Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision.

The life cycle of a primary cilium begins in quiescence and ends prior to mitosis. In quiescent cells, the primary cilium insulates itself from contiguous dynamic membrane processes on the cell surface to function as a stable signaling apparatus. Here, we demonstrate that basal restriction of ciliary structure dynamics is established by the cilia-enriched phosphoinositide 5-phosphatase, Inpp5e. Growth induction displaces ciliary Inpp5e and accumulates phosphatidylinositol 4,5-bisphosphate in distal cilia. This change triggers otherwise-forbidden actin polymerization in primary cilia, which excises cilia tips in a process we call cilia decapitation. While cilia disassembly is traditionally thought to occur solely through resorption, we show that an acute loss of IFT-B through cilia decapitation precedes resorption. Finally, we propose that cilia decapitation induces mitogenic signaling and constitutes a molecular link between the cilia life cycle and cell-division cycle. This newly defined ciliary mechanism may find significance in cell proliferation control during normal development and cancer.

Increased presynaptic excitability in a migraine with aura mutation.

Migraine is a common and disabling neurological disorder. The headache and sensory amplifications of migraine are attributed to hyperexcitable sensory circuits, but a detailed understanding remains elusive. A mutation in casein kinase 1 delta (CK1δ) was identified in non-hemiplegic familial migraine with aura and advanced sleep phase syndrome. Mice carrying the CK1δT44A mutation were more susceptible to spreading depolarization (the phenomenon that underlies migraine aura), but mechanisms underlying this migraine-relevant phenotype were not known. We used a combination of whole-cell electrophysiology and multiphoton imaging, in vivo and in brain slices, to compare CK1δT44A mice (adult males) to their wild-type littermates. We found that despite comparable synaptic activity at rest, CK1δT44A neurons were more excitable upon repetitive stimulation than wild-type, with a reduction in presynaptic adaptation at excitatory but not inhibitory synapses. The mechanism of this adaptation deficit was a calcium-dependent enhancement of the size of the readily releasable pool of synaptic vesicles, and a resultant increase in glutamate release, in CK1δT44A compared to wild-type synapses. Consistent with this mechanism, CK1δT44A neurons showed an increase in the cumulative amplitude of excitatory post-synaptic currents, and a higher excitation-to-inhibition ratio during sustained activity compared to wild-type. At a local circuit level, action potential bursts elicited in CK1δT44A neurons triggered an increase in recurrent excitation compared to wild-type, and at a network level, CK1δT44A mice showed a longer duration of 'up state' activity, which is dependent on recurrent excitation. Finally, we demonstrated that the spreading depolarization susceptibility of CK1δT44A mice could be returned to wild-type levels with the same intervention (reduced extracellular calcium) that normalized presynaptic adaptation. Taken together, these findings show a stimulus-dependent presynaptic gain of function at glutamatergic synapses in a genetic model of migraine, that accounts for the increased spreading depolarization susceptibility and may also explain the sensory amplifications that are associated with the disease.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

Abnormal causal connectivity of anterior cingulate cortex-visual cortex circuit related to nonsteroidal anti-inflammatory drug efficacy in migraine.

The anterior cingulate cortex (ACC) and visual cortex are integral components of the neurophysiological mechanisms underlying migraine, yet the impact of altered connectivity patterns between these regions on migraine treatment remains unknown. To elucidate this issue, we investigated the abnormal causal connectivity between the ACC and visual cortex in patients with migraine without aura (MwoA), based on the resting-state functional magnetic resonance imaging data, and its predictive ability for the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs). The results revealed increased causal connectivity from the bilateral ACC to the lingual gyrus (LG) and decreased connectivity in the opposite direction in nonresponders compared with the responders. Moreover, compared with the healthy controls, nonresponders exhibited heightened causal connectivity from the ACC to the LG, right inferior occipital gyrus (IOG) and left superior occipital gyrus, while connectivity patterns from the LG and right IOG to the ACC were diminished. Based on the observed abnormal connectivity patterns, the support vector machine (SVM) models showed that the area under the receiver operator characteristic curves for the ACC to LG, LG to ACC and bidirectional models were 0.857, 0.898, and 0.939, respectively. These findings indicate that neuroimaging markers of abnormal causal connectivity in the ACC-visual cortex circuit may facilitate clinical decision-making regarding NSAIDs administration for migraine management.

