A physics link between venous stenosis and multiple sclerosis

Tucker, Trevor

doi:10.1016/j.mehy.2011.09.006

Cited by 11 publications

(5 citation statements)

References 16 publications

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“…This is a controversial hypothesis, yet it is consistent with the predominantly venocentric orientation of the MS inflammatory lesions and with the otherwise unexplained perivenular iron deposition observed in many clinical cases [Adams, 1988]. A possible path connecting cerebrospinal venous stenosis to chronic fatigue and MS was proposed by Tucker [2011] on the basis of qualitative considerations of elementary fluid mechanics.…”

Section: Introductionmentioning

confidence: 80%

A simple model of filtration and macromolecule transport through microvascular walls

Facchini¹,

Bellin²,

Toro³

2012

Numerical Methods for Hyperbolic Equations

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Multiple Sclerosis (MS) is a disorder that usually appears in adults in their thirties. It has a prevalence that ranges between 2 and 150 per 100 000. Epidemiological studies of MS have provided hints on possible causes for the disease ranging from genetic, environmental and infectious factors to other factors of vascular origin. Despite the tremendous effort spent in the last few years, none of the hypotheses formulated so far has gained wide acceptance and the causes of the disease remain unknown. From a clinical point of view, a high correlation has been recently observed between MS and Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) in a statistically significant number of patients. In this pathological situation CCSVI may induce alterations of blood pressure in brain microvessels, thereby perturbing the exchange of small hydrophilic molecules between the blood and the external cells. In the presence of large pressure alterations it cannot be excluded also the leakage of macromolecules that otherwise would not cross the vessel wall. All these disorders may trigger immune defenses with the destruction of myelin as a side effect. In the present work we investigate the role of perturbed blood pressure in brain microvessels as driving force for an altered exchange of small hydrophilic solutes and leakage of macromolecules into the interstitial fluid. With a simplified, yet realistic, model we obtain closed-form steadystate solutions for fluid flow and solute transport across the microvessel wall. Finally, we use these results (i) to interpret experimental data available in the literature and (ii) to carry out a preliminary analysis of the disorder in the exchange processes triggered by an increase of blood pressure, thereby relating our preliminary results to the hypothesised vascular connection to MS.1991 Mathematics Subject Classification. 82C70; 65C20 .

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Section: Introductionmentioning

confidence: 80%

A simple model of filtration and macromolecule transport through microvascular walls

Facchini¹,

Bellin²,

Toro³

2012

Numerical Methods for Hyperbolic Equations

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“…In other words, "… altered endothelial cell function and might be the common final pathway leading to changes in perfusion and BBB leakage" [37]. The cause of endothelial malfunction is not clear but one theory suggests that venous stenoses may contribute [43].…”

Section: The Hydrostatic Approachmentioning

confidence: 99%

“…The effect of an anatomical restriction may be augmented by a resonant standing wave created through reflection and convergence of transmitted arterial pressure waves along the vein [43]. The result is a localized increase in intravascular pressure at the venous end of the capillary bed (local hypertension), which, coupled with pulsatile shear stress and cyclic strain of the vessel wall can result in rupture of endothelial tight junctions and BBB breakdown [44].…”

Section: The Hydrostatic Approachmentioning

confidence: 99%

“…According to Darcy's law, the rate of blood flow in a vessel of specific length is proportional to the pressure difference between its ends. Increased venous capillary pressure in the face of normal arterial capillary pressure would lead to hypoperfusion [43] and "virtual hypoxia" [45], both of which have been described in the setting of MS.…”

Section: The Hydrostatic Approachmentioning

confidence: 99%

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Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

Ng¹,

VE²

2013

J Mult Scler

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In recent years, chronic cerebro-spinal venous insufficiency (CCSVI) has been associated with multiple sclerosis (MS). Balloon angioplasty of the affected veins (internal jugulars, azygos) has been proposed as a treatment method, with controversial results. The conflict is based on how a primarily immune disease can be affected by a primarily hydrostatic condition and its reversal. In our paper we briefly review novel paradigms in multiple sclerosis pathogenesis and propose a mechanism by which CCSVI could theoretically lead to blood brain barrier disruption, altered neuronal microenvironment, astrocyte and oligodendrocyte loss and demyelination. Altered antigen transfer to regional lymph nodes, affecting antigen presentation and processing could also contribute, affecting the sensitive balance between tolerance and immunity. Thus, a combined hydrostatic-immune paradigm of MS emerges, which may explain the potential role of CCSVI in MS pathogenesis and provide a theoretical framework for future research.

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“…While the new disease-modifying drugs are a major leap forward, they are not a cure, nor are they effective for all patients. MS remains a mysterious disease with no known pathogen or even known determinants of its severity and course [10]. Basic research provides a crucial foundation for innovative approaches to the discovery of effective therapies.…”

Section: Multiple Sclerosis and Researchmentioning

confidence: 99%

Multiple Sclerosis & Research

Kalodimou¹

2013

J Mult Scler

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A physics link between venous stenosis and multiple sclerosis

Cited by 11 publications

References 16 publications

A simple model of filtration and macromolecule transport through microvascular walls

A simple model of filtration and macromolecule transport through microvascular walls

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

Multiple Sclerosis & Research

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