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Migraine Disorders: HELP
Articles by Marcelo Eduardo Bigal
Based on 116 articles published since 2008

Between 2008 and 2019, M. Bigal wrote the following 116 articles about Migraine Disorders.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial BMS-927711 for the acute treatment of migraine. 2014

Bigal, Marcelo E. ·Chief Medical Officer, Labrys Biologics, Inc., PA, USA. ·Cephalalgia · Pubmed #23943638.

ABSTRACT: -- No abstract --

2 Editorial The association between migraine and obesity: empty calories? 2012

Bigal, Marcelo E. · ·Cephalalgia · Pubmed #23014637.

ABSTRACT: -- No abstract --

3 Editorial Migraine and cardiovascular disease. A call for action. 2010

Bigal, Marcelo E. · ·Headache · Pubmed #20546322.

ABSTRACT: -- No abstract --

4 Editorial Migraine, lipid profile, and cardiovascular disease. 2010

Bigal, M E. · ·Eur J Neurol · Pubmed #19930446.

ABSTRACT: -- No abstract --

5 Editorial Is there an inherent limit to acute migraine treatment efficacy? 2009

Bigal, Marcelo E / Ho, Tony W. ·Merck Research Laboratories, Whitehouse Station, NJ, USA. marcelo_bigal@merck.com ·J Headache Pain · Pubmed #19820895.

ABSTRACT: -- No abstract --

6 Review TEV-48125: a review of a monoclonal CGRP antibody in development for the preventive treatment of migraine. 2015

Walter, Sarah / Bigal, Marcelo E. ·Migraine & Headache, Clinical Development, Global Branded R&D, Teva Pharmaceuticals, 41 Moores Road, Frazer, PA, 19355, USA. ·Curr Pain Headache Rep · Pubmed #25754596.

ABSTRACT: Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide whose involvement in migraine pathophysiology is well established. Originally migraine was believed to be a disease of the vasculature, but research has highlighted this to be a disease of the brain with CGRP playing an important role. While targeting CGRP using small molecule antagonists against the receptor has been effective, long-term use of these agents has not been possible due to safety concerns and/or formulation challenges. Recent advances in therapeutic antibodies have opened up new possibilities for treatment of migraine. TEV-48125 is one of four monoclonal antibodies targeting CGRP or its receptors, currently in development for the preventive treatment of migraine. This article discusses the in vitro and in vivo pharmacology of TEV-48125 as well as highlighting its safety profile through the six Phase 1 studies that have been conducted. Finally, the current state of development and future studies for TEV-48125 will be reviewed.

7 Review Therapeutic antibodies against CGRP or its receptor. 2015

Bigal, Marcelo E / Walter, Sarah / Rapoport, Alan M. ·Vice President, Migraine & Headache Clinical Development, Teva Pharmaceuticals, Frazer, PA. · Department of Neurology, Albert Einstein College of Medicine, Bronx, NY. · Director of Preclinical Research, Labrys Biologics, Inc, San Mateo, CA. · Director-Emeritus, New England Center for Headache, Stamford, CT. · Clinical Professor of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ·Br J Clin Pharmacol · Pubmed #25614243.

ABSTRACT: CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off-target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re-investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.

8 Review Association between tension-type headache and migraine with sleep bruxism: a systematic review. 2014

De Luca Canto, Graziela / Singh, Vandana / Bigal, Marcelo E / Major, Paul W / Flores-Mir, Carlos. ·Department of Dentistry, Federal University of Santa Catarina, Florianópolis, Brazil; School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. ·Headache · Pubmed #25231339.

