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Background and purpose: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. Methods: All consecutive patients who met the definition criteria of influenza‐like illness during the influenza seasons 2010–2011 through 2021–2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. Results: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020–2021) and 21.69 cases per 1000 patients (season 2017–2018). The prevalence of headache was 66.1% (95% CI = 65.1%–67.1%), varying between 49.6% (season 2021–2022) and 80.1% (season 2010–2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. Conclusions: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections. [ABSTRACT FROM AUTHOR]

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial. [ABSTRACT FROM AUTHOR]

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longerterm exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns. [ABSTRACT FROM AUTHOR]

Background and purpose: Anti‐calcitonin gene‐related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti‐CGRP drugs in concomitant preventive treatment in patients with migraine. Methods: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti‐CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. Results: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti‐CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). Conclusions: Anti‐CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real‐life conditions. [ABSTRACT FROM AUTHOR]

Introduction: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine. Methods: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8–12 and 20–24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models. Results: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3–50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75–3) prior preventive treatments. At baseline patients had 14 (10–24) headache and 8 (5–11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8–12, and 48.8%, 36%, and 18.6% between weeks 20–24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0–12 and 12–24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20–24. Conclusion: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials' efficacy. Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316). [ABSTRACT FROM AUTHOR]

Background and purpose: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP MAb) may be considered after 12–18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. Methods: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti‐CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti‐CGRP MAb (T‐baseline); last month of first treatment period (T‐suspension); month of restart due to worsening (T‐worsening); and 3 months after resumption (T‐reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. Results: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T‐baseline was 20 (13) and MMD was 5 (6); at T‐suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T‐worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T‐reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). Conclusion: The results suggest that anti‐CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period. [ABSTRACT FROM AUTHOR]

Background: The burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost. Methods: Case–control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1–3, 4–7, 8–14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables. Results: The survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1–3 MHD also increased costs by 51.3%. Conclusions: Having migraine not only causes a massive impact on patients' quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1–3 MHD. [ABSTRACT FROM AUTHOR]

Objective To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. Design We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. Methods We included the demographic characteristics, effectiveness—reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates—and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20–24; exploratory 50% response predictors in the elderly were evaluated. Results In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66–86); mean age of controls was 42.9 years old(range: 38–49). Cases had a higher percentage of vascular risk factors (P  < .05),older age of onset (P  < .001) and more reported prior preventive treatments (P  < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20–24 weeks, with lower reduction in the MHD at 8–12 weeks (5 [7.2], 8 [9.1]; P  = .001) and a higher reduction in MMD at 20–24 weeks (10.7 [9.1], 9.2 [7.7]; P  = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P  = .03) and lower number of MHD at baseline (P  =.001) were associated with a 50% response in the elderly in univariate analysis. Conclusions Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly. [ABSTRACT FROM AUTHOR]

Current definitions of migraine that are based mainly on clinical characteristics do not account for other patient's features such as those related to an impaired quality of life, due to loss of social life and productivity, and the differences related to the geographical distribution of the disease and cultural misconceptions which tend to underestimate migraine as a psychosocial rather than neurobiological disorder. Global differences definition, care access, and health equity for headache disorders, especially migraine are reported in this paper from a collaborative group of the editorial board members of the Journal of Headache and Pain. Other components that affect patients with migraine, in addition to the impact promoted by the migraine symptoms such as stigma and social determinants, are also reported. [ABSTRACT FROM AUTHOR]

