Connecting the Dots Between Multiple Sclerosis and CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Connecting the Dots Between Multiple Sclerosis and CCSVI

Postby North52 » Wed Oct 06, 2010 7:34 am

Dear Thisisms,

I am a medical doctor with multiple sclerosis and would like to propose a theory that ties together MS and CCSVI. I did this in point form. I tried to keep it simple but still used medical terminology in an effort to get this out soon. Much of what I have written requires a certain base knowledge but I know many of you on the site possess this base. Please excuse any grammatical or spelling errors as this was written with cognitive deficits during my most severe MS exacerbation. Here it goes:

1) MS is a disease of hypercoagulability that is manifest predominantly at the micro-vascular level (capillaries and post capillary venules) of central nervous system tissue.
2) This local hypercoagulability in the MS population can be a result of numerous factors. The predominant factor is likely venous outflow obstruction from the larger veins that drain the central nervous system.
3) This outflow obstruction of the larger veins results in reduced blood flow and stasis at the microvascular level.
4) Stasis in turn triggers an environment of hypercoagulability and reduced blood flow at the mircovascular level through the resultant activation of the coagulation cascade and though related local cell adhesion factors.
5) Stasis in turn results in local ischemia of the CNS tissue and impaired functioning of this tissue resulting in a number of central nervous system deficits.
6) Certain deficits related to ischemia may rapidly reversible if the if the axons and myelin sheaths are still intact. Deficits that result in myelin breakdown but not cell death will improve at the rate of myelin repair. Deficits that result from cell death will be permanent and may explain stepwise deterioration following exacerbations in relapsing remitting MS.
7) I suspect that stepwise deterioration in some patients may be a result of thrombosed collateral veins as well.
8) Stasis can be worsened by a number of factors that can result in multiple sclerosis exacerbations, pseudo-exacerbation of or just temporary worsening of symptoms.
9) Infections can precipitate exacerbations by creating an environment or hypercoagulabilty that is manifest predominantly at the microvascular level. Numerous viruses are known to create states of hypercoagulabilty and many virus may be associated with or implicated in the pathophysiology of MS. Examples of such pathogens include herpes virus 6, epstein barr virus, chalamydia pneumonia.
10) Certain antibiotics such as minocycline and antivirals such as valacyclovir have been shown to reduce exacerbations. This is likely a result of suppressing replication of these viruses and reducing microvascular hypercoagulability.
11) Heat, either through fever or external sources worsens MS symptoms by increasing coagulability. It is common knowledge that heat can increase coagulability. This in turn results in reduced blood flow and increased symptoms though worsened ischemia.
12) Hypercoagulability in MS is not detectable using traditional methods because it is present only at the microvascular level.
13) Anecdotally, angioplasty patients have experienced rapid and dramatic improvement following the procedure. This is likely a result elimination of stasis at the microvascular level by the improvement of macrovascular venous blood flow.
14) One must keep in mind that sudden improvements may also be a result of the use of heparins both during and post procedure. Heparins may have the ability to increase flow even in the presence of venous outflow obstruction.
15) Vitamin D likely exerts its beneficial effects by maintaining endothelial health. An important part of endothelial health is the endothelium’s ability to activate cell surface heparins which will decrease blood cell adhesion and maintain blood flow and prevent stasis at the microvascular level.
16) Vascular comorbidity has been shown recently to correlate very well with MS progression. This is likely though the same mechanism of maintenance of endothelial health.
17) Natalizuamab (Tysabri) likely exerts its beneficial effects by activating and maintaining activation of endothelial cell heparans. Nathalizuamab binds to alpha-4-integrin a molecule and receptor that mediates attachment between the endothelial cell and lymphocytes and likely other blood cells. Alpha-4-integrin is intimately involved with endothelial heparans. Once endothelial heparans are activated, stasis of blood in the microvasculature is reduced because passage of these cells though the very narrow endothelium (about the width of a blood cell) is facilitated.
18) Rapid removal of natalizumab from the blood stream as occurs with plasmapheresis has been shown to result in severe progression and even death. This likely occurs because the removal of natalizumab results in a marked decrease in the cell,s ability to produce heparin, inducing a severe hypercoagulable state at the microvascular level.
19) Severe MS exacerbations that occur following nathalizumab drug holidays likely operate through the same mechanism. I would suggest extreme caution in anyone considering a drug holiday if my proposed theories are correct.
