Role of Nrf2 in Epilepsy Treatment.

Oxidative stress is a consequence of the disruption of the balance between the generation of reactive nitrogen and oxygen species and the biological system's ability to neutralize those reactive products. Oxidative stress is involved in the generation of many disorders, including epilepsy, which is a prevalent chronic neurological disease that affects the lives of millions of people around the world. Epilepsy is characterized by unforeseeable and repeated seizures that can be very disturbing. Studies have reported that oxidative stress occurs before and after seizures. A transcription factor named Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) controls genes related to the induction of oxidative stress and defends cells against oxidative stress. The Nrf2 protein has seven different domains, ranging from Neh1 to Neh7. Each domain is responsible for a distinctive function of this protein. Keap1 binds to Nrf2, but during oxidative stress, Nrf2 detaches from the Keap1 protein, moves to the nucleus, and binds to DNA. The result of this translocation and binding is the initiation of transcription of detoxifying genes to control the harmful effects of oxidative stress. There is some evidence of oxidative stress involvement in epilepsy. In this review, we have listed potential Nrf2-related therapeutic targets for treating and controlling epilepsy, such as Berberis alkaloids, pentoxifylline, lovastatin, progesterone, and chrysin nanoparticles. These activators were tested in animals (in vivo) and cells (in vitro), and most of these experiments showed promising results in different epilepsy models. Finally, the results have suggested that the activation of Nrf2 can be an option for controlling epilepsy.

Effects of passive smoking on cortical spreading depolarization in male and female mice.

BACKGROUND: Patients with migraine are typically advised to avoid passive smoking because it may aggravate headaches and other health conditions. However, there is insufficient high-quality evidence on the association between passive smoking and migraine, which warrants further investigation using animal models. Therefore, using a mouse model, we examined the effect of passive smoking on susceptibility to cortical spreading depolarization (CSD), the biological basis of migraine with aura. FINDINGS: Fifty C57BL/6 mice (25 males and 25 females) were exposed for one hour to cigarette smoke or room air. Subsequently, potassium chloride (KCl) was administered under isoflurane anesthesia to induce CSD, and the CSD threshold, frequency of induction, and propagation velocity were determined. The threshold to induce CSD (median [interquartile range (IQR)]) was significantly lower in female mice (adjusted p = 0.01) in the smoking group (0.05 [0.05, 0.088]) than in the sham group (0.125 [0.1, 0.15]); however, there was no significant difference in the male mice (adjusted p = 0.77). CSD frequency or propagation velocity did not differ significantly between the two groups for either sex. CONCLUSIONS: Female mice in the smoking group showed lower CSD threshold compared to the sham group, suggesting a potential sex-specific difference in the effect of smoking on the pathogenesis of CSD and migraine with aura. This finding may contribute to the understanding of migraine pathophysiology in association with passive smoking and sex difference.

No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study.

OBJECTIVE: To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex-specific factors. BACKGROUND: It has long been hypothesized that inflammation contributes to migraine pathophysiology. This study examined the association between migraine and alleles in the HLA system, a key player in immune response and genetic diversity. METHODS: We performed a case-control study and included 13,210 individuals with migraine and 86,738 controls. All participants were part of the Danish Blood Donor Study Genomic Cohort. Participants were genotyped and 111 HLA alleles on 15 HLA genes were imputed. We examined the association between HLA alleles and migraine subtypes, considering sex-specific differences. RESULTS: We found no association between HLA alleles and migraine, neither overall, nor in the sex-specific analysis. In the migraine subtype analysis, three HLA alleles were associated with migraine without aura; however, these associations could not be replicated in an independent Icelandic cohort (2191 individuals with migraine without aura and 278,858 controls). Furthermore, we found no association between HLA alleles and migraine with aura or chronic migraine. CONCLUSION: We found no evidence of an association between the HLA system and migraine, suggesting that genetic factors related to the HLA system do not play a significant role in migraine susceptibility.

Cerebral Artery Vasoconstriction After Galcanezumab Loading Dose for Migraine Prevention: A Case Report.

Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies that target CGRP ligands or receptors, may cause a very rare side effect of reversible cerebral vasoconstriction syndrome (RCVS). This study is a case report of a patient who developed cerebral artery vasoconstriction documented on serial brain magnetic resonance angiography (MRA) scans without the typical manifestations of RCVS following galcanezumab loading dose. Case report: A 40-year-old female patient with high-frequency episodic migraine with visual aura on topiramate 100 mg/day developed transient numbness of the right upper and lower extremities and right face without headache and a normal neurological examination 10 min after a loading dose of galcanezumab, which resolved over the next 2 days. Magnetic resonance angiography brain imaging showed segmental arterial constriction of both middle cerebral arteries in the M1-2 segments and both posterior cerebral arteries in the P1-2 segments, which partial resolved in a subsequent study by the end of 6 months. There were no other supporting examination data, such as transcranial Doppler, which might provide additional information on the progression and improvement of the vasoconstriction. Her differential diagnosis included prolonged migraine sensory aura without headache, RCVS, or cerebral vasoconstriction secondary to the effect of an anti-CGRP monoclonal antibody. Further research needs to be conducted.

We report a case with numbness on the right upper and lower extremities and right face without headache 10 min after the loading dose of galcanezumab. These stroke-like symptoms resolved within 2 days. Cerebral blood vessels showed narrowing and then dilatation with residual narrowing of two or more vessels. The differential diagnosis is prolonged migraine aura without headache, reversible cerebral vasoconstriction syndrome, or cerebral vasoconstriction due to the effects of galcanezumab.

Migraine With Aura Accompanied by Myoclonus: A Case Report.

Migraine is a condition characterized by pulsating headaches, often accompanied by photophobia, phonophobia, and/or gastrointestinal symptoms such as nausea and vomiting. Approximately 15% to one-third of migraine patients experience an aura either before or during the headache. To the best of our knowledge, the occurrence of migraine with myoclonus is extremely rare. This report describes a rare case of migraine with aura accompanied by myoclonus. The patient is a 46-year-old man who developed a visual aura followed by vomiting and a throbbing headache on the right side. As the headache intensified, involuntary movements of the left lower extremity appeared. Brain magnetic resonance imaging (MRI) revealed no structural abnormalities or stroke lesions; however, arterial spin labeling MRI showed hypoperfusion in the right cerebral hemisphere. An ophthalmological evaluation was unremarkable. He was diagnosed with migraine with myoclonus, and the intravenous administration of diazepam and sumatriptan resulted in the cessation of the myoclonus and mild relief of the headache. By the day after admission, the myoclonus and visual symptoms had completely disappeared. The headache resolved by the third day of admission.

Application Value of a Machine Learning Model in Predicting Mild Depression Associated with Migraine without Aura.

Aims/Background To investigate the application value of a machine learning model in predicting mild depression associated with migraine without aura (MwoA). Methods 178 patients with MwoA admitted to the Department of Neurology of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from March 2022 to March 2024 were selected as subjects. According to their inpatient medical records, 38 patients were selected as the validation group by random number method, and the remaining 140 patients were included in the modelling group. According to the diagnosis results, the patients in the modelling group and validation group were further divided into a MwoA with mild depression group and a MwoA without mild depression group. Results The results of univariate analysis and Multivariate logistic regression analysis showed that gender, course of disease, attack frequency, headache duration, Migraine Disability Assessment Questionnaire (MIDAS), and Headache Impact Test-6 (HIT-6) score were independent influencing factors for mild depression in MwoA patients (p < 0.05). The receiver operating characteristic (ROC) analysis results showed that the area under the curve of the established prediction model for MwoA patients with mild depression in the modelling group and the validation group was 0.982 and 0.901, respectively, the sensitivity was 0.978 and 0.857, respectively, and the specificity was 0.892 and 0.929, respectively. Conclusion Gender, course of disease, seizure frequency, headache duration, MIDAS score, and HIT-6 score are independent influencing factors for mild depression in patients with MwoA. The model displays good performance for the prediction of mild depression in patients with MwoA.

A Case of Acute Migraine Without Aura Treated With a New FDA-Approved Medication Ubrogepant.

Ubrogepant is the first medication that blocks calcitonin gene-related peptide (CGRP), a protein released during a migraine attack, from binding to its receptors. Ubrogepant has shown positive safety, efficacy, and tolerability results for the treatment of acute migraine in phase 3 randomized trials. At this time, there are very few case reports on ubrogepant. Herein, we describe a complex patient with treatment-resistant migraine who showed substantial improvement in migraine severity, duration, and overall disability after using ubrogepant. A 46-year-old woman with a 25-year history of migraine presented with an improvement in headache severity, duration, and disability after using a new FDA-approved medication, ubrogepant, for less than five months. Before commencing ubrogepant,her headache duration hours ranged from 36 to 60 hours, headache severity was rated 7.5/10, and mean headache days ranged from 10 to 12 days. After taking ubrogepant, her headache duration was less than 12 hours, headache severity was 3/10, and mean headache days was five. Previously, she had been prescribed a combination of first-line medications with little improvement in headache severity. Her Migraine Disability Assessment (MIDAS) score showed moderate disability resulting in missed work and lower quality of life. To date, there have been no case reports showing the efficacy of the new FDA-approved medication, ubrogepant, showing a greater than 50% decrease in headache duration.

