The MIGREX study: Prevalence and risk factors of sexual dysfunction among migraine patients.

BACKGROUND: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. OBJECTIVE: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. METHOD: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. RESULTS: We included 306 patients (85.6% women, mean age 42.3±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17-5.00]; p<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.

Estimation of the density of veins from susceptibility-weighted imaging by using Mamdani fuzzy-type rule-based system. Investigating the neurovascular coupling in migraine.

BACKGROUND AND PURPOSE: An impaired neurovascular coupling has been described as a possible player in neurodegeneration and cognitive decline. Migraine is a recurrent and incapacitating disorder that starts early in life and has shown neurovascular coupling abnormalities. Despite its high prevalence, the physiology and underlying mechanisms are poorly understood. In this context, new biomarkers from magnetic resonance imaging (MRI) are needed to bring new knowledge into the field. The aim of this study was to determine the vein density from Susceptibility-Weighted Imaging (SWI) MRI, in subjects with migraine and healthy controls; and to assess whether it relates to Resting-State functional MRI (RS-fMRI). MATERIALS AND METHODS: The cohort included 30 healthy controls and 70 subjects with migraine (26 episodic, 44 chronic) who underwent a brain 3.0 T MRI. Clinical characteristics were also collected. Maps of density of veins were generated based on a Mamdani Fuzzy-Type Rule-Based System from the SWI MRI. Mean values of vein density were obtained in grey (GM) and white matter (WM) Freesurfer lobar parcellations. The Amplitude of Low-Frequency Fluctuations (ALFF) image was calculated for the RS-fMRI, and the mean values over the parcellated GM lobes were estimated. Differences between groups were assessed through and analysis of variance (age, sex, education and anxiety as covariates; p < 0.05), followed by post-hoc comparisons. Associations were run between clinical and MRI-derived variables. RESULTS: When comparing the density of veins in GM, no differences between groups were found, neither associations with clinical variables. The density of veins was significantly higher in the WM of the occipital lobe for subjects with chronic migraine compared to controls (30%, p < 0.05). WM vein density in either frontal, temporal or cingulate regions was associated with clinical variables such as headache days, disability scores, and cognitive impairment (r between 0.25 and 0.41; p < 0.05). Mean values of ALFF did not differ significantly between controls and subjects with migraine. Strong significant associations between vein density and ALFF measures were obtained in most GM lobes for healthy subjects (r between 0.50 and 0.67; p < 0.05), instead, vein density in WM was significantly associated with ALFF for subjects with migraine (r between 0.32 and 0.58; p < 0.05). CONCLUSIONS: Results point towards an increase in vein density in subjects with migraine, when compared to healthy controls. In addition, the association between GM vein density and ALFF found in healthy subjects was lost in migraine. Taken together, these results support the idea of abnormalities in the neurovascular coupling in migraine. Quantitative SWI MRI indicators in migraine might be an interesting target that may contribute to its comprehension.

A study of differential microRNA expression profile in migraine: the microMIG exploratory study.

BACKGROUND: Several studies have described potential microRNA (miRNA) biomarkers associated with migraine, but studies are scarcely reproducible primarily due to the heterogeneous variability of participants. Increasing evidence shows that disease-related intrinsic factors together with lifestyle (environmental factors), influence epigenetic mechanisms and in turn, diseases. Hence, the main objective of this exploratory study was to find differentially expressed miRNAs (DE miRNA) in peripheral blood mononuclear cells (PBMC) of patients with migraine compared to healthy controls in a well-controlled homogeneous cohort of non-menopausal women. METHODS: Patients diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-3) and healthy controls without familial history of headache disorders were recruited. All participants completed a very thorough questionnaire and structured-interview in order to control for environmental factors. RNA was extracted from PBMC and a microarray system (GeneChip miRNA 4.1 Array chip, Affymetrix) was used to determine the miRNA profiles between study groups. Principal components analysis and hierarchical clustering analysis were performed to study samples distribution and random forest (RF) algorithms were computed for the classification task. To evaluate the stability of the results and the prediction error rate, a bootstrap (.632 + rule) was run through all the procedure. Finally, a functional enrichment analysis of selected targets was computed through protein-protein interaction networks. RESULTS: After RF classification, three DE miRNA distinguished study groups in a very homogeneous female cohort, controlled by factors such as demographics (age and BMI), life-habits (physical activity, caffeine and alcohol consumptions), comorbidities and clinical features associated to the disease: miR-342-3p, miR-532-3p and miR-758-5p. Sixty-eight target genes were predicted which were linked mainly to enriched ion channels and signaling pathways, neurotransmitter and hormone homeostasis, infectious diseases and circadian entrainment. CONCLUSIONS: A 3-miRNA (miR-342-3p, miR-532-3p and miR-758-5p) novel signature has been found differentially expressed between controls and patients with migraine. Enrichment analysis showed that these pathways are closely associated with known migraine pathophysiology, which could lead to the first reliable epigenetic biomarker set. Further studies should be performed to validate these findings in a larger and more heterogeneous sample.

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers.

BACKGROUND: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. METHODS: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. RESULTS: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. CONCLUSIONS: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

The MIGREX study: Prevalence and risk factors of sexual dysfunction among migraine patients.

BACKGROUND: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. OBJECTIVE: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. METHOD: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. RESULTS: We included 306 patients (85.6% women, mean age 42.3±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17-5.00]; p<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.

Evaluation of the concomitant use of oral preventive treatments and onabotulinumtoxinA in chronic migraine: the PREVENBOX study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. METHODS: This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. RESULTS: We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%; P < 0.001). CONCLUSIONS: Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.

Early efficacy and late gain in chronic and high-frequency episodic migraine with onabotulinumtoxinA.

BACKGROUND AND PURPOSE: The aim was to analyse the clinical characteristics of a long-term follow-up of patients with chronic and high-frequency episodic migraine in treatment with onabotulinumtoxinA. METHODS: Patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) according to the International Classification of Headache Disorders 3 beta were included. A comparative analysis was carried out at each study time point identifying outcome measures according to initial diagnosis and treatment duration. RESULTS: In all, 578 patients were recruited and after 24 months outcome data were collected from 100 patients: 84.0% CM and 16.0% HFEM. After 24 months, headache frequency was significantly reduced by 10.5 days from baseline, 64.0% reported a ≥50% reduction in pain intensity and 70.0% of patients had ≥50% reduction in analgesic use. Comparing baseline diagnoses, at month 6 CM patients presented higher mean reduction in frequency (CM 44.3% ± 32.6% vs. HFEM 34.6% ± 24.8%) and analgesic use (CM 53.6% ± 35.4% vs. HFEM 39.3% ± 33.2%). At month 12, the mean reduction in frequency was similar in CM and HFEM patients (CM 44.7% ± 33.4% vs. HFEM 41.2% ± 28.2%). Improvement in pain intensity, analgesic use and Migraine Disability Assessment were proportional in both diagnoses. CONCLUSIONS: OnabotulinumtoxinA efficacy is significant at 6 months in frequency and analgesic intake and remains stable during follow-up, whilst the intensity of pain decreases in a stepwise manner at each time point of the analysis. The improvement in CM and HFEM patients is proportional and significant after 1 year of treatment.