Why does CCSVI treatment help?

[RuralLaundry]

I'm new here and I tried to do a search but didn't find the particular information.

I understand the concept of CCSVI from what I have read so far is that the flow of blood AWAY from the brain and CNS is restricted. This causes "stagnant" blood I'll call it to leave excessive iron deposits and other bad things from poor circulation.

My question is why would CCSVI cause the symptoms seen in RRMS? I could understand with PPMS or even SPMS, where poor blood flood would lead to increasing deposits of harmful substances over time. Why would it have an impact on RRMS? I would think with the cyclical nature of RRMS something that seems to be a persistent issue like CCSVI would not create cyclical problems. It seems unlikely that the deposits would be "flushed" occasionally the build back up to cause problems.

I understand CCSVI is only claimed to be a piece of the puzzle but I'm confused by how it would impact RRMS in any way unless it was simply an additional factor but not the primary causation. If this were the case I would be surprised by dramatic success stories from RRMS individuals.

[cheerleader]

hi laundry--
Welcome. Will try to explain a bit more in layman's terms.
When cerebral blood flow is restricted or slowed, it creates a situation called "hypoperfusion"-- simple lowered blood delivery to the brain.
This is already a known and documented problem for people with MS. Hypoperfusion, in turn, creates other problems---like lowered glucose and oxygen delivery to the brain. Hypoperfusion can also open up the blood brain barrier, and lead to deposition of iron and other plasmic particles (like immune cells) into the brain and spine.

So, it's more than just stagnant blood leading to iron deposition, as Dr. Zamboni first hypothesized....it looks like hypoperfusion affects the cleansing of the brain, by also slowing cerebrospinal fluid---which clears metabolites from the brain. You have a whole slowed down drainage system, which also slows delivery. This new information has come from the work being done by a group of researchers called the International Society for Neurovascular Disease. http://www.isnvd.org

Repairing the venous system and restoring normalized blood flow appears to correct hypoperfusion. Here's a video interview I made with Dr. Zamboni, where he discusses this discovery from a recent pilot study he's completed using SPECT and PET scans after treatment, to see blood flow in the brain after venoplasty for CCSVI.


You've asked about how CCSVI would impact the relapsing nature of MS---and all we have are hypothetical ideas of how this works with RRMS.
I've written up the research in this area---looking at RRMS relapses caused by reperfusion injury.
This is only a theory---

The reason why MS relapses and remits during the onset of the disease has been difficult to understand, and impossible to replicate in animal models of MS. EAE, the current model for MS, is not like MS. EAE is more akin to ADEM, in that it does not relapse and remit. It's a constant immune reaction. I believe stroke and cardiovascular researchers, like Dr. John Cooke at Stanford, will be better able to create animal models of MS using perfusion--or blood flow. Immunology departments have had 60 years to model MS, and they still don't have it right.

What's reperfusion? Most of us know the word hypoperfusion---meaning the slowed or less than normal blood flow we see in the MS brain. Reperfusion simply means to perfuse again, or redeliver blood. Reperfusion is a good thing and a bad thing. Reperfusion is a natural occurrence; it returns blood to tissue after there is an event which stops or slows blood flow, like a stroke or ischemia. Reperfusion brings essential O2 and glucose to cells after such an event, but it also brings inflammation and the immune system with it. Blood returns to the area of tissue where it had been absent, at a cost.

Dr. Dake mentioned in a presentation at ISNVD how hyperperfusion (otherwise known as reperfusion injury) occurs BEFORE an MS lesion forms. He referenced this paper, which discusses how this perfusion change happens before the break in the blood brain barrier, before the immune system entry, before demyelination. The very first step is a change in perfusion. I wanted to know--why?
http://brain.oxfordjournals.org/content ... 1.full.pdf

I believe reperfusion injury explains the relapsing remitting course of early MS and ties together Dr. Zamboni's research into CCSVI, collateral circulation and hypoperfusion in the MS brain. There will be an explanation as to how this theory functions in progressive MS at the end of this note.

more info, with links to published research on reperfusion injury and potential link to relapses--
http://ccsviinms.blogspot.com/2013/09/m ... perfu.html

I'm going to give you some more links to notes I've written up on my blog---in the hopes it might provide more clarity. My husband was the first treated for CCSVI in the US at Stanford--and his new and better venous system has remained open and flowing--now five years later. He's MS progression free, no relapses, still biking, jogging, and skiing--with a reversal of gray matter damage on MRI. He also made many lifestyle changes in nutrition, exercise and lifestyle, to help keep his veins open and patent.