Introduction: Headache is a frequent symptom of infections. We aimed to characterize the clinical phenotype and duration of headache attributed to influenza infection. Methods: Prospective cohort study done in 53 primary care centers between January and April 2023. Patients were included if they had a confirmed influenza diagnosis, were older than 15 years and had a new-onset headache. Patients' demographics, prior medical history, headache phenotype and duration, associated symptoms and patients' outcomes were assessed. The International Classification of Headache Disorders criteria for headache attributed to a systemic viral infection, migraine and tension-type headache were assessed. Results: Of the 478 patients 75 fulfilled eligibility criteria. The mean age was 43, 56% were men, and 27% had a prior headache history. The headache phenotype was a bilateral headache (52%), with frontal topography (48%), pressing quality (61%), moderate intensity, rhinorrhea (79%), nasal congestion (76%), and photophobia (59%). All patients fulfilled headache attributed to acute systemic viral infection criteria, 43% fulfilled migraine criteria and 31% tension-type headache criteria. The median duration of the headache was four (Inter-quartile range: two-six) days. Conclusion: The clinical phenotype of headache attributed to influenza infection was similar to other infections, with more pronounced cranial autonomic symptoms. The headache was an early symptom and was self-limited within a few days. Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT05704335) [ABSTRACT FROM AUTHOR]

Introduction: Neuroimaging has revealed that migraine is linked to alterations in both the structure and function of the brain. However, the relationship of these changes with aging has not been studied in detail. Here we employ the Brain Age framework to analyze migraine, by building a machine-learning model that predicts age from neuroimaging data. We hypothesize that migraine patients will exhibit an increased Brain Age Gap (the difference between the predicted age and the chronological age) compared to healthy participants. Methods: We trained a machine learning model to predict Brain Age from 2,771 T1-weighted magnetic resonance imaging scans of healthy subjects. The processing pipeline included the automatic segmentation of the images, the extraction of 1,479 imaging features (both morphological and intensity-based), harmonization, feature selection and training inside a 10-fold cross-validation scheme. Separate models based only on morphological and intensity features were also trained, and all the Brain Age models were later applied to a discovery cohort composed of 247 subjects, divided into healthy controls (HC, n=82), episodic migraine (EM, n=91), and chronic migraine patients (CM, n=74). Results: CM patients showed an increased Brain Age Gap compared to HC (4.16 vs -0.56 years, P=0.01). A smaller Brain Age Gap was found for EM patients, not reaching statistical significance (1.21 vs -0.56 years, P=0.19). No associations were found between the Brain Age Gap and headache or migraine frequency, or duration of the disease. Brain imaging features that have previously been associated with migraine were among the main drivers of the differences in the predicted age. Also, the separate analysis using only morphological or intensity-based features revealed different patterns in the Brain Age biomarker in patients with migraine. Conclusion: The brain-predicted age has shown to be a sensitive biomarker of CM patients and can help reveal distinct aging patterns in migraine. [ABSTRACT FROM AUTHOR]

Diffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restrict the evaluation of complex structures. The objective of this study was to validate the reliability and robustness of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), with a typical diffusion MRI acquisition from a clinical context in comparison with DTI with application to clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Four DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics to establish reference results. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. To assess the discrimination power of the diffusion measures, we repeated the statistical comparisons with a region-based analysis employing reduced sample sizes with diverse subsets, decreasing 10 subjects per group for consecutive reductions, and using 5,001 different random subsamples. For each sample size, the stability of the diffusion descriptors was evaluated with the coefficient of quartile variation. AMURA measures showed a greater number of statistically significant differences in the reference comparisons between episodic migraine patients and controls compared to DTI. In contrast, a higher number of differences was found with DTI parameters compared to AMURA in the comparisons between both migraine groups. Regarding the assessments reducing the sample size, the AMURA parameters showed a more stable behavior than DTI, showing a lower decrease for each reduced sample size or a higher number of regions with significant differences. However, most AMURA parameters showed lower stability in relation to higher coefficient of quartile variation values than the DTI descriptors, although two AMURA measures showed similar values to DTI. For the synthetic signals, there were AMURA measures with similar quantification to DTI, while other showed similar behavior. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI. [ABSTRACT FROM AUTHOR]

