Visual migraine aura iconography: A multicentre, cross-sectional study of individuals with migraine with aura.

INTRODUCTION: Visual disturbances are the most common symptoms of migraine aura. These symptoms can be described systematically by subdividing them into elementary visual symptoms. Since visual symptoms of migraine aura are not easy to describe verbally, we developed a collection of images illustrating previously reported elementary visual symptoms. OBJECTIVES: To test a standardised visual migraine aura iconography in a large population of migraine with aura patients and to improve it based on the participants' feedback. METHODS: We created a set of images representing 25 elementary visual symptoms and a web-based survey where participants could report whether they recognised these images as part of their visual aura. Elementary visual symptoms could also be recognised via a corresponding text description or described in a free text by participants. Individuals with migraine aura recruited from four tertiary headache centres (in Switzerland, Denmark, Norway and Italy) were invited to complete the survey. RESULTS: Two hundred and fifteen participants completed the study (78.9% women, median age 36). They recognised a total of 1645 elementary visual symptoms from our predefined list. Of those, 1291 (78.4%) where recognised via standardised iconography images. A new type of elementary visual symptom was reported by one participant. CONCLUSION: Most elementary visual symptoms experienced by participants were recognised via the standardised iconography. This tool can be useful for clinical as well as research purposes.

Response to erenumab assessed by Headache Impact Test-6 is modulated by genetic factors and arterial hypertension: An explorative cohort study.

BACKGROUND AND PURPOSE: Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinical characteristics and polymorphisms at calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1) genes and response to ERE treatment measured as clinically meaningful improvement on the Headache Impact Test-6 (HIT-6) score. METHODS: This post hoc analysis of a prospective, multicenter, investigator-initiated study involves 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine-related burden measured by HIT-6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of CALCRL and RAMP1 genes were determined using real-time polymerase chain reaction. Logistic regression models identified independent predictors for response to ERE, defined as HIT-6 score improvement ≥ 8 points (HIT-6 responders [HIT-6 RESP] vs. HIT-6 nonresponders). RESULTS: At Month 3, 58 (52.7%) patients were HIT-6 RESP. Comorbid hypertension predicted a lower probability of being HIT-6 RESP (odds ratio [OR] = 0.160, 95% confidence interval [CI] = 0.047-0.548, p = 0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT-6 RESP (for each G allele: OR = 2.82, 95% CI = 1.03-7.73, p = 0.043; OR = 2.10, 95% CI = 1.05-4.22, p = 0.037). RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability (for each rs13386048A, OR = 0.53, 95% CI = 0.28-0.98, p = 0.042; for each rs12465864G, OR = 0.32, 95% CI = 0.13-0.75, p = 0.009). A genetic risk score based on the presence and number of identified risk alleles was independently associated with HIT-6 RESP (OR = 0.49, 95% CI = 0.33-0.72, p = 0.0003), surviving Bonferroni correction. CONCLUSIONS: Response to ERE was associated with comorbid hypertension and specific allelic variants in CALCRL and RAMP1 genes. Results require confirmation in future studies.

Differential Diagnosis of Visual Phenomena Associated with Migraine: Spotlight on Aura and Visual Snow Syndrome.

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.

Clinic and genetic predictors in response to erenumab.

BACKGROUND AND PURPOSE: Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE. METHODS: Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine-related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50-RESP) and 75% responder patients (75-RESP). RESULTS: At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008-1.120], p = 0.024), number of failed preventive medications (0.753 [0.600-0.946], p = 0.015), and MIDAS score (1.011 [1.002-1.020], p = 0.017) were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75-RESP (per G allele OR [95% CI]: 0.53 [0.29-0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28-1.10], p = 0.09]). CONCLUSIONS: In this real-word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.

Predicting the response to a triptan in migraine using deep attack phenotyping: A feasibility study.

