Migraine With Aura Group Research Articles

The Relationship Between the Circle of Willis Variations and White Matter Hyperintensities in Different Migraine Subtypes

It is known that the Circle of Willis (CoW) variations and white matter hyperintensities (WMHs) are common in migraine. This retrospective study aims to investigate the relationship between the CoW variations and WMHs in migraine without aura (MWoA) (n=38) and migraine with aura (MWA) (n=40) patients. Demographic, clinical and radiological findings (the CoW variations and WMH burden) of the patients were recorded, and the relationship between the variables was evaluated in both groups. The overall incomplete COW, incomplete anterior or vertebrobasilar portion of the CoW, or the presence of fetal PCA showed no significant difference between the MWoA and MWA groups (p > 0.05). An incomplete posterior portion of the CoW was significantly higher in the MWA group than in the MWoA group (p = 0.034). In the WMA group, the visual aura was present in 72% of patients with the overall incomplete CoW; all of these were posterior portion variations of the CoW. When the WMH burden was compared, no significant difference was seen between the MWoA and MWA groups (p > 0.05). Among patients with the CoW variations in the MWoA group, the rate of patients without WMHs was significantly higher (p = 0.030). No significant difference was observed between the CoW variations and WMH burden in the MWA group (p > 0.05). In conclusion incomplete posterior portion of the CoW is common in MWA, and this variation is associated with visual aura but unrelated to WMH burden.

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

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

Reduction in retinal microvascular perfusion during migraine attacks.

To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA). Migraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non-invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs). We performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions. There was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (-7%, 95% confidence interval [CI] -10% to -4%; p = 0.006) and MO (-7%, 95% CI -10% to -3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI -3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye. These results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine.

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

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

Resting-state electroencephalography microstate dynamics altered in patients with migraine with and without aura-A pilot study.

To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.

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

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

Migraine with aura associates with a higher artificial intelligence: ECG atrial fibrillation prediction model output compared to migraine without aura in both women and men.

To compare the artificial intelligence-enabled electrocardiogram (AI-ECG) atrial fibrillation (AF) prediction model output in patients with migraine with aura (MwA) and migraine without aura (MwoA). MwA is associated with an approximately twofold risk of ischemic stroke. Longitudinal cohort studies showed that patients with MwA have a higher incidence of developing AF compared to those with MwoA. The Mayo Clinic Cardiology team developed an AI-ECG algorithm that calculates the probability of concurrent paroxysmal or impending AF in ECGs with normal sinus rhythm (NSR). Adult patients with an MwA or MwoA diagnosis and at least one NSR ECG within the past 20 years at Mayo Clinic were identified. Patients with an ECG-confirmed diagnosis of AF were excluded. For each patient, the ECG with the highest AF prediction model output was used as the index ECG. Comparisons between MwA and MwoA were conducted in the overall group (including men and women of all ages), women only, and men only in each age range (18 to <35, 35 to <55, 55 to <75, ≥75 years), and adjusted for age, sex, and six common vascular comorbidities that increase risk for AF. The final analysis of our cross-sectional study included 40,002 patients (17,840 with MwA, 22,162 with MwoA). The mean (SD) age at the index ECG was 48.2 (16.0) years for MwA and 45.9 (15.0) years for MwoA (p < 0.001). The AF prediction model output was significantly higher in the MwA group compared to MwoA (mean [SD] 7.3% [15.0%] vs. 5.6% [12.4%], mean difference [95% CI] 1.7% [1.5%, 2.0%], p < 0.001). After adjusting for vascular comorbidities, the difference between MwA and MwoA remained significant in the overall group (least square means of difference [95% CI] 0.7% [0.4%, 0.9%], p < 0.001), 18 to <35 (0.4% [0.1%, 0.7%], p=0.022), and 35 to <55 (0.5% [0.2%, 0.8%], p < 0.001), women of all ages (0.6% [0.3%, 0.8%], p < 0.001), men of all ages (1.0% [0.4%, 1.6%], p=0.002), women 35 to <55 (0.6% [0.3%, 0.9%], p < 0.001), and men 18 to <35 (1.2% [0.3%, 2.1%], p=0.008). Utilizing a novel AI-ECG algorithm on a large group of patients, we demonstrated that patients with MwA have a significantly higher AF prediction model output, implying a higher probability of concurrent paroxysmal or impending AF, compared to MwoA in both women and men. Our results suggest that MwA is an independent risk factor for AF, especially in patients <55 years old, and that AF-mediated cardioembolism may play a role in the migraine-stroke association for some patients.

