Brain imaging in migraine with and without aura: Similarities and differences.

Migraine with aura (MwA) is associated with increased brain hyper-responsiveness to visual stimuli and increased visual network connectivity relative to migraine without aura (MwoA). Despite this, prior studies have provided conflicting results regarding whether MwA is associated with higher photophobia symptom scores compared to MwoA. The relationships between MwA and other types of sensory hypersensitivity, such as phonophobia and cutaneous allodynia (CA), have not been previously investigated. The purpose of this cross-sectional observational study was to investigate whether MwA is associated with greater symptoms of photophobia, phonophobia, and CA compared to MwoA. This analysis included 321 migraine patients (146 MwA; 175 MwoA) who had been enrolled into the American Registry for Migraine Research. The diagnosis of either MwoA or MwA was determined by headache specialists using ICHD diagnostic criteria. Patients completed the Photosensitivity Assessment Questionnaire, the Hyperacusis Questionnaire, and the Allodynia Symptom Checklist. Mean or median values were compared between groups. Regression models were created to analyze the relationship between MwA with photophobia scores, hyperacusis scores, and the presence of interictal CA. Those with MwA had higher mean photophobia scores than those with MwoA (4.1 vs 3.0, P=.0003). MwA was positively associated with photophobia symptom severity (B=0.50 [SE=0.14], P=.0003), after controlling for age, patient sex, and headache frequency. Aura was not associated with hyperacusis symptom severity (B=0.07 [SE=0.08], P=.346) or the presence of interictal CA (OR 1.33 [95% CI 0.70-2.53], P=.381). MwA is associated with higher photophobia symptom scores compared to MwoA. Aura is not associated with greater hyperacusis or interictal allodynia scores. These findings complement prior imaging and neurophysiologic studies that demonstrated MwA to be associated with hyper-responsiveness of brain visual processing regions. The findings suggest that MwA is associated specifically with visual hypersensitivity, as opposed to being associated with a general hypersensitivity to multiple types of sensory stimuli.

Dear Sirs, Fahr’s disease is a sporadic or familial rare syndrome characterized by calcification of the basal ganglia, dentate nucleus of the cerebellum, thalamus and centrum semiovale. The most common clinical presentations include movement disorders, cognitive impairment, ataxia, speech abnormalities and psychiatric symptoms. Diagnosis is established by brain computed tomography (CT) or magnetic resonance imaging (MRI). Even if calcium deposits can result in heterogeneous signal intensities, most frequently appear as hyperdense on CT, hypointense on T2weighted MR images and hyperintense on T1-weighted images. Laboratory tests allow exclusion of parathyroid dysfunction, thus confirming the diagnosis and ruling out other major differential diagnoses [3, 4, 7]. In this report, we used voxel based morphometry (VBM) and resting state (RS) functional MRI (fMRI) to define the structural and functional brain abnormalities in two patients with sporadic Fahr’s disease and migraine with aura (MWA). The two patients (patient 1: male, age = 43 years, Fahr’s disease duration from diagnosis = 5 years, MWA disease duration = 10 years; patient 2: female, age = 42 years, Fahr’s disease duration from diagnosis = 10 years, MWA disease duration = 1 year) had a diagnosis of Fahr’s disease based on a typical clinical and neuroimaging pattern (Fig. 1). In addition to MWA, they also suffered from neuropsychiatric symptoms (both of them had panic attacks and patient 1 also had major depression). Neurological examination and biochemical tests (serum calcium, phosphorus, parathyroid hormone and calcitonin) were normal. A neuropsychological assessment disclosed marked deficits in short-term visuospatial memory in both patients. Patient 1 had also mild deficits of attention and inhibitory control and poor verbal fluency; patient 2 showed mild deficits in short-term verbal memory and visuoconstructive ability. Structural (T2and 3D T1-weighted scans) and RS fMRI scans were obtained using a 3.0 Tesla scanner. Regional abnormalities of gray matter (GM) volumes were assessed using VBM, and RS functional connectivity (FC) modifications were estimated using an independent component analysis, as described elsewhere [1, 11]. Patients findings were compared to those of two control groups with a normal neurological examination, consisting of 15 patients with MWA (seven males; mean age = 39 years; mean disease duration = 8 years) and 15 healthy controls (nine males; mean age = 37 years). Compared to MWA patients and controls, Fahr’s disease patients showed atrophy of the left orbitofrontal gyrus (OFG). Compared to controls, they had also atrophy of the left hippocampus. At fMRI analysis, compared to MWA patients and controls, Fahr’s disease patients had decreased RS FC of the executive control and working memory networks. Increased RS FC in the salience, sensorimotor and visual networks was also found. Compared to controls, Fahr’s disease and MWA patients showed decreased RS FC of the left fusiform gyrus (Table 1; Fig. 1). R. Messina M. A. Rocca M. Filippi (&) Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy e-mail: m.filippi@hsr.it

