Circle of Willis variability and migraine

威利斯环变异和偏头痛

• 批准号: 7877768
• 负责人: Brett Lee Cucchiara
• 金额: $ 34.11万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7877768
• 关键词: Accounting; Acute; Address; American Heart Association; Anatomy; Angiography; Arts; Auras; Biological Markers; Biometry; Biophysics; Blood; Blood Vessels; Blood flow; Brain; Cattle; Cerebral Infarction; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Physiology; Cerebrum; Circle of Willis; Classic Migraine; Clinical; Clinical Research; Common Migraine; Control Groups; Data; Decision Making; Development; Diagnostic; Enrollment; Environment; Epidemiology; Evaluation; Fellowship; Floods; Frequencies; Functional disorder; Funding; General Population; Genetic Predisposition to Disease; Human; Image; Incidence; Individual; Infarction; Intervention; Ischemia; Ischemic Stroke; Laboratories; Lead; Lesion; Link; Liquid substance; Literature; Location; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Measures; Medical center; Metabolic; Methods; Migraine; Neurologist; Neurology; Neurons; Neurosciences; Outcome Measure; Outpatients; Pathogenesis; Patients; Pennsylvania; Perfusion; Peripheral; Photic Stimulation; Predisposition; Prevention; Principal Investigator; Procedures; Protocols documentation; Relative (related person); Research; Research Personnel; Research Project Grants; Resolution; Rest; Risk; Risk Factors; Role; Sampling; Schedule; Source; Spin Labels; Spreading Cortical Depression; Stroke; Symptoms; Testing; Therapeutic; Training; Trigeminal nerve structure; Universities; University Hospitals; Variant; Weight; Wolves; base; cerebrovascular; clinical practice; computerized data processing; experience; hemodynamics; imaging modality; insight; interest; ischemic lesion; neuroimaging; novel; primary outcome; prospective; response; vertebral artery; white matter

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）： 一个新兴的文献和初步数据表明，威利斯环异常偏头痛患者比一般人群更普遍。该项目的中心假设是Willis环异常与脑血流动力学的改变相关，并导致偏头痛易感性和偏头痛的缺血性并发症。Willis环的解剖结构是高度可变的，并且在异常Willis血管环供应的区域中已经证明了脑血流量（CBF）的改变。CBF的失调可能允许在与神经元过度兴奋相关的代谢需求增加的情况下发展相对缺血，这可能反过来触发皮质扩散性抑制，并且可能使患有偏头痛的个体易患缺血性病变和中风。使用高分辨率3特斯拉磁共振血管造影，该项目将确定与匹配的对照组相比，偏头痛患者的Willis异常环的频率。将使用预定义的标准解释折叠的最大强度投影（MIP）图像和源图像，以描述Willis异常的分类圈。有先兆和无先兆的偏头痛患者和匹配的对照组将以1：1：1的比例入组，每组75例患者。主要结果测量将是偏头痛组和对照组之间不完整Willis环的频率比较。将对个体Willis环异常、Willis环和颅内椎动脉异常的复合物进行额外评价，并对偏头痛与对照组进行比较，以定量测量异常数量。此外，该项目将基于动脉自旋标记（ASL）灌注MRI将Willis环异常与局部脑血流（CBF）变化相关联。将在静息和光刺激激发期间测量局部CBF。将对血管感兴趣区域（ROI）的脑血流进行量化，并对偏头痛患者和对照组的定量区域CBF和COW异常进行比较。最后，本项目将确定T2加权MRI上的脑病变是否与使用液体抑制T2加权MRI的Willis环异常相关。将根据位置和血管区域对MRI上的缺血性变化进行评分，并使用半定量验证量表对白色病变进行评级。偏头痛患者脑血管结构改变的识别将有几个重要的意义。首先，它将为偏头痛易感性提供一种发育机制，这可能会导致对偏头痛遗传易感性的进一步了解。其次，它将扩大对偏头痛先兆潜在机制的理解，并将偏头痛与临床和亚临床脑梗死联系起来。第三，它可以帮助识别有进行性脑缺血风险的患者亚群，以便适当地进行预防性治疗。这将表明进一步诊断评估的作用，以确定偏头痛的机制，在个别患者，类似于目前的模式，在缺血性中风，中风机制的确定是至关重要的治疗决策。对于与特定机制相关的偏头痛患者，特定的药物干预或多或少也适用于预防和急性治疗。本项目将研究脑血管发育异常导致偏头痛易感性的假设以及偏头痛和中风之间的联系。如果这一假设得到证实，这可能会导致基于更好地理解偏头痛机制的新治疗方法，并可能有助于识别有中风风险的偏头痛患者。

项目成果

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment.

与他汀类药物治疗相关的短暂性缺血性攻击，颈动脉狭窄的早期中风风险降低。

• DOI: 10.1161/strokeaha.113.001576
• 发表时间: 2013-10
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Merwick Á;Albers GW;Arsava EM;Ay H;Calvet D;Coutts SB;Cucchiara BL;Demchuk AM;Giles MF;Mas JL;Olivot JM;Purroy F;Rothwell PM;Saver JL;Sharma VK;Tsivgoulis G;Kelly PJ
• 通讯作者: Kelly PJ