Circle of Willis variability and migraine

描述(由申请人提供)： 一项新的文献和初步数据表明，Willis环状畸形在偏头痛患者中比在普通人群中更常见。该项目的中心假设是，Willis异常环状与脑血流动力学的改变相关，并有助于偏头痛的易感性和偏头痛的缺血性并发症。Willis环的解剖是高度可变的，在Willis血管环异常供血的区域显示了脑血流量的改变。CBF的失调可能会导致相对缺血的发生，这种情况下与神经元的超兴奋性相关的代谢需求增加，进而可能引发皮质弥漫性抑制，并可能使偏头痛患者更容易发生缺血性损害和中风。使用高分辨率3特斯拉磁共振血管成像，该项目将确定与匹配的对照组相比，偏头痛患者的Willis环状畸形的频率。折叠的最大强度投影(MIP)图像和源图像将使用预定义的标准来描述Willis异常的分类圆。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的比例入选，每组75名患者。主要的结果衡量标准将是比较偏头痛组和对照组之间不完整的Willis环的频率。对单独的Willis畸形环、Willis环和颅内椎动脉异常的组合以及解释异常数量的定量测量将进行额外的评估，并将偏头痛与对照组进行比较。此外，该项目将基于动脉自旋标记(ASL)灌注MRI将Willis畸形的环状与局部脑血流(CBF)的变化联系起来。局部脑血流量将在静息状态和光刺激挑战期间进行测量。将对感兴趣血管区域(ROI)的脑血流进行量化，并对偏头痛患者和对照组的定量局部CBF和COW异常进行比较。最后，该项目将使用液体抑制的T2加权MRI来确定脑部病变是否与Willis畸形环状相关。MRI上的缺血性改变将根据位置和血管范围进行评分，脑白质损害将使用半定量验证量表进行评级。确定偏头痛患者脑血管结构的改变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，可能导致对偏头痛遗传易感性的进一步深入了解。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塞联系起来。第三，它可以帮助确定进行性脑缺血风险患者的亚群，以便适当地针对预防性治疗。这将提示进一步的诊断评估在确定个别患者的偏头痛机制方面的作用，类似于目前缺血性卒中的范例，在这种范式中，中风机制的确定对治疗决策至关重要。对于与特定机制相关的偏头痛患者，特殊的药物干预可能或多或少也是合适的，无论是预防还是急性治疗。该项目将调查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，这可能会在更好地了解偏头痛机制的基础上带来新的治疗方法，并可能有助于识别有中风风险的偏头痛患者。

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.