Migraine and circle of Willis anomalies

Department of Neurology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104, United States.
Medical Hypotheses (Impact Factor: 1.07). 02/2008; 70(4):860-5. DOI: 10.1016/j.mehy.2007.05.057
Source: PubMed

ABSTRACT Several mechanisms are currently thought to contribute to migraine pathogenesis, including interictal neuronal hyperexcitability, cortical spreading depression underlying the symptom of aura, and trigeminal nerve activation at a peripheral and central level. However, these mechanistic concepts incompletely explain migraine susceptibility in individual patients and do not fully account for the well documented association between migraine and ischemic cerebrovascular disease, including increased risk of both clinical stroke and subclinical brain lesions in migraine patients. The circle of Willis is a major source of collateral blood flow supply in the human brain, and developmental morphologic variants of the circle of Willis are extremely frequent. Altered cerebral blood flow (CBF) has been demonstrated in regions supplied by variant circle of Willis vessels. Our central hypothesis is that circle of Willis anomalies correlate with alterations in cerebral hemodynamics and contribute to migraine susceptibility and ischemic complications of migraine. Dysregulation of CBF may allow relative ischemia to develop in the setting of increased metabolic demand related to neuronal hyperexcitability, may trigger cortical spreading depression, and may predispose individuals with migraine to ischemic lesions and stroke. Identification of structural alterations in the cerebral vasculature in migraine patients would have several important pathophysiological and clinical 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. Fourth, 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.

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    • "Hypoplasticity or absence of P1 segment or PCoA has been reported in about 15–22 % of individuals with morphological variations in their CoW (Eftekhar et al. 2006; Papantchev et al. 2007). While patients with one of these CoW variations do not become ill under normal circumstances (with the exception that these variations might trigger migraines; Bugnicourt et al. 2009; Cucchiara and Detre 2008), it has been reported that reduced blood flow, due to hypoplasticity of PCoA with accompanying pathologies (e.g., ICA occlusion), could lead to health risks, including ischemic stroke (Schomer et al. 1994). Additionally, the effects of ACA diameter and other collateral abilities of the CoW with ICA occlusion have been investigated (Cassot et al. 1995; Hendrikse et al. 2001; Rutgers et al. 2000; Tanaka et al. 2006; van Raamt et al. 2006). "
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    ABSTRACT: Although cerebral blood flow is the crucial factor for cerebral infarction and the circle of Willis (CoW) is considered the primary control structure for cerebral hemodynamics, risk of cerebral infarction caused by the morphological variation in the CoW has never been studied due to lack of proper tools. Here, the alteration of cerebral blood flow in CoW variation was quantitatively assessed by a new analysis method using a microfluidic device that was controlled by pneumatic valves. Using this device, the occlusion of diverse major arteries was realized by closing the channel with pneumatic valves. The morphological variations of the CoW and their hemodynamics were designed and analyzed after occlusion of the major arteries. While the differences in hemodynamics of CoW variants were not statistically significant compared with a complete CoW without occlusion or with occlusion of the efferent arteries, the occlusion of afferent arteries such as common carotid artery and vertebral artery severely affected the flow rate (28.4–48.8 %) and related arterial pressure of efferent arteries (48.6 ± 6.7–36.0 ± 1.4 mmHg) in CoW variants where the posterior communicating artery and the P1 segment are absent, which is associated with cerebral ischemic infarction. The novel analysis system using microfluidics provides a robust and accurate method, in which the hemodynamics of individual morphological variation and stenosis, and occlusion of vessels can be analyzed. Thus, this method is particularly suitable for personalized analysis of hemodynamics and may find new applications in biomedical researches.
    Microfluidics and Nanofluidics 11/2014; 17(5). DOI:10.1007/s10404-014-1366-2 · 2.67 Impact Factor
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    • "The most common anatomic variation in the group without vascular-related abnormalities was the absence or hypoplasia of the posterior communicating artery (Malamateniou et al., 2009). Dysregulation of cerebral blood flow may allow relative ischemia to develop in the setting of increased metabolic demand related to neuronal hyper excitability, may trigger cortical spreading depression, and may predispose individuals to ischemic lesions and stroke (Cucchiara and Detre, 2008). The study of Sahni et al. (2007) was conducted on brains of 280 adults and 45 children. "
    Forensic Medicine - From Old Problems to New Challenges, 09/2011; , ISBN: 978-953-307-262-3
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    ABSTRACT: Mathematical models of spreading depression are considered in the form of reaction- diffusion systems in two space dimensions. The systems are solved numerically. In the two com- ponent model with potassium and calcium ion concentrations, we demonstrate, using updated pa- rameter values, travelling solitary waves of increased potassium and decreased calcium. These have circular wavefronts emanating from a region of application of potassium chloride. The collision of two such waves does not, as in one space dimension, result in annihilation but the formation of a unified wave with a large wavefront. For the first time we show that the mathematical model repro- duces the actual properties of spreading depression waves in cortical structures. With attention to geometry, timing and location of stimuli we have succeeded in finding reverberating waves matching experiment. By simulating the technique of anodal block, spiral waves have also been demonstrated which parallel those found experimentally. The six-component model, which contains additionally sodium, chloride, glutamate and GABA, is also investigated in 2 space dimensions, including an experimentally based exchange pump for sodium and potassium. Solutions are obtained without (amplitude 29 mM external K+) and with action potentials (amplitude 44 mM external K+) with speeds of propagation, allowing for tortuosity, of 1.4 mm/minute and 2.7 mm/minute, respectively. When action potentials are included a somewhat higher pump strength is required to ensure the return to resting state.
    07/2008; DOI:10.1063/1.2965101
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