More on hypoperfusion:
http://ccsviinms.blogspot.com/2011/03/dr.html
http://ccsviinms.blogspot.com/2009/12/h ... ow-in.html

Take care--keep learning!
cheer

[RuralLaundry]

Cheerleader,

Thank you for the excellent response, very informative. I'm a very logical person, an engineer by trade and training. Like many others the inconsistencies in this disease drive me nuts and I've only just begun. I can't imagine the mental fortitude in the people that have been at if for years.

[MarkW]

................I'm a very logical person, an engineer by trade and training. Like many others the inconsistencies in this disease drive me nuts and I've only just begun. I can't imagine the mental fortitude in the people that have been at if for years.

Hello RuralLaundry,
My pharmacy specialisation was pharmaceutical engineering and I became a management consultant, so I like to think I am a logical person, as well. After much research and analysis I conclude that MS is a multi-factorial disease with no precise cause. However, venoplasty that fully treats CCSVI appears to help MS in most pwMS. Rather than focussing on why de-stenosis works I suggest that you obtain venoplasty from a highly experienced Interventional Radiologist, expert in CCSVI. Tens of thousands of pwMS have been de-stenosed with mostly positive effects. If you have 10K USD plus travel costs then I suggest you have the venoplasty performed rather than waiting for a medical explanation.
Most developments in medicine happened because a treatment was seen to help, rather than explaining what a therapy would do to a disease. I suggest you take this logical approach.
Kind regards,
MarkW

PS Cheerleader's words are very useful but as no one know the cause of MS, it is impossible to know exactly why de-stenosis helps pwMS. However, it does help.

[ttucker3]

Well described Cheer. I would like to add my understanding of the possible underlying mechanics. CCSVI results in, not only hypoperfusion and hypoxia, but also oscillating (changing) blood flow direction every cardiac cycle within select cerebral and spinal veins. Such oscillating flow is measurable with ultrasound (in the right hands) but more reliability with Flow Quantification MRI, measurable at least in the Internal Jugular Veins. Fluid Dynamics dictates that such oscillating flow is transmitted back into the cerebral veins, with oscillatory behaviour attenuated somewhat by the elasticity or compliance of the veins between the lower jugular and the cerebral veins. There are scientific papers that indicate the shape and alignment of the cells in the endothelial layer is affected by the nature of blood flow over the cells, which are substantially elongated with unidirectional flow. However, the cells are more spherical (and random) with oscillating flow. Such modified endothelial cell structure has been observed microscopically in the regions of scleroses and has been related to increased leakage of autoimmune cells. The tightness of the cell junctions in the blood brain barrier is likely reduced with the increased randomness of the cell shapes, increasing porosity to autoimmune cell migration. However, fluid dynamics also requires that localized hypertension goes hand in hand with such oscillatory flow. This would result in a bad combination, increased porosity of the BBB and increased hypertension at the same point in the cerebral vein. (More pressure to push autoimmune cells through a leakier barrier)

At this time and with current limitations on the ability to measure blood flow in the fine cerebral veins, research is beginning to be carried out on extrapolating the oscillating flow, as measured in the larger veins into the finer veins, using modeling techniques that apply fluid dynamics principles.

My view is that the CCSVI scientific community is getting quite close to providing a most persuasive description of all the major processes that underlie the mechanics of autoimmune attack on myelin, but it will only be persuasive to those who have the willingness to broaden their focus from the autoimmune attack process to include the relationship between CCSVI blood flow and BBB continuity.

