Episodic Migraine Patients Research Articles

Gray Matter Structural Alterations in Chronic and Episodic Migraine: A Morphometric Magnetic Resonance Imaging Study.

This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine. Cohort study. Spanish community. Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition. Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed. Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters. Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients.

Functional Alterations in the Posterior Insula and Cerebellum in Migraine Without Aura: A Resting-State MRI Study.

Background: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis.Methods: Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach.Results: Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC.Conclusion: Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.

Alternative Microstructural Measures to Complement Diffusion Tensor Imaging in Migraine Studies with Standard MRI Acquisition.

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine.

Development and Internal Validation of a Multivariable Prediction Model for Individual Episodic Migraine Attacks Based on Daily Trigger Exposures.

To develop and internally validate a multivariable predictive model for days with new-onset migraine headaches based on patient self-prediction and exposure to common trigger factors. Accurate real-time forecasting of one's daily risk of migraine attack could help episodic migraine patients to target preventive medications for susceptible time periods and help decrease the burden of disease. Little is known about the predictive utility of common migraine trigger factors. We recruited adults with episodic migraine through online forums to participate in a 90-day prospective daily-diary cohort study conducted through a custom research application for iPhone. Every evening, participants answered questions about migraine occurrence and potential predictors including stress, sleep, caffeine and alcohol consumption, menstruation, and self-prediction. We developed and estimated multivariable multilevel logistic regression models for the risk of a new-onset migraine day vs a healthy day and internally validated the models using repeated cross-validation. We had 178 participants complete the study and qualify for the primary analysis which included 1870 migraine events. We found that a decrease in caffeine consumption, higher self-predicted probability of headache, a higher level of stress, and times within 2days of the onset of menstruation were positively associated with next-day migraine risk. The multivariable model predicted migraine risk only slightly better than chance (within-person C-statistic: 0.56, 95% CI: 0.54, 0.58). In this study, episodic migraine attacks were not predictable based on self-prediction or on self-reported exposure to common trigger factors. Improvements in accuracy and breadth of data collection are needed to build clinically useful migraine prediction models.

Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study.

Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine. The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components. Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake. The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.clinicaltrials.gov NTC04324710.

Neurophysiological correlates of abnormal auditory processing in episodic migraine during the interictal period.

The characteristics of the hypersensitivity to auditory stimuli during the interictal period in episodic migraine are discussed. The combined use of event-related potentials, time-frequency power and phase-synchronization can provide relevant information about the time-course of sensory-attentional processing in migraine and its underlying mechanisms. The aim of this nested case-control study was to examine these processes in young, female, episodic migraine patients interictally and compare them to controls using an active auditory oddball task. We recorded, using 20 channels, the electrophysiological brain activity of 21 women with episodic migraine without aura and 21 healthy matched controls without family history of migraine, during a novelty oddball paradigm. We collected sociodemographic and clinical data as well as scores related to disability, quality of life, anxiety and depression. We calculated behavioural measures including reaction times, hit rates and false alarms. Spectral power and phase-synchronization of oscillatory activity as well as event-related potentials were obtained for standard stimuli. For target and novel stimuli, event-related potentials were acquired. There were no significant differences at the behavioural level. In migraine patients, we found an increased phase-synchronization at the theta frequency range and a higher N1 response to standard trials. No differences were observed in spectral power. No evidence for a lack of habituation in any of the measures was seen between migraine patients and controls. The Reorienting Negativity was reduced in migraine patients as compared to controls on novel but not on target trials. Our findings suggest that migraine patients process stimuli as more salient, seem to allocate more of their attentional resources to their surrounding environment, and have less available resources to reorient attention back to the main task.

Searching for Predictors of Migraine Chronification: a Pilot Study of 1911A>G Polymorphism of TRPV1 Gene in Episodic Versus Chronic Migraine.

