Migraine With Aura Patients Research Articles

Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

Cortical excitability in patients with migraine with aura and depressive symptoms: a visual evoked potentials study

Background: Migraine is a brain disorder characterized by recurring headache attacks, and emotional comorbidities, such as anxiety and depression, may influence the repetition of these attacks. The lack of sensory habituation is a common neurophysiological abnormality in migraine, and research suggests that it is under the influence of serotonin and other monoamines that are also involved in mood disorders. This study aimed to investigate the influence of emotional symptoms on cortical information processing in patients with migraine with aura by correlating cortical activity with self-perceived emotional distress. Methods: Visual evoked potentials from monocular stimulation were recorded in 16 patients with migraine with aura (MA) and 22 healthy volunteers (HV). The visual stimulus consisted of a full-screen black-and-white checkerboard pattern with a reversal rate of 1.55 Hz. 600 consecutive traces were collected and divided into six sequential blocks of 100 sweeps. Before the recording session, both MA patients and HV completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). Pearson's correlation test was used to find correlations between electrophysiological and psychometric variables in HV and MA patients. Results: Compared to HV, MA patients showed a significant difference in the degree of habituation to repeated visual stimulation between the two groups, resulting in a habitation deficit. Psychometric test results showed that trait STAI and BDI values were significantly higher in MA patients. In the MA group, BDI correlated negatively with the amplitude of the first block and positively with the degree of habituation. Conclusions: These results highlight a link between the level of brain responsiveness and depressive symptoms in patients with MA. Further research is required to confirm whether the same correlations exist in patients with other headache disorders.

Machine learning approach for Migraine Aura Complexity Score prediction based on magnetic resonance imaging data

BackgroundPrevious studies have developed the Migraine Aura Complexity Score (MACS) system. MACS shows great potential in studying the complexity of migraine with aura (MwA) pathophysiology especially when implemented in neuroimaging studies. The use of sophisticated machine learning (ML) algorithms, together with deep profiling of MwA, could bring new knowledge in this field. We aimed to test several ML algorithms to study the potential of structural cortical features for predicting the MACS and therefore gain a better insight into MwA pathophysiology.MethodsThe data set used in this research consists of 340 MRI features collected from 40 MwA patients. Average MACS score was obtained for each subject. Feature selection for ML models was performed using several approaches, including a correlation test and a wrapper feature selection methodology. Regression was performed with the Support Vector Machine (SVM), Linear Regression, and Radial Basis Function network.ResultsSVM achieved a 0.89 coefficient of determination score with a wrapper feature selection. The results suggest a set of cortical features, located mostly in the parietal and temporal lobes, that show changes in MwA patients depending on aura complexity.ConclusionsThe SVM algorithm demonstrated the best potential in average MACS prediction when using a wrapper feature selection methodology. The proposed method achieved promising results in determining MwA complexity, which can provide a basis for future MwA studies and the development of MwA diagnosis and treatment.

The prevalence of positive right to left shunt in migraine patients with and without aura: A new single-center study in China

BackgroundRecently, many studies have reported that there may be association between positive right-to-left shunt (RLS) and migraine, especially Migraine with aura (MA) patients. However, these researches are mostly limited in Western country. And the latest study describing the prevalence of RLS in Chinese patients with migraine was conducted five years ago. It indicated the significant higher rate of positive RLS in MA patients than migraine without aura(MWOA) group. However, no consistent results were observed according to our daily work. ObjectiveTo investigate the prevalence and grade of RLS in migraine patients with and without aura and to evaluate the potential association between positive RLS and migraine with aura. MethodsA total of 91 migraine patients were involved, including 57 MWOA patients and 34 MA patients. MWOA and MA were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3). Contrast transcranial Doppler ultra-sound (cTCD) was used to assess the prevalence of positive RLS, the associations between RLS and presence of aura. ResultsThe overall prevalence of RLS in migraine patients was 35.2%.In MA group, 44.1% (15/34) were positive for RLS overall, higher than MWOA group (29.8%,17/57). However, the differences were not significant (P = 0.167). And there were no marked differences in the prevalence of large, middle and small shunt between MA and MWOA patients. ConclusionOur study suggested MA patients have the slightly higher prevalence of positive RLS than MWOA patients in China. However, there were no significant differences, which was different from the previous studies. Our findings suggested the negative association between the positive RLS and migraine with aura.