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study.

We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9±8.4years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2±1.1 vs 6.4±0.8m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P<.001), as well as higher dp-ucMGP (454.3±116.7pmol/L vs 379.8±126.6pmol/L, 95% CI of mean difference [34.63, 114.31], P<.001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP≥500pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P=.193). Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

Serum apolipoprotein E may be a novel biomarker of migraine.

Migraine attacks alter various molecules that might be related to the pathophysiology of migraine, such as serotonin, calcitonin gene-related peptide, and nitric oxide. The underlying pathophysiology of migraine is as yet unclear. We explored key proteins related to the pathogenesis of migraine here. Serum was collected from two patients with migraine with aura (MA) and seven patients with migraine without aura (MO) during attack-free periods and migraine attacks. Samples were analyzed using 2-dimensional gel electrophoresis. Nineteen protein spots were altered between the attack-free versus migraine attack periods. Mass spectrometric analysis was performed to identify the proteins within each of the 19 altered spots. Thirty-six proteins were significantly altered in samples collected during attack-free periods versus migraine attacks. The protein with the statistically most significant MASCOT/Mowse score (268±112) among lipoproteins was apolipoprotein (ApoE). In the MA and MO groups, ApoE protein levels were significantly higher during migraine attack than during the attack-free period (p<0.05). ApoE protein levels were also significantly increased in the MA group during the attack-free period compared to healthy controls and patients with tension type headaches (p<0.01). Migraine alters ApoE levels, especially in MA. ApoE might play an important role in the pathophysiology of migraine, and may act as a diagnostic biomarker of migraine.

Prevalence of Right to Left Shunts in Japanese Patients with Migraine: A Single-center Study.

Objective Several studies have shown an increased prevalence of right-to-left shunt (RLs) in migraine patients, particularly those with aura. However, the prevalence of RLs and its relation to Japanese patients with migraine are unknown. We investigated the prevalence of RLs in Japanese patients with migraine. Methods In total, 112 consecutive patients with migraine were recruited from our headache outpatient clinic. Migraine with aura (MA) and migraine without aura (MWOA) were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta-version). Contrast transcranial Doppler ultrasound was used to detect RLs, including patent foramen ovale (PFO). Then, the associations between RLs and patients' backgrounds and presence of aura were assessed. Results The overall prevalence of RLs and PFO in migraine patients was 54.5% and 43.8%, respectively. The prevalence of RLs and PFO in the MA group were significantly higher than in the MWOA group (RLs, 62.9% vs. 44.0%, p=0.046; PFO, 54.8% vs. 30.0%, p=0.008). There were no marked differences in the prevalence of large, middle and small shunts between MA and MWOA patients. Compared with the MWOA patients, the MA patients were younger (p=0.013) and had early onset age (p=0.013) and increased prevalence of photophobia (p=0.008). Conclusion RLs were found in over half of the Japanese patients with migraine. Our study suggests a possible link between RLs and MA.

Prevalence and characteristics of migraine in CADASIL.