BACKGROUND: Triptans, specific symptomatic medications for migraine, are not effective in a proportion of patients, or in all attacks, hence the importance of identifying predictors of response. Our aim was to investigate the association between the efficacy of oral frovatriptan 2.5 mg and clinical characteristics of migraine attacks. METHODS: We enrolled 29 consecutive patients affected by migraine without aura at the Headache Center of "Mondino" Institute of Pavia. Each patient was given a diary and asked to record prospectively the features of three consecutive migraine attacks while using frovatriptan. A generalized estimating equations approach was used to determine phenotypic features associated with the pain free response at 2 hours. RESULTS: Participants provided complete data for 85 attacks. Thirty of these (34%) patients reported being pain free 2 hours after taking frovatriptan 2.5 mg intake. Unilateral pain, presence of phonophobia, presence of one or more cranial autonomic symptoms and presence of one or more premonitory symptom were each associated with being pain free at 2 hours. CONCLUSIONS: The response to frovatriptan was associated with particular features of the migraine attack, either before or during the pain phase of attacks. The data support larger studies to explore detailed attack phenotyping, with particular attention to early signs, to enable individualized treatment in migraine.

The depiction of migraine visual aura on the internet.

INTRODUCTION: The most common and multifaceted migraine aura symptoms are visual disturbances. Health information is one of the most popular topics on the internet but the quality and reliability of publicized information is unknown. The aim of this study was to analyze images of migraine aura on Google to determine the frequency of correct presentations of visual aura and distribution of visual aura phenotypes. METHODS: Two authors screened the 100 highest indexed migraine aura related images on Google. The content of the images was categorized into elementary visual symptoms. RESULTS: Forty out of 100 images were accurate representations of visual migraine aura. Such images included 31 different visual aura phenotypes. The majority had more than one elementary visual symptom (median 2, IQR 1-3), most commonly "bean-like" forms (45%), zigzag lines (40%), and foggy/blurred vision (33%). DISCUSSION: Forty percent of images were accurate portrayals of visual migraine aura symptoms, but these presented limited phenotypes. The information derived from the internet photos may hinder the effective recognition of aura symptoms. Thus, there is a need to provide a more comprehensive representation of visual migraine aura symptoms on the internet.

Dysphasia and Other Higher Cortical Dysfunctions During the Migraine Aura-a Systematic Review of Literature.

PURPOSE OF THE REVIEW: Although visual and somatosensory disturbances are the most common migraine aura (MA) symptoms, patients can also experience other symptoms during their MA. The aim of this review is to provide an overview of studies that report symptoms of dysphasia and other higher cortical dysfunctions (HCDs) during MA, as well as to determine the frequency of HCDs. RECENT FINDINGS: Five studies met the inclusion criteria, corresponding to 697 patients overall. The most frequently reported HCDs were those of the language group (range 10-53%). The occurrence of visual HCDs was noted in 12-40 patients, somatosensory HCDs in 12-20%, and memory disturbances in 10-22% of the patients during MAs. MA is associated with a wide range of neurological symptoms, including symptoms of HCD. A better strategy for investigation of the HCD symptoms is needed to correctly stratify patients thus allowing meaningful studies of aura pathophysiology.

Application of the Migraine Aura Complexity Score (MACS): Clinical and Neuroimaging Study.

Background: Manifestations of typical migraine aura can be numerous. Investigation of its pathophysiological mechanisms can be challenging if a stratification of phenotypes is not performed. In this context, the Migraine Aura Complexity Score (MACS), recently developed, may help. Here we aimed to categorize migraine patients into homogenous groups using MACS and to compare those groups with respect to patients' characteristics and neuroimaging findings. Methods: Participants who have a migraine with aura (MwA) were interviewed after each attack in order to obtain the characteristics of migraine aura. Thereafter, we scored the complexity of their auras by MACS. The MACS was used to categorize patients into three groups: MwA-S (with simple aura), MwA-MC (with moderately complex aura), and MwA-C (with complex aura). The patient characteristics and estimated cortical thickness of regions of interest, which are potentially linked to the symptoms that develop during the aura, were used to compare these groups. Results: In total, 338 MwA attacks were recorded in analyzed groups. Scotoma was the most frequently reported symptom in the groups, followed by somatosensory aura in the MwA-C group and zig-zag lines in the MwA-MC and MwA-S groups. Patients in the MwA-C and MwA-MC groups had a thicker cortex in the left primary visual cortex with respect to MwA-S group. In addition, patients in the MwA-C group had a thicker cortex in several visual and somatosensory cortical regions relative to the MwA-S group. Conclusions: Our results show that the newly developed MACS can be used for the stratification of MwA patients, herewith allowing the better investigation of changes in migraineurs' brains.