Current definitions of migraine that are based mainly on clinical characteristics do not account for other patient's features such as those related to an impaired quality of life, due to loss of social life and productivity, and the differences related to the geographical distribution of the disease and cultural misconceptions which tend to underestimate migraine as a psychosocial rather than neurobiological disorder. Global differences definition, care access, and health equity for headache disorders, especially migraine are reported in this paper from a collaborative group of the editorial board members of the Journal of Headache and Pain. Other components that affect patients with migraine, in addition to the impact promoted by the migraine symptoms such as stigma and social determinants, are also reported. [ABSTRACT FROM AUTHOR]

Migraine is a severe and common primary headache disorder, characterized by pain as well as a plethora of non-painful symptoms. Among these, visual phenomena have long been known to be associated with migraine, to the point where they can constitute a hallmark of the disease itself. In this review we focus on two key visual disorders that are directly or indirectly connected to migraine: visual aura and visual snow syndrome (VSS). Visual aura is characterized by the transient presence of positive and negative visual symptoms, before, during or outside of a migraine attack. VSS is a novel stand-alone phenomenon which has been shown to be comorbid with migraine. We discuss key clinical features of the two disorders, including pathophysiological mechanisms, their differential diagnoses and best treatment practices. Our aim is to provide an aid for clinicians and researchers in recognizing these common visual phenomena, which can even appear simultaneously in patients with an underlying migraine biology. [ABSTRACT FROM AUTHOR]

Background and purpose: Several variables have been reported to be associated with anti‐calcitonin gene‐related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine‐learning (ML)‐based models can predict 6‐, 9‐ and 12‐month responses to anti‐CGRP receptor or ligand therapies among migraine patients. Methods: We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti‐CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML‐based predictive models for the response to anti‐CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated. Results: A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty‐four percent of patients had chronic migraine. ML‐based models using headache days/month, migraine days/month and the Headache Impact Test (HIT‐6) yielded predictions with an F1 score range of 0.70–0.97 and an area under the receiver‐operating curve score range of 0.87–0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above‐mentioned response rates. Conclusions: Our results show that ML models can predict anti‐CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real‐world setting. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened. Findings: Among the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups. Conclusions: Although a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing. [ABSTRACT FROM AUTHOR]

Background: Migraine represents a serious burden for national health systems. However, preventive treatment is not optimally applied to reduce the severity and frequency of headache attacks and the related expenses. Our aim was to assess the persistence to traditional migraine prophylaxis available in Spain and its relationship with the healthcare resource use (HRU) and costs. Methods: Retrospective observational study with retrospective cohort design of individuals with migraine treated with oral preventive medication for the first time from 01/01/2016 to 30/06/2018. One-year follow-up information was retrieved from the Big-Pac™ database. According to their one-year persistence to oral prophylaxis, two study groups were created and describe regarding HRU and healthcare direct and indirect costs using 95% confidence intervals (CI). The analysis of covariance (ANCOVA) was performed as a sensitivity analysis. Patients were considered persistent if they continued on preventive treatment until the end of the study or switched medications within 60 days or less since the last prescription. Non-persistent were those who permanently discontinued or re-initiated a treatment after 60 days. Results: Seven thousand eight hundred sixty-six patients started preventive treatment (mean age (SD) 48.2 (14.8) and 80.4% women), of whom 2,545 (32.4%) were persistent for 6 months and 2,390 (30.4%) for 12 months. Most used first-line preventive treatments were antidepressants (3,642; 46.3%) followed by antiepileptics (1,738; 22.1%) and beta-blockers (1,399; 17.8%). The acute treatments prescribed concomitantly with preventives were NSAIDs (4,530; 57.6%), followed by triptans (2,217; 28.2%). First-time preventive treatment prescribers were mostly primary care physicians (6,044; 76.8%) followed by neurologists (1,221; 15.5%). Non-persistent patients required a higher number of primary care visits (mean difference (95%CI): 3.0 (2.6;3.4)) and days of sick leave (2.7 (0.8;4.5)) than the persistent ones. The mean annual expenditure was €622 (415; 829) higher in patients who not persisted on migraine prophylactic treatment. Conclusions: In this study, we observed a high discontinuation rate for migraine prophylaxis which is related to an increase in HRU and costs for non-persistent patients. These results suggest that the treatment adherence implies not only a clinical benefit but also a reduction in HRU and costs. [ABSTRACT FROM AUTHOR]