Background and objective Migraine with aura (MA) is a major symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We assessed the spectrum of migraine symptoms and their potential correlates in a large prospective cohort of CADASIL individuals. Methods A standardized questionnaire was used in 378 CADASIL patients for assessing headache symptoms, trigger factors, age at first attack, frequency of attacks and associated symptoms. MRI lesions and brain atrophy were quantified. Results A total of 54.5% of individuals had a history of migraine, mostly MA in 84% of them; 62.4% of individuals with MA were women and age at onset of MA was lower in women than in men. Atypical aura symptoms were experienced by 59.3% of individuals with MA, and for 19.7% of patients with MA the aura was never accompanied by headache. MA was the inaugural manifestation in 41% of symptomatic patients and an isolated symptom in 12.1% of individuals. Slightly higher MMSE and MDRS scores and lower Rankin score were detected in the MA group. Conclusion MA is observed in almost half of all CADASIL patients. Atypical aura symptoms are reported by more than one in two of them. MA is often inaugural, can remain isolated and is not associated with the severity of the disorder.

Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine.

Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case–control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5′-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523–0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117–2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140–2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.

Painful heating for evaluating trigeminal small nerve fiber function in patients with migraine

Objective To study any functional changes in the trigeminal nociceptive system in cases of migraine with aura (MWA) using painful heat-evoked potentials (CHEPs), and to explore the value of CHEP in evaluating the trigeminal small nerve fibers of patients with MWA. Methods Sixty patients with MWA were recruited as the MWA group, and 60 healthy persons were selected as a normal control group. Thermal stimulation at 51 ℃ was applied to the skin above the patients' right and left eyebrows. The N wave latencies and N-P amplitudes of the CHEPs were recorded at the vertex (Cz) of the head. The intensity of the stimulus was graded using a visual analogue scale (VAS). Results In the control group the simulation produced no significant differences in the N550 or P750 latencies or in the N-P amplitudes. In the MWA group no significant differences were observed when the headache side was stimulated, but the N550 and P750 latencies were both significantly shorter than those of the control group and the N-P amplitude was significantly greater than that of the control group. The average VAS score on both sides in the patients with migraine was significantly higher than those of the control group. However, there was no significant difference in average VAS scores between the headache and non-headache sides of the patients with migraine. Conclusions CHEP is a reliable method for detecting any pathological changes in the trigeminal small nerve sensory pathway. Increased cutaneous allodynia in acute migraine attacks is detectable using CHEPs. Key words: Pain; Heat-evoked potentials; Migraine; Aura; Trigeminal nerves

当院における片頭痛患者の卵円孔開存の頻度に関する検討

Purpose: An increased prevalence of patent foramen ovale (PFO) has been reported in patients with migraine with aura compared with non-migraine subjects. This study aimed to investigate the prevalence of PFO in Japanese patients with migraine. Methods: Fifty-four consecutive patients with migraine were recruited from the headache outpatient clinic of our department. Migraine was diagnosed according to the International Classification of Headache Disorders, second edition. Patients were divided into migraine with aura (MWA) and migraine without aura (MWOA) groups. Transcranial ultrasound was performed, while contrast agent was injected intravenously with the Valsalva maneuver. PFO was diagnosed if micro-embolic signals in the right middle cerebral artery were identified soon after injection of contrast agent and Valsalva load release. Results: No significant differences in patient characteristics were observed between the MWOA group (n=22) and MWA group (n=32). The prevalence of PFO was 46.3% among all migraine patients, 56.3% in the MWA group, and 31.8% in the MWOA group. Patients with MWA thus tended to show a higher prevalence of PFO compared to those with MWOA (p = 0.077). Conclusion: The tendency toward an increased prevalence of PFO in the MWA group in this study suggests a possible association between MWA and PFO.

Spectral changes of near-infrared spectroscopy signals in migraineurs with aura reveal an impaired carbon dioxide-regulatory mechanism

