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Trevor W Tucker, PhD

Fluid Dynamics:The MS – CCSVI Missing

Link?

Presented At The NCS Conference

“Les voix du progrès :: Voices of Progress”

Sherbooke, PQ, Canada, September 2013

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Background About Multiple Sclerosis (sic)

Autoimmune cells attack myelin insulation on neural axons Attacks result in scleroses and nerve damage around fine cerebral veins Symptoms and influences are many and varied

About Chronic Cerebral Spinal Venous Insufficiency Vein obstruction reduces cerebral blood flow

The Scientific Controversy Does MS cause CCSVI? Vis-versa? Or Neither?

About Research Approaches Generally Medical Research – Clinical Trials Physics Research – “The Scientific Method”

My Approach – Applying the Scientific Method Specifically, applying the physics of Fluid Dynamics to cerebral blood flow

Applying The Scientific Method

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What is the CCSVI – MS relationship?

Have Internet, Will Google

Experiments - Literature Reported

Compare Experimental and Model Results

Audience Participation

Venous Reflux

Venule Hypertension

BBB Disruption

T/B Cell Leakage

Myelin Attack

Venous Obstruction

Flu

id

Dyn

amic

s

Cur

rent

Li

tera

ture

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The Physics of Fluid Dynamics Hypothesis: Travelling Pulses In a Tube

Pressure Superposition Standing Pressure Wave

Localized Hypertension On Each and Every Pulse

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One pulse period

FromHeart

TowardHeart

Compare Model and Experimental Results

In a blocked tube the fluid flows back and forth - pushed by a pressure gradient

Graphics from: a) Fendt (above) b) Haacke (MS-MRI.com, left)

PgradFlow

PgradFlow

Back and forth flow in IJV occurs

Increased venous flow occurs with increased pressure gradient (ie hypertension )

Hypertensive FlowCompare Right and Left IJV

9 5

Pgrad

Flow

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Sum Pressure of Direct and Reflux Pulses = Venule Hypertension

Blocked Valve

Venule End

Distance From Blocked Valve (cm)

Sum

Venule Hypertension

Direct

Reflux

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Pressure may become acute (hypertensive) at the drainage end of the capillary bed (ie the venules)

Also from Schelling (2004): “MS lesions’ sizes and numbers increase in the blood’s “counter-flow direction”, consistent with hypertension increasing in that direction

The distance from obstruction to venules and pulsatile wavelength determine if hypertension exists or not at the venules

0 2 4 6 8 10 12 14Blocked

ValveVenule

EndDistance From Blocked Valve (cm)

Hypertension & Lesions

Standing Pressure Wave and Venule Hypertension

Node Node

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Capillary Bed Pressure Changes -IJV Unobstructed IJV Obstructed

Pout increases

Blood Flow Decreases

Pin is constant Capillary Bed

Ve

nu

les

Art

erio

les

Ce

reb

ral A

rte

ry

Inte

rna

l Ju

gu

lar

Ve

in

Blood Flow In Blood Flow Out

Note Shelling’s Comment : “A striking widening of the venous passageways”

Also note the Singh and Zamboni image showing primary and secondary vein stenosis

Also note that if the primary stenosis is removed the secondary stenosis may disappear on its own (my “Eureka” moment)

Venous Hypertension

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Effects of Increased Venule Hypertension (from the Scientific Literature) Blood flow through the capillary bed is reduced by high pressure

(hypertension) at the drainage (venule) end of the capillary bed Hence the amount of oxygen in the blood through the bed is reduced Hence the oxygen transferred into the brain is reduced Oxygen deficiency (hypoxia) in the brain:

Increases fatigue decreases mental acuity (increases brain fog)

The cells (oligodendrocyte cells) that repair the insulation around the nerve channels in the brain (the myelin) begin to die from lack of oxygen

Hence, venous hypertension may cause myelin to deteriorate Observation: “Early loss of oligodendrocytes is a prominent feature in

tissue bordering rapidly expanding MS lesions” (Henderson)

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The Blood Brain Barrier The Blood Brain Barrier is a layer of (endothelial)

cells around the capillaries and venules Its purpose is to protect the brain from large cells and

molecules in the blood Cells such as iron, auto-immune attack cells and bacteria

Allows small molecules (like oxygen, carbon dioxide) and nutrients like glucose to pass between the capillary bed’s blood and the brain

If there is a disruption in the BBB then auto-immune attack cells and iron can make their way into the brain to attack deteriorating myelin

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About Blood Brain Barrier Disruption(From the Scientific Literature) Acute systemic hypertension can cause BBB disruption