20) Administering natalizumab during an exacerbation may result in cessation of progression of the exacerbation and rapid reversal of certain symptoms. This was my experience. On October 3rd during my worst ever exacerbation my symptoms rapidly improved over the next 4-5 hours.
21) It would seem logical to administer heparin to reverse this hypercoagulable state, but I have concerns that this may not be possible as nathalizumab may bind to exogenously administered heparin. This observation is based on personal experience. I am on natalizumab. Following balloon angioplasty of my azygous, I was started on enoxaparin (Lovenox). After about nine days on enoxaparin I developed a pruritic drug rash of my arms, legs and trunk that was typical of a serum sickness rash (aka immune complex rash), which would indicate that the natalizumab binds to enoxaparin and would limit its use in this setting.
22) I suspect that other MS disease modifying drugs work though the optimization or activation of endogenous heparans. In my brief research, I identified studies that link the interferons and copaxone to the functioning and possibly increased expression of heparans.
23) Although the evidence for this is weak, I suspect high dose IV methylprednisolone (IVMP), may create a markedly hypo-coagulable (blood thinning) state and be effective for this reason. I came across a case report of three MS patients on Coumadin and high dose IVMP who developed dangerously high INRs. My assumption here is also based an event that recently occurred to me on high dose IVMP. Ten days ago, in the morning, while receiving the 7th last dose of IVMP 1 gram/day, I stumbled while going down stairs and injured the left lateral aspect of my left shin. I got up and thought everything was fine. I had no pain and felt like I had just bumped my knee. Later, in the evening, I noticed that my left shin felt tight. There was a huge hematoma over it. I went to the emergency room of the hospital that I work at and got an xray which was normal. The doctor suggested I do a coagulation profile, but I brushed this suggestion off as I thought I had no reason believe that I had a coagulation disorder. I had normal coagulation tests a few months ago for my angioplasty procedure. I did not understand it at the time, but I suspect my INR and aPTT were likely extremely high. If what I am saying is true, then steroids used in many conditions for their antiinflammatory/immunosuppressive effect, may in fact work by thinning the blood. One example is its use to decrease brain edema in cancer patients. Perhaps its mechanism of acton is by increasing flow through the venous system. One last observation here. When I started IVMP the nurse inserted a very small 24 gauge needle. Small needles like this tend to clot quickly. Mine lasted the full seven days. I have no expertise here, but I suspect this is unusual.
24) I also suspect that stopping IVMP may result in a severe rebound hypercoabulable state that may result in large vessel thrombosis. This happens when such medication such as Coumadin are stopped. There are case reports of patients developing internal jugular vein thrombosis following cessation of high dose IVMP. This assumption is also based on a personal experience. Five days after stopping the IVMP I decided to do an INR/aPTT. They were low and unmeasureably low, which would imply a severely hypercoagulable state. I had a blood test drawn three time to verify the result and the tests were the same each time.
25) Post angioplasty there have been anecdotal reports of patients deriving significant improvement in some symptoms and either worsening of certain symptom or the creation of new symptoms. This type of phenomenon can be explained if one analyses the fluid dynamics of the arterial and venous systems. If a venous obstruction is relieved on one side, this will result in increased blood flow on the affected side, but it will result in reduced blood flow on the other side. The side with sudden reduced flow will experience either new or worsened symptoms.
26) I suspect that heparin may be the drug of choice to treat MS exacerbations. I also suspect it may also be useful more long term as a disease modifying agent.
27) I suspect fatigue in MS may be a result of overall low flow in the brain but I wonder if another mechanism may be responsible. When a vein is stenosed or blocked it dilates upstream or collapses downstream. Large veins possess baroreceptors that sense stretch of the vein so that it can send signals that regulate overall blood volume. If the vein is inappropriately stretched or collapsed, the body will regulate blood volume inappropriately. Fatigue may be secondary to inappropriately low blood volume. I myself have very low blood pressure and have noticed many patients on the forum seem to have the same.
28) The mechanism of disease theory I am proposing for MS very possibly applies to numerous other autoimmune diseases.
After months of reading and research and perusing Thisisms.com, I was suddenly able to connect the dots three days ago. Much of what I have written about was precipitated by the most severe exacerbation I had (and am still having) in my 10 years with MS. I have been desperately trying to find a way to prevent paralysis. This exacerbation is likely a result of having gone on a Tysabri drug holiday. I hope my theory is correct.
North
Last edited by North52 on Thu Oct 07, 2010 6:06 pm, edited 1 time in total.
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Postby Cece » Wed Oct 06, 2010 8:34 am

