling pathways. Through an in vitro hypoxia-reoxygenation injury cell model, it was discovered that as the Q-markers of GEB, gastrodin and parishin could effectively reduce neuronal hypoxic injury by modulating the expression levels of p-JNK and p-p38 proteins. According to the results of molecular docking, gastrodin and baicalin exhibits strong binding affinity to GAPDH and MAPK3, respectively (≦-7 kcal/mol). ConclusionWe discovered that compound concentration is a key factor that influence the activity of substances, affects the accuracy and reliability of predictive outcomes. Consequently, the study enhances the network pharmacology model by incorporating concentration factors, aiming for a more accurate understanding of the potential mechanisms behind TSD anti-ischemic stroke actions.

Migraine and Stroke: A Scoping Review.

An increased risk of ischemic stroke in migraine with aura (MA) has been consistently demonstrated. The pathophysiology of risk factors is not yet well understood. Several mechanisms have been proposed to explain the association between MA and ischemic stroke including decreased focal cerebral blood flow and other phenomena linked with cortical spreading depression (CSD) as well as neurovascular pathology, which appear to play a key role in MA. In addition to genetic predisposition, other classic stroke risk factors such as atrial fibrillation, emboli, migraine-associated vasculopathy, endothelial dysfunction, platelet dysfunction, coagulation pathway abnormalities, and inflammatory factors have been examined and investigated. For further clarification, distinctions have been made between features of migrainous infarctions and non-migrainous infarctions among migraineurs. Furthermore, the association is less clear when considering the mixed results studying the risk of ischemic stroke in migraines without aura (MO) and the risk of hemorrhagic stroke in people with all types of migraine. Translational research is investigating the role of biomarkers which can help identify vascular links between stroke and migraine and lead to further treatment developments. We performed a scoping review of the PubMed database to further characterize and update the clinical connections between migraine and stroke.

The Burden of Stroke Mimics Among Hyperacute Stroke Unit Attendees with Special Emphasis on Migraine: A 10-Year Evaluation.

Stroke and migraine are common neurological illnesses that cause tremendous suffering for patients. Certain diseases can mimic the clinical manifestations of an actual stroke. Migraine is one of the most commonly reported stroke mimics. The main goals of this study are to look at the prevalence of stroke mimics on the stroke pathway of Sheffield Teaching Hospitals and how many of them are migraines. A retrospective service evaluation was conducted at the hyperacute stroke unit (HASU) of the Royal Hallamshire Hospital (RHH) in the United Kingdom. The total admissions from 2013 to 2022 were collected from the Sentinel Stroke National Audit Programme database, and the number of stroke mimics was evaluated each year. The burden of migraine stroke mimics was also evaluated. Then, a one-year sample of stroke mimics was extracted to look for the types of each mimic. From 2013 to 2022, 45.75% (n = 12156) of the stroke pathway patients (n = 26573) were stroke mimics, with an increment of up to 55% in the years 2021and 2022. During these10 years, migraine stroke mimics accounted for 10.21% of admissions (n = 1240). The three most common mimics in a one-year sample of stroke pathway patients were migraine (14.70%) (n = 373), functional neurological disorders (FNDs) (7.17%) (n = 182), and Guillain-Barré syndrome (6.66%) (n = 169). Seizures, syncope, and metabolic derangements were reported as mimics in 4.17% (n = 106), 3.14% (n = 80), and 1.77% (n = 45), respectively. About half of the HASU attendees were stroke mimics rather than actual strokes, and the most common mimics were migraines.