ABSTRACT: AIM: To evaluate the association between tension-type headache and migraine with sleep bruxism (SB). BACKGROUND: The association between SB and headaches has been discussed in both children and adults. Although several studies suggested a possible association, no systematic analysis of the available published studies exists to evaluate the quantity, quality, and risk of bias among those studies. METHODS: A systematic review was undertaken, including articles that classified the headaches according to the International Classification of Headache Disorders and SB according to the criteria of the American Association of Sleep Medicine. Only articles in which the objective was to investigate the association between primary headaches (tension-type and migraine) and SB were selected. Detailed individual search strategies for The Cochrane Library, MEDLINE, EMBASE, PubMed, and LILACS were developed. The reference lists from selected articles were also checked. A partial grey literature search was taken by using Google Scholar. The methodology of selected studies was evaluated using the quality in prognosis studies tool. RESULTS: Of 449 identified citations, only 2 studies, both studying adults, fulfilled the inclusion criteria. The presence of SB significantly increased the odds (study 1: odds ratio [OR] 3.12 [1.25-7.7] and study 2: OR 3.8; 1.83-7.84) for headaches, although studies reported different headache type. CONCLUSION: There is not enough scientific evidence to either support or refute the association between tension-type headache and migraine with SB in children. Adults with SB appear to be more likely to have headache.

9 Review Monoclonal antibodies for migraine: preventing calcitonin gene-related peptide activity. 2014

Bigal, Marcelo E / Walter, Sarah. ·Labrys Biologics Inc, 1810 Gateway Drive, Suite 230, San Mateo, CA, USA, mbigal@labrysbiologics.com. ·CNS Drugs · Pubmed #24638916.

ABSTRACT: Calcitonin gene-related peptide (CGRP) is a well-studied neuropeptide of relevance for migraine pathophysiology. Jugular levels of CGRP are increased during migraine attacks, and intravenous CGRP administration induces migraine-like headache in most individuals with migraine. Several CGRP receptor antagonists (CGRP-RAs) were shown to be effective for the acute treatment of migraine, validating the target for the treatment of migraine. However, for a number of reasons, including issues of liver toxicity with chronic use, the development of CGRP-RAs has yet to produce a viable clinical therapeutic. Development of monoclonal antibodies (mAbs) targeting the CGRP pathway is an alternative approach that should avoid many of the issues seen with CGRP-RAs. The exquisite target specificity, prolonged half-lives, and reduced potential for hepatotoxicity and drug-drug interactions make mAbs suitable for the preventive treatment of migraine headaches. This manuscript provides an overview of the role of CGRP in the pathophysiology of migraine, followed by a review of the clinical development of CGRP-RAs. Some basic concepts on antibodies are then discussed along with the publicly disclosed information on the development of mAbs targeting the CGRP pathway.

10 Review Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development. 2013

Bigal, Marcelo E / Walter, Sarah / Rapoport, Alan M. ·Labrys Biologics, Inc, San Mateo, CA, USA. ·Headache · Pubmed #23848260.

ABSTRACT: Calcitonin gene-related peptide (CGRP) is a ubiquitous neuropeptide found at the very centers of the migraine process, both centrally and peripherally. It has been under careful study for approximately 25 years. Several CGRP-receptor antagonists are being evaluated for acute treatment of episodic migraine. Three monoclonal antibodies are being studied for prevention of episodic migraine, and 1 monoclonal antibody is being studied for prevention of chronic migraine. In this review, we discuss the role of CGRP in normal physiology and the consequences of CGRP inhibition for human homeostasis. We then review the current state of development for CGRP-receptor antagonists and CGRP monoclonal antibodies. We close by speculating on the potential clinical role of CGRP antagonism in the acute and preventive treatment of episodic and chronic migraine.

11 Review How to investigate and treat: migraine in patients with temporomandibular disorders. 2012

Gonçalves, Daniela A G / Camparis, Cinara M / Franco, Ana Lucia / Fernandes, Giovana / Speciali, José G / Bigal, Marcelo E. ·Faculdade de Odontologia de Araraquara, Departamento de Materiais Dentários e Prótese, Univ Estadual Paulista, Araraquara, São Paulo, Brazil. danielagg@foar.unesp.br ·Curr Pain Headache Rep · Pubmed #22610505.

ABSTRACT: Migraine and temporomandibular disorders (TMD) are highly prevalent conditions that frequently coexist in the same patient. The relationship between migraine and TMD is complex. Migraineurs often have pain in the TMD area; TMD sufferers, in turn, often experience headaches in addition to the pain in the jaw. Finally, migraine and TMD are comorbid, and the final phenotype of patients with the comorbidity may represent the aggregated contribution of both. Herein we briefly discuss the clinical commonalities of migraine and TMD, and the differential diagnosis of these conditions with other causes of facial pain. We close by presenting our experience in the treatment of patients with the comorbidity.