Objective Previous studies have demonstrated that emotional stress, changes in lifestyle habits and infections can worsen the clinical course of migraine. We hypothesize that changes in habits and medical care during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine. Design Retrospective survey study collecting online responses from migraine patients followed-up by neurologists at three tertiary hospitals between June and July 2020. Methods We used a web-based survey that included demographic data, clinical variables related with any headache (frequency) and migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress. Results The response rate of the survey was 239/324 (73.8%). The final analysis included 222 subjects. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine during lockdown was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods or drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of post-traumatic stress, older age and living with five or more people. Conclusions Approximately half the migraine patients reported worsening of their usual pain during the lockdown. Worse clinical course in migraine patients was related to changes in triggers and the emotional impact of the lockdown. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the presence of post-coronavirus disease (COVID) symptoms. Background: No study has investigated the role of migraine as a risk factor for development of post-COVID symptoms. Methods: A case-control study including individuals hospitalised during the first wave of the pandemic (from February 20 to May 31, 2020) was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed. Results: Overall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months (SD 0.6) after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater (OR 1.70, 95% CI 1.29–2.25, P < 0.001) than in the non-migraine group. Fatigue was significantly more prevalent (OR 2.89, 95% CI 1.32–6.32, P = 0.008) in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected. Conclusion: Patients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms. [ABSTRACT FROM AUTHOR]

Objective Linear headache has been recently described as an episodic or chronic unilateral pain distributed along a fixed linear trajectory, which combines some characteristics of epicrania fugax and nummular headache. The aim of this study was to describe the clinical characteristics and therapeutic response of a series of 16 new patients. Design This is an observational study with a series of cases. Setting The study period encompassed June 2014 to June 2019. Demographic, clinical, and therapeutic response data were recorded. Methods We included all consecutive patients who presented pain with the following characteristics: sharply contoured, fixed in size and shape, with linear shape, without movement along a trajectory, and not circumscribed to the territory of any nerve. Results Twelve patients were women, and four were men. The mean age at onset was 40.1 years. Pain was described as pressing in seven patients, burning in five, and electric or stabbing in two each. Symptomatic treatment had been used by 13 patients (81.2%), with analgesics being the most frequent treatment used. Thirteen patients received preventive treatment. The response to oral medications and anesthetic blockade was insufficient. OnabotulinumtoxinA was used in six cases, with an optimal (>75%) response observed in half. Conclusion Linear headache appears to be a distinct headache syndrome from epicrania fugax or nummular headache. Preventive treatment is often required. The drug with the best response was onabotulinumtoxinA. [ABSTRACT FROM AUTHOR]

No specific migraine biomarkers have been found in single‐modality MRI studies. We aimed at establishing biomarkers for episodic and chronic migraine using diverse MRI modalities. We employed canonical correlation analysis and joint independent component analysis to find structural connectivity abnormalities that are related to gray matter morphometric alterations. The number of streamlines (trajectories of estimated fiber‐tracts from tractography) was employed as structural connectivity measure, while cortical curvature, thickness, surface area, and volume were used as gray matter parameters. These parameters were compared between 56 chronic and 54 episodic migraine patients, and 50 healthy controls. Cortical curvature alterations were associated with abnormalities in the streamline count in episodic migraine patients compared to controls, with higher curvature values in the frontal and temporal poles being related to a higher streamline count. Lower streamline count was found in migraine compared to controls in connections between cortical regions within each of the four lobes. Higher streamline count was found in migraine in connections between subcortical regions, the insula, and the cingulate and orbitofrontal cortex, and between the insula and the temporal region. The connections between the caudate nucleus and the orbitofrontal cortex presented worse connectivity in chronic compared to episodic migraine. The hippocampus was involved in connections with higher and lower number of streamlines in chronic migraine. Strengthening of structural networks involving pain processing and subcortical regions coexists in migraine with weakening of cortical networks within each lobe. The multimodal analysis offers a new insight about the association between brain structure and connectivity. [ABSTRACT FROM AUTHOR]