The aim of this exploratory study was to investigate the underlying pathomechanisms of migraine with aura (MA) and migraine without aura (MO) in the interictal phase using a connectivity analysis. We prospectively enrolled patients who were newly diagnosed with migraine. All patients underwent brain MRI, including diffusion tensor imaging and arterial spin labeling perfusion MRI. We analyzed the differences between patients with MA and those with MO in structural connectivity based on diffusion tensor imaging and functional connectivity based on arterial spin labeling perfusion MRI using a graph theoretical analysis. We enrolled 58 patients with migraine (11 patients with MA and 47 patients with MO). There were no differences between patients with MA and those with MO in the network measures of global structural connectivity. However, differences in global functional connectivity were found between the two groups. The assortative coefficient was lower in patients with MA than in those with MO (-0.050 vs. -0.012, p=.017). There were no differences in local structural and functional connectivity between patients with MA and those with MO. We found differences in global functional connectivity between patients with MO and those with MA. The study of MA and MO using a connectivity analysis may shed light on migraine pathophysiology. We suggest it is worthwhile to investigate if changes in functional connectivity may serve as novel biomarkers in MA. In this regard, ASL MRI appears to be valuable in the context of network analysis, but further studies are needed to confirm our findings.

Lamotrigine is not recommended in the prevention of migraine in general but some reports suggest that it might be effective for treating specifically migraine with aura (MA). This review aims to summarize the related data from the literature and to better understand this discrepancy. All reports from the literature related to the use of lamotrigine in migraine with or without aura published prior to February 2019 found using PUBMED and the 2 keywords "migraine" AND "lamotrigine" were reviewed. Original studies, published in full, systematic reviews, and all case reports were synthetized. We also examined the risk profile, pharmacokinetics, and mode of action of lamotrigine in view of the presumed mechanism of MA. Lamotrigine was tested in different populations of migraineurs, but previous studies had small sample sizes (n<35) and might not have been powered enough for detecting a potential benefit of lamotrigine in MA. Accumulating data suggest that the drug can reduce both the frequency and severity of aura symptoms in multiple conditions and is well tolerated. Lamotrigine appears promising for treating attacks of MA and related clinical manifestations because of its high potential of efficacy, low-risk profile, and cost. Additional studies are needed for testing lamotrigine in patients with MA.

Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients. A comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software. 13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients. This meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS. https://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

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.

