MwoA Patients Research Articles

Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache.

We herein investigated the role of polymorphisms in calcitonin gene-related peptide (CGRP)-related genes looking at the association of rs3781719 (T > C) in the calcitonin gene-related polypeptide-alpha (CALCA) gene and of rs3754701 (T > A) and rs7590387 (C > G) at the receptor activity modifying 1 (RAMP1) locus with triptan response in patients with migraine without aura (MwoA). In addition, their role was evaluated as risk factors for transformation of episodic migraine into medication overuse headache (MOH). The CGRP has a central role in the pathogenesis of migraine; however, little information is currently available concerning the role of polymorphisms in CGRP-related genes as determinants of clinical response to anti-migraine drugs or as risk factors for migraine chronification. Genotyping was conducted retrospectively by real-time polymerase chain reaction allelic discrimination assay in 219 patients with MwoA and 130 with MOH in whom migraine was the primary headache type. Gene variants association was evaluated by logistic regression analysis adjusted by confounding factors. The threshold of statistical significance was set according to the total number of polymorphisms analyzed in the current study and in previous publications arising from overlapping datasets. No evidence of association was found between the three polymorphisms tested and triptan response in MwoA patients. Conversely, carriers of RAMP1 rs7590387GG displayed a lower risk of episodic migraine transformation into MOH (vs C allele carriers, odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.13-0.57, P = 0.0002; threshold of significance set at P < 0.0029). When genotype distribution for RAMP1 rs7590387 was compared between healthy controls (n = 209) and MOH patients, carriers of rs7590387GG were found at lower risk of developing MOH (OR: 0.43, 95%CI: 0.22-0.85, P = 0.011). These results suggest that RAMP1 rs7590387 may have a role in the transformation of episodic migraine into MOH.

Measurement of visual sensitivity in migraine: Validation of two scales and correlation with visual cortex activation.

The objectives of this article are to compare interictal and ictal visual sensitivity between migraine and controls using two published questionnaires, and to correlate responses with a physiologic measure of visual cortex activation. Migraine with (MWA, n = 51) and without (MwoA, n = 45) aura and control individuals (n = 45) were enrolled and underwent BOLD fMRI with a visual stimulus. The visual discomfort score (VDS) assessed interictal and the migraine photophobia score (MPS) assessed ictal visual sensitivity. VDS was significantly higher both in MWA and MwoA vs controls (both p = 0.0001). MPS was greater in MWA vs MwoA (p = 0.008). Ictal and interictal visual sensitivity strongly correlated in MWA (p = 0.004) but not MwoA patients (p = 0.12). BOLD activation in visual cortex was greater in MWA vs controls (2.7% vs 2.3%, p = 0.003) but similar between MwoA and controls. Increasing VDS was associated with greater BOLD signal change in MWA (p = 0.03) but not MwoA (p = 0.65) or controls (p = 0.53). MPS did not correlate with BOLD activation in either group. Increased interictal visual sensitivity is present both in MWA and MwoA. However, the correlation with ictal visual sensitivity and with cortical hyper-responsivity varies between MWA and MwoA, suggesting underlying differences between groups.

Subclinical cerebellar dysfunction in patients with migraine: Evidence from eyeblink conditioning

Clinical findings suggest cerebellar dysfunction in patients with migraine. Eyeblink classical conditioning (EBCC) is a simple form of associative learning which depends on the integrity of the cerebellum. The aim of this study was to assess whether EBCC is disturbed in patients with migraine. A delay conditioning paradigm was used in the headache-free interval in 32 female patients with migraine, in 24 of them without (MwoA) and eight with aura (MwA), and in 32 age-matched female controls. As primary outcome measure acquisition and as secondary outcome measures timing and extinction of conditioned eyeblink responses (CR) were assessed. CR acquisition was significantly reduced in all migraine patients (mean total CR incidence 35.2 ± 22.1%) compared to controls (54.7 ± 21.3%; p < 0.001; Bonferroni-corrected p level < 0.025) and in MwA patients (19.9 ± 20.2%) compared to matched controls (58.2 ± 27.0%; p = 0.006) but not in MwoA patients (40.3 ± 20.6%) compared to matched controls (53.6 ± 19.7%; p = 0.028; Bonferroni-corrected p level < 0.0166). Decrease of CR incidences in MwA patients was not significantly different compared to MwoA patients (p = 0.021; Bonferroni-corrected p level < 0.0166). CR timing and extinction was not affected in migraine patients. Reduced acquisition of CRs in the cohort of female patients studied here supports findings of a cerebellar dysfunction in migraine.

Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study.

Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper- or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf-rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state. Twenty-two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5-Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf-rTMS trains were compared with those of 14 healthy subjects. We observed abnormal inhibitory responses to the hf-rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001).The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf-rTMS trains in both MwA and MwoA. The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.

Alterations in regional homogeneity assessed by fMRI in patients with migraine without aura stratified by disease duration

BackgroundAdvanced neuroimaging approaches have been employed to prove that migraine was a central nervous system disorder. This study aims to examine resting-state abnormalities in migraine without aura (MWoA) patients stratified by disease duration, and to explore the neuroimaging markers for reflecting the disease duration.Methods40 eligible MWoA patients and 20 matched healthy volunteers were included in the study. Regional homogeneity (ReHo) analysis was used to identify the local features of spontaneous brain activity in MWoA patients stratified by disease duration, and analysis was performed to investigate the correlation of overlapped brain dysfunction in MWoA patients with different disease duration (long-term and short-term) and course of disease.ResultsCompared with healthy controls, MWoA patients with long-term disease duration showed comprehensive neuronal dysfunction than patients with short-term disease duration. In addition, increased average ReHo values in the thalamus, brain stem, and temporal pole showed significantly positive correlations with the disease duration. On the contrary, ReHo values were negatively correlated with the duration of disease in the anterior cingulate cortex, insula, posterior cingulate cortex and superior occipital gyrus.ConclusionsOur findings of progressive brain damage in relation to increasing disease duration suggest that migraine without aura is a progressive central nervous disease, and the length of the disease duration was one of the key reasons to cause brain dysfunction in MwoA patients. The repeated migraine attacks over time result in resting-state abnormalities of selective brain regions belonging to the pain processing and cognition. We predict that these brain regions are sensitive neuroimaging markers for reflecting the disease duration of migraine patients without aura.

The missing link: Enhanced functional connectivity between amygdala and visceroceptive cortex in migraine

Migraine is a neurovascular disorder in which altered functional connectivity between pain-modulating circuits and the limbic system may play a role. Cortical spreading depression (CSD), which underlies migraine aura (MWA), induces C-fos expression in the amygdala. The role of CSD and amygdala connectivity in migraine without aura (MwoA) is less clear and may differentiate migraine from other chronic pain disorders. Using resting-state functional MRI, we compared functional connectivity between the amygdala and the cortex in MWA and MWoA patients as well as in healthy subjects and in two other chronic pain conditions not associated with CSD: trigeminal neuralgia (TGN) and carpal tunnel syndrome (CTS). Amygdala connectivity in both MWA and MWoA was increased to the visceroceptive insula relative to all other groups examined. The observed increased connectivity within the limbic/viscerosensory network, present only in migraineurs, adds to the evidence of a neurolimbic pain network dysfunction and may reflect repetitive episodes of CSD leading to the development of migraine pain.

Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T.

The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P ≤ 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura.

Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura

Although previous resting-state studies have reported abnormal functional cerebral changes in patients with migraine without aura (MwoA), few have focused on alterations in both regional spontaneous neuronal activity and corresponding brain circuits in MwoA patients during rest. Eighteen MwoA patients and 18 age- and gender-matched healthy controls (HC) were recruited in the current study. Baseline cerebral alterations were investigated using amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) analyses. Compared with HC, MwoA patients showed decreased ALFF values in the left rostral anterior cingulate cortex (rACC) and bilateral prefrontal cortex (PFC) as well as increased ALFF values in the right thalamus. FC analysis also revealed abnormal FCs associated with these ROIs. In addition, ALFF values of the left rACC correlated with duration of disease in MwoA. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in MwoA, providing both regional and brain circuit spontaneous neuronal activity properties.

Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI.

BackgroundPrevious studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting functional magnetic resonance imaging (fMRI) data which reflect functional interactions among distinct brain areas. We sought to explore whether and how repeated migraine attacks influence intrinsic brain connectivity, as well as how activity in these networks correlates with clinical indicators of migraine.Methods/Principal FindingsResting-state fMRI data in twenty-three patients with migraines without aura (MwoA) and 23 age- and gender-matched healthy controls (HC) were analyzed using independent component analysis (ICA), in combination with a “dual-regression” technique to identify the group differences of three important pain-related networks [default mode network (DMN), bilateral central executive network (CEN), salience network (SN)] between the MwoA patients and HC. Compared with the HC, MwoA patients showed aberrant intrinsic connectivity within the bilateral CEN and SN, and greater connectivity between both the DMN and right CEN (rCEN) and the insula cortex - a critical region involving in pain processing. Furthermore, greater connectivity between both the DMN and rCEN and the insula correlated with duration of migraine.ConclusionsOur findings may provide new insights into the characterization of migraine as a condition affecting brain activity in intrinsic connectivity networks. Moreover, the abnormalities may be the consequence of a persistent central neural system dysfunction, reflecting cumulative brain insults due to frequent ongoing migraine attacks.

Executive resting-state network connectivity in migraine without aura

Converging neuropsychological evidence suggests that in migraine executive functions (EF) may be affected during interictal periods. To evaluate the functional connectivity of the fronto-parietal networks (FPN) known to be associated with EF, in migraine without aura (MwoA) patients, in the interictal period, in comparison to healthy controls (HC). Using resting-state functional MRI (RS-fMRI), we compared functional connectivity within the FPN in 14 patients with MwoA versus 14 sex- and age-matched HC, and assessed the correlation between functional connectivity within FPN, clinical features of MwoA patients, and EF. We used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. Neuropsychological data revealed no significant executive dysfunction in MwoA patients. RS-fMRI showed that MwoA patients, compared to HC, had significant functional connectivity reduction within the right FPN and specifically in the middle frontal gyrus (MFG) and the dorsal anterior cingulate cortex. In addition, we found that MFG reduced connectivity was negatively correlated with the pain intensity of migraine attacks. There were no structural differences between the two groups. Our data suggest that, even in the absence of clinically evident EF deficits, MwoA is associated with reduced FPN functional connectivity. This study provides further insights into the complex scenario of migraine mechanisms.

Absence of haemodynamic refractory effects in patients with migraine without aura – an interictal fMRI study

In healthy controls, haemodynamic refractory effects are observed with blood-oxygenation-level dependent (BOLD) functional MRI (fMRI): the haemodynamic response function (HRF) to the second stimulus in a pair of stimuli with short interstimulus interval (ISI) shows a decreased amplitude and an increased time-to-peak. We hypothesize that there may be interictal haemodynamic abnormalities in migraineurs. An event-related fMRI design with paired face stimuli and varying ISIs was used to measure interictal HRFs in the face recognition area of patients with migraine without aura (MwoA) and controls. Net responses to the second stimulus in a pair were calculated and averaged per participant. Several characterizing parameters of the net responses were quantified and examined within each group. Refractory effects were not observed in our patient group. There are no changes in the net responses compared with the reference situation in patients, irrespective of the ISI, whereas in controls all HRF parameters are decreased or delayed for an ISI of 1 second. This is the first fMRI study investigating the haemodynamic refractory effects in MwoA patients. Unlike in controls, these effects are not observed in migraineurs. Although currently unclear, it is tempting to speculate that this observation reflects the neurovascular correlate of lack of habituation measured with evoked potentials in migraineurs.

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study.

Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS (31P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional 1H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1–0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.

