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Migraine Disorders: HELP
Articles from Los Angeles area
Based on 178 articles published since 2008

These are the 178 published articles about Migraine Disorders that originated from Los Angeles area during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Editorial Sounding out migraine-related interactions between the brainstem and cortex. 2015

Charles, Andrew. ·Headache Research and Treatment Program, Department of Neurology, UCLA School of Medicine, USA acharles@ucla.edu. ·Cephalalgia · Pubmed #25616609.

ABSTRACT: -- No abstract --

2 Review CGRP and Migraine: The Role of Blocking Calcitonin Gene-Related Peptide Ligand and Receptor in the Management of Migraine. 2018

Maasumi, Kasra / Michael, Rebecca L / Rapoport, Alan M. ·Department of Neurology, University of California, San Francisco, USA. kmaasumi@gmail.com. · Department of Neurology, University of California, San Francisco, USA. · Department of Neurology, University of California, Los Angeles, USA. ·Drugs · Pubmed #29869205.

ABSTRACT: Migraine is a highly prevalent, complex neurological disorder. The burden of disease and the direct/indirect annual costs are enormous. Thus far, treatment options have been inadequate and mostly based on trial and error, leaving a significant unmet need for effective therapies. While the underlying pathophysiology of migraine is incompletely understood, blocking the calcitonin gene-related peptide (CGRP) using monoclonal antibodies targeting CGRP or its receptor and small molecule CGRP receptor antagonists (gepants) have emerged as a promising therapeutic opportunity for the management of migraine. In this review, we discuss new concepts in the pathophysiology of migraine and the role of CGRP, the current guidelines for treating migraine preventively, the medications that are being used, and their limitations. We then discuss small molecule CGRP receptor antagonists, monoclonal antibodies to CGRP ligand and receptor, as well as the detailed results of Phase II and III trials involving these novel treatments. We conclude with a discussion of the implications of blocking CGRP and its receptor.

3 Review PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma. 2018

Waschek, James A / Baca, Serapio M / Akerman, Simon. ·Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. jwaschek@mednet.ucla.edu. · Department of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA. serapio.baca@ucdenver.edu. · Department of Oral and Maxillofacial Pathology, Radiology and Medicine, New York University College of Dentistry, New York, NY, 10010, USA. sakerman@umaryland.edu. · Department of Neural and Pain Sciences, University of Maryland Baltimore, Maryland, Baltimore, MD, 21201, USA. sakerman@umaryland.edu. ·J Headache Pain · Pubmed #29536279.

ABSTRACT: The discovery that intravenous (IV) infusions of the neuropeptide PACAP-38 (pituitary adenylyl cyclase activating peptide-38) induced delayed migraine-like headaches in a large majority of migraine patients has resulted in considerable excitement in headache research. In addition to suggesting potential therapeutic targets for migraine, the finding provides an opportunity to better understand the pathological events from early events (aura) to the headache itself. Although PACAP-38 and the closely related peptide VIP (vasoactive intestinal peptide) are well-known as vasoactive molecules, the dilation of cranial blood vessels per se is no longer felt to underlie migraine headaches. Thus, more recent research has focused on other possible PACAP-mediated mechanisms, and has raised some important questions. For example, (1) are endogenous sources of PACAP (or VIP) involved in the triggering and/or propagation of migraine headaches?; (2) which receptor subtypes are involved in migraine pathophysiology?; (3) can we identify specific anatomical circuit(s) where PACAP signaling is involved in the features of migraine? The purpose of this review is to discuss the possibility, and supportive evidence, that PACAP acts to induce migraine-like symptoms not only by directly modulating nociceptive neural circuits, but also by indirectly regulating the production of inflammatory mediators. We focus here primarily on postulated extra-dural sites because potential mechanisms of PACAP action in the dura are discussed in detail elsewhere (see X, this edition).