I hope you recover soon and do not suffer paralysis as a result of this.

The stakes are so high.

Thank you for putting this theory together. Interesting idea about heparin as a drug of choice for MS.
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Postby cheerleader » Wed Oct 06, 2010 8:42 am

Welcome, North-
great information you've compiled.
we've discussed coagulation many times of these forums. Search MRhodes as author + coagulation with the search function for the most in-depth discussions. Marie has just completed the first book to be published on CCSVI, it will be available for purchase soon.

My endothelial health program was based on the idea of endothelial dysfunction and nitric oxide disruption contributing to hypercoagulation. That's how I met the Stanford doctors. The program information is here on the CCSVI Alliance website, under helping yourself-
www.ccsvi.org

Sadly, Dr. Tracy Putnam tried for many years to help pwMS using blood thinning medications, to no avail. Hypercoagulation is part of the puzzle, but not all of it.
wish you well-
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby Merlyn » Wed Oct 06, 2010 3:24 pm

Among the more important things to show up in the recent literature is
the working out of the mechanisms of action for how low level mercury
exposure causes cardiovascular disease, including hypertension, arterial
thickening and the tendency for blood to clot. 36% of the US adult
population is suffering from some version of cardiovascular disease.
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Postby Jugular » Wed Oct 06, 2010 3:27 pm

I used to think that my quick coagulating blood was one of my superpowers. Who knew it was actually my Kryptonite.
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Physicians please help us

Postby 1eye » Wed Oct 06, 2010 3:44 pm

I wrote this in response to Dr. Embry's letter to physicians on Facebook. Thrombosis in stented veins is not an unusual event. But the Medical Establishment's attitude to treating it is.

http://www.facebook.com/note.php?note_i ... 6568095094

This letter to doctors is good, but the examples of some of our own pioneers in this treatment (patients) have shown us that the care afforded to the people who have had to travel outside their home states and countries varies from abysmal to non-exis...tent. These individuals, some of them very sick, are being punished for the crime of going outside their local medical systems for this procedure. This behaviour is vengeful, immoral, unethical and a crime in its own right. These patients whose lives are and may be in danger, are not being treated as human beings. They are being told "go back to Poland" or wherever they had to travel to get this procedure. Is that why you went to medical school? Is that what you meant by your precious Hippocratic oath? Are you all really even interested in medical care of other humans, or perhaps only ones who have followed "doctors orders" to remain sick as long as they are told?

Please, at long last, show some human decency and come to the aid of these people. Yes, they have defied doctors' orders, Association's orders, and Society's orders. They have paid thousands of their own money to get this treatment. That they have thrombosis is not anyone's fault and they should not be punished. Saying "I told you so" to a dying person: is that how you really want your family, your friends and your descendants to remember you?
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Postby Billmeik » Wed Oct 06, 2010 4:22 pm

Certain deficits related to ischemia may rapidly reversible if the if the axons and myelin sheaths are still intact. Deficits that result in myelin breakdown but not cell death will improve at the rate of myelin repair. Deficits that result from cell death will be permanent and may explain stepwise deterioration following exacerbations in relapsing remitting MS



I think that's petty old school thinking. I am of the belief that there is no remission just reorganization. Neural plasticity plays a way bigger role than old models suggest. I'm not sure if most myelin repair isn't just new growth too..
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Postby malden » Wed Oct 06, 2010 6:52 pm

cheerleader wrote:...
Sadly, Dr. Tracy Putnam tried for many years to help pwMS using blood thinning medications, to no avail.
...