Abstract WP252: MARS: Migraine and Retinal Stroke - A Population-Based Cohort Study of 39 Million Patients

Introduction: Migraine is a risk factor for cerebral ischemic stroke. However, it is not known if migraine is a risk factor for retinal stroke (central retinal artery occlusion, CRAO). Methods: We performed a retrospective cohort study using population-based data from the State Inpatient Databases and State Emergency Department Databases from New York (2006-2015), California (2003-2011), and Florida (2005-2015) to determine the association between hospital-documented migraine and retinal stroke. The primary exposure was hospital-documented migraine. The primary endpoint was hospital-documented CRAO (ICD-9-CM code 362.31 in the primary diagnosis position) and secondary endpoints included BRAO and any retinal artery occlusion (RAO). Cause-specific hazard models were used to model the association between migraine and CRAO. Results: Of 39,835,024 patients included in the study, 1,109,140 had migraine documented during the exposure window. Patients with migraine were younger (40.2±15.2 vs. 46.9±19.8, standardized difference (SD) 0.38), more likely to be female (81.4% vs. 54.7%, SD 0.6), and had a lower burden of atrial fibrillation (4.5% vs. 6.9%, SD 0.1), chronic kidney disease (1.9% vs. 3.6%, SD 0.2), and congestive cardiac failure (2.7% vs. 5.1%, SD 0.12). Migraine was not associated with CRAO in the primary diagnostic position (adjusted hazard rate (aHR) 1.15 (95% CI: 0.79-1.67). However, it was associated with CRAO in any diagnostic position (aHR 1.39 (95% CI: 1.08-1.78). As positive controls, we replicated previously established associations of migraine with cerebral ischemic stroke (aHR 1.35 (95% CI: 1.32-1.38) and embolic ischemic stroke (aHR 1.15 (95% CI: 1.08-1.22). Conclusions: In a large, claims-based study, we found a risk-adjusted association between migraine and CRAO considered in any diagnostic position. This finding sets the stage for future work leveraging both outpatient and pharmacy-based claims to further explore this finding.

Reviewing migraine-associated pathophysiology and its impact on elevated stroke risk.

Migraine affects up to 20 percent of the global population and ranks as the second leading cause of disability worldwide. In parallel, ischemic stroke stands as the second leading cause of mortality and the third leading cause of disability worldwide. This review aims to elucidate the intricate relationship between migraine and stroke, highlighting the role of genetic, vascular, and hormonal factors. Epidemiological evidence shows a positive association between migraine, particularly with aura, and ischemic stroke (IS), though the link to hemorrhagic stroke (HS) remains inconclusive. The shared pathophysiology between migraine and stroke includes cortical spreading depression, endothelial dysfunction, and genetic predispositions, such as mutations linked to conditions like CADASIL and MELAS. Genetic studies indicate that common loci may predispose individuals to both migraine and stroke, while biomarkers such as endothelial microparticles and inflammatory cytokines offer insights into the underlying mechanisms. Additionally, hormonal influences, particularly fluctuations in estrogen levels, significantly impact migraine pathogenesis and stroke risk, highlighting the need for tailored interventions for women. The presence of a patent foramen ovale (PFO) in migraineurs further complicates their risk profile, with device closure showing promise in reducing stroke occurrence. Furthermore, white matter lesions (WMLs) are frequently observed in migraine patients, suggesting potential cognitive and stroke risks. This review hopes to summarize the links between migraine and its associated conditions and ischemic stroke, recognizing the profound implications for clinical management strategies for both disorders. Understanding the complex relationship between migraine and ischemic stroke holds the key to navigating treatment options and preventive interventions to enhance overall patient outcomes.

Comparative analysis of cognitive function at vascular complications of migraine. Diagnosis and clinical approach

Migraine affects 11-15% of the adult population, frequent and prolonged migraine attacks, untimely correction, the absence of preventive measures can form vascular complications with the development of cognitive dysfunctions. The aim of this study was to study and analyze cognitive function in various variants of the course of complicated migraines in a comparative aspect. We studied 378 (100%) patients with various options for the course of migraine. Of these, 78 (20.6%) examined with migraine status, 82 (21.7%) with chronic migraine, 52 (13.8%) with migraine strokes, 87 (23.0%) chemoprophylaxis with migraine, considered as the main group, and the comparative group included 79 (20.9%) patients with uncomplicated migraine. The study demonstrate that cognitive dysfunction complicated by migraine develops due to cerebral vascular reactions modelled on vasodilation / vasoconstriction against the background of migraine attacks that cause hypoxia and then local ischemia with the formation of encephalomalacia in “strategic areas” and can be considered as a predisposition of patients with migraine to vascular dementia.