No wearing-off effect of erenumab or fremanezumab for chronic migraine prevention: a single-center, real-world, observational study.

BACKGROUND: The present study investigates the wearing-off effect in adults with chronic migraine treated with erenumab or fremanezumab. METHODS: This real-world observational study was based on pre-collected headache diaries from chronic migraine patients in treatment with either monthly injections of 140 mg of erenumab or 225 mg of fremanezumab. Consistent wearing-off was defined as an increase of ≥2 weekly migraine days in the last week compared to the second week over two consecutive 4-week treatment periods. The primary endpoint was wearing-off in the total population. The secondary endpoints were difference in wearing-off in (i) a subgroup of patients treated with erenumab and fremanezumab and (ii) consistent wearing-off in patients with a ≥30% reduction in monthly migraine days, compared to baseline, in the two consecutive treatment months. RESULTS: In total, 100 patients (erenumab: n = 60, fremanezumab: n = 40) were included. Sixty-two out of 100 (62%) patients had consistent ≥30% treatment response on antibody therapy in both months (erenumab: n = 36, fremanezumab: n = 26). There was no consistent wearing-off over the two consecutive months from week 2 to week 4 (3.04%, p = 0.558). There was no wearing-off within the erenumab (p = 0.194) or the fremanezumab (p = 0.581) groups. Among the ≥30% treatment responders, there was no consistent wearing-off over the two consecutive months (2.6%, p = 0.573). CONCLUSIONS: There was no wearing-off in treatment responders, which is in alignment with premarketing data from placebo-controlled phase III studies. These data suggest that patients should be informed upfront that no wearing-off effect is expected because anxiety for attacks at the end of the month per se may generate migraine attacks.

Visual migraine aura iconography: A multicentre, cross-sectional study of individuals with migraine with aura.

INTRODUCTION: Visual disturbances are the most common symptoms of migraine aura. These symptoms can be described systematically by subdividing them into elementary visual symptoms. Since visual symptoms of migraine aura are not easy to describe verbally, we developed a collection of images illustrating previously reported elementary visual symptoms. OBJECTIVES: To test a standardised visual migraine aura iconography in a large population of migraine with aura patients and to improve it based on the participants' feedback. METHODS: We created a set of images representing 25 elementary visual symptoms and a web-based survey where participants could report whether they recognised these images as part of their visual aura. Elementary visual symptoms could also be recognised via a corresponding text description or described in a free text by participants. Individuals with migraine aura recruited from four tertiary headache centres (in Switzerland, Denmark, Norway and Italy) were invited to complete the survey. RESULTS: Two hundred and fifteen participants completed the study (78.9% women, median age 36). They recognised a total of 1645 elementary visual symptoms from our predefined list. Of those, 1291 (78.4%) where recognised via standardised iconography images. A new type of elementary visual symptom was reported by one participant. CONCLUSION: Most elementary visual symptoms experienced by participants were recognised via the standardised iconography. This tool can be useful for clinical as well as research purposes.

Grey matter structure within the visual networks in migraine with aura: multivariate and univariate analyses.

BACKGROUND: The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used mass-univariate analyses. METHODS: Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. RESULTS: A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. CONCLUSIONS: Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms.

Characteristics of acute ischemic stroke and unusual aura in patients with migraine with aura.