4 Review Migraine Care Challenges and Strategies in US Uninsured and Underinsured Adults: A Narrative Review, Part 1. 2018

Charleston, Larry / Royce, Jeffrey / Monteith, Teshamae S / Broner, Susan W / O'Brien, Hope L / Manrriquez, Salvador L / Robbins, Matthew S. ·Department of Neurology, University of Michigan, Ann Arbor, MI, USA. · Neuro and Headache Center, SwedishAmerican Hospital, Rockford, IL, USA. · Headache Division, Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL, USA. · Weill Cornell Medicine Headache Program, Department of Neurology, Weill Cornell Medical College, New York, NY, USA. · Division of Neurology, Cincinnati Children's Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA. · Department of Neurology, Albert Einstein College of Medicine, Montefiore Headache Center, Bronx, NY, USA. ·Headache · Pubmed #29516470.

ABSTRACT: OBJECTIVE: To review the scope of the problem facing individuals with migraine who are under- or uninsured. In this first of a 2-part narrative review, we will explore migraine epidemiology and the challenges that face this vulnerable population. BACKGROUND: Implementation of the Affordable Care Act has improved access to health care for many individuals who were previously uninsured, but there are many, particularly those of certain demographics, who are at high risk for worse outcomes. METHODS: A narrative review was performed after a series of discussions within the Underserved Populations in Headache Medicine Special Interest Section meetings of the American Headache Society. Literature was reviewed for key concepts underpinning conceptual boundaries and a broad overview of the subject matter. Published guidelines, state-specific Medicaid websites, headache quality measurement set, literature review, and expert opinion were used to tailor suggested treatment options and therapeutic strategies. RESULTS: Migraine is common, yet remains underdiagnosed and associated with worse outcomes among those of under-represented backgrounds and those who are underinsured or uninsured. Low socioeconomics may play an important role in the disease progression, characteristics, outcome, and quality of life of patients with migraine and other headache disorders. Other barriers to optimal care include time constraints, lack of access to specialty providers, transportation, and financial limitations. CONCLUSION: There are many barriers and challenges that affect people with migraine who are underinsured or uninsured, particularly those of under-represented racial backgrounds and of lower socioeconomic status.

5 Review Glutamate and Its Receptors as Therapeutic Targets for Migraine. 2018

Hoffmann, Jan / Charles, Andrew. ·Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, 20246, Hamburg, Germany. j-r.hoffmann@uke.de. · Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), 635 Charles Young Drive, Los Angeles, CA, 90095, USA. ·Neurotherapeutics · Pubmed #29508147.

ABSTRACT: There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling. Animal studies indicate that glutamate plays a key role in pain transmission, central sensitization, and cortical spreading depression. Multiple therapies that target glutamate receptors including magnesium, topiramate, memantine, and ketamine have been reported to have efficacy in the treatment of migraine, although with the exception of topiramate, the evidence for the efficacy of these therapies is not strong. Also, because all of these therapies have other mechanisms of action, it is not possible to conclude that the efficacy of these drugs is entirely due to their effects on glutamate receptors. Further studies are needed to more clearly delineate the possible roles of glutamate and its specific receptor subtypes in migraine and to identify new ways of targeting glutamate for migraine therapy.

6 Review The pathophysiology of migraine: implications for clinical management. 2018

Charles, Andrew. ·UCLA Goldberg Migraine Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: acharles@ucla.edu. ·Lancet Neurol · Pubmed #29229375.

ABSTRACT: The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients.