A clinical case of migrainous stroke

Migrainous stroke is a rare combination of frequently occurring diseases; only a few cases have been described in the domestic literature. The complexity of differential diagnosis is due to the fact that at the stage of initial manifestations, these two conditions can mimic each other. Treatment strategy and further prevention for each of these diseases is different, so timely and convincing early diagnosis is crucial. The presented clinical case describes a case of ischemic stroke in a young woman who had been suffering from migraine for a long time, which did not fully meet the criteria for migrainous infarction. The patient was treated at the regional vascular center of the Tomsk Regional Clinical Hospital, there was a positive trend in the neurological status. The catamnesis of the disease was tracked. It was suggested that endothelial dysfunction is the main pathogenetic factor in the formation of an ischemic focus against the background of a protracted migraine attack.

Neurological and psychiatric comorbidities of migraine: Concepts and future perspectives.

This narrative review aims to discuss several common neurological and psychiatric disorders that show comorbidity with migraine. Not only can we gain pathophysiological insights by studying these disorders, comorbidities also have important implications for treating migraine patients in clinical practice. A literature search on PubMed and Embase was conducted with the keywords "comorbidity", "migraine disorders", "migraine with aura", "migraine without aura", "depression", "depressive disorders", "epilepsy", "stroke", "patent foramen ovale", "sleep wake disorders", "restless legs syndrome", "genetics", "therapeutics". Several common neurological and psychiatric disorders show comorbidity with migraine. Major depression and migraine show bidirectional causality and have shared genetic factors. Dysregulation of both hypothalamic and thalamic pathways have been implicated as a possibly cause. The increased risk of ischaemic stroke in migraine likely involves spreading depolarizations. Epilepsy is not only bidirectionally related to migraine, but is also co-occurring in monogenic migraine syndromes. Neuronal hyperexcitability is an important overlapping mechanism between these conditions. Hypothalamic dysfunction is suggested as the underlying mechanism for comorbidity between sleep disorders and migraine and might explain altered circadian timing in migraine. These comorbid conditions in migraine with distinct pathophysiological mechanisms have important implications for best treatment choices and may provide clues for future approaches.

Linear Scleroderma en Coup de Sabre Presenting with Stroke and Seizure (P3-5.022)

<h3>Objective:</h3> To describe the neurologic complications and imaging findings in a patient with linear scleroderma <i>en coup de sabre</i> (LScs) and associated Parry-Romberg syndrome. <h3>Background:</h3> LScs is a rare subset of localized scleroderma. Once thought to be an exclusively cutaneous disorder, recent studies suggest that rheumatologic, ophthalmologic, and neurologic symptoms occur in up to 20% of cases. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 32-year-old woman with LScs, associated Parry-Romberg syndrome, migraine, and prior left hemispheric stroke thought to be secondary to vasculitis presented with right arm and leg numbness. She had left hemifacial atrophy. Brain MRI showed an acute ischemic stroke in the posterior limb of the left internal capsule and a chronic T2/FLAIR-hyperintensity in the left frontal lobe immediately beneath the cutaneous forehead and scalp scar. She was previously on mycophenolate for presumed vasculitis, however she had discontinued it due to concern about immunosuppression during the COVID-19 pandemic. Computed tomography angiography, digital subtraction angiography and lumbar puncture were normal. Her stroke was thought to be due to small vessel occlusion. The occurrence of two ischemic strokes ipsilateral to the cutaneous changes and facial atrophy, the ipsilateral MRI findings mirroring the <i>coup de sabre</i> scar, and the occurrence of the new stroke after discontinuation of mycophenolate together suggest an underlying vasculopathy/vasculitis associated with her scleroderma. Her hospital course was complicated by episodes of rapid rhythmic shaking of the right leg with no alteration of awareness, suggesting simple focal motor seizures. She was started on a prednisone with plans for steroid-sparing immunosuppressive therapy (rituximab and mycophenolate). On follow-up evaluation, she was recovering well. <h3>Conclusions:</h3> LScs and Parry-Romberg syndrome are associated with multiple neurologic complications including ischemic strokes, seizures, and headaches. This case highlights the underrecognized relationship between neurologic complications and LScs and suggests an underlying inflammatory process responsive to immunosuppressive therapy. <b>Disclosure:</b> Dr. Greige has nothing to disclose. Dr. Feske has received publishing royalties from a publication relating to health care.