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2  = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.

Clinical features of visual migraine aura: a systematic review.

BACKGROUND: Migraine aura (MA) is a common and disabling neurological condition, characterized by transient visual, and less frequently sensory and dysphasic aura disturbances. MA is associated with an increased risk of cardiovascular disorders and is often clinically difficult to distinguish from other serious neurological disorders such as transient ischemic attacks and epilepsy. Optimal clinical classification of MA symptoms is important for more accurate diagnosis and improved understanding of the pathophysiology of MA through clinical studies. MAIN BODY: A systematic review of previous prospective and retrospective systematic recordings of visual aura symptoms (VASs) was performed to provide an overview of the different types of visual phenomena occurring during MA and their respective frequencies in patients. We found 11 retrospective studies and three prospective studies systematically describing VASs. The number of different types of VASs reported by patients in the studies ranged from two to 23. The most common were flashes of bright light, "foggy" vision, zigzag lines, scotoma, small bright dots and 'like looking through heat waves or water'. CONCLUSIONS: We created a comprehensive list of VAS types reported by migraine patients based on all currently available data from clinical studies, which can be used for testing and validation in future studies. We propose that, based on this work, an official list of VAS types should be developed, preferably within the context of the International Classification of Headache Disorders of the International Headache Society.

Negative Short-Term Outcome of Detoxification Therapy in Chronic Migraine With Medication Overuse Headache: Role for Early Life Traumatic Experiences and Recent Stressful Events.

Background: Early traumatic experiences and Stressful episodes appear to be associated to the development and perpetuation of chronic pain disorders and to dependence-related behaviors. Objective: The present study evaluated whether these factors can be predictors, together with psychiatric conditions, of the outcome of a detoxification treatment in patients suffering from chronic migraine and medication-overuse headache in a 2-month follow-up. Methods: Consecutive patients undergoing a detoxification program as therapy for treating chronic migraine and medication overuse headache at the Pavia Headache Center were analyzed. During this program, lasting about 1 week, all patients received the standard CARE in-patient withdrawal protocol, which consisted in discontinuing abruptly the overused drug(s) and receiving daily detoxification therapy. Data on childhood traumatic events and recent stressful ones were analyzed by means of the Childhood Trauma Questionnaire and Stressful life-events Questionnaire. Psychiatric conditions were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of mental disorders. Results: A total of 166 (80% females; mean age 44.7) patients completed the follow-up at 2 months after the detoxification program: of these 118 (71%) (78% females; mean age 44.7) stopped overuse and reverted to an episodic pattern of headache (Group A); 19 (11%) (89% females; mean age 41.3) kept overusing and maintained a chronic pattern of headache (Group B); and 29 (18%) (79% females; mean age 46.9) stopped overuse without any benefit on headache frequency (Group C). At the multivariate analyses, a higher number of early life emotional distress (Odds Ratio 11.096; p = 0.037) arose as a prognostic factor for the outcome in Group B, while major depression during life-time (Odds Ratio 3.703; p = 0.006) and higher number of severe stressful episodes in the past 10 years (Odds Ratio 1.679; p = 0.045) were prognostic factors for the outcome of Group C. Conclusions: Data suggest that early life traumas and stressful events have a negative impact on the outcome of the detoxification program in subjects overusing acute medication for headache. The history of emotional childhood traumas is associated to the failure to cease overuse, whereas recent very serious life events are associated to the persistence of headache chronicity.

Using a Genetic Risk Score Approach to Predict Headache Response to Triptans in Migraine Without Aura.

