Genomes and Genes
Circle of Willis variability and migraine
Principal Investigator: BRETT LEE CUCCHIARA
Abstract: An emerging literature and preliminary data suggest that circle of Willis anomalies are more prevalent in migraine patients than in the general population. The central hypothesis of this project is that circle of Willis anomalies correlate with alterations in cerebral hemodynamics and contribute to migraine susceptibility and ischemic complications of migraine. The anatomy of the circle of Willis is highly variable and altered cerebral blood flow (CBF) volume has been demonstrated in regions supplied by anomalous circle of Willis vessels. Dysregulation of CBF may allow relative ischemia to develop in the setting of increased metabolic demand related to neuronal hyperexcitability, which may in turn trigger cortical spreading depression, and may predispose individuals with migraine to ischemic lesions and stroke. Using high-resolution 3 Tesla MR angiography, this project will determine the frequency of circle of Willis anomalies in patients with migraine compared to matched controls. Collapsed maximum intensity projection (MIP) images and source images will be interpreted using pre-defined criteria to describe classify circle of Willis anomalies. Patients with migraine with and without aura and matched controls will be enrolled in a 1:1:1 ratio, with 75 patients in each group. The primary outcome measure will be a comparison of the frequency of an incomplete circle of Willis between migraine and control groups. Additional evaluation of individual circle of Willis anomalies, the composite of circle of Willis and intracranial vertebral artery anomalies, and a quantitative measure accounting for the number of anomalies will be performed comparing migraine to controls. Further, this project will correlate circle of Willis anomalies with alterations in regional cerebral blood blow (CBF) based on arterial spin labeled (ASL) perfusion MRI. Regional CBF will be measured both at rest and during a photic stimulation challenge. Cerebral flood flow in vascular regions of interest (ROI) will be quantified, and comparison of quantitative regional CBF and COW anomalies in both migraine patients and controls will be performed. Finally, this project will determine if brain lesions on T2-weighted MRI correlate with circle of Willis anomalies using fluid suppressed T2-weighted MRI. Ischemic changes on MRI will be scored based on location and vascular territory, and white matter lesions will be rated using a semi-quantitative validated scale. Identification of structural alterations in the cerebral vasculature in migraine patients would have several important implications. First, it would provide a developmental mechanism for migraine susceptibility that may lead to further insights into genetic predisposition to migraine. Second, it would expand understanding of potential mechanisms underlying migraine aura and linking migraine with both clinical and subclinical cerebral infarction. Third, it could help to identify the subpopulation of patients at risk of progressive cerebral ischemia so as to target preventative therapies appropriately. It would suggest a role for further diagnostic evaluation to determine migraine mechanism in individual patients, analogous to the current paradigm in ischemic stroke in which determination of stroke mechanism is critical to therapeutic decision-making. Particular pharmacologic interventions may also be more or less appropriate in patients with migraine associated with particular mechanisms, both for prevention and acute treatment. This project will investigate the hypothesis that developmental abnormalities in the cerebral blood vessels contribute to migraine susceptibility and the link between migraine and stroke. If this hypothesis is confirmed, this could lead to new treatments based on a better understanding of migraine mechanisms and might help identify patients with migraine who are at risk of stroke.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT
- Interictal cortical hyperresponsiveness in migraine is directly related to the presence of auraRitobrato Datta
Department of Neurology, University of Pennsylvania, USA
Cephalalgia 33:365-74. 2013..The objective of this study was to compare the interictal cortical response to a visual stimulus between migraine with aura (MWA), migraine without aura (MwoA), and control subjects...
- Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatmentAine Merwick
From the Neurovascular Unit for Translational and Therapeutics Research, Stroke Service and Department of Neurology, Mater Misericordiae University Hospital Dublin Academic Medical Centre, Dublin, Ireland Á M, P J K Department of Neurology and Neurological Sciences, Stanford Stroke Centre, Palo Alto, CA G W A, J M O Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA E M A, H A Department of Neurology, Sainte Anne Hospital, Paris Descartes University, Paris, France D C, J L M Department of Clinical Neurosciences, and Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada S B C, A M D Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA B L C Stroke Prevention Research Unit, John Radcliffe Hospital, Oxford, United Kingdom M F G, P M R Stroke Unit, Department of Neurology, Hospitalt Universitari Arnau de Vilanova de Lleida and Universitat de Lleida, Biomedical Research Institute of Lleida, Lleida, Spain F P Department of Neurology, UCLA Stroke Center J L S Division of Neurology, CA 92138
Stroke 44:2814-20. 2013..Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis...
- Migraine with aura is associated with an incomplete circle of willis: results of a prospective observational studyBrett Cucchiara
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
PLoS ONE 8:e71007. 2013..To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion...
- Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of NeurologyP D Schellinger
National Institutes of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
Neurology 75:177-85. 2010..To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke...
- Absence of changes in cortical thickness in patients with migraineRitobrato Datta
University of Pennsylvania, USA
Cephalalgia 31:1452-8. 2011..We attempted to replicate these findings in a larger patient population...