Cortical spreading depolarization-induced constriction of penetrating arteries can cause watershed ischemia: A potential mechanism for white matter lesions

Periventricular white matter lesions (WMLs) are common MRI findings in migraine with aura (MA). Although hemodynamic disadvantages of vascular supply to this region create vulnerability, the pathophysiological mechanisms causing WMLs are unclear. We hypothesize that prolonged oligemia, a consequence of cortical spreading depolarization (CSD) underlying migraine aura, may lead to ischemia/hypoxia at hemodynamically vulnerable watershed zones fed by long penetrating arteries (PAs). For this, we subjected mice to KCl-triggered single or multiple CSDs. We found that post-CSD oligemia was significantly deeper at medial compared to lateral cortical areas, which induced ischemic/hypoxic changes at watershed areas between the MCA/ACA, PCA/anterior choroidal and at the tip of superficial and deep PAs, as detected by histological and MRI examination of brains 2–4 weeks after CSD. BALB-C mice, in which MCA occlusion causes large infarcts due to deficient collaterals, exhibited more profound CSD-induced oligemia and were more vulnerable compared to Swiss mice such that a single CSD was sufficient to induce ischemic lesions at the tip of PAs. In conclusion, CSD-induced prolonged oligemia has potential to cause ischemic/hypoxic injury at hemodynamically vulnerable brain areas, which may be one of the mechanisms underlying WMLs located at the tip of medullary arteries seen in MA patients.

Migraine with aura detection and subtype classification using machine learning algorithms and morphometric magnetic resonance imaging data.

Migraine with aura (MwA) is a neurological condition manifested in moderate to severe headaches associated with transient visual and somatosensory symptoms, as well as higher cortical dysfunctions. Considering that about 5% of the world's population suffers from this condition and manifestation could be abundant and characterized by various symptoms, it is of great importance to focus on finding new and advanced techniques for the detection of different phenotypes, which in turn, can allow better diagnosis, classification, and biomarker validation, resulting in tailored treatments of MwA patients. This research aimed to test different machine learning techniques to distinguish healthy people from those suffering from MwA, as well as people with simple MwA and those experiencing complex MwA. Magnetic resonance imaging (MRI) post-processed data (cortical thickness, cortical surface area, cortical volume, cortical mean Gaussian curvature, and cortical folding index) was collected from 78 subjects [46 MwA patients (22 simple MwA and 24 complex MwA) and 32 healthy controls] with 340 different features used for the algorithm training. The results show that an algorithm based on post-processed MRI data yields a high classification accuracy (97%) of MwA patients and precise distinction between simple MwA and complex MwA with an accuracy of 98%. Additionally, the sets of features relevant to the classification were identified. The feature importance ranking indicates the thickness of the left temporal pole, right lingual gyrus, and left pars opercularis as the most prominent markers for MwA classification, while the thickness of left pericalcarine gyrus and left pars opercularis are proposed as the two most important features for the simple and complex MwA classification. This method shows significant potential in the validation of MwA diagnosis and subtype classification, which can tackle and challenge the current treatments of MwA.

Microvascular involvement in migraine: an optical coherence tomography angiography study.

The aim of this study was to evaluate the microvasculature of the macula and the optic nerve in patients affected by migraine with aura (MA) and without aura (MO) by optical coherence tomography angiography (OCTA), comparing the findings with healthy controls (HC). We collected data from ocular and orthotic examinations, including eye motility, intraocular pressure measurement, best-corrected visual acuity (BCVA) measurement, objective refraction measurement, fundus examination, macular and optic disk OCTA examination. All subjects were imaged with solix fullrange OCT. The following OCTA parameters were recorded: macular vessel density (VD), inside disc VD, peripapillary VD, disc whole image VD, fovea choriocapillaris VD, fovea VD, parafovea VD, peripapillary thickness, fovea thickness, parafovea thickness, macular full retinal thickness, and foveal avascular zone (FAZ) parameters. Clinical and demographical data about migraine patients were collected by a neurologist. We included 56 eyes from 28 patients with a diagnosis of MO, 32 eyes from 16 patients with a diagnosis of MA, and 32 eyes from 16 HC subjects. The FAZ area was 0.230 ± 0.099 mm2 in the MO group, 0.248 ± 0.091 mm2 in the MA group and 0.184 ± 0.061 mm2 in the control group. The FAZ area was significantly larger in the MA group than in the HC group (p = 0.007). The foveal choriocapillaris VD was significantly lower in MA patients (63.6 ± 2.49%) when compared with MO patients (65.27 ± 3.29%) (p = 0.02). An impairment of retinal microcirculation can be detected in patients with MA, as demonstrated by the enlargement of FAZ. Moreover, the study of choroid circulation may reveal microvascular damage in patients with migraine with aura. OCTA is a useful non-invasive screening tool for the detection of microcirculatory disturbance in patients with migraine.