A large meta-analysis of genome-wide association studies has recently identified a number of risk loci for migraine without aura (MwoA). In this study, we tested the hypothesis that a genetic risk score based on single-nucleotide polymorphisms (SNPs), previously reported to be associated with MwoA at genome-wide significance, may influence headache response to triptans in patients with migraine without aura. Genotyping of rs9349379, rs2078371, rs6478241, rs11172113, rs1024905, and rs6724624 was conducted with a real-time PCR allelic discrimination assay in 172 MwoA patients, of whom 36.6% were inconsistent responders to triptans. Each genetic risk score model was constructed as an unweighted score, calculated by adding the number of risk alleles for MwoA across each SNP at selected loci. The association with headache response to triptans was evaluated by logistic regression analysis adjusted for triptan, and the P values were corrected for the false discovery rate. The genetic risk score including susceptibility risk alleles at TRPM8 rs6724624 and FGF6 rs1024905 was found to be inversely associated with risk of inconsistent response to triptans (OR, 0.62; 95%CI, 0.43-0.89; false discovery rate q value, 0.045). In addition, adding this genetic risk score to the triptan-adjusted logistic regression model significantly improved (P = .037) the discrimination accuracy, from 0.57 (95%CI, 0.50-0.65) to 0.64 (95%CI, 0.57-0.72). A modest but significant effect on risk of inconsistent response to triptans was identified for a genetic risk score model composed of 2 known risk alleles for MwoA, suggesting its potential utility in predicting headache response to triptan therapy.

Proposal for a Migraine Aura Complexity Score.

OBJECTIVES: Currently, there is no scoring system for assessing the complexity of migraine aura. Our goal was to develop a Migraine Aura Complexity Score that synthesizes the quantity and quality of aura symptoms and to test its applicability in neuroimaging studies. METHODS: Patients with migraine aura were interviewed in order to obtain characteristics of migraine aura. Explorative and confirmatory analyses were used to develop the Migraine Aura Complexity Score. Median values were derived from 10 consecutive migraine auras in each patient. The Migraine Aura Complexity Score was correlated with an average cortical thickness of different brain areas in studied patients. The Surface-based Morphometric Analysis approach was used to estimate cortical thickness. RESULTS: This study included 23 (16 females and seven males) migraineurs with aura. Confirmatory factor analysis suggested the second-order model with three-factor measurement for grading migraine aura. The first factor is linked to higher cortical dysfunction during migraine aura, while the second is associated with the degree of involvement of primary visual and somatosensory cortices; the third linked symptoms of somatosensory aura and hand and head involvement. Positive correlation of Migraine Aura Complexity Score and averaged cortical thickness were found in the left and right hemispheres overall (r = 0.568, p = 0.007; r = 0.617, p = 0.003) and in some of their regions. CONCLUSIONS: This study demonstrates that the Migraine Aura Complexity Score could be a valuable tool for assessing migraine aura. The score could be used in neuroradiological studies in order to achieve a stratification of patients with migraine aura.

Prolonged migraine aura: new insights from a prospective diary-aided study.

BACKGROUND: There is limited literature on prolonged aura (PA - defined as an aura including at least one symptom for > 1 h and < 7d), and there are no prospective studies. The aim of this study is to characterize prospectively the phenotype and prevalence of PA. FINDINGS: Two hundred and twenty-four patients suffering from migraine with aura were recruited from the Headache Centers of Pavia and Trondheim. Patients prospectively described, on an ad hoc diary, each aura symptom (AS), the duration of AS and headache, and headache features. Seventy-two patients recorded three consecutive auras in their diaries. 19 (26.4%) of patients suffered at least one PA. Out of 216 recorded auras, 38 (17.6%) were PAs. We compared PAs with non-PAs with respect to 20 features; PAs were characterized by a higher number of non-visual symptoms (non-VS) (p < 0.001). No other differences were found. We obtained similar results when we compared auras with at least one symptom with a duration of > 2 h (n = 23) or > 4 h (n = 14) with the the others (n = 193 and n = 202 respectively). CONCLUSION: PAs are quite common. They do not differ from the other auras (even when their duration extends to 2 and/or 4 h) with the exception of a higher number of non-VS.

Traumatic Experiences, Stressful Events, and Alexithymia in Chronic Migraine With Medication Overuse.