12 Review The paradoxical effects of analgesics and the development of chronic migraine. 2011

Bigal, Marcelo E. ·Office of the Chief Medical Officer, Merck & Co., Inc, North Wales, PA 19454, USA. marcelo_bigal@merck.com ·Arq Neuropsiquiatr · Pubmed #21755137.

ABSTRACT: In a subgroup of individuals episodic migraine evolves into a stage where individuals have headaches on more days than not. Among the risk factors for chronification, excessive use of analgesic medications figure prominently and reviewing this topic is the scope of this article. The issue of causality is discussed and evidence suggesting that specific medications, at critical doses, are risk factors for chronic migraine (CM) is reviewed. The concept of critical dose of exposure for different classes is presented and biological plausibility and putative mechanisms are reviewed.

13 Review Uncommon headache syndromes in the pediatric population. 2011

Arruda, Marco A / Albuquerque, Regina C A P / Bigal, Marcelo E. ·Glia Institute, Child and Adolescent Neurology, Avenida Braz Olaia Acosta, 727, sala 310, Ribeirão Preto, CEP14026040 SP, Brazil. arruda@institutoglia.com.br ·Curr Pain Headache Rep · Pubmed #21403994.

ABSTRACT: Headache is one of the most common symptoms in children and adolescents, and headache syndromes are an important reason for medical consulting. According to the second edition of the International Classification of Headache Disorders, there are 196 possible headache diagnoses, of which 113 have been described in pediatric population. Herein, we focus on unusual pediatric headache syndromes. We group them as headaches with migraine features, short-duration headaches with autonomic features, short-duration headaches without autonomic features, and potentially ominous forms of headaches. Although rare as single entities, providers focusing on pediatric headaches certainly will face some of these headaches and need to be comfortable on the diagnostic approach.

14 Review Migraine and cardiovascular disease. 2011

Bigal, Marcelo E. ·Head of the Merck Investigator Studies Program, Scientific Education Group, Office of the Chief Medical Officer, Merck Inc., Upper Gwynedd, PA, USA. marcelo_bigal@merck.com ·Arq Neuropsiquiatr · Pubmed #21359435.

ABSTRACT: Migraine, especially migraine with aura is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine with and without aura to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication and cardiovascular mortality. The topic is therefore of considerable interest. Accordingly, herein we review the association between migraine and cardiovascular disease. We start by briefly presenting diagnostic criteria for migraine and revising its pathophysiology. We follow by summarizing the evidence on the topic. We then briefly present the results of a recent meta-analysis. We close by highlighting results of a large epidemiological study conducted after the publication of the meta-analysis.

15 Review Migraine in the pediatric population--evolving concepts. 2010

Bigal, Marcelo E / Arruda, Marco A. ·Office of the Chief Medical Officer-Merck inc. Upper Gwynedd, PA, USA. ·Headache · Pubmed #20572878.

ABSTRACT: Studying the prevalence of headaches at age extremes is of important clinical relevance. Pediatric studies inform us about determinants of incident disease; studies of elderly populations inform us about the long-term consequences of headaches, as well as about determinants of headache remission. As with other subspecialties of headache research, research on pediatric headache is an evolving field. However, although substantial advances have been achieved in understanding headaches in adolescents, knowledge of early childhood headaches is not as advanced conceptually. This review provides a theoretical framework for our current understanding, then summarize the results of a large, ongoing, epidemiological study in pre-adolescent children. It is clear that both in adolescents and in pre-adolescents, migraine is frequent. Diagnostic criteria for migraine and chronic migraine are certainly over-restrictive for young children. Migraine often lasts less than 1 hour in young children. A vulnerable population at risk of migraine progression also exists, likely reflecting increased biological predisposition, but also early life exposures. Indeed, it seems that even prenatal exposures of certain substances may increase the risk of migraine progression. Of relevance is the frequency of headaches within a family. Finally, migraine seems to be associated with behavioral hyperactivity, but is not comorbid with attention-deficit disorder and hyperactivity.