7 Review Experts' opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents. 2017

Özge, Aynur / Faedda, Noemi / Abu-Arafeh, Ishaq / Gelfand, Amy A / Goadsby, Peter James / Cuvellier, Jean Christophe / Valeriani, Massimiliano / Sergeev, Alexey / Barlow, Karen / Uludüz, Derya / Yalın, Osman Özgür / Lipton, Richard B / Rapoport, Alan / Guidetti, Vincenzo. ·Department of Neurology, Mersin University Medical Faculty, Mersin, Turkey. · Phd program in Behavioural Neuroscience, Department of Paediatrics and Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Rome, Italy. · Royal Hospital for Sick Children, Glasgow, G3 8SJ, UK. · UCSF Headache Center and UCSF Benioff Children's Hospital, Pediatric Brain Center 2330 Post St 6th Floor San Francisco, Campus Box 1675, San Francisco, CA, 94115, USA. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, England. · Division of Paediatric Neurology, Department of Paediatrics, Lille Faculty of Medicine and Children's Hospital, Lille, France. · Division of Neurology, Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio 4, 00165, Rome, Italy. · Center for Sensory-Motor Interaction Aalborg University, Aalborg, Denmark. · Department of Neurology and Clinical Neurophysiology, University Headache Clinic, Moscow State Medical University, Moscow, Russia. · Faculty of Medicine, University of Calgary, Alberta Children's Hospital, C4-335, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6A8, Canada. · Cerrahpaşa Medical Faculty, Department of Neurology, İstanbul University, Kocamustafapaşa, İstanbul, Turkey. · İstanbul Research and Education Hospital, Kocamustafapaşa, İstanbul, Turkey. · Department of Neurology Montefiore Headache Center, Albert Einstein College of Medicine, Louis and Dora Rousso Building, 1165 Morris Park Avenue, Room 332, Bronx, NY, 10461, USA. · The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Department of Pediatrics and Child and Adolescent Neuropsychiatry, Sapienza University, Rome, Italy. vincenzo.guidetti@uniroma1.it. ·J Headache Pain · Pubmed #29285570.

ABSTRACT: BACKGROUND: The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments. METHODS: Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents. RESULTS: Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults. CONCLUSIONS: Several recommendations are presented in order to make ICHD-3 more appropriate for use with children.

8 Review Migraine. 2017

Charles, Andrew. ·From the UCLA Goldberg Migraine Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles. ·N Engl J Med · Pubmed #28792865.

ABSTRACT: -- No abstract --

9 Review Calcitonin Gene-Related Peptide-Targeted Therapies for Migraine and Cluster Headache: A Review. 2017

Schuster, Nathaniel M / Rapoport, Alan M. ·*Center for Pain Medicine, Department of Anesthesia, Critical Care, and Pain Medicine, Wang Ambulatory Care Center, Boston, MA; and †Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. ·Clin Neuropharmacol · Pubmed #28644160.

ABSTRACT: Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in headache and facial pain disorders. There are a handful of CGRP-targeted therapies currently in phase 3 studies for migraine acute treatment or prevention. Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine. Two of these anti-CGRP monoclonal antibodies are in clinical trials for cluster headache prevention as well. Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. In this review, we will discuss the growing body of clinical trials studying CGRP-targeted therapies for migraine and cluster headache.

10 Review Neurological Disease in Women: Stroke, Cognition, and Headache. 2017

Kransdorf, Lisa N / Mayer, Anita P / Files, Julia A. ·1 Division of Internal Medicine and Pediatrics, University of California Los Angeles , Los Angeles, California. · 2 Division of Women's Health Internal Medicine, Mayo Clinic , Scottsdale, Arizona. ·J Womens Health (Larchmt) · Pubmed #28388266.

ABSTRACT: In this clinical update, we selected recent publications relevant to common neurological concerns in women, with specific attention to stroke, cognition, and headache. We have chosen to highlight articles on sex differences in stroke and stroke treatment, the effect of hormone therapy on stroke risk and on cognition, and symptoms of the migraine postdrome.

11 Review Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies. 2017

Aurora, Sheena K / Brin, Mitchell F. ·Stanford University, Stanford, CA, USA. · Allergan plc, Irvine, CA, USA. · Department of Neurology, University of California, Irvine, CA, USA. ·Headache · Pubmed #27910097.