Oxytocin shortens spreading depolarization-induced periorbital allodynia.

BACKGROUND: Migraine is among the most prevalent and burdensome neurological disorders in the United States based on disability-adjusted life years. Cortical spreading depolarization (SD) is the most likely electrophysiological cause of migraine aura and may be linked to trigeminal nociception. We previously demonstrated, using a minimally invasive optogenetic approach of SD induction (opto-SD), that opto-SD triggers acute periorbital mechanical allodynia that is reversed by 5HT1B/1D receptor agonists, supporting SD-induced activation of migraine-relevant trigeminal pain pathways in mice. Recent data highlight hypothalamic neural circuits in migraine, and SD may activate hypothalamic neurons. Furthermore, neuroanatomical, electrophysiological, and behavioral data suggest a homeostatic analgesic function of hypothalamic neuropeptide hormone, oxytocin. We, therefore, examined the role of hypothalamic paraventricular nucleus (PVN) and oxytocinergic (OXT) signaling in opto-SD-induced trigeminal pain behavior. METHODS: We induced a single opto-SD in adult male and female Thy1-ChR2-YFP transgenic mice and quantified fos immunolabeling in the PVN and supraoptic nucleus (SON) compared with sham controls. Oxytocin expression was also measured in fos-positive neurons in the PVN. Periorbital mechanical allodynia was tested after treatment with selective OXT receptor antagonist L-368,899 (5 to 25 mg/kg i.p.) or vehicle at 1, 2, and 4 h after opto-SD or sham stimulation using von Frey monofilaments. RESULTS: Opto-SD significantly increased the number of fos immunoreactive cells in the PVN and SON as compared to sham stimulation (p < 0.001, p = 0.018, respectively). A subpopulation of fos-positive neurons also stained positive for oxytocin. Opto-SD evoked periorbital mechanical allodynia 1 h after SD (p = 0.001 vs. sham), which recovered quickly within 2 h (p = 0.638). OXT receptor antagonist L-368,899 dose-dependently prolonged SD-induced periorbital allodynia (p < 0.001). L-368,899 did not affect mechanical thresholds in the absence of opto-SD. CONCLUSIONS: These data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration.

Lack of a direct link between macular cones function and photophobia in interictal migraine.

BACKGROUND: It is still debatable whether the mechanisms underlying photophobia are related to altered visual cortex excitability or specific abnormalities of colour-related focal macular retino-thalamic information processing. METHODS: This cross-sectional study examined Ganzfeld blue-red (B-R) and blue-yellow (B-Y) focal macular cone flash ERG (ffERG) and focal-flash visual evoked potentials (ffVEPs) simultaneously in a group of migraine patients with (n = 18) and without (n = 19) aura during the interictal phase, in comparison to a group of healthy volunteers (HVs) (n = 20). We correlate the resulting retinal and cortical electrophysiological responses with subjective discomfort from exposure to bright light verified on a numerical scale. RESULTS: Compared to HVs, the amplitude and phase of the first and second harmonic of ffERG and ffVEPs were non-significantly different in migraine patients without aura and migraine patients with aura for both the B-R and the B-Y focal stimuli. Pearson's correlation test did not disclose correlations between clinical variables, including the photophobia scale and electrophysiological variables. CONCLUSIONS: These results do not favour interictal functional abnormalities in L-M- and S-cone opponent visual pathways in patients with migraine. They also suggest that the discomfort resulting from exposure to bright light is not related to focal macular retinal-to-visual cortex pathway.

Evaluation of nerve fiber layer and ganglion cell complex changes in patients with migraine using optical coherence tomography.