Background: Many factors are involved in the prognosis and outcome of Chronic Migraine and Medication Overuse Headache (CM+MOH), and their understanding is a topic of interest. It is well known that CM+MOH patients experience increased psychiatric comorbidity, such as anxiety, depression, or personality disorders. Other psychological factors still need to be explored. The present study is aimed to evaluate whether early life traumatic experiences, stressful life events, and alexithymia can be associated with CM+MOH. Methods: Three hundred and thirty-one individuals were recruited for this study. They belonged to one of the two following groups: CM+MOH (N = 179; 79% females, Age: 45.2 ± 9.8) and episodic migraine (EM) (N = 152; 81% females; Age: 40.7 ± 11.0). Diagnosis was operationally defined according to the International Classification of Headache Disorders 3rd edition (ICHD-IIIß). Data on early life (physical and emotional) traumatic experiences, recent stressful events and alexithymia were collected by means of the Childhood Trauma Questionnaire, the Stressful life-events Questionnaire, and the Toronto Alexithymia Scale (TAS-20), respectively. Results: Data showed a higher prevalence of emotional (χ2 = 6.99; d.f. = 1; p = 0.006) and physical (χ2 = 6.18; d.f. = 1; p = 0.009) childhood trauma and of current stressful events of important impact (χ2 = 4.42; d.f. = 1; p = 0.025) in CM+MOH patients than in EM ones. CM+MOH patients were characterized by higher difficulties in a specific alexithymic trait (Factor 1 subscale of TAS-20) [F(1, 326) = 6.76, p = 0.01, η p2 = 0.02] when compared to the EM group. The role of these factors was confirmed in a multivariate analysis, which showed an association of CM+MOH with emotional (OR 2.655; 95% CI 1.153-6.115, p = 0.022) or physical trauma (OR 2.763; 95% CI 1.322-5.771, p = 0.007), and a high score at the Factor 1 (OR 1.039; 95% CI 1.002-1.078, p = 0.040). Conclusions: Our findings demonstrated a clear relationship between CM+MOH and life traumas, stressful events, and alexithymia. These observations have a relevant role in multiple fields of related to chronic headache: from the management to the nosographic framing.

Factors associated to chronic migraine with medication overuse: A cross-sectional study.

BACKGROUND AND AIM: Factors implicated in the evolution of episodic migraine into chronic migraine are largely elusive. Medication overuse is considered to be one of the main determinants, but other possible clinical and psychological factors can play a role. The aim of this study is to identify factors that are associated with chronic migraine with medication overuse. METHOD: We enrolled consecutive migraine patients, subdividing them in two groups: Subjects with a long history of episodic migraine and subjects with chronic migraine and medication overuse. We then compared their clinical and psychological variables in a cross-sectional study. RESULTS: Three hundred and eighteen patients were enrolled, of which 156 were episodic migraine and 162 were chronic migraine and medication overuse patients. The mean age was 42.1 ± 10.3, 80.8% were female. The duration of migraine was 24.6 years in episodic migraine and 24.0 years in chronic migraine and medication overuse ( p = 0.57). After the multivariate analysis, the factors associated to chronic migraine and medication overuse were: Marital status (married vs. unmarried, OR 3.65, 95% CI 1.63-8.19, p = 0.002; separated/divorced/widowed vs. unmarried, OR 4.19, 95% CI 1.13-15.47, p = 0.031), physical activity (OR 0.42, 95% CI 0.19-0.91, p = 0.029), age at onset of migraine (OR 0.94, 95% CI 0.89-0.98, p = 0.016), use of at least one migraine preventive medication (OR 2.36, 95% CI 1.18-4.71, p = 0.014), history of depression (OR 2.91, 95% CI 1.25-6.73, p = 0.012), insomnia associated with the use of hypnotics (OR 5.59, 95% CI 1.65-18.93, p = 0.006), traumatic head injuries (OR 3.54, 95% CI 1.57-7.99, p = 0.002), snoring (OR 2.24, 95% CI 1.05-4.79, p = 0.036), previous and/or actual use of combined oral contraceptives (OR 3.38, 95% CI 1.10-10.3, p = 0.031) and higher scores in the Childhood Trauma questionnaire (OR 1.48, 95% CI 1.09-2.02, p = 0.012). CONCLUSION: We considered several aspects that may be involved in the development of chronic migraine and medication overuse. A multivariate analysis identified 10 factors belonging to five different areas, to suggest that chronic migraine and medication overuse onset is likely influenced by a complex mixture of factors. This information is useful when planning strategies to prevent and manage chronic migraine and medication overuse.

A systematic review and critical appraisal of gene polymorphism association studies in medication-overuse headache.