ABSTRACT: Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity-specific metabolic, functional, and structural abnormalities in the brainstem. Without longitudinal studies, it is unclear whether these changes may represent a continuum of individual progression and/or are reversible. Furthermore, chronic migraine is associated with larger impairments in cortical processing of sensory stimuli when compared with episodic migraine, possibly caused by more pronounced cortical hyperexcitability. Progressive changes in nociceptive thresholds and subsequent central sensitization due to recurrent migraine attacks in vulnerable individuals contribute to the chronic migraine state. This may result in changes to baseline neurologic function between headache attacks, evident in both electrophysiological and functional imaging research. Patients experiencing migraine chronification may report increased non-headache pain, fatigue, psychiatric disorders (eg, depression, anxiety), gastrointestinal complaints, and other somatic conditions associated with their long-term experience with migraine pain. Recent research provides a foundation for differentiating episodic and chronic migraine based on neurophysiologic and neuroimaging tools. In this literature review, we consider these findings in the context of models designed to explain the physiology and progression of episodic migraine into chronic migraine, and consider treatment of chronic migraine in susceptible individuals. Advances in pharmacotherapy provide treatment options for chronic migraine. Of the currently available treatment options, only onabotulinumtoxinA and topiramate have received regulatory approval and have demonstrated efficacy in patients with chronic migraine, although the exact mechanisms of action are not fully elucidated.

12 Review Temporomandibular Disorders and Headache. 2016

Graff-Radford, Steven B / Abbott, Jeremy J. ·The Pain Center, Cedars-Sinai Medical Center, 444 South San Vicente Boulevard #1101, Los Angeles, CA 90048, USA; The Program for Headache and Orofacial Pain, Cedars-Sinai Medical Center, Los Angeles, CA, USA; UCLA School of Dentistry, Los Angeles, CA, USA. Electronic address: graffs@cshs.org. · West Coast Ear, Nose & Throat Medical Group, 301 South Moorpark Road, Thousand Oaks, CA 91361, USA. ·Oral Maxillofac Surg Clin North Am · Pubmed #27475510.

ABSTRACT: Temporomandibular disorders (TMD) and primary headaches can be perpetual and debilitating musculoskeletal and neurological disorders. The presence of both can affect up to one-sixth of the population at any one time. Initially, TMDs were thought to be predominantly musculoskeletal disorders, and migraine was thought to be solely a cerebrovascular disorder. The further understanding of their pathophysiology has helped to clarify their clinical presentation. This article focuses on the role of the trigeminal system in associating TMD and migraine. By discussing recent descriptions of prevalence, diagnosis, and treatment of headache and TMD, we will further elucidate this relationship.

13 Review Update on the Pharmacological Treatment of Chronic Migraine. 2016

Sun-Edelstein, Christina / Rapoport, Alan M. ·Department of Medicine, St Vincent's Hospital, The University of Melbourne, Melbourne, Australia. Christina.Sun-Edelstein@svha.org.au. · The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. alanrapoport@gmail.com. ·Curr Pain Headache Rep · Pubmed #26728188.

ABSTRACT: Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

14 Review New players in the preventive treatment of migraine. 2015

Mitsikostas, Dimos D / Rapoport, Alan M. ·Neurology Department, Athens Naval Hospital, 70 Dinokratous Street, 11521, Athens, Greece. dimosmitsikostas@icloud.com. · The David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. · , 4255 Jefferson Avenue, Suite 27, Woodside, California, CA, 94062, USA. ·BMC Med · Pubmed #26555040.

ABSTRACT: Migraine is a common, chronic disorder of the brain causing much disability, as well as personal, familial and societal impact. Several oral preventive agents are available in different countries for the prevention of migraine, but none have performed better than 50% improvement in 50% of patients in a clinical trial. Additionally, each has various possible adverse events making their tolerability less than optimal. Recently, three monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) ligand (LY2951742, ALD403 and TEV-48125) and one targeting the CGRP receptor (AMG 334) have completed phase 2 trials, and the results have been reported. These early results show them all to be somewhat more effective than placebo, with no serious adverse events. Three have been studied for episodic migraine, and only TEV-48125 has been studied for both high frequency episodic and chronic migraine. Moreover, preliminary data suggests that neurostimulation is effective in migraine treatment, including stimulation of the sphenopalatine ganglion, transcutaneous supraorbital and supratrochlear nerve, and transcutaneous vagus nerve. In this article, these innovative therapies will be reviewed.