Cortical spreading depression (CSD) has been considered the prominent theory for migraine with aura (MwA). However, it is also argued that CSD can exist in patients in a silent state, and not manifest as aura. Thus, the MwA classification based on aura may be questionable. This study aimed to capture whole-brain connectome-based imaging markers with identifiable signatures for MwA and migraine without aura (MwoA). A total of 88 migraine patients (32 MwA) and 49 healthy controls (HC) underwent a diffusion tensor imaging and resting-state functional magnetic resonance imaging scan. The whole-brain structural connectivity (SC) and functional connectivity (FC) analysis was employed to extract imaging features. The extracted features were subjected to an all-relevant feature selection process within cross-validation loops to pinpoint attributes demonstrating substantial efficacy for patient categorization. Based on the identified features, the predictive ability of the random forest classifiers constructed with the 88 migraine patients' sample was tested using an independent sample of 32 migraine patients (eight MwA). Compared to MwoA and HC, MwA showed two reduced SC and six FC (five increased and one reduced) features [all P<0.01, after false discovery rate (FDR) correction], involving frontal areas, temporal areas, visual areas, amygdala, and thalamus. A total of four imaging features were significantly correlated with clinical rating scales in all patients (r=-0.38 to 0.47, P<0.01, after FDR correction). The predictive ability of the random forest classifiers achieved an accuracy of 78.1% in the external sample to identify MwA. The whole-brain connectivity features in our results may serve as connectome-based imaging markers for MwA identification. The alterations of SC and FC strength provide possible evidence in further understanding the heterogeneity and mechanism of MwA which may help for patient-specific decision-making.

Migraine with aura (MwA) is a common and severely disabling neurological disorder, characterised by transient yet recurrent visual disturbances, including scintillating scotomas, flickering photopsias, and complex geometric patterns. These episodic visual phenomena significantly compromise daily functioning, productivity, and overall quality of life. Despite extensive research, the underlying pathophysiological mechanisms remain only partially understood. Cortical spreading depression (CSD), a propagating wave of neuronal and glial depolarisation, has been identified as a central process in MwA. This phenomenon is triggered by ion channel dysfunction, leading to elevated intracellular calcium levels and excessive glutamate release, which contribute to widespread cortical hyperexcitability. Genetic studies, particularly involving the CACNA gene family, further implicate dysregulation of calcium channels in the pathogenesis of MwA. Recent advances in neuroimaging, particularly functional magnetic resonance imaging (fMRI), have provided critical insights into the neurophysiology of MwA. These results support the central role of CSD as a basic mechanism behind MwA and imply that cortical dysfunction endures beyond brief episodes, possibly due to chronic neuronal dysregulation or hyperexcitability. The visual cortex of MwA patients exhibits activation patterns in comparison to other neuroimaging studies, supporting the possibility that it is a disease-specific biomarker. Its distinctive sensory and cognitive characteristics are influenced by a complex interplay of cortical, vascular, and genetic factors, demonstrating the multifactorial nature of MwA. We now know much more about the pathophysiology of MwA thanks to the combination of molecular and genetic research with sophisticated neuroimaging techniques like arterial spin labelling (ASL) and fMRI. This review aims to synthesize current knowledge and analyse molecular and neurophysiological targets, providing a foundation for developing targeted therapies to modulate cortical excitability, restore neural network stability, and alleviate the burden of migraine with aura. The most important and impactful research in our field has been the focus of this review, which highlights important developments and their contributions to the knowledge and treatment of migraine with aura.

Basilar artery curvature is associated with migraine with aura in the Northern Manhattan Study

Introduction: Genetic and imaging studies demonstrate a link between vascular morphology and migraine with aura (MA). As aura typically originates from the occipital cortex, the vertebrobasilar system that supplies this area is of particular interest. We examined the relationship between basilar artery (BA) curvature and MA in a large, population-based cohort of stroke-free participants. Methods: We analyzed Northern Manhattan Study participants who had undergone time of flight MRA at 1.5 Tesla. Migraine, with or without aura, was ascertained through structured interviews. BA curvature was defined as the sum of the total horizontal deviation of the BA at the distal tip, mid-pons, and vertebrobasilar junction, and was used as the primary independent variable in unadjusted and adjusted logistic regression analyses. BA measurements were obtained blinded to migraine status. Results: Of 805 participants (mean age 70±9.3 years, 55% women, 66% Hispanic), migraine without aura was present in 13% (N=105) and MA in 3% (N=24). MA was more common among women (P=0.03) and Hispanics (P=0.001). Mean BA curvature was 16 ± 10 mm. In unadjusted analysis, BA curvature was greater in participants with MA than those without MA (19 vs 15 mm, P=0.02). In a model adjusted for demographics, vascular risk factors, head size and height, greater BA curvature was associated with MA (OR 1.06 per mm, 95% CI 1.01-1.11) compared to participants with no migraine. The association between BA curvature and migraine without aura did not reach significance (OR 1.01, 95% CI 0.99-1.04). Conclusions: Greater BA curvature was associated with migraine with aura but not migraine without aura. Understanding the physiopathology of this association may provide clues to the underlying mechanisms of migraine and the relationship between migraine and stroke.