31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients

Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy ((31)P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by (31)P-MRS at 3 tesla. Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls. A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([P(i)]) and magnesium ([Mg(2+)]) concentrations were not significantly different between MwoA patients and controls. The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.

1H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique

Several studies have demonstrated differences in migraine patients when performing (1)H-MRS; however, no studies have performed (1)H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this (1)H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification. (1)H-MRS was performed in 22 MwoA patients and 25 control subjects. Absolute quantification was based on the phantom replacement technique. Corrections were made for T (1) and T (2) relaxation effects, CSF content, coil loading and temperature. The method was validated by phantom measurements and in vivo measurements in the occipital visual cortex. After calibration of the quantification procedure and the implementation of the required correction factors, measured absolute concentrations in the visual cortex of MwoA patients showed no significant differences compared to controls, in contrast to relative results obtained in earlier studies. In this study, we demonstrate the implementation of quantitative in vivo (1)H-MRS spectroscopy in migraine patients. Despite rigorous quantification, no spectroscopic abnormalities could be found in patients with migraine without aura.

Differential activation of the middle-temporal complex to visual stimulation in migraineurs

Differences between people with and without migraine on various measures of visual perception have been attributed to abnormal cortical processing due to the disease. The aim of the present study was to explore the dynamics of the basic interictal state with regard to the extrastriate, motion-responsive middle temporal area (MT-complex) with functional magnetic resonance imaging (fMRI) at 3 tesla using coherent/incoherent moving dot stimuli. Twenty-four migraine patients (12 with aura [MwA], 12 without aura [MwoA]) and 12 healthy subjects participated in the study. The individual cortical folding pattern was accounted for by using a cortical matching approach. In the inferior-posterior portion of the MT-complex, most likely representing MT, control subjects showed stronger bilateral activation compared to MwA and MwoA patients. Compared with healthy controls MwoA and MwA patients showed significantly stronger activation mainly at the left side in response to visual stimulation in the superior-anterior portion of the MT-complex, representing the medial-superior temporal area (MST). Our findings strengthen the hypothesis that hyperresponsiveness of the visual cortex in migraine goes beyond early visual areas, even in the interictal period.

Cytokine Polymorphism in Patients with Migraine: Some Suggestive Clues of Migraine and Inflammation

There are contrasting results obtained in migraineurs concerning the levels and the role of both pro-inflammatory and anti-inflammatory cytokines. In this study, the association of the occurrence and clinical characteristics of migraine with the polymorphisms of tumor necrosis factor alpha (TNF-alpha) -308 G/A (rs1800629), interleukin-1alpha (IL-1alpha) +4845 G/T (rs17561), IL-1beta+3953 C/T (rs1143634) and interleukin-1 receptor antagonist variable number tandem repeat (IL-1RA VNTR) genes were studied. We also investigated the genetic linkage between these genes. Sixty-seven patients with migraine without aura (MwoA) and 96 unrelated, age- and sex-matched migraine-free, healthy control subjects from the same geographic area were investigated. We observed significant differences in the genotypic distribution of the TNF-alpha-308 G/A and IL-1beta+3953 C/T polymorphism for migraineurs compared with controls (P = 0.004). Frequency of the TNF-alpha-308 GG genotype was higher in the control group than MwoA group (82.1% vs 55.2%). Differences in the distribution of the allele frequencies were also observed, being the TNF-alpha-308 G allele overrepresented in control group and TNF-alpha-308 A allele in MwoA group. In addition, there was a significant increase of the IL-1beta+3953 T allele in MwoA cases compared with controls (P = 0.004). In conclusion, the present results indicate the possible contribution of TNF-alpha and IL-1beta gene polymorphisms to migraine headache generation in MwoA patients.

Patients with migraine with aura have increased flow mediated dilation.