Purpose: To analyze changes in peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness in migraine patients with and without aura compared to healthy controls and to identify factors influencing the occurrence of these anomalies. Methods: This is a cross-sectional case-control study including migraine patients and control subjects. All patients and controls underwent a complete ophthalmological examination, RNFL and GCC thickness measurements using a spectral domain-OCT device.The duration of migraine, the frequency and duration of migraine attacks, the migraine disability assessment (MIDAS) and migraine severity scale (MIGSEV) questionnaire scores were recorded. Results: One hundred and twenty eyes from 60 patients (60 eyes in the migraine without aura (MWoA) group and 60 eyes in the migraine with aura (MWA) group) were included. Control group included 30 age and gender matched healthy participants (60 eyes). OCT revealed that RNFL and GCC thickness were significantly reduced in the migraine without aura (MWoA) and in the migraine with aura (MWA) groups compared to the control group and in the migraine with aura (MWA) group compared to the migraine without aura (MWoA) group. Prolonged disease duration was associated to decreased GCC thickness. RNFL and GCC thickness were correlated to disease severity, attack frequency and duration. In the multivariate study, duration of migraine and attack frequency were the main determinant factors of nasal GCC thickness. Disease severity was the main determinant of RNFL and GCC thickness, with the exception of the nasal sector. Conclusion: Our study emphasize the significant impact of both types of migraine on retinal structures. OCT would serve as a valuable biomarker in migraine.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

Exploring the effects of extracranial injections of botulinum toxin type A on activation and sensitization of central trigeminovascular neurons by cortical spreading depression in male and female rats.

BACKGROUND: OnabotulinumtoxinA (onabotA), is assumed to achieve its therapeutic effect in migraine through blocking activation of unmyelinated meningeal nociceptors and their downstream communications with central dura-sensitive trigeminovascular neurons in the spinal trigeminal nucleus (SPV). The present study investigated the mechanism of action of onabotA by assessing its effect on activation and sensitization of dura-sensitive neurons in the SPV by cortical spreading depression (CSD). It is a follow up to our recent study on onabotA effects on activation and sensitization of peripheral trigeminovascular neurons. METHODS: In anesthetized male and female rats, single-unit recordings were used to assess effects of extracranial injections of onabotA (five injections, one unit each, diluted in 5 µl of saline were made along the lambdoid (two injection sites) and sagittal (two injection sites) suture) vs. vehicle on CSD-induced activation and sensitization of high-threshold (HT) and wide-dynamic range (WDR) dura-sensitive neurons in the SPV. RESULTS: Single cell analysis of onabotA pretreatment effects on CSD-induced activation and sensitization of central trigeminovascular neurons in the SPV revealed the ability of this neurotoxin to prevent activation and sensitization of WDR neurons (13/20 (65%) vs. 4/16 (25%) activated neurons in the control vs. treated groups, p = 0.022, Fisher's exact). By contrast, onabotA pretreatment effects on CSD-induced activation and sensitization of HT neurons had no effect on their activation (12/18 (67%) vs. 4/7 (36%) activated neurons in the control vs. treated groups, p = 0.14, Fisher's exact). Regarding sensitization, we found that onabotA pretreatment prevented the enhanced responses to mechanical stimulation of the skin (i.e. responses reflecting central sensitization) in both WDR and HT neurons. In control but not treated WDR neurons, responses to brush (p = 0.004 vs. p = 0.007), pressure (p = 0.002 vs. p = 0.79) and pinch (p = 0.007 vs. 0.79) increased significantly two hours after CSD. Similarly, in control but not treated HT neurons, responses to brush (p = 0.002 vs. p = 0.79), pressure (p = 0.002 vs. p = 0.72) and pinch (p = 0.0006 vs. p = 0.28) increased significantly two hours after CSD. Unexpectedly, onabotA pretreatment prevented the enhanced responses of both WDR and HT neurons to mechanical stimulation of the dura (commonly reflecting peripheral sensitization). In control vs. treated WDR and HT neurons, responses to dural stimulation were enhanced in 70 vs. 25% (p = 0.017) and 78 vs. 27% (p = 0.017), respectively. CONCLUSIONS: The ability of onabotA to prevent activation and sensitization of WDR neurons is attributed to its preferential inhibitory effects on unmyelinated C-fibers. The inability of onabotA to prevent activation of HT neurons is attributed to its less extensive inhibitory effects on the thinly myelinated Aδ-fibers. These findings provide further pre-clinical evidence about differences and potentially complementary mechanisms of action of onabotA and calcitonin gene-related peptide-signaling neutralizing drugs.

Patent Foramen Ovale and Coronary Artery Spasm: A New Patent Foramen Ovale-associated Condition that May Explain the Mechanism of Vasospastic Angina.