BTW Cheer, the mechanics I describe above are all entirely consistent with the views you have expressed about the relationships between lifestyle and diet and endothelial health. Also, with some scientific evidence having been reported that the compliance in female veins is less than that of male veins (except during pregnancy), any cerebral vein oscillating flow would tend to be greater in females and hence lead to a greater predisposition to increased vulnerability to MS.

[MarkW]

........My view is that the CCSVI scientific community is getting quite close to providing a most persuasive description of all the major processes that underlie the mechanics of autoimmune attack on myelin, but it will only be persuasive to those who have the willingness to broaden their focus from the autoimmune attack process to include the relationship between CCSVI blood flow and BBB continuity.

I agree with you.....but it is likely to take 2-3 years to get CCSVI scientists to publish this research and then 3-5 years to argue the point with MS Neuros. I suggest there is sufficient CCSVI patient experience to have de-stenosis today. Rather than wait for maybe 7 years for medical science to catch up. MS usually progresses a great deal in 7 years, mine has.
My advice is simple - treat this observed symptom, while waiting for medical science to explain why CCSVI is an issue for pwMS.
MarkW

[ttucker3]

I totally agree. Get angioplasty as soon after MS diagonosis as you can. The longer you wait the more irreversible damage to the neural axons may occur. Besides, increasing blood flow and oxygen to the brain can not be a bad thing.

[MarkW]

..... Such modified endothelial cell structure has been observed microscopically in the regions of scleroses and has been related to increased leakage of autoimmune cells. ..........................would result in a bad combination, increased porosity of the BBB and increased hypertension at the same point in the cerebral vein. (More pressure to push autoimmune cells through a leakier barrier).......

As a leading thinker on CCSVI, please take care using 'autoimmune' in the context of MS. Many diseases like MS are 'immune-mediated' with as yet unknown triggers. MS Neuros call MS an autoimmune disease and this says only treating the immune system will work (the disease is entirely due to immune system problems in their theory).
You and I argue that it is logical to treat possible triggers (eg low vit D3 (me)) and symptoms (eg stenosed veins (both)). Neither of these therapies would be considered by an MS neuro as a reasonable therapy for an autoimmune disease.

CCSVI proponents need to explain why any therapy is logical without playing into the hands of MS neuros. Hence, I never use the term 'autoimmune' in conjunction with MS and recommend this approach to all CCSVI leaders.
Kind regards,
MarkW

[CureIous]

(Did I really just type all this on my phone?)

Fantastic question, great answers, so much more than was known 5 years ago. And so many more additional questions which open even more windows into this thing called the human body. Just when we think we've got it...

Keep in mind also, that MS, and especially RRMS, are by their very nature, highly variable in many respects, not only by virtue of a particular symptom or other, but severity, duration, intensity, is it a week, month or two/three for a particular relapse or remission, or is it years? Or like some, so mild in the early stages and moving very slow in the intervening years.

Toss in differences in individual habits and lifestyles, and it becomes nearly impossible to define one patient's experience by using labels such as RR or SP or PP, solely. So we go to the Dr's who run the statistical numbers and try to put a face to the name, of our particular variant, and all it is, is a good guess.

But, if the last five years are any indication, I can say based on my one man study, that what Dr. Dake described as "global type symptoms", ergo heat stress, cognitive function etc. are indeed "the first to go." And agreed, sooner the better, cause axons rock, and we want the whole lot of them or as many as we can keep.

Now myself, having worked in an industrial trade where supply, and return, heat transfer and boiling points are like a second language, back in 2007 I understood that when working 12 hour shifts in 108 degree heat, putting icy cold water about the head and neck area was a good way to transfer heat, what most describe as "cooling off", Sure, it was mostly a stopgap measure, but for a time, I could function, and think, and deal with complex instrumentation problems, as long as that neck and head stayed as cool as I could make them, with no knowledege of veins or CCSVI, and with no coworkers even knowing I had "MS". And now, having had stents artificially maintaining those veins in the open position for two months shy of five years, myself, along with trailblazers like Jeff, can equate open veins with obliterated symptoms,, in an unequivocating fashion.