Multiple sclerosis: the history of a disease
by T. J. Murray
page 411 (MS trerapy 1940-1950)

...Putnam and his group published a study of 43 patients; the relapsing cases showed striking improvement, but progressive cases remaind unchanged or continued to progress. The extensive statistical study of 3,797,attacks in 810 patients over an average observation period of 9,7 years seemed to confirm the results with dicoumerol....

...Two years later, Lesny and Polacek used Swedish heparin in 27 cases and Chech preparation of dicoumerol in 40 patients for up to 14 months and reported that the good results were seen not only in the "fresh" cases, but also in those who had been paraplegic and now could walk again.


(dicoumerol - similar to warfarin)

That study show that blood thinners are conected with some symptom improvements in MS, and that must be considered when evaluating Liberation treatment benefits.

Best regards, M.
malden
 

Postby Cece » Wed Oct 06, 2010 6:57 pm

Malden, that is interesting.
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Postby North52 » Wed Oct 06, 2010 7:25 pm

Thank you for your responses.

Regarding heparin, I came across an old article. Because it was scanned it is very difficult to cut and past. Here is a portion of it. Part of it talks about ms and heparin. Look at the bottom as well. There are 3 articles/studies about heparin treatment in ms. There is no text, though. It would be very interesting to track these down. I will see what I can do. I may not be able to respond for a day or 2, as I will likely be admitted to the hospital tomorrow

patients with autoimmune hemolytic anemia.
Donzelot and Kaufmann34 found that heparin
ameliorated bad cases of rheumatism, supposedly
by an antiexudative action. But Burkls5
suggested that it acts by the inhibition of hyaluronidase
activity. The action of heparin
in rheumatism is an example of its antiinflammatory
influence on connective tissue. Other
such examples are its ameliorating effect in
thrombophlebitis36 and its action in interstitial
cystitis.37
Heparin has been used with some success
in multiple sclerosis,3840 and the authors suggest
that this may be due to its action on lipid
metabolism.
Heparin was also...

References:

COURVILLE, C. B. The effects of heparin in acute
exacerbations of multiple sclerosis. Observations
and deductions. Bull. Los Angeles Neural. Sod., 24:
187,1959.

MASCHMEYER, J., SHEARER, R., LONSER, E. and
SPINDLE, D. K. Heparin potassium in the treatment
of chronic multiple sclerosis. Bull. Los
Angeles Neural. Sot., 26: 165, 1961.

28. PARROT, J. L., NICOT, G. and LABORDE, C. Capta- 42. SIKORSKI, H. Hyaluronidase und Heparinoide bei
tion de l’histamine par I’heparine. Influence du der Behandlung entzuendlicher Stauungen.
PH., Compt. rend Sot. biol., 154: 1426, 1960. Ztschr. bout. Geschlechtskr., 31 : 225, 1961.

Jimmy
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Postby bluesky63 » Wed Oct 06, 2010 8:35 pm

And I remember the studies that showed a high d-dimer in people with MS during their relapses (I was interested because this happened to me). Oddly enough you can have bleeding problems but still have hypercoaguable blood, so even if you bruise easily you may suffer from this issue depending on the clotting factors in your blood.

Wouldn't aspirin be an option for treatment?
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Postby malden » Wed Oct 06, 2010 11:26 pm

bluesky63 wrote:...Wouldn't aspirin be an option for treatment?

Aspirin is a pain reliever with anti-inflammatory effects. Antiinflammatory steroids (or corticosteroids) have good efects in MS pulse therapy - we all know this, I personaly with Solu-Medrol infusions. I decided rather to take aspirin-like pills than go with corticosteroids.

Here is my post from Jun:
http://www.thisisms.com/ftopicp-116247.html#116247
...last month I started with Aspirin 500 mg 2x per day, 5 days, then reduce it to 1 per day, 10 days, and now I am on 200 mg per day.

Suprisingly, I feel better (less morning fatigue, less sluggishness, able to focus on work, more stable on legs, less stagering...)

Btw, I didn't take any medications before this Aspirin treatment.

I take a break in August and then started that treatment again in Septembre, this time I take Andol (acetylsalicylic acid with buffer) instead of Aspirin.