Relationship between Migraine and Patent Foramen Ovale Observed by Contrast-enhanced Transthoracic Echocardiography.

To observe the association between migraine and patent foramen ovale (PFO) using contrast-enhanced transthoracic echocardiography (cTTE). Eighty-five migraine with aura (MA) patients and 85 migraine without aura (MO) patients from January 2020 to February 2022 were divided into group A and group B, respectively. Sixty-five healthy people were included in normal control group. Difference of PFO positive rate among group A, group B, and normal control group was significant (p=0.002). Difference of PFO related right-to-left shunt (PFO-RLS), Grade 2 shunt, and Grade 3 shunt among group A, group B, and normal control group was significant (p=0.043 and p=0.013 respectively). PFO-RLS Grade 2 and 3 shunts may play an important role in MA patients and MO patients, and the size of PFO-RLS shunt may be associated with migraine. Key Words: Migraine, Patent foramen ovale (PFO), Right-to-left shunt (RLS), Contrast-enhanced transthoracic echocardiography (cTTE).

Meta-analytical evidence of functional and structural abnormalities associated with pain processing in migraine patients: An activation likelihood estimation.

Migraine is a primary headache disorder that causes debilitating throbbing pain. Several functional MRI (fMRI) and voxel-based morphometry (VBM) studies have been used to investigate the structural and functional alteration in migraine. Here, we aim to study the converged brain regions of functional and structural abnormalities in gray matter volume (GMV) associated with pain processing and management in migraineurs and healthy controls (HC). A systematic search through PubMed and Sleuth was carried out for peer-reviewed functional and structural neuroimaging studies on migraine patients and HC yielded a total of 1136 studies. We performed an activation likelihood estimation (ALE) meta-analysis on VBM and pain stimulation task-based fMRI studies to investigate the converged areas of GMV and functional abnormalities between migraineurs and HC. We performed two subgroup analyses between migraine with aura (MwA) and migraine without aura (MwoA) relative to HC, and between chronic migraine (CM) and episodic migraine (EM) compared to HC. The total sample included 16 fMRI and 22 VBM studies, consisting of 1295 migraine patients, compared to 995 HC. In fMRI analysis, ALE maps for pain stimulation tasks revealed hyperactivation in migraineurs in the substantia nigra compared to HC, whereas hypoactivation was seen in the cerebellum. For the VBM analysis, ALE clusters of increased GMV in migraineurs were observed in the parahippocampus and putamen nucleus. Whereas clusters of reduced GMV in migraineurs were seen in the frontal gyri. Compared to HC, MwoA patients showed a GMV reduction in the insula, and anterior cingulate, whereas MwA patients showed GMV reduction in the cerebellum, cingulate gyrus, and insula. CM patients showed decreased GMV in the precentral gyrus, whereas EM patients showed decreased GMV in the parahippocampus, and inferior frontal gyrus when compared to HC. Our findings represent a potential biomarker for the diagnosis and management of migraine, by showing clustered brain regions of abnormal patterns of activation and GMV changes between migraineurs and HC which might be associated with hyposensitivity to pain in migraineurs. Further studies are required to determine disease progression or therapeutic interventions' effect on migraine.

Cerebral blood flow alterations in migraine patients with and without aura: An arterial spin labeling study

BackgroundMigraine 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).MethodsWe 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).ResultsIn 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.ConclusionIn 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.

Insular functional connectivity in migraine with aura

IntroductionInsula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.MethodsTwenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.ResultsSeed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.DiscussionThe anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.ConclusionThe anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.Trial registrationNCT02708797.

Computed tomographic perfusion abnormalities in acute migraine with aura: Characteristics and comparison with transient ischemic attack.