Purpose of review Medication-overuse headache is a secondary chronic headache disorder, evolving from an episodic primary headache type, caused by the frequent and excessive use of headache symptomatic drugs. While gene polymorphisms have been deeply investigated as susceptibility factors for migraine, little attention has been paid to medication-overuse headache genetics. In the present study we conducted a systematic review to identify, appraise and summarize the current findings of gene polymorphism association studies in medication-overuse headache. Methods A comprehensive literature search was conducted on PubMed and Web of Knowledge databases of primary studies that met the diagnostic criteria for medication-overuse headache according to the temporally-relevant Classification of Headache Disorder of the International Headache Society. Results A total of 17 candidate gene association studies focusing on medication-overuse headache were finally included in the qualitative review. Among these, 12 studies investigated the role of common gene polymorphisms as risk factors for medication-overuse headache susceptibility, six studies focused on the relationship with clinical features of medication-overuse headache patients, and four studies evaluated their role as determinants of clinical outcomes in medication-overuse headache patients. Conclusion Results of single studies show a potential role of polymorphic variants of the dopaminergic gene system or of other genes related to drug-dependence pathways as susceptibility factors for disease or as determinants of monthly drug consumption, respectively. In this systematic review, we summarize the findings of gene polymorphism association studies in medication-overuse headache and discuss the methodological issues that need to be addressed in the design of future studies.

When cervical pain is actually migraine: An observational study in 207 patients.

Introduction A large proportion of migraine patients remain undiagnosed or misdiagnosed in Italy. In our experience, many migraineurs self-diagnose their condition as "cervical pain attack" or "cervical pain syndrome" (CP), assuming cervical spine pathology as the cause. We aimed to phenotype and classify the headache of patients with self-diagnosed CP, and to describe this sample of patients. Methods Consecutive patients aged 18 to 75 years, referred to the Headache Center of the Mondino Institute (Pavia, Italy) for a first visit for headache, completed a questionnaire about CP and were subsequently examined by an experienced clinician. Results Out of 207 patients, 132 (64%) believed they suffered from CP. According to ICHD-IIIß criteria, these patients suffered from migraine or probable migraine in 91% of cases. The great majority of patients who believed that they suffered from CP underwent unnecessary medical exams (including radiation exposure in 40% of cases) and used treatments that were inadequate for their real diagnosis. Conclusion The majority of patients with CP suffer from typical migraine. The misdiagnosis produces an economic burden (for patients and the health care system) and leads to impaired quality of life of patients.

Migraine with prolonged aura: phenotype and treatment.

We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine Susceptibility: A Meta-analysis of Case-Control Studies.

Inconclusive results have been reported in studies investigating the association between the brain-derived neurotrophic factor (BDNF) rs6265 polymorphism and migraine. In the present study, we conducted a systematic review and meta-analysis on the published data in order to quantitatively estimate the relationship between rs6265 and migraine susceptibility. A comprehensive search was performed through PubMed, Web of Knowledge, and Cochrane databases up to October 2016. The pooled odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to estimate the strength of the association with rs6265 under an additive, dominant, or recessive model of inheritance. A total of five studies including 1,442 cases and 1,880 controls were identified for the meta-analysis. The pooled data showed an increased risk of migraine for the allelic (OR: 1.17, 95% CI: 1.03-1.34, p = 0.014) or the dominant model of rs6265 (OR: 1.22, 95% CI: 1.05-1.41, p = 0.011). Statistical significance of rs6265 was lost when one single study was excluded from the analysis (dominant OR: 1.17, 95% CI: 1.00-1.38, p = 0.054; allelic OR: 1.14, 95% CI: 0.99-1.31, p = 0.067), suggesting lack of robustness of pooled estimates. When stratified by migraine type, a similar trend of association was detected with both MA and MO, but a statistically significant association of rs6265 was reached only with the MA subtype in the dominant model (OR: 1.22, 95% CI: 1.00-1.47, p = 0.047). The present meta-analysis supports that BDNF rs6265 may act as a genetic susceptibility factor for migraine. Nevertheless, large-scale studies are required to confirm our findings and to assess potential modifiers of the relationship between rs6265 and migraine.