Circle of Willis variability and migraine

威利斯环变异和偏头痛

• 批准号: 7408399
• 负责人: Brett Lee Cucchiara
• 金额: $ 34.45万
• 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408399
• 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; Invasive; 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; Numbers; Outcome Measure; Outpatients; Pathogenesis; Patients; Pennsylvania; Perfusion; Peripheral; Photic Stimulation; Predisposition; Prevention; Principal Investigator; Procedures; Protocols documentation; Rate; Relative (related person); Research; Research Personnel; Research Project Grants; Resolution; Rest; Risk; Risk Factors; Role; Sampling; Schedule; Score; Source; Spin Labels; Spreading Cortical Depression; Stroke; Symptoms; Testing; Therapeutic; Thinking; Training; Trigeminal nerve structure; Universities; University Hospitals; Variant; Weight; Wolves; base; cerebrovascular; computerized data processing; concept; experience; hemodynamics; insight; interest; ischemic lesion; neuroimaging; novel; prospective; response; size; 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）： 新兴文献和初步数据表明，威利斯环异常在偏头痛患者中比在一般人群中更常见。该项目的中心假设是，威利斯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 血管的解剖结构变化很大，并且在由异常 Willis 血管环供应的区域中已证实脑血流量 (CBF) 量发生改变。 CBF 失调可能导致在与神经元过度兴奋相关的代谢需求增加的情况下发生相对缺血，这反过来可能引发皮质扩散性抑制，并可能使偏头痛患者易患缺血性病变和中风。该项目将使用高分辨率 3 特斯拉 MR 血管造影术，确定偏头痛患者与匹配对照组相比，威利斯环异常的频率。将使用预定义的标准解释折叠最大强度投影 (MIP) 图像和源图像，以描述 Willis 异常的分类圈。有先兆和无先兆偏头痛患者以及匹配对照者将以1:1:1的比例入组，每组75名患者。主要结果指标是比较偏头痛组和对照组之间威利斯不完整环的频率。将偏头痛与对照进行比较，对单个 Willis 环异常、Willis 环和颅内椎动脉异常的复合以及异常数量的定量测量进行额外评估。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) 的变化联系起来。将在休息时和光刺激挑战期间测量区域 CBF。将量化感兴趣血管区域 (ROI) 的脑血流，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，该项目将使用液体抑制 T2 加权 MRI 确定 T2 加权 MRI 上的脑部病变是否与 Willis 环异常相关。 MRI 上的缺血性变化将根据位置和血管区域进行评分，白质病变将使用半定量验证量表进行评级。识别偏头痛患者脑血管系统的结构变化将具有几个重要意义。首先，它将提供偏头痛易感性的发育机制，可能有助于进一步了解偏头痛的遗传易感性。其次，它将扩大对偏头痛先兆潜在机制以及偏头痛与临床和亚临床脑梗塞之间联系的理解。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。这表明进一步诊断评估的作用，以确定个体患者的偏头痛机制，类似于当前缺血性中风的范例，其中中风机制的确定对于治疗决策至关重要。特定的药物干预措施也可能或多或少适合与特定机制相关的偏头痛患者，无论是预防还是急性治疗。该项目将研究脑血管发育异常导致偏头痛易感性以及偏头痛和中风之间联系的假设。如果这一假设得到证实，这可能会导致基于更好地了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。