To date, two randomized, controlled studies support the use of candesartan for migraine prophylaxis but with limited external validity. We aim to evaluate the effectiveness and tolerability of candesartan in clinical practice and to explore predictors of patient response. Retrospective cohort study including all patients with migraine who received candesartan between April 2008-February 2019. The primary endpoint was the number of monthly headache days during weeks 8–12 of treatment compared to baseline. Additionally, we evaluated the frequency during weeks 20–24. We analysed the percentage of patients with 50% and 75% response rates and the retention rates after three and 6 months of treatment. 120/4121 patients were eligible, aged 45.9 [11.5]; 100 (83.3%) female. Eighty-four patients (70%) had chronic migraine and 53 (42.7%) had medication-overuse headache. The median number of prior prophylactics was 3 (Inter-quartile range 2–5). At baseline, patients had 20.5 ± 8.5 headache days per month, decreasing 4.3 ± 8.4 days by 3 months (weeks 12–16) and by 4.7 ± 8.7 days by 6 months (paired Student's t-test, p < 0.001). The percentage of patients with a 50% response was 32.5% at 3 months and 31.7% at 6 months, while the retention rate was 85.0% and 58.3%. The number of prior treatments (Odds ratio 0.79, 95% CI 0.64–0.97) and the presence of daily headache (Odds ratio 0.39, 95% CI 0.16–0.97) were associated with a lower probability of response. Candesartan showed beneficial effects in the preventive treatment of migraine in clinical practice, including patients with chronic migraine, medication-overuse headache and resistance to prior prophylactics. [ABSTRACT FROM AUTHOR]

Background: Triptanophobia is the excessive and inadequately justified concern about potential risks of triptans. We evaluated causes and consequences of nonuse of triptans in chronic migraine (CM) Methods: Case-control study. We included CM patients firstly referred to aheadache unit. Patients were cases or controls depending on whether they were triptan naïve, or not. We analyzed if nonuse of triptans was justified by formal contraindications or adverse events. We assessed if triptan naïve patients had higher frequency of vascular risk factors (VRF), contraceptive drugs or older age. Results: We included 941 patients, 247 (26.2%) triptan users. Triptans had been discontinued due to tolerability in 116 patients (12.3%), being 578 patients (61.4%) triptan naïve. Formal contraindications were found in 23 patients (2.4%). Frequency of VRF, contraceptive drugs or age did not differ between the groups (p > 0.1). Triptan users consumed symptomatic medications fewer days/month (13.9 vs 17.1, p < 0.001), were under prophylactic treatment more frequently (79.4% vs 34.8%, p < 0.001) and had medication overuse headache less frequently (55.1% vs. 63.0%, p = 0.03). Conclusion: Triptans were not used by three-quartersof CM patients. Nonuse of triptans was not justified by tolerability, frequency of contraindications, or frequency of VRF. Expert opinion: In the present study, we evaluated causes and consequences of the nonuse of triptans in CM sufferers. We analyzed frequency of triptan use in CM patients. We compared, between triptan users and triptan naïve patients, the presence of contraindications, frequency of vascular risk factors, and differences in management prior to the referral to a headache unit. [ABSTRACT FROM AUTHOR]