Role of Migraine as a Risk Factor of Ischemic Stroke in Young Women

Background: Migraine is a chronic primary headache disorder with episodic attacks which affects the people in the most productive periods of their working lives; women are affected up to four times more often than men. Objective: The purpose of the present study was to identify the association of migraine and risk of ischemic stroke in young women.&#x0D; Methodology: It’s a hospital based case-control study carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University from January 2010 to December, 2012.&#x0D; Results: The result obtained from our study shows that migraine and ischemic stroke were strongly associated; 60% (95% confidence interval 48% to 71%) of cases had migraine compared with 30%(23% to 37%) of controls (P &lt; 000 1). This association persisted after we controlled for age, history of hypertension, use of oral contraceptives, and smoking.Women with migraine had a more than threefold increased risk of ischemic stroke compared with women without migraine. This increase occurred with both types of migraine, although the risk was higher with migraine with aura (odds ratio 6-2) than with migraine without aura.&#x0D; Conclusion: In conclusion, the risk of ischemic stroke was higher among young women with migraine who smoked or who took oral contraceptives.&#x0D; Journal of National Institute of Neurosciences Bangladesh, July 2022;8(2):193-197

Microembolism and Other Links Between Migraine and Stroke: Clinical and Pathophysiologic Update.

Migraine and stroke are highly prevalent diseases with a high effect on quality of life, with multiple epidemiologic, pathophysiologic, clinical, and prognostic areas of overlap. Migraine is a risk factor for stroke. This risk is explained by common risk factors, migraine-specific mechanisms, and non-migraine-specific mechanisms that have a relevant role in patients with migraine with aura (e.g., atrial fibrillation and paradoxical embolism through a patent foramen ovale). Another important link between migraine aura and ischemic stroke is cardiac embolism. Cardioembolism is the most frequent cause of ischemic stroke, and increasing evidence suggests that microembolism, predominantly but not exclusively originating in the heart, is a contributing mechanism to the development of migraine aura. In this review, we discuss epidemiologic aspects of the association between migraine and ischemic stroke, the clinical presentation of ischemic strokes in patients with migraine, and the differentiation between migrainous and nonmigrainous infarctions. After that, we review migraine-specific and non-migraine-specific stroke mechanisms. We then review updated preclinical and clinical data on microembolism as a cause of migraine aura. In the last section, we summarize knowledge gaps and important areas to explore in future research. The review includes a clinical vignette with a discussion of the most relevant topics addressed.

Are patients with Parkinson's disease at a lower risk of catching the common cold? Propensity score matching

IntroductionAccumulating evidence indicating that inflammatory responses play crucial roles in Parkinson's disease (PD) development provided a hypothesis that physiological alpha-synuclein may contribute to inflammatory responses against infections during non-advanced stages of PD. Thus, we examined the risk of catching a common cold in patients with PD as compared to other common brain diseases. MethodsWe extracted PD (non-advanced; without dementia) and control (AD: Alzheimer's disease, migraine, epilepsy, and ischemic stroke) patient data from insurance claim data available between 2010 and 2021. After confirming the clinical PD diagnosis, we investigated factors associated with cold diagnoses and used propensity score matching to identify differences in the incidence of colds between PD and control patients. ResultsDiagnosis of colds in PD patients (n = 726) and controls (AD = 377, migraine = 1019, epilepsy = 3414, ischemic stroke = 6943) was found in 1186 (9.5%) patients, which was independently associated with being female (odds ratio: OR 1.59; 95%CI 1.41–1.79; P < 0.0001), follow-up by neurologists (OR 1.30; 95%CI 1.15–1.48; P < 0.0001), diagnosis of PD (OR 0.30; 95%CI 0.20–0.45; P < 0.0001) and COVID-19 pandemic period (OR 0.58; 95%CI 0.47–0.72; P < 0.0001). After propensity score matching, the incidence of colds was significantly lower in PD (3.4%) versus in controls; AD (9.8%; P < 0.0001), migraine (13.3%; P < 0.0001), epilepsy (11.0%; P < 0.0001), ischemic stroke (8.8%; P < 0.0001). ConclusionsPatients with PD were less likely to be diagnosed with colds. However, several confounding factors will need to be examined. Moreover, alpha-synuclein may provide protective resistance to viral infections by activating the immune system due to chronic inflammation in non-advanced PD patients.

Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura.

Background and objectivesIn general, suddenly occurring neurological deficits, i.e., negative neurological symptoms, are considered symptoms of focal cerebral ischemia, while positive irritative symptoms with gradual onset are viewed as the characteristics of migraine aura. Nevertheless, cortical spreading depolarization, the pathophysiological basis of migraine aura, has also been observed in acute ischemic stroke. The aim of our study was to determine the frequency of migraine aura-like symptoms at ischemic stroke onset and stroke-like symptoms in migraine with aura.MethodsWe interviewed 350 consecutive patients with ischemic stroke and 343 with migraine with aura using a structured questionnaire. Stroke diagnosis was confirmed by imaging, and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Patients with wake-up strokes or severe cognitive deficits that precluded a useful interview were excluded from the study.ResultsSeventy-eight patients with stroke (22.3%) reported visual symptoms, 145 (41.4%) sensory symptoms, 197 (56.3%) a paresis, and 201 patients (57.4%) more than one symptom, compared to 326 migraine patients with aura (95%) with visual symptoms (P < 0.001), 175 (51%) with sensory symptoms (p = 0.011), 50 (14.6%) with paresis (P < 0.001), and 211 (61.5%) with more than one symptom (p = 0.27). Among patients with stroke, migraine-like symptoms were frequent: 36 patients (46.2%) with visual disturbance and 78 (53.8%) with sensory symptoms experienced irritative sensations. Paresis-onset in stroke lasted longer than 5 min in 43 patients (21.8%). Spreading of sensory and motor symptoms occurred in 37 (25.5%) and 37 (18.8%) patients, respectively. Stroke-like negative symptoms in migraine with aura occurred in 39 patients (12%) with visual symptoms, in 55 (31.4%) with sensory symptoms, and paresis appeared suddenly in 14 patients (28%). More than one symptom in succession occurred in 117 patients with stroke (58.2%) and in 201 migraine with aura patients (95.3%; P < 0.001).ConclusionMany patients with stroke experience migraine-like symptoms at stroke onset, and many migraine with aura patients have stroke-like symptoms. Though overall the symptom frequencies of the two groups are significantly different, clarifying the differential diagnosis in an individual patient requires additional history elements, physical findings, or results of ancillary investigations.

Diagnosing and treating Patent Foramen Ovale (PFO) from various manifestations in adults: case series

Background. Patent foramen ovale (PFO) is a part of atrial septal defects (ASD) entities. While mostly asymptomatic, some adults with PFO will develop symptoms, from mild complaints such as migraine or palpitation to more debilitating complications such as syncope or cryptogenic stroke. Therefore, it is highly crucial that PFO be diagnosed and treated promptly. Echocardiography, trans-thoracal and or trans-esophageal, is the main diagnosis modality. For treatment, antiplatelet with or without anticoagulation, trans-catheter closure, and surgery are utilized in accordance with their indications. Case Presentation. We present four adult patients referred with various symptoms: vertigo, migraine, palpitation, and cryptogenic stroke. Three of them had no explicit risk factors for the cerebrovascular event, with one patient having a co-existing hypercoagulable state. Echocardiography revealed a positive bubble test, which meant that PFO was the primary etiology of those cases. We then treated each of them with transcatheter device closure, which improved their symptoms, before adding antiplatelet for six months. Conclusion. Proper diagnosis and prompt treatment of PFO are imperative in reducing complications. Echocardiography, mainly TEE, is the main diagnostic tool for PFO. Antithrombotic (with or without anticoagulant), minimally invasive procedure and surgery in some cases are the modalities available.

