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One of the topics I have been pursuing is the connection between MS and endothelial cell activation, creating thrombic events and hypercoagulation in MSers. We already know about the association of a sub-group of MS patients with Hughes Syndrome (antiphospholipid antibodies) identified in the 1980's. I have hypothesized on the endothelial thread that there is some type of MS specific antibody which is activated in MS, creating coagulation problems in patients negative for APS. Here is more recent, specific research on the correlation found in CNS specific anti-Endothelial Cell antibodies.

From Journal of Neuroinflammation
Antiphospholipid Antibodies: Paradigm in Transition
Posted 03/18/2009

Lawrence L Horstman; Wenche Jy; Carlos J Bidot; Yeon S Ahn; Roger E Kelley; Robert Zivadinov; Amir H Maghzi; Masoud Etemadifar; Seyed Ali Mousavi; Alireza Minagar

http://www.medscape.com/viewarticle/587338_1

MS is an inflammatory disorder believed to be autoimmune in etiology, and can present with features resembling APS.[294-297] Several reviews of the neurological symptoms of APS/SLE are available,[298-300] and many case reports, e.g., cerebral ischemia.[301] However, MS is not thought to involve ischemia, although elements of the coagulation cascade are present in MS lesions, including fibrinogen and recently, tissue factor and protein C inhibitor.[302]

In 2000, our collaborative investigation demonstrated elevated endothelial microparticles (EMP) during exacerbations of MS.[303,304] Those findings motivated further investigations, this time of aPL in MS, with the hypothesis that aPL might be involved in endothelial activation in MS. Several prior reports had established that aPL commonly occur in MS, but in most of them the patient population was heterogeneous or inadequately defined, and there was no indication of a relation between aPL and the pathophysiology of MS.

To examine the relationship more closely, we tested samples of well-defined, treatment-naive MS patients in either exacerbation or remission, documented by neurological as well as brain MRI with and without contrast. The central finding was that all aPL measured were significantly elevated in acute phases vs. remission, and correlated strongly with MRI imaging, p = 0.002.[136] The antigens tested included β2GPI, FVII, and four pure PL (CL, PC, PS, PE). Of interest, aFVII was never detected in remission but was present in 60% of acute MS; and anti-β2GPI was positive in 80% of acute MS. It is possible that unidentified and possibly MS-specific auto antibodies were also present, judging by the strong reaction to the pure PL in acute, but not remission, cases. Unexpectedly, aPL in MS were exclusively of IgM class, with no IgG detected.

Because that work showed a direct relation between aPL and clinical state in MS, it is plausible to suspect that aPL may be involved in the pathogenesis of MS. Of course, the possibility exists that aPL in acute MS are epiphenomenal; but the same argument could be levelled against the hypothesis that aPL cause thrombosis. In further support, Shoenfeld and colleagues clearly demonstrated neuropathological effects of aPL in animal models.[305-307]

Since some aPL have been identified with anti-endothelial (anti-EC) antibodies (earlier cited), and since our group[303] and others have documented endothelial activation in MS, it is relevant to note that anti-EC have been detected in MS and were proposed to contribute to its pathogenesis. In 1989, Tsukada et al. found anti-EC in 75% of active MS but in only 4% of remission.[308] However, a 1992 report found only 13% positive[309] and a later report found only 10% reactive to human umbilical vein EC (HUVEC).[310] On the other hand, another report around the same time, but using brain microvascular EC rather than HUVEC, found that 12/16 active vs 0/15 inactive MS reacted to EC.[311] This suggests that anti-EC in MS are specific for brain microvessels, and would be consistent with the fact that CNS lesions in MS tend to develop around brain microvessels (Dawson fingers).[312] Thus, brain-specific anti-EC could be a pivotal pathogenic mechanism of aPL in MS.

The picture now emerging is that aPL are part of a large spectrum of autoantibodies, including, for example, those of ITP, and that APS is just one manifestation of a particular constellation of aPL. We may be better served by abandoning the concept that aPL are exclusively thrombogenic.

In regard to the cause of aPL-associated pathologies, a promising hypothesis is dysregulation of anti-idiotype networks. Many of the consequences appear to be best explained in terms of complement-mediated effects. However, full understanding of the aPL phenomenon remains a challenge for the future.

AC

I'm with you Sou, the crabs have proven very low effectiveness.

But I believe the concordance that we see in Zamboni's research makes it the most interesting thing to some along in--well forever. Nothing else has 100%, you can't even say 100% have lesions in the brain on MRI.