Transient receptor potential vanilloid type 1 (TRPV1) receptors activated by heat and capsaicin are expressed in trigeminal nociceptive neurons and implicated in the generation of migraine pain. Genetic studies suggested that single-nucleotide polymorphism (SNP) 1911A>G (rs8065080), leading to amino acid substitution Ile585Val, in the TRPV1 gene affects functional activity of TRPV1 receptors and is involved in different pain conditions. However, this polymorphism has not been tested in migraine patients. The objective of this pilot study was to investigate genetic factors of migraine susceptibility. We evaluated frequency distribution of AA, AG, and GG variants of SNP 1911A>G in the TRPV1 gene in patients with episodic and chronic migraine compared with healthy individuals. The study included 46 patients diagnosed with migraine (27 episodic and 19 chronic) and 50 healthy individuals as a control group. DNA from peripheral blood was used to test TRPV1 SNP using allele-specific PCR combined with gel electrophoresis. The genotype frequency distribution in episodic migraine was comparable with that in controls (AA 33%, AG 56%, GG 11% and AA 34%, AG 46%, GG 20%, respectively). On the contrary, in chronic migraine, the distribution differed significantly (p < 0.05) (AA 68%, AG 32%, GG 0%). This are first indications for a distinctive genotype frequency distribution of TRPV1 1911A>G in chronic migraine patients compared with episodic migraine patients and controls. Our data confirm a different predisposition to chronic pain in migraine and give a prerequisite for a new look at the nature of chronification of migraine, proposing that the absence of GG genotype may be considered as possible risk biomarker of episodic migraine evolution to chronic form.

Peripheral, Interictal Serum S100B Levels are Not Increased in Chronic Migraine Patients.

The trigemino-vascular system (TVS) plays a key role in migraine pathophysiology. Glial cells are abundant in the TVS system and mainly in the trigeminal ganglion. S100B protein is a calcium-binding protein, found in the cytoplasm of glial cells in the central nervous system, which is released in response to inflammatory stimuli. Previous works analyzing S100B in migraineurs have offered contradictory results. In this case-control study, we analyzed serum levels of S100B as a possible biomarker of the glial TVS activation in chronic migraine (CM). The study group consisted of patients attending our clinic with CM and, as control groups, patients with episodic migraine (EM), cluster headache (CH) outside of a bout and healthy volunteers (HV) with no headache history. S100B levels were determined interictally in peripheral blood samples by ELISA. We assessed serum samples from 43 patients with CM, 19 with EM, 29 HV (mostly women), and 22 with (CH). S100B levels in CM (mean 22.9±9.8 pg/mL) were not different (P=.727) when compared to EM patients (21.2±9.3 pg/mL), difference of 1.7 (95% CI -5.7 to 8.9), CH patients (22.4±7.8 pg/mL), difference of 0.5 (-5.7 to 6.7), and HV (20.6±8.3 pg/mL), difference of 2.3 (-3.7 to 8.3). In contrast to other neuropeptides such as calcitonin gene-related-peptide and vasoactive intestinal peptide, which are increased in CM, interictal serum S100B levels are not elevated in these patients. According to our results, S100B levels do not seem to be a useful peripheral biomarker of the glial TVS activation in CM.

Estimating the savings associated with a migraine-free life: results from the Spanish Atlas.

Migraine is a common and costly neurological disorder. The aims of this study were to quantify the costs of chronic (CM) and episodic migraine (EM) in Spain, evaluating the impact of psychiatric comorbidities and disability, and to estimate the economic savings associated with reducing the number of migraine-days by 50%. This was an observational, cross-sectional analysis of data from migraine patients who participated in the Spanish Migraine Atlas. The participants were invited to complete a structured questionnaire including the following scales: the Headache Needs Assessment, the Hospital Anxiety and Depression Scale, and the Migraine Disability Assessment Scale (MIDAS). A total of 475 patients were included, of whom 187 had CM (39.4%). Total costs per patient/year were: €16578.2±€34568.1 for CM and €6227.8±€6515.7 for EM. A higher degree of disability, according to MIDAS, significantly increased the total cost of migraine, while the presence of psychiatric comorbidity increased costs for EM patients only. A reduction of 1 migraine-day per month decreased average total costs by €744.14 per patient/year for EM and €663.20 per patient/year for CM, while a reduction in the number of migraine-days by 50% would result in economic savings of €2232.44 per patient/year (R2 =0.927) for EM and €6631.99 per patient/year (R2 =0.886) for CM. The costs associated with migraine were driven by migraine frequency and the degree of disability, whereas psychiatric comorbidity only influenced the cost of EM. These results highlight the need to optimize migraine management to reduce the economic migraine burden. Future studies are needed to confirm our results.