Cryptogenic Ischemic Stroke in Migraine: Role of Patent Foramen Ovale.

IntroductionMigraine with aura (MWA) has been associated with cryptogenic ischemic stroke (CIS) after adjustment for the presence of a patent foramen ovale (PFO) assessed by a transcranial Doppler. This study aimed at evaluating the association of MWA with causal PFO assessed by Transesophageal echocardiography (TEE) in CIS.MethodsPatients aged 18–54 years consecutively treated for first acute ischemic stroke in a university hospital stroke unit, between January 2017 and December 2019, were included in this cross-sectional study. Associations between migraine subtypes and PFO were tested for all PFO, possibly causal PFO (PFO with large shunt and/or atrial septal aneurysm [ASA]), and the probably causal PFO subset (large shunt and/or ASA, plus risk of paradoxical embolism [RoPE] score ≥ 7). We adjusted the association between migraine subtypes and possibly causal PFO, which included the probably causal subset for age, sex, large artery atherosclerosis, and small vessel disease.ResultsA total of two hundred and two patients with CIS were included, of whom 42/202 (20%) had MWA, 32/202 (15%) had migraine without aura, and 128/202 (63%) had no migraine. MWA was associated with possibly causal PFO (OR = 4.0, 95%CI [1.78–9.3], P < 0.001) and with probably causal PFO (OR = 5.4, 95%CI [2.37–13], P < 0.001). In a multinomial logistic regression analysis, MWA remained associated with possibly causal PFO (OR = 3.24, 95% CI [1.45–7.2], P = 0.004).ConclusionIn a young adult population with CIS, MWA was strongly associated with possibly causal PFO, i.e., with a large shunt or combined with an interatrial septal aneurysm.

Migraine, Stroke, and Cervical Arterial Dissection: Shared Genetics for a Triad of Brain Disorders With Vascular Involvement.

Background and ObjectivesMigraine, stroke, and cervical artery dissection (CeAD) represent a triad of cerebrovascular disorders with pairwise comorbid relationships and vascular involvement. Larger samples and recent advances in methodology invite systematic exploration of their shared genetics.MethodsGenetic analyses leveraged summary statistics from genome-wide association studies of the largest available samples of each disorder, including subtypes of stroke (ischemic stroke, large artery stroke, small vessel stroke, and cardioembolic stroke) and migraine (with aura and without aura). For each pair of disorders, genetic correlation was assessed both on a genome-wide basis and within independent segments across the genome including known specific loci for each disorder. A cross-trait meta-analysis was used to identify novel candidate loci. Finally, potential causality of migraine susceptibility on stroke and CeAD was assessed by Mendelian randomization.ResultsAmong all pairs of disorders, genome-wide genetic correlation was observed only between CeAD and migraine, particularly MO. Local genetic correlations were more extensive between migraine and CeAD than those between migraine and stroke or CeAD and stroke and revealed evidence for novel CeAD associations at rs6693567 (ADAMTSL4/ECM1), rs11187838 (PLCE1), and rs7940646 (MRVI1) while strengthening prior subthreshold evidence at rs9486725 (FHL5) and rs650724 (LRP1). At known migraine loci, novel associations with stroke had concordant risk alleles for small vessel stroke at rs191602009 (CARF) and for cardioembolic stroke at rs55884259 (NKX2-5). Known migraine loci also revealed novel associations but with opposite risk alleles for all stroke, ischemic stroke, and small vessel stroke at rs55928386 (HTRA1), for large artery stroke at rs11172113 (LRP1), and for all stroke and ischemic stroke at rs1535791 and rs4942561 (both LRCH1), respectively. rs182923402 (near PTCH1) was a novel concordant locus for migraine and cardioembolic stroke. Mendelian randomization supported potential causal influences of migraine on CeAD (odds ratio [95% confidence interval] per doubling migraine prevalence = 1.69 [1.24–2.3], p = 0.0009) with concordant risk, but with opposite risk on large artery stroke (0.86 [0.76–0.96], p = 0.0067).DiscussionThe findings emphasize shared genetic risk between migraine and CeAD while identifying loci with likely vascular function in migraine and shared but opposite genetic risk between migraine and stroke subtypes, and a central role of LRP1 in all 3 cerebrovascular disorders.