BACKGROUND: Sometimes migraine aura changes from attack to attack, raising the question of whether the change is heralding an ischemic stroke or an unusual aura. Differentiating unusual migraine aura from the onset of an acute ischemic stroke in patients with migraine with aura (MwA) can be challenging. OBJECTIVE: The aim of this cohort study was to assess clinical characteristics that help distinguish between MwA and minor stroke in patients with a previous history of MwA who presented with suspicion of stroke. METHODS: We interviewed patients with MwA and ischemic stroke (MwA + IS) and patients with MwA and unusual aura, but without ischemic stroke (MwA - IS) from a tertiary hospital using a structured questionnaire. We assessed how symptoms of ischemic stroke or unusual aura differed from usual, that is, the typical aura in each patient. Stroke or exclusion of stroke was verified by multimodal magnetic resonance imaging. RESULTS: Seventeen patients with MwA + IS and twelve patients with MwA - IS were included. New focal neurological symptoms (13/17 [76%] vs. 3/12 [25%]), change of the first symptom (10/17 [59%] vs. 1/12 [8%]), and absence of headache (6/15 [40%] vs. 2/10 [20%]) were more often reported during ischemic stroke. The physical examination was normal in 8/17 (47%) MwA + IS and in 6/12 (50%) MwA - IS patients. In 5/17 (29%) patients with MwA + IS, there were unequivocal physical signs suggestive of stroke such as persistent visual loss, ataxia, or paresis. CONCLUSION: There are clues from the history that might help identify stroke in patients with MwA with changed aura symptoms. These might be particularly useful in patients presenting without physical findings suggestive of stroke.

Virtual dynamic interaction games reveal impaired multisensory integration in women with migraine.

OBJECTIVE: In this cross-sectional observational study, we aimed to investigate sensory profiles and multisensory integration processes in women with migraine using virtual dynamic interaction systems. BACKGROUND: Compared to studies on unimodal sensory processing, fewer studies show that multisensory integration differs in patients with migraine. Multisensory integration of visual, auditory, verbal, and haptic modalities has not been evaluated in migraine. METHODS: A 12-min virtual dynamic interaction game consisting of four parts was played by the participants. During the game, the participants were exposed to either visual stimuli only or multisensory stimuli in which auditory, verbal, and haptic stimuli were added to the visual stimuli. A total of 78 women participants (28 with migraine without aura and 50 healthy controls) were enrolled in this prospective exploratory study. Patients with migraine and healthy participants who met the inclusion criteria were randomized separately into visual and multisensory groups: Migraine multisensory (14 adults), migraine visual (14 adults), healthy multisensory (25 adults), and healthy visual (25 adults). The Sensory Profile Questionnaire was utilized to assess the participants' sensory profiles. The game scores and survey results were analyzed. RESULTS: In visual stimulus, the gaming performance scores of patients with migraine without aura were similar to the healthy controls, at a median (interquartile range [IQR]) of 81.8 (79.5-85.8) and 80.9 (77.1-84.2) (p = 0.149). Error rate of visual stimulus in patients with migraine without aura were comparable to healthy controls, at a median (IQR) of 0.11 (0.08-0.13) and 0.12 (0.10-0.14), respectively (p = 0,166). In multisensory stimulation, average gaming score was lower in patients with migraine without aura compared to healthy individuals (median [IQR] 82.2 [78.8-86.3] vs. 78.6 [74.0-82.4], p = 0.028). In women with migraine, exposure to new sensory modality upon visual stimuli in the fourth, seventh, and tenth rounds (median [IQR] 78.1 [74.1-82.0], 79.7 [77.2-82.5], 76.5 [70.2-82.1]) exhibited lower game scores compared to visual stimuli only (median [IQR] 82.3 [77.9-87.8], 84.2 [79.7-85.6], 80.8 [79.0-85.7], p = 0.044, p = 0.049, p = 0.016). According to the Sensory Profile Questionnaire results, sensory sensitivity, and sensory avoidance scores of patients with migraine (median [IQR] score 45.5 [41.0-54.7] and 47.0 [41.5-51.7]) were significantly higher than healthy participants (median [IQR] score 39.0 [34.0-44.2] and 40.0 [34.0-48.0], p < 0.001, p = 0.001). CONCLUSION: The virtual dynamic game approach showed for the first time that the gaming performance of patients with migraine without aura was negatively affected by the addition of auditory, verbal, and haptic stimuli onto visual stimuli. Multisensory integration of sensory modalities including haptic stimuli is disturbed even in the interictal period in women with migraine. Virtual games can be employed to assess the impact of sensory problems in the course of the disease. Also, sensory training could be a potential therapy target to improve multisensory processing in migraine.