BackgroundEndothelium-derived nitric oxide (NO) mediates the arterial dilation following a flow increase (i.e. flow-mediated dilation, FMD), easily assessed in the brachial artery. NO is also involved in cerebral hemodynamics and it is supposed to trigger vascular changes occurring during migraine. This study aimed at investigating whether migraine patients present an altered response to NO also in the peripheral artery system.MethodsWe enrolled 21 migraineurs (10 with aura [MwA], 11 without aura [MwoA]), and 13 controls. FMD was evaluated with ultrasound in all subjects by measuring the percentage increase of the brachial artery diameter induced by hyperaemia reactive to sustained cuff inflation around the arm above systolic pressure. FMD values were then normalized for shear stress.ResultsNormalized FMD values were higher in patients with MwA (28.5 10-2%.s) than in controls (9.0 10-2%.s) and patients with MwoA (13.7 10-2%.s) (p < 0.001). FMD was over the median value (19%) in 23.1% of controls, in 45.5% of the MwoA patients, and in 90% of the MwA patients.ConclusionsMigraineurs with aura present an excessive arterial response to hyperaemia, likely as an effect of an increased sensitivity to endothelium-derived nitric oxide. This phenomenon observed peripherally might reflect similar characteristics in the cerebral circulation.

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5 Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz-rTMS in the three groups tested. The 5 Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.

Migraine–Patent Foramen Ovale Connection: Role of Prominent Eustachian Valve and Large Chiari Network in Migrainous Patients

We postulated that eustachian valve (EV) and Chiari network (CN) play a role in the pathophysiology of both migraine and paradoxical embolism. We sought to prospectively investigate the potential role of EV/CN in migraine-patent foramen ovale (PFO) connection assessing their prevalence by intracardiac echocardiography (ICE) in patients with migraine submitted to PFO transcatheter closure. Over a 24-month period, we prospectively enrolled 50 consecutive patients (mean age 37+/-12.5 years, 38 females) with previous stroke and migraine referred to our centre for PFO catheter-based closure. Migraine with aura (MwA) and migraine without aura (MwoA) were diagnosed according to the International Headache Society criteria and Migraine Disability Assessment Score (MIDAS). Patients who met the inclusion criteria for closure underwent ICE study and closure attempt. After ICE study, a prominent EV or CN were diagnosed on ICE in 41 patients (82%): 100% in MwA patients, 60% in MwoA patients (p<0.001) and in 55.5% of patients with no migraine. Patients with EV and CN had more frequently a curtain pattern on TC Doppler, a larger right-to-left shunt, more recurrent cerebral paradoxical embolism before closure, and a higher preoperative MIDAS score. Patients with EV/CN had a larger decrease in MIDAS score after closure. This study suggests that EV and CN have a deep impact on MwA and paradoxical embolism pathophysiology: EV, CN, and MwA should be considered as adjunctive risk factors for paradoxical embolism in the work-up of both symptomatic and asymptomatic PFO patients.

Visual evoked potential latency, amplitude and habituation in migraine: A longitudinal study

Objective It has not been previously studied with a paired longitudinal design if visual excitability changes occur in the preattack period across the migraine cycle, or how excitability and habituation relate to migraine-attack severity, clinical photophobia and serotonin metabolism. Methods Monocular 62′ check reversals were applied in 33 adult migraine patients without aura (MwoA), 8 with aura (MA) and 31 controls. VEP was recorded in four blocks of 50 stimuli. P1 (P100) and N2 (N145) latency and N1P1 and P1N2 amplitude were measured. Serotonin was measured in plasma and platelets sampled before each session. Sessions were classified as preattack, attack, postattack or interictal. Results Migraine patients had significantly higher P1N2 amplitude before the attack compared to a paired interictal recording ( n = 13, p = 0.03), but habituation difference was not found. MA patients had significantly higher P1N2 and N1P1 amplitude than controls and MwoA. P1 latency correlated positively with headache history duration. During attack, a positive correlation between P1N2 amplitude habituation and serotonin emerged in MA patients. Conclusions Increased VEP P1N2 amplitude was observed within a few days before the attack. Visual cortex excitability seems to be generally increased in MA as compared to MwoA patients and controls. Significance Increased excitability of the visual cortex seems to be detectable in the preattack state, supporting the concept of a cyclic CNS dysfunction in migraine.