Classical prescription Dachuanxiong Formula delays nitroglycerin-induced pain response in migraine mice through reducing endothelin-1 level and regulating fatty acid biosynthesis

Ethnopharmacological relevanceDachuanxiong Formula (DCXF) is a classical Chinese medicine prescription and is composed of dried rhizomes from Ligusticum striatum DC. (Chuanxiong Rhizoma) and Gastrodia elata Bl. (Gastrodiae Rhizoma) at the ratio of 4:1 (w/w). It has been used as Chinese medicine prescription for thousands of years. DCXF is used traditionally to treat many diseases, including migraine, atherosclerosis and ischemic stroke. Aim of the studyThis study aimed to investigate the effects of DCXF on pain response in migraine mice, and the underlying mechanisms using proteomics and bioinformatics analyses. Materials and methodsDCXF extract was prepared by mixing Chuanxiong Rhizoma and Gastrodiae Rhizoma at a mass ratio of 4:1 (w/w). After extraction, the extract was filtered prior to high performance liquid chromatography (HPLC) analysis. Nitroglycerin (NTG) was used to establish a mouse migraine model, and a behaviour study was conducted by hot plate test. In addition, proteomics and bioinformatics studies were conducted to investigate the mechanisms of DCXF-mediating anti-migraine treatment. ResultsOur results showed that there were significant differences in the latencies between NTG-treated and DCXF low dose- and high doses-treated groups at 30 min after NTG injection, this suggested that DCXF could ameliorate pain response in migraine mice. Besides, the plasma levels of endothelin-1 were also measured. NTG group significantly enhanced the endothelin-1 level compared to the control group. In contrast, DCXF low dose and high dose groups significantly reduced this level compared to NTG group. In addition, the underlying mechanisms were also investigated. Our results demonstrated that the anti-migraine treatment of DCXF was highly associated with fatty acid synthesis, suggesting that DCXF ameliorated pain response through reducing endothelin-1 level and regulating fatty acid synthesis. ConclusionsThe present study revealed the anti-migraine effect of DCXF in migraine mice and provided insights into the mechanisms of DCXF-mediating anti-migraine treatment.

Risk of peripheral artery disease and stroke in migraineurs with or without aura: a nationwide population-based cohort study.

Background: Migraine is deemed a neurovascular disorder and there is growing evidence on the increased risk of cardiovascular disease, especially ischemic stroke, in patients with migraine. However the risk of peripheral artery disease (PAD) and stroke in migraineurs and the association between migraineurs with or without aura is still under debate. Our study aimed to identify the risk of PAD and stroke in migraineurs with or without aura.Methods: This was a population-based cohort study utilizing Taiwan Longitudinal Health Insurance Database (LHID2010). Patients with coding of migraine from 2002 to 2011 were enrolled and those with established cardiovascular disease defined as myocardial infarction, stroke, PAD, venous thromboembolism, atrial fibrillation and heart failure diagnosis before the index date were excluded. Participants were categorized into migraine group, migraine without aura group, and migraine with aura group respectively. The subjects in the three groups were propensity score-matched randomly to their counterparts without migraine. The study outcome was PAD and stroke. The Cox proportional hazard model was used to estimate the hazard ratios with 95% confidence interval (CI) for the association between migraine and the incident events of disease, after controlling for related variables.Results: The migraine, migraine without aura, and migraine with aura group included 5,173 patients, 942 patients and 479 patients respectively after propensity score-matching. The migraine group had an increased risk of PAD [adjusted hazard ratio (aHR): 1.93; 95% confidence interval (CI): 1.45-2.57; p < 0.001] and stroke (aHR: 1.55; 95% CI: 1.35-1.77; p < 0.001) compared to their non-migraine controls. Both the groups of migraine without aura and with aura had an increased risk of stroke (aHR: 1.49, 95% CI: 1.11-2.00; p = 0.008; aHR: 1.63, 95% CI: 1.10-2.43; p = 0.016). With regards to the outcome of PAD, the group of migraine with aura had a trend of an increased risk but did not reach statistical significance (aHR: 1.95, 95% CI: 0.86-4.40; p = 0.108).Conclusion: Migraineurs without established cardiovascular disease had a significantly increased risk of PAD and stroke, and the risk of stroke persists in migraineurs with or without aura, with an increased trend of PAD in migraineurs with aura. Our study result should remind clinical physicians of the risk of PAD in the future among migraineurs even without established cardiovascular disease currently, and screening for PAD and stroke may be needed in caring patients with migraine.