Objectives: Headache is a common symptom in systemic infections, and one of the symptoms of the novel coronavirus disease 2019 (COVID-19). The objective of this study was to characterize the phenotype of COVID-19 headache via machine learning. Methods: We performed a cross-sectional study nested in a retrospective cohort. Hospitalized patients with COVID-19 confirmed diagnosis who described headache were included in the study. Generalized Linear Models and Principal Component Analysis were employed to detect associations between intensity and self-reported disability caused by headache, quality and topography of headache, migraine features, COVID-19 symptoms, and results from laboratory tests. Results: One hundred and six patients were included in the study, with a mean age of 56.6 ± 11.2, including 68 (64.2%) females. Higher intensity and/or disability caused by headache were associated with female sex, fever, abnormal platelet count and leukocytosis, as well as migraine symptoms such as aggravation by physical activity, pulsating pain, and simultaneous photophobia and phonophobia. Pain in the frontal area (83.0% of the sample), pulsating quality, higher intensity of pain, and presence of nausea were related to lymphopenia. Pressing pain and lack of aggravation by routine physical activity were linked to low C-reactive protein and procalcitonin levels. Conclusion: Intensity and disability caused by headache attributed to COVID-19 are associated with the disease state and symptoms. Two distinct headache phenotypes were observed in relation with COVID-19 status. One phenotype seems to associate migraine symptoms with hematologic and inflammatory biomarkers of severe COVID-19; while another phenotype would link tension-type headache symptoms to milder COVID-19. [ABSTRACT FROM AUTHOR]

Objective The analysis of particular (electroencephalographic) EEG frequency bands has revealed new insights relative to the neural dynamics that, when studying the EEG spectrum as a whole, would have remained hidden. This study is aimed at characterizing spectral resting state EEG patterns for assessing possible differences of episodic and chronic migraine during the interictal period. For that purpose, a novel methodology for analyzing specific frequencies of interest was performed. Methods Eighty-seven patients with migraine (45 with episodic and 42 with chronic migraine) and 39 age- and sex-matched controls performed a resting-state EEG recording. Spectral measures were computed using conventional frequency bands. Additionally, particular frequency bands were determined to distinguish between controls and migraine patients, as well as between migraine subgroups. Results Frequencies ranging from 11.6 Hz to 12.8 Hz characterized migraine as a whole, with differences evident in the central and left parietal regions (controlling for false discovery rate). An additional band between 24.1 Hz and 29.8 Hz was used to discriminate between migraine subgroups. Interestingly, the power in this band was positively correlated with time from onset in episodic migraine, but no correlation was found for chronic migraine. Conclusions Specific frequency bands were proposed to identify the spectral characteristics of the electrical brain activity in migraine during the interictal stage. Our findings support the importance of discriminating between migraine subgroups to avoid hiding relevant features in migraine. [ABSTRACT FROM AUTHOR]

Objective 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. Design Cohort study. Setting Spanish community. Subjects 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Introduction: Headache is a common symptom of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we aimed to characterize the phenotype of headache attributed to SARS-CoV-2 infection and to test the International Classification of Headache Disorders (ICHD-3) phenotypic criteria for migraine and tension-type headache.Methods: The study design was a cross-sectional study nested in a cohort. We screened all consecutive patients that were hospitalized and had a positive SARS-CoV-2 test. We included patients that described headache if the headache was not better explained by another ICHD-3 diagnosis. Patients were interviewed by two neurologists.Results: We screened 580 patients and included 130 (mean age 56 years, 64% female). Headache was the first symptom of the infection in 26% of patients and appeared within 24 hours in 62% of patients. The headache was bilateral in 85%, frontal in 83%, and with pressing quality in 75% of patients. Mean intensity was 7.1, being severe in 64%. Hypersensitivity to stimuli occurred in 57% of patients. ICHD-3 criteria for headache attributed to systemic viral infection were fulfilled by 94% of patients; phenotypic criteria for migraine were fulfilled by 25% of patients, and tension-type headache criteria by 54% of patients.Conclusion: Headache attributed to SARS-CoV-2 infection in hospitalized patients has severe intensity, frontal predominance and oppressive quality. It occurs early in the course of the disease. Most patients fulfilled ICHD-3 criteria for headache attributed to systemic viral infection; however, the phenotype might resemble migraine in a quarter of cases and tension-type headache in half of the patients. [ABSTRACT FROM AUTHOR]