Just for giggles (okay more for food on the table), I recently went out on a job that was a major refinery shutdown in El Segundo, meaning the refinery basically hits the off switch, and major 40 year maintenance is performed on a very strict timetable. Millions and millions are at stake, with every second of delay. But hey, no pressure. And yours truly, who was plumb out of hope five years ago, showed up and ate the pressure for lunch, so well so, that I was handed a radio, a foreman's radio, within a week of showing up there, doing 84 hours a week with 4 hours of commute time.

K, nuff of the sales pitch, point is, when the veins stay open, night and day, day after day, month and year after year,, these particular sx remain at bay. That's what my one patient study shows. Absolutely , there's quite a bit more involved with what may or may not repair or resolve over time, method of treatment, followup, AGING, again, that's another discussion.

Perhaps the variability of (getting back to RR specifically) symptoms, all lesions aside for now (of which I still have plenty), is itself being driven by veins stenosing, then destenosing naturally, and not just in one particular location of say the IJV's, but also these narrowings are as variable as our disease state, moving up and down, whack-a-mole if you will, hither and yon, here one day, gone the next, AND those stenosed areas also relate to our collective Sx, then perhaps the sympathetic, and parasympathetic nervous system are related to this inherent variability?

Would that help to understand the how's and why's of Sx that pop up say in times of severe stress, emotional and otherwise, leading to various stenotic areas in diverse locations, then Poof! Gone the next day, week month six months, however long, taking their concomitant Sx with them? Trying to resolve this at any one part of what I'll call the Variability Puzzle, or imaging said same at a particular point in time, invariably leads to incomplete information, and that limited purview information is then acted on, with a thought to correct what is clearly visible. And for some, this is good enough, and for most others, it is not, at least with traditional venoplasty. Now, for those with stents (assuming of course no complications), this is less of an issue, ANS be damned, stents are overriding the impulses, and over time, I believe the body retrains itself, and learns to not fire those nerve impulses any more. Yet another discussion, and I would never tell anyone EVER to get stents, or that stents are the answer, they aren't, but I will definitely take mine!

Problem with all this nerves/ANS talk, as it relates to specifically CCSVI (or the flavor of the week), is that we cannot image nerves, we cannot tell precisely where they are, short of a knife, we also want to be careful with these buggers, after all, we call them "wiring" but they are anything but wires. Abuse em, and lose em. Witness our early issues with the ACC nerve, little bumps can lead to big bruises, best to tread carefully.

Nerves, boy oh boy those are some kind.of difficult, and sensitive, but they are also on specific pathways. And they have intersections, nodes, circuits. What you do up here, can have positive or deleterious effects down there. IJV's have their own nerves, which also (as I understand) feed the Azy later on down the road. And that is precisely the tact my local guy here decided to follow, after hearing about CCSVI from me (an incidental mention during a routine workup), and modifying an existing treatment method he already had tremendous success with, (and is pursuing patent on), specifically (at that time), to help his childhood friend from the Motherland who was declining rapidly, dx'd with typical neurologist doublespeak, after every test under the sun. Not MS not this exclude that, then one day, hmmm, CCSVI, please tell more...

This could also help explain the how's and why's of restenosis, or how ultrasounding this week or this day, then treating, is merely treating something that may or may not exist in its present state in the future. I've seen the US results, and I will tell you, when they are charted out over time, they are all over the map.

Keeping the Variability Puzzle in mind, is it any wonder we see so many treatments>retreatments ? Or that stents, or rather those of us with stents, circumvented that VP in the first place?

Just a few things to chew on. I will proffer that aggressively going after this or that particular nerve is a total shot in the dark. Hey, if you want an invasive procedure that drains your pocketbook to just experiment on healthy veins, go for it. For once, I'm speechless.

Mark