КЛІНІЧНИЙ ВИПАДОК МОЖЛИВОЇ МІГРЕНІ З АУРОЮ, УСКЛАДНЕНОЇ МІГРЕНОЗНИМ ІНФАРКТОМ

We present a clinical case of ischemic stroke in a man with a new-onset migraine attack. Clinical case. A 25-year-old man was admitted to the acute cerebrovascular department due to severe throbbing headache in the left temporal area, vomiting, impaired vision on the right and numbness of the right leg. Complaints appeared abruptly in the form of scotoma in the right visual field. 20 minutes later, severe throbbing headache, nausea and numbness of the right leg developed. The event was preceded by sleep deprivation for 2 days. The patient’s mother has migraine with aura. Previously, the patient never had such attacks. On examination: right-sided homonymous upper-quadrant hemianopsia, hypoesthesia of the right leg. Brain MRI - focal hyperintensity at T2 and DWI in the left occipital region (acute ischemic stroke). The patient took aspirin at a dose of 300 mg for the first day, then 100 mg per day and valproic acid at a dose of 1200 mg per day. Two days after hospitalization, the patient experienced recovery of sensitivity in the right leg and regression of right-sided homonymous upper quadrant hemianopsia to small scotoma. The patient was discharged on the 5th day with a small right scotoma. It is recommended to continue taking aspirin 100 mg/day and valproic acid 1200 mg/day for the secondary prevention of migraine attacks and stroke. Discussion. The peculiarities of this case include the lack of history of migraine (at least 5 or more migrainous headache attacks) and the development of severe migraine attack with prolonged aura symptoms, which was triggered by sleep deprivation and eventually evolved into ischemic stroke. Conclusions. It is necessary to consider the possibility of ischemic stroke even in the cases of a new-onset migraine attack. If migrainous aura duration exceeds 60 minutes, it is necessary to perform a brain MRI to detect the early signs of cerebral ischemia.

Migraine and Ischemic Stroke: A Mendelian Randomization Study.

Introduction Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)].MethodsWe used data on genetic variants associated with migraine identified from a genome-wide association study (GWAS) meta-analysis among 889,018 European ancestries. Summary data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium including up to 438,847 participants. We performed two-sample Mendelian randomization (MR) analyses using the inverse-variance-weighted method as the primary approach. The MR-Egger, weighted median, simple median, simple mode, and weighted mode methods were also conducted as sensitivity analyses to determine the robustness of our results.ResultsWe failed to detect statistically significant associations between migraine and ischemic stroke (OR, 0.935; 95% CI 0.851–1.027; P = 0.159) and its subtypes (LAS: OR, 0.818; 95% CI 0.692–0.967; P = 0.018) (SVS: OR, 0.935; 95% CI 0.781–1.119; P = 0.460) (CES: OR, 1.015; 95% CI 0.867–1.189; P = 0.850). The results were consistent with the sensitivity analyses.ConclusionsBy conducting a series of causal inference approaches, this study supports no causal effect of migraine on ischemic stroke and its subtypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00310-y.