Background: Series of patients with SARS‐CoV‐2 infection report headache in 6%‐15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients. Objective: To analyze the characteristics of COVID‐19 related headaches. Methods: We conducted a survey of Spaniard healthcare professionals who have been infected by SARS‐CoV‐2 and presented headache during the course of the disease. The survey addressed respondents' medical history and headache characteristics, and we analyzed the association between both. Results: We analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tension‐type headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P =.013). Conclusion: Headache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVID‐19. [ABSTRACT FROM AUTHOR]

Objective: To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data.Methods: Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed.Results: Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls (p < .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity.Conclusions: Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze the potential association between personality traits and onabotulinumtoxin A (onabotA) response in patients with chronic migraine (CM). Background: Previous studies from a categorial perspective show that patients with CM have anxious or obsessive personality according to the Salamanca screening test. However, the influence of personality traits in onabotA response in patients with CM has not yet been studied. We hypothesize that cluster C personality traits may be associated with non‐response to onabotA. Methods: This case‐control observational study includes patients with CM who received at least 2 treatment cycles of onabotA in 2 headache units between January and May 2018. onabotA response was defined as a reduction of at least 50% in the number of monthly migraine days. Personality traits were evaluated using the Salamanca questionnaire, a validated categorial inventory assessing 11 personality traits. Results: One hundred and twelve patients, 100/112 (89.6%) females, mean age (standard deviation): 43 (11) years, were recruited. 96/112 (85.7%) achieved response to onabotA. Dependent trait was significantly associated with non‐response to onabotA (P =.008; OR: 0.223 [95%CI: 0.074 to 0.675]). Significant association with other personality traits or confounders was not found. Conclusions: To the best of our knowledge, this is the first study showing personality traits may predict onabotA response in patients with CM. The presence of dependent personality trait in patients with CM is associated with non‐response to onabotA. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate self-reported periodontitis (PD) prevalence in migraineurs as well as to investigate the association between both diseases. A cross-sectional survey was carried out including patients diagnosed with migraine attending 12 Spanish Headache Units. We determined diagnosis of PD administering a validated self-reported questionnaire. Socio-demographic, clinical and medical information, comorbidities, daily habits, migraine characteristics and medication were collected using a questionnaire. Of the 651 consecutive migraineurs included in the study, 393 suffered from chronic migraine (CM). Self-reported PD was detected in 327 patients with migraine (50.2%). Migraineurs with self-reported PD were significantly older and had a previous history of fibromyalgia, stress, anxiety, depression, and allodynia (all P < 0.001). Additionally, this group of patients consumed more topiramate (P = 0.008) and simple analgesics (P < 0.001) than patients with migraine and without self-reported PD. Also, they were less active physically and belonged to a low education level (both P < 0.001). Prevalence of self-reported PD was significantly higher in chronic migraineurs compared to those diagnosed with episodic migraine (EM) (53.9% vs. 44.6%, P = 0.019). Logistic regression analyses showed that self-reported PD was associated with CM (OR 1.456; 95% CI 1.062–1.997, P = 0.020). However, after adjusting for significant confounders, the association was attenuated (OR 1.100; 95% CI 0.784–1.543, P = 0.581). We concluded that self-reported PD was significantly more frequent in CM compared to EM. Self-reported PD was associated with the presence of CM, although some comorbidities shared by both diseases could have an effect on this association. [ABSTRACT FROM AUTHOR]

Objective Long-term real-life studies have supported a cumulative effect of OnabotulinumtoxinA (OnabotA) for the prophylactic treatment of chronic migraine (CM) during consecutive cycles, and individual adaptations have been described to improve clinical response. Methods This was a cohort longitudinal retrospective study of consecutive adult patients from the Headache Unit of the Hospital Clínico Universitario de Valladolid and the Hospital Universitario de La Princesa (Madrid) on OnabotA treatment for chronic migraine from May 2012 to December 2017. All patients were followed for 24 weeks. Full-length response to OnabotA was defined as ≥50% reduction in headache days for at least 12 weeks, and wearing off response was defined as a clinical response but with duration shorter than 10 weeks. We have analyzed the incidence and clinical predictors of this wearing off response. Results A total of 193 patients were included, of whom 91 (47.1%) were considered full-length responders and 45 (23.3%) wearing off responders. No statistically significant clinical predictors (including demographic variables and baseline headache characteristics) of full-length response or wearing off response were detected in our study. An increase in dose during the second treatment cycle was attempted in 68.9% of the wearing off patients, achieving a longer duration of response of up to 12 weeks in 74.2%. Conclusions Wearing off response to OnabotA during the first treatment cycle is not uncommon in patients with CM. Increasing the dose in subsequent cycles could improve clinical response, but further multicenter long-term studies are needed to establish predictors and solutions to this problem. [ABSTRACT FROM AUTHOR]