Migraine with aura (MA) accounts for up to 10% of "stroke mimics" and can present cerebral perfusion abnormalities. We aimed to compare perfusion-CT (PCT) findings in acute-onset MA mimicking an ischemic stroke with those observed in transient ischemic attack (TIA). We retrospectively studied patients admitted to our hospital between 2002 and 2014 with suspicion of acute ischemic stroke, having PCT and receiving a final diagnosis of MA. We visually assessed PCT for the presence and extent of focal hypoperfusion (FHP). MA patients with FHP were compared with consecutive TIA patients showing FHP. We performed both qualitative and quantitative analysis of PCT. Of 47 patients with MA (median age = 33 years, 55% females), 16 (34%) displayed FHP. Compared to MA patients without FHP, MA patients with FHP had similar headaches and aura features, but a less frequent history of MA (p = 0.010). Compared to 74 TIA patients with FHP (median age = 69 years, 43% females), MA patients with FHP showed hypoperfusion that more frequently involved adjacent vascular territories or a whole hemisphere (p < 0.001). In addition, hypoperfusion in MA patients had a less pronounced increase in rMTT (1.2 vs 1.8, p < 0.001) and rTTP (1.1 vs 1.2, p < 0.001), and a lesser decrease in rCBF (0.8 vs 0.6, p < 0.001) compared to hypoperfusion in TIA. rMTT displayed the best discriminative ability to differentiate MA from TIA. Focal perfusion abnormalities in acute MA often involve adjacent vascular territories and hypoperfusion is less pronounced than in TIA. MA can be best differentiated from TIA by a smaller rMTT increase.

Cerebral Hemodynamics, Right-to-Left Shunt and White Matter Hyperintensities in Patients with Migraine with Aura, Young Stroke Patients and Controls.

Background: Migraine with aura (MA) patients present an increased risk of cerebrovascular events. However, whether these patients present an increased white matter hyperintensities (WMHs) load compared to the general population is still under debate. Our study aimed to evaluate the relationship between cerebral hemodynamics, right-to-left shunt (RLS) and WMHs in MA patients, young patients with cryptogenic stroke or motor transient ischemic attack (TIA) and controls. Methods: We enrolled 30 MA patients, 20 young (<60 years) patients with cryptogenic stroke/motor TIA, and 10 controls. All the subjects underwent a transcranial Doppler bubble test to detect RLS and cerebral hemodynamics assessed by the breath holding index (BHI) for the middle (MCA) and posterior (PCA) cerebral arteries. Vascular risk factors were collected. The WMHs load on FLAIR MRI sequences was quantitatively assessed. Results: The stroke/TIA patients presented a higher prevalence of RLS (100%) compared with the other groups (p < 0.001). The MA patients presented a higher BHI compared with the other groups in the PCA (p = 0.010) and higher RLS prevalence (60%) than controls (30%) (p < 0.001). The WMHs load did not differ across groups. BHI and RLS were not correlated to the WMHs load in the groups. Conclusions: A preserved or more reactive cerebral hemodynamics and the presence of a RLS are likely not involved in the genesis of WMHs in MA patients. A higher BHI may counteract the risk related to their higher prevalence of RLS. These results need to be confirmed by further studies to be able to effectively identify the protective role of cerebral hemodynamics in the increased RLS frequency in MA patients.

Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients: a study of resting-state functional networks

IntroductionSeveral functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks.MethodsBefore and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features.ResultsBefore visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura.ConclusionsIn individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.

Abstract TP176: Arrhythmia And Stroke Risk Among Migraineurs With Aura As Predicted By CHA 2 Ds 2 -VASc Scoring Tool