CGRP Modulating Therapies: An Update.

INTRODUCTION: Calcitonin-gene related peptide (CGRP) is a vasoactive neuropeptide involved in the pathophysiology ofmigraine. CGRP has been targeted for both preventive and acute treatment of migraine. OBJECTIVE: Provide a summary of the most clinically relevant literature surrounding CGRP modulating therapies. METHODS: This update on CGRP modulating therapies includes articles selected as most clinically relevant by theauthors. CONCLUSION: CGRP modulating therapies are an exciting new addition to migraine treatment given their safety andtolerability. Additionally, compared to traditional migraine preventive medication these treatments are migrainespecific.Further real-world and clinical data is ongoing to better understand these treatments that continue to gainfavor in the management of migraine.

An "epileptic scent": Olfactory auras in tumor-related epilepsy.

OBJECTIVES: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras. MATERIALS AND METHODS: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts. RESULTS: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222). DISCUSSION: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras. CONCLUSIONS: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.

Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.

BACKGROUND: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. METHODS: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. RESULTS: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4-16; after 12 months: 1, interquartile range: 0-3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16-30; after 12 months: 5, interquartile range: 4-7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. CONCLUSION: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache.

The imaging findings of migraine with visual aura in a CADASIL patient.

Head MRI images of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients during migraine attacks are rare.

SEEG study of a rare male temporal lobe epilepsy with orgasmic aura originating from the right amygdala.

As a primitive driving force for biological reproduction, sexual behavior (and its associated mechanisms) is extremely complex, and orgasm plays an essential role. The limbic system plays a very important role in regulating human sexual behavior. However, it is not clear which components of the limbic system are related to orgasm sensation. We studied a rare case of spontaneous orgasmic aura in a male patient with temporal lobe epilepsy. Stereoelectroencephalography (SEEG) revealed that the right amygdala was the origin of orgasmic aura. Surgical removal of the medial temporal lobe, including the right amygdala, completely eliminated the patient's seizures. This study demonstrates the critical role of the amygdala in human male orgasm.

Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura.

BACKGROUND: Spreading depolarization (SD), underlying mechanism of migraine aura and potential activator of pain pathways, is known to elicit transient local silencing cortical activity. Sweeping across the cortex, the electrocorticographic depression is supposed to underlie spreading negative symptoms of migraine aura. Main information about the suppressive effect of SD on cortical oscillations was obtained in anesthetized animals while ictal recordings in conscious patients failed to detect EEG depression during migraine aura. Here, we investigate the suppressive effect of SD on spontaneous cortical activity in awake animals and examine whether the anesthesia modifies the SD effect. METHODS: Spectral and spatiotemporal characteristics of spontaneous cortical activity following a single unilateral SD elicited by amygdala pinprick were analyzed in awake freely behaving rats and after induction of urethane anesthesia. RESULTS: In wakefulness, SD transiently suppressed cortical oscillations in all frequency bands except delta. Slow delta activity did not decline its power during SD and even increased it afterwards; high-frequency gamma oscillations showed the strongest and longest depression under awake conditions. Unexpectedly, gamma power reduced not only during SD invasion the recording cortical sites but also when SD occupied distant subcortical/cortical areas. Contralateral cortex not invaded by SD also showed transient depression of gamma activity in awake animals. Introduction of general anesthesia modified the pattern of SD-induced depression: SD evoked the strongest cessation of slow delta activity, milder suppression of fast oscillations and no distant changes in gamma activity. CONCLUSION: Slow and fast cortical oscillations differ in their vulnerability to SD influence, especially in wakefulness. In the conscious brain, SD produces stronger and spatially broader depression of fast cortical oscillations than slow ones. The frequency-specific effects of SD on cortical activity of awake brain may underlie some previously unexplained clinical features of migraine aura.