Patent foramen ovale (PFO) may be an underlying factor in the pathogenesis of migraine, vasospastic angina, and Takotsubo cardiomyopathy. This article reviews the role that PFO may play in each of these clinical entities and discusses potential interventions. It also proposes a novel clinical syndrome wherein PFO may be the unifying link among migraine, coronary vasospasm, and Takotsubo cardiomyopathy in predisposed individuals.

Headache-related disability as a function of migraine aura: A daily diary study.

OBJECTIVE: To examine the unique role of migraine aura in predicting day-to-day levels of headache-related disability. BACKGROUND: Migraine symptoms and psychological variables contribute to headache-related disability. Migraine aura may be associated with more severe symptom profiles and increased risk of psychiatric comorbidities, but the impact of aura on daily functioning is unknown. The present study sought to evaluate the role of migraine aura in predicting same-day and subsequent-day migraine-related disability while accounting for demographic, headache, and psychological variables. METHODS: This was an observational prospective cohort study among 554 adults with migraine. For each participant, data on migraine symptoms and psychological variables were collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days). Analyses assessed whether the presence of aura predicted daily ratings of migraine-related disability independently of other headache and psychological variables. Given the number of predictors examined, statistical significance was set at p < 0.01. RESULTS: The mean (standard deviation, range) patient-level Migraine Disability Assessment questionnaire score across days of the migraine episode was 1.18 (1.03, 0-3). Aura was significantly associated with higher disability ratings on all days of the migraine episode (odds ratio [OR] 1.40, 99% confidence interval [CI] 1.13-1.74; p < 0.001). This relationship remained unchanged after adjusting for patient-level variables (OR 1.40, 99% CI 1.13-1.73; p < 0.001) and day-level psychological variables (OR 1.39, 99% CI 1.12-1.73; p < 0.001) but was fully negated after controlling for day-level headache variables (OR 1.19, 99% CI 0.95-1.49; p = 0.039). Aura on the first day of the episode was associated with increased odds of allodynia (OR 1.87, 99% CI 1.22-2.86; p < 0.001), phonophobia (OR 1.62, 99% CI 1.17-2.25; p < 0.001), photophobia (OR 1.89, 99% CI 1.37-2.59; p < 0.001), and nausea/vomiting (OR 1.54, 99% CI 1.17-2.02; p < 0.001) on all days of the episode, but not episode duration (p = 0.171), peak severity (p = 0.098), or any examined psychological variables (sleep duration [p = 0.733], sleep quality [p = 0.186], stress [p = 0.110], anxiety [p = 0.102], or sadness [p = 0.743]). CONCLUSION: The presence of aura is predictive of increased headache-related disability during migraine episodes, but this effect is attributable to associated non-pain symptoms of migraine.

Average steps per day as marker of treatment response with anti-CGRP mAbs in adults with chronic migraine: a pilot study.

Physical activity can worsen migraine, leading to reduced activity levels in adults with chronic migraine. This study investigated the change in average steps per day, as a surrogate marker of physical activity, in adults with chronic migraine successfully treated with monoclonal antibodies against calcitonin gene-related peptide or its receptor. Data were obtained from adults with chronic migraine, who were classified as responders to preventive treatment with monoclonal antibodies. The primary endpoint was the difference in a mean number of steps per day between the 3 months prior to treatment initiation and the first 3 months after treatment initiation. The secondary endpoint was the correlation between the change in steps per day and the change in monthly migraine days. Twenty-two (20 females) participants with a median age of 48.5 years were enrolled. The median number of steps per day increased from 4421 at baseline to 5241 after treatment (P = 0.039). We found a positive correlation between the increase in steps per day and the treatment response (P = 0.013). In conclusion, an increase in physical activity, based on steps per day, positively correlated with treatment response to monoclonal antibodies. Automatically registered daily step count data might be used to monitor physical activity as a response to preventive treatment in adults with chronic migraine.

Migraine versus tension-type headache in automatic emotional processing: A visual mismatch negativity study.

