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Licensed Unlicensed Requires Authentication Published by De Gruyter August 2, 2013

Spreading depression and the clinical correlates of migraine

  • Katharina Eikermann-Haerter

    Katharina Eikermann-Haerter is a principal investigator at the Massachusetts General Hospital, Department of Radiology, on pathophysiology of migraine and stroke. She receives peerreviewed funding, and publishes in leading scientific journals in the areas of neuroscience and cardiovascular medicine. Her accomplishments have been acknowledged by numerous prestigious awards, such as the Harold Wolff - John Graham Award from the American Academy of Neurology. Her work demonstrates that spreading depression can produce migraine aura-like symptoms, and increase the vulnerabi lity to stroke. Other important studies revealed mechanisms that can explain the female preponderance in migraine.

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    , Andrea Negro

    Andrea Negro received his medical degree from the ‘Sapienza’ University of Rome, Italy. He completed his residency in Internal Medicine at the same university and during this time he spent one year as a research fellow at the Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School. Negro is currently a clinical research fellow at the Regional Referral Headache Center, Sant′Andrea Hospital, Rome. He has a specific interest in chronic headache disorders, especially migraine, medication overuse headache and refractory migraine.

    and Cenk Ayata

    Cenk Ayata is a neurologist and a clinician-scientist dedicated to translational research in a broad spectrum of neurovascular diseases including migraine, stroke and other brain injury states, and small vessel disease. Ayata lab integrates electrophysiological and multimodal optical imaging techniques to investigate spreading depression and its impact on neurovascular function and dysfunction. His most recent research efforts have been on the interface between migraine and stroke, injury depolarizations in stroke and other brain injury states, targeting spreading depression in migraine, and characterization of animal models of familial migraine syndromes.

Abstract

Migraine is the most common neurologic condition. One-third of migraineurs experience transient neurologic symptoms, the so-called aura. There is strong evidence that spreading depression (SD) is the electrophysiologic substrate of migraine aura. SD is an intense pan-depolarization wave that slowly propagates in gray matter by way of contiguity and transiently disrupts neuronal function. When induced subcortically, striatal SD causes hemiparesis, hippocampal SD can trigger seizures and impact cognition, and bilateral thalamic SD can diminish consciousness. Recent data show that transgenic mice expressing familial hemiplegic migraine (FHM) type 1 mutations in voltage-gated Ca2+ channels (Cav2.1) develop mutation-specific aura-like signs after a cortical SD similar to patients with the respective mutation. These signs are associated with facilitated subcortical SD propagation. As in FHM, mice with the R192Q mutation develop pure hemiplegia associated with cortical SDs propagating into caudoputamen. S218L mice display additional signs such as seizures and coma when SD propagates into hippocampus and thalamus. In hyperexcitable FHM brains, SD may propagate between cortex and subcortical structures via permissive gray matter bridges, or originate de novo in subcortical structures, to explain unusual and severe aura signs and symptoms. Reciprocal spread and reverberating waves can explain protracted attacks.


Corresponding author: Katharina Eikermann-Haerter, Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA

About the authors

Katharina Eikermann-Haerter

Katharina Eikermann-Haerter is a principal investigator at the Massachusetts General Hospital, Department of Radiology, on pathophysiology of migraine and stroke. She receives peerreviewed funding, and publishes in leading scientific journals in the areas of neuroscience and cardiovascular medicine. Her accomplishments have been acknowledged by numerous prestigious awards, such as the Harold Wolff - John Graham Award from the American Academy of Neurology. Her work demonstrates that spreading depression can produce migraine aura-like symptoms, and increase the vulnerabi lity to stroke. Other important studies revealed mechanisms that can explain the female preponderance in migraine.

Andrea Negro

Andrea Negro received his medical degree from the ‘Sapienza’ University of Rome, Italy. He completed his residency in Internal Medicine at the same university and during this time he spent one year as a research fellow at the Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School. Negro is currently a clinical research fellow at the Regional Referral Headache Center, Sant′Andrea Hospital, Rome. He has a specific interest in chronic headache disorders, especially migraine, medication overuse headache and refractory migraine.

Cenk Ayata

Cenk Ayata is a neurologist and a clinician-scientist dedicated to translational research in a broad spectrum of neurovascular diseases including migraine, stroke and other brain injury states, and small vessel disease. Ayata lab integrates electrophysiological and multimodal optical imaging techniques to investigate spreading depression and its impact on neurovascular function and dysfunction. His most recent research efforts have been on the interface between migraine and stroke, injury depolarizations in stroke and other brain injury states, targeting spreading depression in migraine, and characterization of animal models of familial migraine syndromes.

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Received: 2013-2-28
Accepted: 2013-6-27
Published Online: 2013-08-02
Published in Print: 2013-08-01

©2013 by Walter de Gruyter Berlin Boston

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