16 Review Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. 2010

Bianchin, Marino Muxfeldt / Londero, Renata Gomes / Lima, José Eduardo / Bigal, Marcelo Eduardo. ·Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. mmbianchin@hotmail.com ·Curr Pain Headache Rep · Pubmed #20495966.

ABSTRACT: The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

17 Review Migraine treatment and placebo effect. 2010

Speciali, José G / Peres, Mário / Bigal, Marcelo E. ·Department of Neurology, School of Medicine at Ribeirão Preto, São Paulo University, São Paulo, Brazil. speciali@netsite.com.br ·Expert Rev Neurother · Pubmed #20187863.

ABSTRACT: Placebos are typically defined as physiologically inactive substances that elicit a therapeutic response. The antipode of the placebo effect is the nocebo effect, or the negative effects of placebo, where unpleasant symptoms (e.g., adverse events) emerge after the administration of placebo. Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception. Herein we focus on the importance of placebo in headache research. We first review the mechanisms of the placebo effect. We then focus on the importance of placebo in the acute treatment of migraine. We follow by discussing the importance of placebo on the preventive treatment of migraine and our perspectives for the 5 years to come regarding the study of the placebos.

18 Review Adherence to acute migraine medication: what does it mean, why does it matter? 2010

Katić, Bozena J / Krause, Steven J / Tepper, Stewart J / Hu, Henry X / Bigal, Marcelo E. ·Merck & Co., Inc, Global Outcomes Research, Whitehouse Station, NJ, USA. ·Headache · Pubmed #19817884.

ABSTRACT: Proper use of medications is an important part of successfully managing migraine headache, yet migraineurs frequently switch, discontinue, or delay taking effective prescription therapies such as triptans. Medication persistence in the treatment of chronic-episodic disorders such as migraine is not well understood. In this article we review this topic, by critically reviewing studies conducted using pharmacy claims, clinical records, survey, and patient-reported data to explore acute medication use for migraine headache. While efficacy, cost, drug tolerability, and side effects impact whether a patient takes migraine medication, low perceived disease importance and factors related to the patient's internal decision-making process play a strong role in the sustained use of acute medication for migraine attack. We propose a model that combines the patient's perceived severity of migraine, their beliefs regarding the safety of acute medications, and factors related to the physician-patient relationship to identify migraineurs at high risk for medication adherence problems.

19 Review Migraine and cardiovascular disease: systematic review and meta-analysis. 2009

Schürks, Markus / Rist, Pamela M / Bigal, Marcelo E / Buring, Julie E / Lipton, Richard B / Kurth, Tobias. ·Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215-1204, USA. mschuerks@rics.bwh.harvard.edu ·BMJ · Pubmed #19861375.

ABSTRACT: OBJECTIVE: To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. DATA EXTRACTION: Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. RESULTS: Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. CONCLUSION: Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

20 Review Migraine chronification--concept and risk factors. 2009

Bigal, Marcelo. ·Merck Research Laboratory, Whitehouse Statoin, New Jersey 08889, United States. ·Discov Med · Pubmed #19833063.

ABSTRACT: Migraine is a chronic disease with episodic attacks and a variable prognosis. In a subgroup, migraine evolves into a more protracted condition (migraine transformation or progression). Transformation of migraine may be subdivided into three partially overlapping forms. Clinical transformation describes the evolution from episodic into chronic migraine. Physiological transformation refers to alterations in nociceptive thresholds and in pain pathways that precede or accompany clinical transformation. Anatomical transformation refers to the emergence of definitive brain lesions (e.g., stroke and deep white matter lesions) in some migraineurs. Herein we conceptualize migraine as a progressive disease and discuss risk factors for transformation.

21 Review Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. 2009

Diener, H-C / Dodick, D W / Goadsby, P J / Bigal, M E / Bussone, G / Silberstein, S D / Mathew, N / Ascher, S / Morein, J / Hulihan, J F / Biondi, D M / Greenberg, S J. ·Department of Neurology, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45122, Germany. h.diener@uni-essen.de ·Cephalalgia · Pubmed #19735529.