The role of the immune system and the biomarker CD3\u2009+\u2009CD4\u2009+\u2009CD45RA\u2212CD62L\u2212 in the pathophysiology of migraine

The role of the immune system as an integral component of the inflammatory response in the pathophysiology of migraine remains unclear. The aim of this study was to evaluate the differences in immune system parameters (acquired immunity parameters) in patients with episodic migraine (EM) and in healthy controls. In EM patients, we aimed to determine whether the changes found in peripheral blood parameters were related to migraine severity according to the standardised MIDAS and HIT-6 tests. Forty-nine patients with EM and 50 healthy controls were included in this study. The authors compared different lymphocyte parameters obtained by multicolor flow cytometry in the EM and control groups by performing statistical tests. The relationship between the changes in peripheral blood parameters and migraine severity in EM patients was investigated using correlation and regression analysis. EM patients showed higher values than healthy controls, especially in nine parameters: relative count of lymphocytes, relative and absolute counts of CD3 T cells, relative and absolute counts of CD8 suppressor cytotoxic T cells, relative and absolute counts of CD4 + TEMRA (terminally differentiated helper T lymphocytes), absolute count of CD8 naïve T cells, and absolute count of CD19 switched memory B cells. Among the lymphocyte parameters, CD4 + TEM (effector memory helper T lymphocytes) and CD8 + TEMRA (terminally differentiated cytotoxic T lymphocytes) were statistically significantly associated with HIT-6. Patients with a CD4 + TEM value below 15 had a high probability (90%) that the HIT-6 value would be higher than 60. The results of this study show that EM patients have changes in immune system parameters measured in the peripheral blood. Changes in the abundance of CD4 + TEM could be used as a biomarker for disease severity.

Dopaminergic symptoms in migraine: A cross-sectional study on 1148 consecutive headache center-based patients.

Dopaminergic symptoms may be extremely pronounced in some migraine patients during the attack, representing a major source of disability. We aimed to carefully characterize the clinical picture of migraine patients with dopaminergic symptoms in a large patients' population as a putative migraine endophenotype, allowing more precise disease management, treatment and outcome prediction. We screened 1148 consecutive tertiary care episodic and chronic migraine patients with face-to-face interviews collecting thorough data on lifestyle, socio-demographic factors, and clinical migraine features. We identified 374 patients with migraine with dopaminergic symptoms (32.6%). The most frequent dopaminergic symptom was yawning followed by somnolence, nausea, vomiting, fatigue, mood changes and diuresis. Migraine patients with dopaminergic symptoms had longer attack duration (OR: 1.82; 95% CI: 1.41-2.36, p < 0.0001), more frequent osmophobia (OR: 2.01; 95% CI: 1.50-2.69, p < 0.0001), allodynia (OR: 1.43; 95% CI: 1.10-1.85, p = 0.0071) and unilateral cranial autonomic symptoms (OR: 1.31; 95% CI: 1.01-1.68, p = 0.045), but used less preventative treatments (OR: 0.74; 95% CI: 0.57-0.98, p = 0.033) than patients without dopaminergic symptoms. Migraine patients with dopaminergic symptoms are characterized by a full-blown, more disabling migraine. Dopaminergic system modulation should be carefully considered in individuals with migraine with dopaminergic symptoms for both acute and preventative treatments in future ad hoc designed studies.

Volume of the rectus capitis posterior minor muscle in migraine patients: a cross-sectional structural MRI study

BackgroundNeck pain in migraine patients is very prevalent between and during migraine attacks, but the underlying mechanism behind neck pain in migraine is unknown. The neck muscle rectus capitis posterior minor muscle (RCPmi) may be important since it is connected to the occipital dura mater. In this study, we examined the RCPmi volume in migraine patients and compared with controls.MethodsWe conducted a cross-sectional MRI study examining muscle volume in 40 episodic migraine patients and 40 controls in preexisting images from prior studies. Three-dimensional T1 weighted sequences were collected with a 3.0 T MRI Scanner. The volume of RCPmi was examined by manually tracing the muscle circumference with Horos medical image viewer. The observer was blinded to participant information. No information regarding neck pain status during or between migraine attacks were available.ResultsThe mean RCPmi volume was 1.22cm3 in migraine patients and 1.17cm3 in controls (p = 0.549). We found no differences in RCPmi volume on the pain side vs. the non-pain side (p = 0.237) in patients with unilateral migraine. There were no association between the muscle volume and years with migraine, headache or migraine frequency, age or BMI.ConclusionsWe found no difference in RCPmi volume between migraine patients and controls, suggesting no structural RCPmi pathology in migraine.

Mechanical punctate pain threshold is associated with headache frequency and phase in patients with migraine.