Clinical features of migraine with aura: a REFORM study.

BACKGROUND: About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura. METHODS: Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study - a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms. RESULTS: Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache. CONCLUSIONS: This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians' acumen in diagnosing migraine with aura in clinical settings.

Assessment of spatiotemporal variability of ultraviolet index (UVI) over Kerala, India, using satellite remote sensing (OMI/AURA) data.

The spatial and temporal dynamics of daily ultraviolet index (UVI) for a period of 18 years (2004-2022) over the Indian state of Kerala were statistically characterised in the study. The UVI measurements used for the study were derived from the ultraviolet-B (UVB) irradiance measured by the Ozone Monitoring Instrument (OMI) of the AURA satellite and classified into different severity levels for analysis. Basic statistics of daily, monthly and seasonal UVI as well as Mann-Kendall (MK) statistical trend characteristics and the rate of change of daily UVI using Theil-Sen's slope test were also evaluated. A higher variability of UVI characteristics was observed in the Kerala region, and more than 79% of the measurements fell into the categories of very high and extreme UVI values, which suggests the need of implementation of appropriate measures to reduce health risks. Although the UVI measured during the study period shows a slight decrease, most of the data show a seasonal variation with undulating low and peak values. Higher UVI are observed during the months of March, April and September. The region also has higher UVI during the southwest monsoon (SWM) and summer seasons. Although Kerala region as a single whole unit, UVI show a non-significant decreasing trend (-0.83), the MK test revealed the increasing and decreasing trends of UVI ranging from -1.96 to 0.41 facilitated the delineation of areas (domains) where UVI are increasing or decreasing. The domain of UVI increase occupies the central and southern (S) parts, and the domains of decrease cover the northern (N) and S parts of the Kerala region. The rate of change of daily UVI in domain of increase and decrease shows an average rate of 0.34 × 10-5 day-1 and -2 × 10-5 day-1, respectively. The parameters (rainfall, air temperature, cloud optical depth (COD) and solar zenith angle (SZA)) that affect the strength of UV rays reaching the surface indicate that a cloud-free atmosphere or low thickness clouds prevails in the Kerala region. Overall, the study results indicate the need for regular monitoring of UVI in the study area and also suggest appropriate campaigns to disseminate information and precautions for prolonged UVI exposure to reduce the adverse health effects, since the study area has a high population density.

Migraine or any headaches and white matter hyperintensities and their progression in women and men.

BACKGROUND: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. METHODS: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders. RESULTS: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. CONCLUSIONS: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

Inflammatory response of leptomeninges to a single cortical spreading depolarization.

BACKGROUND: Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges. METHODS: A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR. RESULTS: Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression. CONCLUSION: A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack.

[The hereditary vessel disease CADASIL].

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease of the brain characterized by progressive white matter lesions, subcortical infarcts, and cognitive decline. This autosomal dominant disorder is caused by mutations in the NOTCH3 gene located on chromosome 19, resulting in the accumulation of granular osmiophilic material within the walls of small arteries and arterioles. Clinically, CADASIL typically manifests in mid-adulthood with recurrent ischemic events, migraine with aura, mood disturbances, and cognitive impairment. Neuroimaging plays a crucial role in the diagnosis of CADASIL, with characteristic findings including white matter hyperintensities particularly in the anterior temporal lobe and external capsule.