Introduction: Migraine with aura (MWA) is associated with increased risk of atrial fibrillation (AF) and stroke. A recent study found that among young adults with MWA, AF was the second most common cause of ischemic stroke behind high-risk patent foramen ovale. The CHA 2 DS 2 -VASc score predicts 1 year risk of thromboembolic events, and may further characterize stroke risk in this population. Objectives: We hypothesize that arrhythmias are more common in patients with MWA than migraine without aura (MWoA); and that among migraine patients with arrhythmia, MWA leads to higher ischemic stroke risk, as predicted by CHA 2 DS 2 -VASc. Methods: The American Registry for Migraine Research (ARMR) database consists of patient questionnaires and headache diagnoses from 9 headache centers. Data on history of arrhythmia can be used as a marker for AF and other arrhythmias with stroke risk. Patients in ARMR ages 18-86 with ICHD-3 diagnosis of migraine were divided into MWA or MWoA based on survey responses, and evaluated for history of arrhythmia. Predicted stroke risk in migraineurs with arrhythmia was then characterized by CHA 2 DS 2 -VASc score calculation. Results: 2406 patients were included in the analysis (21.8% MWA, 78.1% MWoA). Patient groups had comparable age and gender composition. Arrhythmias were more common in MWA patients (N=30, 5.7%) than MWoA (N=11, 0.58%) after adjusting for age, gender, substance abuse and cardiac risk factors (p&lt;0.05). Among patients with arrhythmia, there was no significant difference between median CHA 2 DS 2 -VASc score in MWA (1, IQR1-2) and MWoA (2, IQR 1-3) groups (p=0.32), nor among individual CHA 2 DS 2 -VASc scores (p=0.449). This persisted when score was dichotomized with a cutoff of 2. Conclusions: Arrhythmia is more prevalent in patients with MWA than MWoA. However, higher risk of stroke in arrhythmic patients with aura is not predicted by CHA 2 DS 2 -VASc. This suggests that increased stroke risk in these patients may be independent of other stroke risk factors, and perhaps linked to the arrhythmias themselves. Our findings support the need for further large-scale studies to evaluate arrhythmia in MWA patients, and bring into question whether routine screening for arrhythmia is of benefit for stroke prevention in select migraine patients.

Functional connectivity changes in complex migraine aura: beyond the visual network.

Background and purposeAlthough the majority of migraine with aura (MwA) patients experience simple visual aura, a discrete percentage also report somatosensory, dysphasic or motor symptoms (the so‐called complex auras). The wide aura clinical spectrum led to an investigation of whether the heterogeneity of the aura phenomenon could be produced by different neural correlates, suggesting an increased visual cortical excitability in complex MwA. The aim was to explore whether complex MwA patients are characterized by more pronounced connectivity changes of the visual network and whether functional abnormalities may extend beyond the visual network encompassing also the sensorimotor network in complex MwA patients compared to simple visual MwA patients.MethodsBy using a resting‐state functional magnetic resonance imaging approach, the resting‐state functional connectivity (RS‐Fc) of both visual and sensorimotor networks in 20 complex MwA patients was compared with 20 simple visual MwA patients and 20 migraine without aura patients.ResultsComplex MwA patients showed a significantly higher RS‐Fc of the left lingual gyrus, within the visual network, and of the right anterior insula, within the sensorimotor network, compared to both simple visual MwA and migraine without aura patients (p < 0.001). The abnormal right anterior insula RS‐Fc was able to discriminate complex MwA patients from simple aura MwA patients as demonstrated by logistic regression analysis (area under the curve 0.83).ConclusionOur findings suggest that higher extrastriate RS‐Fc might promote cortical spreading depression onset representing the neural correlate of simple visual aura that can propagate to sensorimotor regions if an increased insula RS‐Fc coexists, leading to complex aura phenotypes.

Shorter visual aura characterizes young and middle-aged stroke patients with migraine with aura.

To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA-) MwA and aura features in MwA patients with (S+MwA+) or without (S-MwA+) stroke. In this retrospective multicenter case-control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA- patients younger than 60years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S-MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). 539 stroke (7.7% S+MwA+) and 94 S-MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12-11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15-6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26-14.18)] than S+MwA- subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S-MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36-10.66)] and shorter-lasting (20.0min IQr 13.1 vs 30.0min IQr 25.0; p < 0.001) aura, and PFO [OR 1.26 (95% CI 1.03-1.54)]. Regression analysis evidenced that only shorter aura duration associated with stroke (p = 0.001). High-risk PFO was equally represented in S+MwA-, S+MwA+, S-MwA+ groups. Shorter visual aura and CIS characterize MwA patients with stroke. Although more prevalent, PFO can not be considered the main responsible for the increased stroke risk in MwA patients but as a part of a complex multifactorial condition.

Increased Cortical Excitability in Female Migraineurs: A Transcranial Magnetic Stimulation Study Conducted in the Preovulatory Phase.