15 Review New therapeutic approaches for the prevention and treatment of migraine. 2015

Diener, Hans-Christoph / Charles, Andrew / Goadsby, Peter J / Holle, Dagny. ·Department of Neurology and Headache Center, University of Duisburg-Essen, Essen, Germany. Electronic address: hans.diener@uk-essen.de. · Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK. · Department of Neurology and Headache Center, University of Duisburg-Essen, Essen, Germany. ·Lancet Neurol · Pubmed #26376968.

ABSTRACT: The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. Successful new approaches for the treatment of acute migraine target calcitonin gene-related peptide (CGRP) and serotonin (5-hydroxytryptamine, 5-HT1F) receptors. Other approaches targeting the transient receptor potential vanilloid (TRPV1) receptor, glutamate, GABAA receptors, or a combination of 5-HT1B/1D receptors and neuronal nitric oxide synthesis have been investigated but have not been successful in clinical trials thus far. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use.

16 Review Migraine aura: new ideas about cause, classification, and clinical significance. 2015

Charles, Andrew / Hansen, Jakob Møller. ·aHeadache Research and Treatment Program, Department of Neurology, University of California Los Angeles, California, USA bDanish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ·Curr Opin Neurol · Pubmed #25923125.

ABSTRACT: PURPOSE OF REVIEW: The migraine aura is a dramatic spontaneous change in brain activity resulting in a variety of transient neurological symptoms. The purpose of this review is to address recent advances in the understanding of aura and its role in migraine. RECENT FINDINGS: The formal classification of migraine aura is becoming both broader and more detailed. Traditionally viewed as a primary event that triggers a migraine attack, studies regarding the timing of aura relative to other symptoms of migraine indicate that it may not in fact play a primary role in initiating an attack. Careful recording and analysis of visual aura symptoms provides new insight into the initiation and propagation of the underlying brain phenomenon, and the different regions of visual cortex that produce different visual perceptions. Migraine with aura may have different responses to acute and preventive therapies. SUMMARY: There has been significant evolution of concepts regarding the causes of migraine aura, how it is best defined, and how it fits into the picture of the migraine disorder as a whole. Regardless of its exact role in the genesis of migraine, an increased understanding of aura has the potential to provide important new insight into not only migraine but also fundamental mechanisms of brain physiology.

17 Review Stroke Mimics and Acute Stroke Evaluation: Clinical Differentiation and Complications after Intravenous Tissue Plasminogen Activator. 2015

Nguyen, Peggy L / Chang, Jason J. ·Department of Neurology, University of Southern California, Los Angeles, California. · Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee. ·J Emerg Med · Pubmed #25802155.

ABSTRACT: BACKGROUND: Intravenous tissue-plasminogen activator remains the only U.S. Food and Drug Administration-approved treatment for acute ischemic stroke. Timely administration of fibrinolysis is balanced with the need for accurate diagnosis. Stroke mimics represent a heterogeneous group of patients presenting with acute-onset focal neurological deficits. If these patients arrive within the extended time window for acute stroke treatment, these stroke mimics may erroneously receive fibrinolytics. OBJECTIVE: This review explores the literature and presents strategies for differentiating stroke mimics. DISCUSSION: Clinical outcome in stroke mimics receiving fibrinolytics is overwhelmingly better than their stroke counterparts. However, the risk of symptomatic intracranial hemorrhage remains a real but rare possibility. Certain presenting complaints and epidemiological risk factors may help differentiate strokes from stroke mimics; however, detection of stroke often depends on presence of posterior vs. anterior circulation strokes. Availability of imaging modalities also assists in diagnosing stroke mimics, with magnetic resonance imaging offering the most sensitivity and specificity. CONCLUSION: Stroke mimics remain a heterogeneous entity that is difficult to identify. All studies in the literature report that stroke mimics treated with intravenous fibrinolysis have better clinical outcome than their stroke counterparts. Although symptomatic intracranial hemorrhage remains a real threat, literature searches have identified only two cases of symptomatic intracranial hemorrhage in stroke mimics treated with fibrinolytics.