Previous studies regarding the quantitative sensory testing are inconsistent in migraine. We hypothesized that the quantitative sensory testing results were influenced by headache frequency or migraine phase. This study recruited chronic and episodic migraine patients as well as healthy controls. Participants underwent quantitative sensory testing, including heat, cold, and mechanical punctate pain thresholds at the supraorbital area (V1 dermatome) and the forearm (T1 dermatome). Prospective headache diaries were used for headache frequency and migraine phase when quantitative sensory testing was performed. Twenty-eight chronic migraine, 64 episodic migraine and 32 healthy controls completed the study. Significant higher mechanical punctate pain thresholds were found in episodic migraine but not chronic migraine when compared with healthy controls. The mechanical punctate pain thresholds decreased as headache frequency increased then nadired. In episodic migraine, mechanical punctate pain thresholds were highest (p < 0.05) in those in the interictal phase and declined when approaching the ictal phase in both V1 and T1 dermatomes. Linear regression analyses showed that in those with episodic migraine, headache frequency and phase were independently associated with mechanical punctate pain thresholds and accounted for 29.7% and 38.9% of the variance in V1 (p = 0.003) and T1 (p < 0.001) respectively. Of note, unlike mechanical punctate pain thresholds, our study did not demonstrate similar findings for heat pain thresholds and cold pain thresholds in migraine. Our study provides new insights into the dynamic changes of quantitative sensory testing, especially mechanical punctate pain thresholds in patients with migraine. Mechanical punctate pain thresholds vary depending on headache frequency and migraine phase, providing an explanation for the inconsistency across studies.

PND89 CLINICAL, ECONOMIC AND HUMANISTIC OUTCOMES OF PATIENTS WITH EPISODIC AND CHRONIC MIGRAINE ACCORDING TO THEIR LEVEL OF PATIENT ACTIVATION IN THE USE

Activated patients are those who have the motivation, knowledge, skills, and confidence to make effective decisions to manage their health. The objective of this study was to compare patient characteristics and economic outcomes of patients with episodic migraine (EM) and chronic migraine (CM) by level of patient activation. Data were included from the 2017 US National Health and Wellness Survey (NHWS), a self-administered, nationally representative, Internet-based questionnaire of US adults. Patients with self-reported physician diagnosis of migraine were included in this analysis. Subgroups included patients with EM (0-14 headache days), and CM (≥15 headache days) in the past 30 days. Respondents were grouped into four levels of activation based on the Patient Activation Measure (PAM), from low (1) to high (4). Data collected included patient characteristics, health-related quality of life (EQ5D-5L) and resource utilization. Descriptive and bivariate analyses examined the differences between PAM groups. Overall, 6,094 migraine patients were included (87% EM; 13% CM). 76.6% of patients had higher levels of activation (levels 3 and 4). Most patients were females (74.1%, level 1; 77.2%, level 4). Patients with higher levels of activation were more likely to be older, have higher income levels, and have private insurance, and were less likely to be obese. Patients in PAM level 1 had significantly more healthcare provider visits (means, 7.07 vs. 6.57 vs. 5.95 vs. 5.57, p=0.003), higher rates of absenteeism (means, 16.38 vs. 10.94 vs. 8.79 vs. 9.35, p<0.001), higher total indirect costs (means, $14,789.07 vs. $11,779.32 vs. $10,501.34 vs $10,134.82, p<0.001) and lower EQ5D-5L Index score (means, 0.65 vs. 0.71 vs. 0.76 vs. 0.78, p<0.001) than those with higher PAM levels. These findings appear to be driven largely by EM versus CM patients. Increasing activation level in patients with migraine was associated with better health and economic outcomes, particularly in EM patients.

Impact of dissociative experiences in migraine and its close relationship with osmophobia

ABSTRACT Objective Migraine is a complex episodic disease manifested by dysfunction of the sympathetic nervous system along with numerous neuropsychiatric symptoms. The aim of this study was to identify the dissociative symptoms with neurobiological similarities in episodic and chronic migraine patients and to evaluate their correlation with migraine frequency and severity of attacks. Methods The study included 61 episodic, 45 chronic migraine patients diagnosed using the criteria of the International Headache Society and 54 healthy control subjects. Dissociative Experiences Scale, Beck Anxiety Scale and Beck Depression Inventory were filled with the interviews. Demographic, clinical and headache characteristics of the patients were recorded according to migraine types. Results were analyzed by Kruskal–Wallis method and Spearman’s correlation tests. Results Dissociative symptoms were more common in the patients with chronic migraine, and there was a statistically significant difference between the chronic migraine group and the episodic migraine and control groups (p = 0.001, p < 0.001). Dissociative experiences were correlated with depression and anxiety findings, and in both groups, there was a significant correlation between clinical characteristics of migraine and osmophobia in the controlled partial correlation analysis (p < 0.05). Conclusion This study revealed that dissociative symptoms are more common especially in patients with chronic migraine and there is a significant association with osmophobia in both migraine groups. According to these data, we think that dissociative symptoms in chronic migraine patients will be questioned and osmophobia may be a guide in this regard.