Any hypertension-induced BBB disruption would occur at the venule end of the cerebral capillary bed

Venous reflux standing pressure wave may increase going into the venules causing local hypertension

Localized venule hypertension may (and this may be the biggest hypothesis) also be sufficiently large to trigger a disruption in the Blood Brain Barrier

With the failure of the blood-brain barrier, autoimmune attack cells may (certainly will?) enter the brain and may attack weakened or deteriorated myelin

Observation: Blood Brain Barrier disruption has been widely observed in association with Multiple Sclerosis (Kermode, Gay, Simka)

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Removing An Obstruction In A Cerebral Vein

Increases blood flow through the capillaries Increases the transfer of oxygen, glucose and

other nutrients into the brain (reduces hypoxia) This reduces chronic fatigue and brain fog May clear a secondary stenosis above a primary

obstruction Doesn’t impact existing scleroses and iron

deposits Disabilities from existing nerve damage remain However, may significantly improve quality of life

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Does The Hypothesis Explain Other MS Risk Factors, Including:

Twice as many female MS patients as male The Influence of geographic distribution The influence of vitamin D The influence of aging The influence of cigarette smoking The influence of previous viral infection The influence of genetics

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Have Internet: Will Google

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Impact of Hypoxia (Lack of Oxygen) On The BBB(From the Scientific Literature) Long term hypoxia reduces endothelial layer compliance (reduces venule elasticity)

Hypoxia promotes adherence of autoimmune attack cells (leukocytes) to endothelial cells

Hypoxia induces endothelial & oligodendrocyte cell death Hypoxia increases endothelial permeability (porosity) to

larger molecules and cells Hypoxia promotes angiogenesis (growth of new vessels, like

collaterals) to help restore the oxygen supply Hypoxia also induces fatigue and brain fog Observation - The above characteristics are all observed in

the literature to be associated with MS

Predicted Results of a Reduction in Vein and Venule Compliance

Less compliant (less elastic) veins have less capacity to expand to store blood pulses in the veins between the obstruction and the venules

Hence, more blood and pressure is forced higher into the venules

Hence reduced venous compliance: Increases hypertension at the venules Increases risk of Blood Brain Barrier disruption Increases Multiple Sclerosis risk

Factors That Reduce Vein Compliance and/or Endothelial Continuity (From the Scientific Literature)

Female (whose compliance is 50% less than males’) Vitamin D deficiency (and sunshine deficiency) Dietary influences such as coffee and gluten Cigarette smoking Previous Epstein Barr Virus infection Aging and genetics Observation: Such factors, through reducing vein

compliance, increase venule hypertension, and hence the risk of BBB disruption, immune cell leakage, myelin attack and scleroses

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Summary

GenderFemale veins are

less complianthence, more hypertension

Sunshine/Vitamin DVitamin D deficiency

reduces vein compliance and increases hypertension

AgingReduces vein compliance

And Increases hypertension

SmokingImpairs endothelium,

reduces vein compliance and

increases hypertension

Epstein-BarrImpairs endothelium

GeneticsVein malformation &BBB susceptible toleukocyte passage

IJV

Venules

ObstructionCauses venule hypertension

Venule HypertensionCauses hypoxia

HypoxiaReduces vein compliance

Increases leukocyte adhesionIncreases endothelial permeability

Increases endothelial cell deathPromotes collateral vein growth

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Progressing the Simple Fluid Dynamics Model

Use Computation Fluid Dynamics (CFD) to Solve the Navier-Stokes equations

(Navier-Stokes is the fluid equivalent of Newton’s law)

ma = f

Measure with 4D MRI Enter Gravity, Compliance, ForcesSolve Pressure

Determine Venule Pressure - Is it Hypertensive? (Note: Commercial CFD Software Is Available)

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CFD Is Currently Applied to Blood Flow

Recent Progress: A Symposium on CCSVI Computer Modeling: (Zamboni, Toro, Beggs et al)

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My Observations Arising From The Hypothesis

Venous reflux can result from many types of obstructions in many cerebral & spinal vein places

Existence of CCSVI (venous reflux) does not ensure MS

Existence of MS does not require CCSVI Existence and severity of MS is affected by:

Placement, number and sizes of venous obstructions Properties of the endothelial layer (affected by diet,

gender, pharmaceuticals, sunshine, smoking, etc.) Immune system modulation via pharmaceuticals

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Fluid Dynamics:The MS – CCSVI Missing

Link?Do the results predicted by the fluid dynamics hypothesis match the characteristics of MS as

reported in the scientific literature?

Would this persuade a broad medical community?

(I remain very optimistic, I have seen progress)

Questions and Comments?

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