Background and PurposeThe cerebral cortex has been the focus of investigations of the pathogenesis of migraine for a long time. Transcranial magnetic stimulation (TMS) is a safe and effective technique for evaluating cortex excitability. Previous studies of the duration of the cortical silent period (CSP)—a measure of intracortical inhibition—in migraine patients have yielded conflicting results. We aimed to characterize cortical excitability by applying TMS to female migraineurs during the preovulatory phase of the menstrual cycle, in order to eliminate the effects of variations in sex hormones.MethodsWe enrolled 70 female subjects: 20 migraine with aura (MA) patients, 20 migraine without aura (MO) patients, and 30 healthy controls. We measured the CSP, resting motor threshold (rMT), and motor evoked potential (MEP) induced by TMS to evaluate cortical excitability during the preovulatory phase of the menstrual cycle.ResultsThe CSP was shorter in MA patients (88.93±3.82 ms, mean±SEM) and MO patients (86.98±2.72 ms) than in the control group (109.06±2.85 ms) (both p=0.001), and did not differ significantly between the MA and MO groups (p=0.925). The rMT did not differ significantly among the groups (p=0.088). MEPmax was higher in MA patients than in healthy controls (p=0.014), while that in MO patients did not differ from those in MA patients and healthy controls (p=0.079 and p=0.068).ConclusionsWe detected a shorter CSP in both MA and MO patients. This finding may indicate the presence of motor cortex hyperexcitability, which is probably due to reduced GABAergic neuronal inhibition in migraine.

Extra-Axial Inflammatory Signal in Parameninges in Migraine with Visual Aura.

Cortical spreading depression (CSD) underlies the neurobiology of migraine with aura (MWA). Animal studies reveal networks of microvessels linking brain-meninges-bone marrow. CSD activates the trigeminovascular system, evoking a meningeal inflammatory response. Accordingly, this study examines the upregulation of an inflammatory marker in extra-axial tissues in migraine with visual aura. We used simultaneously acquired 11 C-PBR28 positron emission tomography/magnetic resonance imaging data of 18kDa translocator protein (an inflammatory marker) in MWA patients (n = 11) who experienced headaches and visual aura in the preceding month. We measured mean tracer uptake (standardized uptake value ratio [SUVR]) in 4 regions of interest comprising the meninges plus the adjacent overlying skull bone (parameningeal tissues [PMT]). These data were compared to healthy controls and patients with pain (chronic low back pain). MWA had significantly higher mean SUVR in PMT overlying occipital cortex than both other groups, although not in the PMT overlying 3 other cortical areas. A positive correlation was also found between the number of visual auras and tracer uptake in occipital PMT. A strong persistent extra-axial inflammatory signal was found in meninges and calvarial bone overlying the occipital lobe in migraine with visual auras. Our findings are reminiscent of CSD-induced meningeal inflammation and provide the first imaging evidence implicating inflammation in the pathophysiology of migraine meningeal symptoms. We suspect that this inflammatory focus results from a signal that migrates from underlying brain and if so, may implicate newly discovered bridging vessels that crosstalk between brain and skull marrow, a finding of potential relevance to migraine and other neuroinflammatory brain disorders. ANN NEUROL 2020;87:939-949.

Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine.

Background Migraine is a polygenetic disease, considered as a channelopathy. The dysregulation of ion functioning due to genetic changes may activate the trigeminovascular system and induce migraine attack both migraine with aura (MA) and without aura (MO).Objectives The aim of the study was to analyze the following variants of genes encoding ion channels and associated protein: c.3199G>A SCN1A, c.56G>A SCN2A, c.28A>G and c.328T>C KCNK18, c.3053A>G TRPA1, c.31-1811C>T STX1A in migraine patients.Patients and Methods The study included 170 migraine patients and 173 controls. HRMA and Sanger sequencing were used for genotyping. Meta-analysis was performed for c.28A>G, c.328T>C KCNK18, and c.31-1811C>T STX1A.Results AA genotype of c.56G>A SCN2A was found only in migraine patients. Patients with c.328T>C KCNK18 mutation had an increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of KCNK18 had higher attack frequency than those with AA/TT (p<0.05). T allele of c.31-1811C>T STX1A was more frequent in MA patients than MO (p<0.05). The c.3053A>G TRPA1 polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T STX1A and c.3199G>A SCN1A before the age of 10 (p<0.01). Meta-analysis showed a significant association of c.31-1811C>T STX1A polymorphism with migraine overall (OR=1.22, p=0.0086), MA, and MO. No association was found for c.28A>G KCNK18, c.328T>C KCNK18, and migraine overall.ConclusionChanges in genes encoding ion channels or proteins regulating their functioning may increase the risk of migraines and correlate with clinical features of disease, e.g. age of onset and attack frequency.