Subjects suffering from migraine with aura (MwA) present an altered cerebral autoregulation during migraine attacks. It is still unclear whether MwA sufferers present a normal autoregulation during attack-free periods. In this study, we characterized cerebral autoregulation in the frequency domain by analyzing the spontaneous oscillations superimposed on the cerebral hemodynamic signals, as detected by near-infrared spectroscopy (NIRS). Ten healthy women (age: 38.4 +/- 9.5 years) and ten women suffering from MwA (age: 35.2 +/- 10.5 years) underwent NIRS recording in resting conditions and during breath-holding (BH). Being the NIRS signals during BH nonstationary, we used the Choi-Williams time-frequency distribution to perform spectral analysis. We considered 256 s of signals and quantified the variation in the power of the very-low frequencies (VLF: 20-40 mHz) and of the low frequencies (LF: 40-140 mHz) as response to BH. Results showed that BH increases the power in the LF band both in healthy and MwA subjects. Considering the signal of the deoxygenated hemoglobin, the average power increase in the LF band was equal to 20% +/- 15.4% for the healthy group and significantly lower, 4.8% +/- 8.3%, in the MwA group (Student's t test, P < 0.02). No significant difference was observed in the VLF band or in the oxygenated hemoglobin signal power variations of the LF and VLF bands. The resulting data reveal a possible impairment in the carbon dioxide-regulatory mechanism in MwA subjects.

Binocular Rivalry in Migraine

Cortical hyperexcitability in migraine could arise from abnormally weak inhibition or from strengthened intracortical excitatory mechanisms. The present study employed binocular rivalry to differentiate between these possibilities. Rivalry between static oriented grating patterns was examined in migraine with aura (MA), migraine without aura (MoA) and headache-free control participants. A non-significant trend toward elevated mean dominance intervals (monocular percepts, in seconds) was seen in both migraine groups at all contrasts. Second, significant interocular differences in rivalry dominance durations were seen in the MoA group compared with controls; this difference also approached significance in the MA group. Finally, both MA and MoA exhibited significantly greater visual discomfort than the control group in the presence of both static stripes and flickering visual stimuli. The rivalry results provide no support for weakened intracortical inhibition in migraine. Optical or neural precortical differences in the eyes' input strengths paired with enhanced recurrent cortical excitation can explain these findings.

High prevalence of Dopaminergic Premonitory Symptoms in migraine patients with Restless Legs Syndrome: a pathogenetic link?

In order to assess the prevalence of Dopaminergic Premonitory Symptoms (DPS) in migraine patients with Restless Legs Syndrome (RLS), we chose migraine patients from a large Italian clinical headache population previously investigated for an association between primary headaches and RLS. We evaluated a total sample of 164 patients with migraine, in particular 114 with migraine without aura (MO), 10 with migraine with aura (MA) and 40 with MO and MA in various combinations between them or with episodic tension-type headache (ETTH), defined as a "mixed group". About 20% of all migraine patients referred at least one of the following DPS: yawning, nausea, somnolence or food craving, confirming data already indicated in the literature. Among migraine patients with RLS (25.6%), DPS were referred from about half of the patients (47.6%) compared to those without RLS (47.6% vs. 13.1%; p<0.001). Based on migraine subtype, patients with MO referred DPS (26.3%) more frequently compared to the MA group and "mixed group" (12.0%, p<0.05), particularly in the presence of RLS (63.0% vs. 20.0%, p<0.01). No statistical differences were found between clinical and demographic data of the subgroups or related to medical conditions investigated (anxiety, depression, sleep disorders, body mass index). It is interesting that the chances of having RLS in migraine patients were more than 5 times higher in the presence of DPS. These results could support a hypothetical dopaminergic imbalance in RLS and migraine, as the dopamine is involved in the pathogenesis of both disorders and it is responsible for the migraine DPS reported above.

Migraine, patent foramen ovale and migraine triggers

Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MAgroup OR 2.7 [1.02–7.17] and in all migraine patients OR 2.5 [1.01–6.11]. According to our results, patients with migraine who have larger RLS tend to recognize activities that increase the extent of the shunt as a trigger of their migraine attacks.

Influence of MTHFR Genotype on Contingent Negative Variation And MRI Abnormalities in Migraine

The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke. The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non-migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case-control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor. One hundred and five 18-45 year old out-patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation. The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was 26.6%. Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities. This unrelated and clinical based case-control study showed that genetically induced hyper-homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.

MTHFR T677 Homozygosis Influences the Presence of Aura in Migraineurs

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.