The article presents the discussion on silent burden of migraine comprising all the changes related to habits and behaviors people living with migraine. Topics include diet and nutrition being among the most frequently reported trigger factors, particularly caffeine and alcohol; and inhibiting the secretion of antidiuretic hormone, causing a systemic dehydration and an intracranial hypotension.

Background Methods Results Conclusions Visual snow (VS) and visual snow syndrome (VSS) are becoming increasingly recognized. However, their prevalence worldwide is unknown. This study aimed to investigate lifetime prevalence and describe the clinical characteristics of VS and VSS in a representative population sample from Italy.This cross‐sectional study was conducted among students attending different faculties in three universities in the central and southern regions of Italy. Eligible participants completed a self‐administered questionnaire. In patients fulfilling possible criteria for VS/VSS, the diagnosis was validated by an on‐site visit conducted by experienced neurologists and neuro‐ophthalmologists that included optical coherence tomography angiography (OCTA).A total of 750 participants completed the study. Seven (0.9%) reported symptoms compatible with VS (mean age 24.8 ± 3.85 years). Among the seven patients, five (0.7%) also met the phenomenological and temporal criteria for VSS. Neuroimaging and ophthalmological examinations showed normal results upon review or during the on‐site visit including OCTA. For the five patients with full VSS, the other visual symptoms reported were enhanced entoptic phenomenon (n = 5), photophobia (n = 5), palinopsia (n = 1), and nyctalopia (n = 4). In four of the seven patients (57%) reporting VS symptoms, there was a concomitant diagnosis of migraine with aura, and in one (14%) migraine without aura. All patients (n = 7) reported tinnitus. Six of the seven (85.7%) patients with VS/VSS had never used specific treatments for the condition. None of the seven patients had received a previous diagnosis of VS/VSS.The prevalence in Italy of VSS is around 1%. However, there is a limited tendency for affected individuals to seek medical attention, leading to a low rate of diagnosis and treatment. [ABSTRACT FROM AUTHOR]

OnabotulinumtoxinA is one of the main preventive treatments for chronic migraine. Despite that up to one third of patients with chronic migraine suffer from daily headache, these individuals have hardly been studied. We conducted a prospective cohort study, including patients with chronic migraine and treated with OnabotulinumtoxinA according to the PREEMPT paradigm. The primary endpoint was to assess whether patients with chronic migraine and daily headache had a different response after three sessions of OnabotulinutoxinA than patients without daily headache. The secondary endpoint was to analyse the presence of predictive factors that could be associated with a higher response to OnabotulinumtoxinA. Patients with daily headache had a reduction of 14.9 (SD: 9.7) headache days per month, patients with 22–29 headache days a reduction of 10.6 (SD: 9.9) days, and patients with 15–21 headache days a reduction of 8.6 (SD: 7.1) days (p < 0.001). In the univariate regression analysis, a higher number of headache days per month at baseline was associated with higher odds of reduction in the number of headache days per month after OnabotulinumtoxinaA treatment (OR: 0.474, 95% CI: 0.278–0.670, p < 0.001). This association was maintained in the multivariate regression analysis (OR: 0.540, 95% CI: 0.333–0.746, p < 0.001). In our sample, daily headache was not associated with a worse response to OnabotulinumtoxinA treatment. A higher frequency of headache at baseline was a predictor of better response to OnabotulinumtoxinA treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]