But the idea that two anomalies are seen in MS I think was probably a serendipitous finding, they were looking for a way to tell who was MS and who not in blinded studies so they could prove the concept.

But is the occurance of 2 anomalies rather than one vitally important to show that venous issues are at fault in MS?

From Zamboni et al '09 "The value of doppler haemodynamics in the assessment of multiple sclerosis" available CLICK HERE (I bought this paper-well worth it)

ABSTRACT
Iron stores in the white and deep grey matter in course of multiple sclerosis (MS) have never been explained and could be related to abnormalities in venous drainage, but this possibility has never before been investigated.
From an initial cohort of 320 subjects, after application of exclusion criteria, we selected 109 patients affected by MS, and 177 controls respectively composed by age- and sex-matched, healthy aged, and patients affected by other neurological diseases. They blindly underwent transcranial and extracranial Color–Doppler sonographic examination (TCCS-ECD), aimed at investigating five parameters related to normal cerebral venous outflow haemodynamics.
Overall we analyzed 1430 TCSS-ECD parameters. In controls we found 861 normal parameters of cerebral venous return vs. 24 anomalous, whereas in MS 288 parameters were normal and 257 anomalous,
respectively. Consequently, each of the considered Doppler aemodynamic parameters, when compared to revised McDonald criteria as a gold standard of MS diagnosis, showed separately a highly significant sensitivity and a noteworthy specificity. However, the detection ≥2 parameters in the same subject, never observed in controls, perfectly overlapped the diagnosis of MS (value, 95%CI: sensitivity 100%, 97–100; specificity 100%, 98–100; positive predictive value 100%, 97–100, negative predictive value 100%, 98–100; pb0.0001). Moreover, this study demonstrates a significant impairment of cerebral venous drainage in patients affected by MS, a mechanism potentially related to increased iron stores

You might wonder how it can be that the individual tests are ALSO highly significant and noteworthy specificity for MS.

Let's look at the number of test failures in controls and MSers

There were 109 MSers, 177 controls

In test one, reflux in the IJV or VV
failures were 76/109 MSers............0/177 controls

test two, reflux propagated to the DCV
failures 55/109 MSers...................0/177 controls

test three, B mode evidence of stenoses
failures 30/109 MSers........................1/177 controls

test four, flow not doppler detectable
failures 35/109 MSers...........................1/177 controls

test five, negative change in CSA
failures 61/109...............................21/177 controls

The last test was the least specific, but MSers still failed that test nearly 3 times as often! Be logical, if you failed one of these tests it is highly probable you have MS because they are the ones, as a group, that fail these tests by a LARGE MARGIN the most. All MSers failed at least 2 tests, some more than that!

But overall it is easy to see that MSers failed these tests far FAR more often than controls. That is how it can be that even failing one test is, as Zamboni put it, highly significant and having noteworthy specificity for MS.

What's it mean for us? Not a lot right now because this is at this point still unproven and not offered as a treatment option, so people probably will not even find anyone to evaluate them for this, but getting tested by doppler is actually a preamble to getting venography, it is not and end point in itself.

Venography is to have them inject dye into the vein then use what is basically an x-ray type device to watch the progress of the dye through the veins to find the areas of stenosis causing the slow flow seen in the dopplers.

that test, venography, is a preamble to getting endovascular surgery to remove the stenoses so the blood flow is returned to normal.

If you took 100 MSers and put them all through this entire routine they should have 0/100 failures after all that. What that will do to MS progression, disability etc is anyone's guess at this point, the Z team hos not offered and hard evidence it would help--YET.

But the Zamboni team did treat a batch of MSers with the full regimen all the way to the final phase of this treatment, removing the stenoses, last Sept/October. They will report their findings in just 2 weeks, say tuned; someone will post the link to the presentation after it is availble on this thread. The downside of that is that this roughly 6 month time frame is small for any changes in EDSS or disbility to show up. It may also be hard to show reduction in lesion loads, 6 months is just awfully short in MS.

Realistically it will be a couple of years before we get through the whole scientific process and the usefulness of this procedure is known by all.
edit to add:

Nice breakdown, Marie...

Thanks excpet I never made my point darn it! I got lost mentally My point was if you have one finding rather than 2 you still have evidence of a venous problem as Zamboni describes it and you and your doctor may want to talk about venograms

Loobie wrote:I'm sending the 'stuff' to Dr. William Snead, Ohio State University Medical Center, Department of Vascular surgery. I have a call into him this morning to see if he will consider this. I don't even plan on involving my neurologist until after it's done. He's very open minded and all and would never say "don't do this", but it really is happening outside his care, so I don't really care if he wants me to do it or not!