18 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.

19 Review The place of corticosteroids in migraine attack management: A 65-year systematic review with pooled analysis and critical appraisal. 2015

Woldeamanuel, Y W / Rapoport, A M / Cowan, R P. ·Stanford Headache and Facial Pain Program, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, USA ywoldeam@stanford.edu yohannes.woldeamanuel@gmail.com. · Department of Neurology, The David Geffen School of Medicine at UCLA in Los Angeles, USA. · Stanford Headache and Facial Pain Program, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, USA. ·Cephalalgia · Pubmed #25576463.

ABSTRACT: BACKGROUND AND OBJECTIVES: Headaches recur in up to 87% of migraine patients visiting the emergency department (ED), making ED recidivism a management challenge. We aimed herein to determine the role of corticosteroids in the acute management of migraine in the ED and outpatient care. METHODS: Advanced search strategies employing PubMed/MEDLINE, Web of Science, and Cochrane Library databases inclusive of a relevant gray literature search was employed for Clinical Studies and Systematic Reviews by combining the terms "migraine" and "corticosteroids" spanning all previous years since the production of synthetic corticosteroids ca. 1950 until August 30, 2014. Methods were in accordance with MOOSE guidelines. RESULTS: Twenty-five studies (n = 3989, median age 37.5 years, interquartile range or IQR 35-41 years; median male:female ratio 1:4.23, IQR 1:2.1-6.14; 52% ED-based, 56% randomized-controlled) and four systematic reviews were included. International Classification of Headache Disorders criteria were applied in 64%. Nineteen studies (76%) indicated observed outcome differences favoring benefits of corticosteroids, while six (24%) studies indicated non-inferior outcomes for corticosteroids. Median absolute risk reduction was 30% (range 6%-48.2%), and 11% (6%-48.6%) for 24-, and 72-hour headache recurrence, respectively. Parenteral dexamethasone was the most commonly (56%) administered steroid, at a median single dose of 10 mg (range 4-24 mg). All meta-analyses revealed efficacy of adjuvant corticosteroids to various abortive medications-indicating generalizability. Adverse effects were tolerable. Higher disability, status migrainosus, incomplete pain relief, and previous history of headache recurrence predicted outcome favorability. CONCLUSIONS: Our literature review suggests that with corticosteroid treatment, recurrent headaches become milder than pretreated headaches and later respond to nonsteroidal therapy. Single-dose intravenous dexamethasone is a reasonable option for managing resistant, severe, or prolonged migraine attacks.

20 Review Development of onabotulinumtoxinA for chronic migraine. 2014

Whitcup, Scott M / Turkel, Catherine C / DeGryse, Ronald E / Brin, Mitchell F. ·Allergan, Inc, Irvine, California. ·Ann N Y Acad Sci · Pubmed #25399521.