Object: To verify the efficacy and safety of the new combination of Tanacetum parthenium 150 mg, 5-hydrossitriptophan (5-HTTP) 20 mg and magnesium 185 mg (Aurastop) in the prophylactic treatment of high frequency migraine with aura (MWA). According to the international headache classification (IHCD 3 beta version) the aura phenomena have a duration of 5 - 60 minutes for any of the usual disturbances (visual, somatosensory and speech disturbance) but no classification describes the frequency of this phenomena. Patients who experience migraine aura emphasize the emotional impact of such a phenomenon, mostly because of the severe, though transient, disability caused by the aura symptoms (i.e., inability to work or driving a vehicle). Furthermore, a profound asthenia lasts for about 48 hours after the resolution of the painful phase. Materials and Method: 18 patients (F: n = 10, M: n = 8, mean age: 28) presenting with an ICHD-3 beta diagnosis of migraine with aura (MWA) with a frequency of more than 5 attacks of migraine with aura per month since at least 6 months, were enrolled in the survey and treated with Aurastop? twice a day for a period of 3 months. Diary cards were filled in during a 3-month period before the beginning of the survey and during the 3-month duration of the study. The reduction of MWA attacks per month was assessed as the primary end-point; the reduction of the duration and disability of the aura and of the intensity of the headache were considered as secondary end-points. Results: A statistically significant reduction of MWA attacks/month was observed: more than 95% of the patients referred a reduction >50% of the frequency, 66.6% a reduction of more than 70%, and 16.6% a complete disappearance of the attacks after the first week of therapy. Moreover, a sensible reduction of the duration and disability of the aura phenomena was reported by more than 90% of the patients and, in the 55% of the patients also a reduction of the intensity of the headache. No side effects were reported. The efficacy started to appear during the first month of intake and was maintained during the three months of therapy.

BackgroundPrevious studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.MethodsWe utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970–375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.ResultsGenetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.ConclusionThis study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.

Conduct problems (CP) encompass a wide array of behavioral difficulties in youths, including aggression, defiance, and rule-breaking, resulting in interpersonal conflicts. CP comprises various psychiatric conditions, constituting a significant public health burden. This study performed a whole-brain coordinate-based meta-analysis (CBMA) that synthesized findings from diffusion tensor imaging (DTI), voxel-based morphometry (VBM), and surface-based morphometry (SBM) studies to investigate consistent structural brain abnormalities in children and adolescents with CP. A total of 35 studies were eventually included. Altered white matter integrity in the right lenticular nucleus and the right inferior longitudinal fasciculus (ILF) were observed. Gray matter volume (GMV) alterations included increased volume in the right superior frontal gyrus, as well as reduced volume in the right supramarginal gyrus and left amygdala. Cortical thickness reductions were detected in the left precentral gyrus and right superior frontal gyrus. These findings underscored the intricate neurobiological basis of CP, and the meta-regression analysis revealed age-related variations in structural brain alterations, further highlighting the need for early and personalized interventions. This comprehensive study advanced our understanding of the neural underpinnings of CP, and future research and interdisciplinary collaboration to translate our findings into meaningful interventions for individuals with CP should be further explored.

The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk. Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk. Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000). There is a relationship between lipid metabolism characteristics and migraine risk. Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

Background: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).Methods: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.Results: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.Conclusions: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.