I am still on one/day Andol 300mg , and still feel goood - without stents or ballooning ;)

And the cost is low, cca 24$ per year. Plus twice a year simple blood test.

Best regards, M.
malden
 

thin blood

Postby 1eye » Thu Oct 07, 2010 2:24 pm

Oh, please...

If you people are taking bee stings or snake venom or blood thinners and feel better, great. But don't try to convince a bunch of Liberated people they don't. They won't believe you.

I had blood thinners for six months in 2009. The asperin continues. So does the very high dose of statins. It was for my heart, for 3 stents which I had had inserted into arteries. None of it made my MS feel any better, or I would not have been still looking in late 2009, when I read of Dr. Zamboni and started reading this forum. I was Liberated in late August 2010. I have been having results I never looked for (though not yet all the ones I do) since then. I no longer take effexor or baclofen. I do not believe I am inflamed at all any more. The ironic thing about my heart attack is it may have been induced 5 years ago by mitoxantrone.

I feel a lot better and day by day continue to do so. I have gone back to (attempting) to play the piano. My singing voice even made a cameo appearance. I do not trace any of this to blood thinners, or to the large dose of statin I have also been on since the heart attack. I trace this to the day I was liberated. And I'd like to know, if it does nothing why has the Canadian medical community so carefully ignored my friend with the blood clot? She traces the return of her 'MS' symptoms to this clot. She has a family and little kids. You hear their voices on her telephone message. They sound scared.

The deal here in Canada (of which I am becoming ashamed of being a citizen) is, you go to an IR, vascular surgeon or hematologist, and they won't see you, insisting on a referral from a neurologist. Not a GP. The neurologist won't care, telling you to 'go back to Poland'. It is as if they are hoping she will die, and provide more 'evidence' (read press-fodder) against Liberation. I got a US flag when I went to Albany. I will soon start flying one on my lawn, in the middle of a federal election. :evil: :evil: :evil: :evil: :evil: :evil: :evil:
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Re: thin blood

Postby North52 » Thu Oct 07, 2010 2:52 pm

1eye wrote:Oh, please...

If you people are taking bee stings or snake venom or blood thinners and feel better, great. But don't try to convince a bunch of Liberated people they don't. They won't believe you.

I had blood thinners for six months in 2009. The asperin continues. So does the very high dose of statins. It was for my heart, for 3 stents which I had had inserted into arteries. None of it made my MS feel any better, or I would not have been still looking in late 2009, when I read of Dr. Zamboni and started reading this forum. I was Liberated in late August 2010. I have been having results I never looked for (though not yet all the ones I do) since then. I no longer take effexor or baclofen. I do not believe I am inflamed at all any more. The ironic thing about my heart attack is it may have been induced 5 years ago by mitoxantrone.

I feel a lot better and day by day continue to do so. I have gone back to (attempting) to play the piano. My singing voice even made a cameo appearance. I do not trace any of this to blood thinners, or to the large dose of statin I have also been on since the heart attack. I trace this to the day I was liberated. And I'd like to know, if it does nothing why has the Canadian medical community so carefully ignored my friend with the blood clot? She traces the return of her 'MS' symptoms to this clot. She has a family and little kids. You hear their voices on her telephone message. They sound scared.

The deal here in Canada (of which I am becoming ashamed of being a citizen) is, you go to an IR, vascular surgeon or hematologist, and they won't see you, insisting on a referral from a neurologist. Not a GP. The neurologist won't care, telling you to 'go back to Poland'. It is as if they are hoping she will die, and provide more 'evidence' (read press-fodder) against Liberation. I got a US flag when I went to Albany. I will soon start flying one on my lawn, in the middle of a federal election. :evil: :evil: :evil: :evil: :evil: :evil: :evil:


Dear 1eye,

I in no way suggested that people should not get the liberation procedure. In fact I am all for angiolplasty and think it most probably is the treatment of choice for ms. Heparin, if it works, could be used to treat patients who are awaiting angioplasty, who failed angioplasty or those who cannot have angioplasty. I myself had venous angioplasty about 5 months ago.

North
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Postby Lyon » Thu Oct 07, 2010 3:05 pm

..
Last edited by Lyon on Thu Jun 23, 2011 5:50 pm, edited 1 time in total.
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