ABSTRACT: Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

22 Review Migraine in the triptan era: progresses achieved, lessons learned and future developments. 2009

Bigal, Marcelo E / Krymchantowski, Abouch V / Ho, Tony. ·Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA. marcelo_bigal@merck.com ·Arq Neuropsiquiatr · Pubmed #19623468.

ABSTRACT: Triptans, serotonin 5-HT1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans--mechanism of action and clinical evidence. We close by briefly discussing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.

23 Review Temporomandibular disorders and migraine chronification. 2009

Bevilaqua Grossi, Debora / Lipton, Richard B / Bigal, Marcelo E. ·Department of Biomechanics Medicine and Rehabilitation of the Locomotor Apparatus, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. deborabg@fmrp.usp.br ·Curr Pain Headache Rep · Pubmed #19586596.

ABSTRACT: Among the established and potential comorbidities of migraine, the temporomandibular disorders (TMD) are rarely discussed, although they are of importance for several reasons. TMD may cause headaches per se, worsen existent primary headaches, and add to the burden of headache disorders. This article explores the potential comorbidity between migraine and TMD and the role of TMD as a potential factor to induce chronic migraine. We discuss the similarities between both conditions, review evidence to support the idea that both disorders are comorbid, and highlight the limited evidence suggesting that TMD influence migraine progression. Finally, we discuss the importance of cutaneous allodynia mediating the TMD/frequent headache relationship.

24 Review Overuse of acute migraine medications and migraine chronification. 2009

Bigal, Marcelo E / Lipton, Richard B. ·Merck Research Laboratories, Whitehouse Station, NJ 08889, USA. marcelo_bigal@merck.com ·Curr Pain Headache Rep · Pubmed #19586594.

ABSTRACT: Among individuals with episodic migraine, the influence of excessive acute medication use on the development of chronic migraine depends upon within-person characteristics (eg, headache frequency), class of drug, and frequency of medication use. Available data suggest that opioids induce migraine chronification (progression), and the effect is dose dependent (critical dose around 8 days of exposure per month) and more pronounced in men. Barbiturates also induce migraine progression, and the effect is dose dependent (critical dose around 5 days of exposure per month) and more pronounced in women. Triptans induce migraine progression only in those with high migraine frequency at baseline (10-14 days per month), but not overall. NSAIDs protect against migraine progression unless individuals have 10 or more headache days per month (when they become inducers, rather than protective). Finally, caffeine-containing over-the-counter products increase risk of progression. While we await randomized trials, these findings should inform the choice of acute migraine treatments with the goal of reducing the risk of migraine progression to chronic migraine.

25 Review Migraine and cardiovascular disease: possible mechanisms of interaction. 2009

Bigal, M E / Kurth, T / Hu, H / Santanello, N / Lipton, R B. ·Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA. marcelo_bigal@merck.com ·Neurology · Pubmed #19470970.

ABSTRACT: Migraine, especially migraine with aura (MA), is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication, and cardiovascular mortality. The mechanisms which link migraine to ischemic vascular disease remain uncertain and are likely to be complex. Cortical spreading depression, the presumed substrate of aura, may directly predispose to brain lesions and that would explain why MA is consistently demonstrated as a risk factor for cerebral ischemia, while for migraine without aura (MO), the evidence is less consistent. Additionally, individuals with migraine have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD), including hypertension, diabetes, and hyperlipidemia. The increased prevalence of CVD risk factors is also higher for MA than for MO. Since the evidence linking migraine and CVD is getting robust, neurologists should be aware of this association. Individuals with MO seem to be at little increased risk of CVD. MA is associated with an increased risk of ischemic stroke and likely also for other ischemic CVD events. Accordingly, heightened vigilance is recommended for modifiable cardiovascular risk factors in migraineurs, especially with MA. Ultimately, it will be important to determine whether MA is a modifiable risk factor for CVD and if preventive medications for migraine or antiplatelet therapy might reduce the risk of CVD in patients with MA.