ABSTRACT: Discovery of the neuromuscular effects of botulinum toxin began in the early 19th century and has continued to evolve. Currently, onabotulinumtoxinA is approved by the U.S. Food and Drug Administration for two cosmetic and eight medical indications, including chronic migraine (CM). CM is a disabling form of migraine characterized by ≥15 headache days monthly and is believed to result from neuronal hypersensitivity to proinflammatory mediators, upregulation of sensory receptors, and consequent maladaptive pain responses with peripheral and central sensitization. OnabotulinumtoxinA achieves migraine prophylaxis in CM through regulation of vesicular trafficking and exocytosis, inhibition of peripheral release of neuropeptides and inflammatory peptides, and reduced cell surface expression of certain ion channels and receptors. Clinically, efficacy of onabotulinumtoxinA for CM has been shown in two phase III, placebo-controlled trials (PREEMPT 1 and PREEMPT 2). OnabotulinumtoxinA significantly reduced the number of headache days per 28-day cycle relative to placebo at week 24 (change from baseline: -8.4 days for onabotulinumtoxinA versus -6.6 days for placebo; P < 0.001, pooled data). OnabotulinumtoxinA improved health-related quality of life and had an acceptable safety profile. OnabotulinumtoxinA is the only approved treatment specifically for CM prevention and represents a safe and effective therapeutic for chronic migraineurs.

21 Review Treatment persistence and switching in triptan users: a systematic literature review. 2014

Messali, Andrew J / Yang, Mo / Gillard, Patrick / Tsai, Kimberly / Tepper, Stewart J / Bloudek, Lisa M / Kori, Shashidhar H. ·Allergan, Inc., Irvine, CA, USA; University of Southern California, Los Angeles, CA, USA. ·Headache · Pubmed #24912394.

ABSTRACT: OBJECTIVE: To conduct a systematic review to evaluate persistence to and switching of triptan therapy for the acute treatment of migraine. BACKGROUND: Migraine affects over 12% of adults in Western countries and an estimated 36 million people in the United States. Triptans are an abortive treatment option in patients with moderate to severe migraine. Despite the safety and efficacy of triptans reported in clinical trials, observational studies have consistently demonstrated low persistence to therapy and frequent switching among products over time. METHODS: The following databases were researched: Medline, CENTRAL, and EMBASE. Detailed inclusion and exclusion criteria were specified a priori before conducting abstract and full-text screening. Included studies were required to: (1) report triptan use for migraine treatment; (2) report measures of persistence and/or switching patterns; (3) study migraineurs aged 18 years or older; and (4) conduct an observational study. Studies were excluded if they (1) incorporated interventional study design; (2) lack information or relevance to outcome of interest; (3) were not original research; (4) did not clearly state the results; and (5) were not written in English. Abstracts and full-text articles were reviewed independently by two investigators. RESULTS: Out of 595 studies identified, 380 studies were included for abstract screening. A total of 12 articles met the eligibility criteria after full-text screening of 44 studies, including four studies from reference search. The proportion of patients that remained persistent up to six refills of an index triptan ranged from 3.2% to 12.6% and the proportion of patients that never refilled their index triptan ranged from 38% to 65.8%. In addition to those patients who discontinued, several studies reported that 5-9% of newly initiating triptan users switch to a different triptan before refilling their original medication. Finally, several studies reported the 1-year probability of discontinuation among a general group of triptan users (not limited to treatment naïve patients) to be between 30% and 60%. CONCLUSIONS: Triptans can be a valuable option for acute treatment of migraine. However, studies have shown that treatment persistence is low. This, along with frequent switching behaviors, suggests that a significant unmet clinical need remains despite the wide availability of triptans.

22 Review Migraine and reward system-or is it aversive? 2014

Cahill, Catherine M / Cook, Christopher / Pickens, Sarah. ·Department of Anesthesiology & Perioperative Care, 837 Health Sciences Rd, 2117 Gillespie Neuroscience Research Facility, Irvine, CA, 92697, USA, cmcahill@uci.edu. ·Curr Pain Headache Rep · Pubmed #24671390.

ABSTRACT: Migraine is a debilitating neurological disorder with grave consequences for both the individual and society. This review will focus on recent literature investigating how brain structures implicated in reward and aversion contribute to the genesis of migraine pain. There exist many overlapping and interacting brain regions within pain and reward circuitry that contribute to negative affect and subjective experience of pain. The emotional component of pain has been argued to be a greater metric of quality of life than its sensory component, and thus understanding the processes that influence this pain characteristic is essential to developing novel treatment strategies for mitigating migraine pain. We emphasize and provide evidence that abnormalities within the mesolimbic cortical reward pathways contribute to migraine pain and that there are structural and functional neuroplasticity within the overlapping brain regions common to both pain and reward.