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case-Control and Case-Crossover Settings: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients. Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models. Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial

BackgroundEmerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects.MethodsThe present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method.ResultsThe mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22–26.77)) compared to placebo (31.16 (25.51–36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03–173.49) ng/L) than the patients in the placebo arm (188.35 (167.15–209.54) ng/L) (P value = 0.022).ConclusionAccording to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings.Trial registrationThe trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Multisensorial Perception in Chronic Migraine and the Role of Medication Overuse

Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by 2 or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (ie, fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine (CM) patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in CM patients (n = 63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (P < .0001). Triptan MOH patients (n = 23) presented significantly less fission effects than other CM groups (P = .008). This exploratory study suggests that CM – both with and without medication overuse – is associated to a higher visual cortical responsiveness which causes deficit of multisensorial processing, as assessed by the SIFI. PerspectiveThis observational study shows reduced susceptibility to the SIFI in CM, confirming and extending previous results in episodic migraine. MOH contributes to this phenomenon, especially in case of triptans.

White matter changes in chronic and episodic migraine: a diffusion tensor imaging study

BackgroundWhite matter alterations have been observed in patients with migraine. However, no microstructural white matter alterations have been found particularly in episodic or chronic migraine patients, and there is limited research focused on the comparison between these two groups of migraine patients.MethodsFifty-one healthy controls, 55 episodic migraine patients and 57 chronic migraine patients were recruited and underwent brain T1-weighted and diffusion-weighted MRI acquisition. Using Tract-Based Spatial Statistics (TBSS), fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were compared between the different groups. On the one hand, all migraine patients were compared against healthy controls. On the other hand, patients from each migraine group were compared between them and also against healthy controls. Correlation analysis between clinical features (duration of migraine in years, time from onset of chronic migraine in months, where applicable, and headache and migraine frequency, where applicable) and Diffusion Tensor Imaging measures was performed.ResultsFifty healthy controls, 54 episodic migraine and 56 chronic migraine patients were finally included in the analysis. Significant decreased axial diffusivity (p < .05 false discovery rate and by number of contrasts corrected) was found in chronic migraine compared to episodic migraine in 38 white matter regions from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas. Significant positive correlation was found between time from onset of chronic migraine and mean fractional anisotropy in the bilateral external capsule, and negative correlation between time from onset of chronic migraine and mean radial diffusivity in the bilateral external capsule.ConclusionsThese findings suggest global white matter structural differences between episodic migraine and chronic migraine. Patients with chronic migraine could present axonal integrity impairment in the first months of chronic migraine with respect to episodic migraine patients. White matter changes after the onset of chronic migraine might reflect a set of maladaptive plastic changes.

Headache frequency associates with brain microstructure changes in patients with migraine without aura

Neuroimaging studies have implicated abnormal brain microstructure in episodic migraine (EM), but whether the pattern is altered during migraine chronification is not well known. Fifty-six patients with migraine without aura, including 39 EM patients and 17 chronic migraine (CM) patients, and 35 healthy controls (HCs) were enrolled. Voxel-based morphometry analysis was performed to assess gray matter (GM) volume differences among groups and their association with clinical feature was examined. Compared with the HC group, both migraine groups showed increased GM volume in the periaqueductal grey matter (PAG) and decreased GM volume in the anterior cingulate cortex (ACC). The left hippocampus/parahippocampal gyrus (PHG) volume of the HC group was smaller than that of the EM group, but was larger than that of the CM group. For the dorsolateral prefrontal cortex (dlPFC), the EM group showed the smallest GM volume while the CM group had the largest volume. Higher headache frequency was associated with greater GM volume in the PAG and dlPFC, but was associated with smaller GM volume in the ACC and hippocampus/PHG across all patients. GM volume changes in regions involved in pain generation and control are potential neural mechanism underlying migraine, and are associated with migraine types and headache frequency.