OBJECTIVE: It is important to discriminate different headaches in clinical practice, and neurocognitive biomarkers may serve as objective tools. Several reports have suggested potential cognitive impairment for primary headaches, whereas cognitions within specific domains remain elusive, e.g., emotional processing. In this study, we aimed to characterize processing of facial expressions in migraine and tension-type headache (TTH) by analyzing expression-related visual mismatch negativity (EMMN) and explored whether their processing patterns were distinct. METHODS: Altogether, 73 headache patients (20 migraine with aura (MA), 28 migraine without aura (MwoA), 25 TTH) and 27 age-matched healthy controls were recruited. After a battery of mood/neuropsychological evaluations, an expression-related oddball paradigm containing multiple models of neutral, happy and sad faces was used to investigate automatic emotional processing. RESULTS: We observed cognitive impairment in all headache patients, especially in attention/execution subdomains, but no discrepancy existed among different headaches. Although analyses of P1/N170 did not reach significant levels, amplitude of early and late EMMN was markedly diminished in MA and MwoA compared with controls and TTH, regardless of happy or sad expression. Moreover, sad EMMN was larger (more negative) than happy EMMN only in controls, while not in all headache groups. CONCLUSIONS: Our findings implied that migraine, rather than TTH, might lead to more severe impairment of automatic emotional processing, which was manifested as no observable EMMN elicitation and disappearance of negative bias effect. The EMMN component could assist in discrimination of migraine from TTH and diagnosis of undefined headaches, and its availability needed further validations.

New-Onset Occipital Lobe Epilepsy in an Elderly Patient With Visual Hallucinations and Hemianopia.

Occipital lobe epilepsies (OLEs) are a subset of epileptic disorders manifesting predominantly with visual and oculomotor abnormalities that are often misdiagnosed due to similarities with migraines with visual aura and other central nervous system (CNS) pathologies. This case study describes an 88-year-old male with a three-week history of intermittent kaleidoscopic visual phenomena, accompanied by blurring of vision and altered level of consciousness. Neurological examination revealed right homonymous hemianopsia and focal neurological deficits, including forced right gaze preference and nystagmus. Diagnostic modalities, MRI and MRA, ruled out ischemic stroke but indicated mild to moderate cerebral atrophy and chronic microvascular ischemic changes. The patient exhibited a seizure episode characterized by right-sided gaze preference and altered consciousness. Postictally, transient right homonymous hemianopsia was observed, consistent with Todd's phenomenon. Treatment with intravenous levetiracetam and lorazepam led to a reduction in seizure frequency. This case highlights the importance of comprehensive evaluation in distinguishing OLEs from other conditions with similar visual presentations like migraine with aura or occipital lobe stroke being more predominant.

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.

Aberrant functional connectivity in anterior cingulate gyrus subregions in migraine without aura patients.

Background: The anterior cingulate gyrus (ACG) is an important regulatory region for pain-related information. However, the ACG is composed of subregions with different functions. The mechanisms underlying the brain networks of different subregions of the ACG in patients with migraine without aura (MwoA) are currently unclear. Methods: In the current study, resting-state functional magnetic resonance imaging (rsfMRI) and functional connectivity (FC) were used to investigate the functional characteristics of ACG subregions in MwoA patients. The study included 17 healthy volunteers and 28 MwoA patients. The FC calculation was based on rsfMRI data from a 3 T MRI scanner. The brain networks of the ACG subregions were compared using a general linear model to see if there were any differences between the two groups. Spearman correlation analysis was used to examine the correlation between FC values in abnormal brain regions and clinical variables. Results: Compared with healthy subjects, MwoA patients showed decreased FC between left subgenual ACG and left middle cingulate gyrus and right middle temporal gyrus. Meanwhile, MwoA patients also showed increased FC between pregenual ACG and right angular gyrus and increased FC between right pregenual ACG and right superior occipital gyrus. The FC values between pregenual ACG and right superior occipital gyrus were significantly positively correlated with the visual analogue scale. Conclusion: Disturbances of FC between ACG subregions and default model network and visual cortex may play a key role in neuropathological features, perception and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.

Red ear syndrome: a case series and review of the literature.

BACKGROUND: Red Ear Syndrome is a burning sensation and erythema of the ear, associated with a various number of disorders including migraine, trigeminal neuralgia, autoimmune disorders etc. Theories for RES pathophysiology have developed from current understandings of comorbid conditions. Characterizing the underlying mechanism of RES is crucial for defining effective treatments. CASE PRESENTATION: Three caucasian patients, ages 15, 47, and 67 years, with migraine, one with erythromelalgia are reported in this manuscript. RES pathophysiology is not fully understood due to its variable clinical presentation and numerous comorbid conditions, making it difficult to identify effective treatments. CONCLUSION: RES seems to be largely treatment-resistant, and most options involve treating the associated disorders and minimizing pain. Further investigation of future cases should lead to a more comprehensive understanding of the fundamental cause of RES and, hopefully, successful treatments.