23 Review Systematic review of migraine prophylaxis adherence and persistence. 2014

Hepp, Zsolt / Bloudek, Lisa M / Varon, Sepideh F. ·Global Health Outcomes Strategy and Research, Allergan, 2525 Dupont Dr., MI3-110A, Irvine, CA 92612, USA. Hepp_Zsolt@Allergan.com. ·J Manag Care Pharm · Pubmed #24372457.

ABSTRACT: BACKGROUND: Migraine is a common neurological disease affecting 12% of Americans and millions worldwide. Medication adherence has been studied extensively in many chronic conditions, with poor adherence adversely affecting treatment outcomes. However, little is known about adherence to oral prophylaxis for migraine. OBJECTIVE: To examine the literature on assessing oral prophylaxis medication adherence and persistence among migraine patients. METHODS: A systematic search of the PubMed (1966 to present) and EMBASE (1974 to present) databases was conducted to locate prospective and retrospective observational studies and randomized controlled trials (RCTs) of propranolol, amitriptyline, and topiramate. RCTs were pooled, weighted by sample size, and stratified by drug and length of study. Average persistence rates and reasons for discontinuation cited in RCTs were examined for each medication. RESULTS: A total of 788 unique articles were identified using the search criteria, 33 of which were included in the final review. Observational studies (n = 14) showed adherence ranges of 41% to 95% at 2 months, 21% to 80% at 6 months, and 35% to 56% at 12 months and persistence ranges of 41% to 88% at 2 months, 19% to 79% at 6 months, and 7% to 55% at 12 months. Pooled persistence from RCTs on propranolol, amitriptyline, and topiramate (n = 19) showed rates of 77%, 55%, and 57%, respectively, at 16-26 weeks. Adverse events were the most common reason for discontinuation cited (24% for topiramate and 17% for amitriptyline). CONCLUSION: Observational studies and pooled data from RCTs demonstrate poor adherence and persistence to oral migraine prophylaxis.

24 Review Cortical spreading depression and migraine. 2013

Charles, Andrew C / Baca, Serapio M. ·Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine at UCLA, Neuroscience Research Building 1, Room 575, 635 Charles Young Drive South, Los Angeles, CA 90095-7335, USA. ·Nat Rev Neurol · Pubmed #24042483.

ABSTRACT: Cortical spreading depression (CSD), a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the 1940s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. Substantial evidence from animal models provides indirect support for this hypothesis, and studies showing that CSD is common in humans with brain injury clearly demonstrate that the phenomenon can occur in the human brain. Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon.

25 Review Migraine: a brain state. 2013

Charles, Andrew. ·Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. acharles@ucla.edu ·Curr Opin Neurol · Pubmed #23493160.

ABSTRACT: PURPOSE OF REVIEW: Migraine has traditionally been categorized as a pain disorder, focusing on headache as its central feature. This narrow view does not account for the complex array of premonitory and postrdromal symptoms that occur in the hours before and after headache. This review outlines evidence that supports a broader view of migraine as a pathological brain state. RECENT FINDINGS: Studies of the clinical features of a migraine attack, in combination with imaging and electrophysiological studies, provide evidence that migraine involves widespread changes in brain function and connectivity. These changes parallel those seen in other brain states such as sleep. Neurochemical mediators, including adenosine, and nonsynaptic signalling mechanisms involving astrocytes may play a role in the migraine state. SUMMARY: Consideration of a migraine attack as a brain state provides an expanded framework for understanding all of its symptoms, and the underlying alterations in the activity of multiple brain networks. Mechanisms driving the transition to the migraine state may represent novel targets for acute and preventive therapies.