I checked for about 4 hours yesterday for local, university based doctors, and this looked the best, so keep your fingers crossed!

GO LEW!!!!! Good job on the research. Being dopplered is not harmful in any way, and there's no need to consult your neuro until after the findings, if you choose to. FYI-You can use your pressure/straining headaches for insurance purposes, since the doppler testing is exploratory in nature.
AC

Nice breakdown, Marie...

Cheer,
Sorry I got out of synch there we must have typ,ed the same time
I had some thoughts about the aPL idea
note from the paper above

Unexpectedly, aPL in MS were exclusively of IgM class, with no IgG detected

This is important because IgM is a class of antibodies made on the fly, suddenly, in response to an immediate need, they are present in acute infections and not later. IgG is the antibody you find later, it is the long term "we're on patrol for this" antibody. If you have IgM but not IgG then you are seeing a recent activation in response to some event, not long term activation of the immune system. Note that they were surprised to see IgM not IgG, that's because it shows the immune system is not primed to do this, it is doing it in reposen to something.

Could it be doing it in reponse to damage of the endothelial cells by venous backjets?

In this case let's say we accept the Zamboni idea and backjets are at issue, the person then does something unusual...let's say it is spring and they sneeze fiercely and often with hay fever an the back jets ramp up and some local damage to the endothelium is garnered, phospholipids would be expressed naturally there right? You'd end up with IgM being made to clean up? that's not rhetorical, I don't know.

germs do cause a variant aPL too. it is a regular diagnosis on the "super bill" form at the doctor's office I worked at: a chronic disease specialist she is. In that case it is an accidental side effect of the inflammation cascade. can these be related? just an idea I do not know.

The idea that MS is really all about the BBB and why in the heck it is open, the BBB being endothelium of course, has been offered as the "it" of MS in the past as well. There is a lot ot know in that area, it is complex
Intersting

Marie, I think you're being too easy on doctors

I will gladly accept that. I try to be as cheritable as I can in assessment of human motivation in general, and I have two MD friends--actual FRIENDS. These people really do care about patients, but I absolutely accept and agree with the "comapny line" criticism! Way too much group think!

Yeah Lew!! I am glad for you and hope they answer yes! fingers crossed!

I think changes in EDSS will show up quite quickly after surgery. This because I react to the vasoactive herbs within the hour. If you effect an even greater change to the vasculature by surgery I should think the effects will be almost instantaneous. Just extrapolating from herbal experience.

Without getting too technical could gently simulating the cvs with Andrew's inclined bed and daily inversions on a inversion table help strengthen the now open bbb. Has there been any prior discussion related to what this could do? Keeping it simple… Mark

skydog wrote:Without getting too technical could gently simulating the cvs with Andrew's inclined bed and daily inversions on a inversion table help strengthen the now open bbb. Has there been any prior discussion related to what this could do? Keeping it simple… Mark

Honestly, I don't think anyone really knows, Mark.

The lifting of the head of the bed was suggested by our vascular doc, who was concerned that blood pooling overnight or building up in my husband's brain would be a bad thing and create damage to cerebral tissue. The tilting uses gravity to aid return of blood to the heart. He did not mention IBT.

Inversion positions encourage blood to head to the brain. Venous insufficiency means that this is already an issue. According to Zamboni's research, blood is not able to return to the heart in a timely matter because of blockage. In my viewpoint, inversions are contraindicated. I, personally, practice yoga and inversions. My husband stays clear.
AC

Thanks Cheer I started using the table just too see if surging the blood could help some of the issues that plagued me early on. I knew even then before the MRI and confirmed MS there was something going on in my head. Might have been a dangerous move. When I first started using the inversion table my head felt weird. I guess sloshing would best describe the feeling. Also light vertigo at first, but now it just feels good. With my back injury when I was allot younger I feel like it has helped tremendously in relieving the pain. I have actually increased my height at least a quarter inch and improved my posture. I have heard stunt pilots that pull high G's use them to train with. Wish I had more info from others on this. Will keep searching for the answers. Would love to hear a professionals thoughts. Wouldn't recommend trying one without first consulting your Dr. Mark

I started doing yoga six years ago to heal disc disease, and it worked quite well...also got taller! I do lots of shoulder stands, down dog, and inversion positions, and my spine feels great. If it works for you, Mark, go for it! After Jeff gets dopplered in April, we'll see if venous reflux is part of his MS. For now, he's keeping his head in an upright position-
Marie....your vetebral vein reflux only happens when you're sitting up, right? why do you think?
AC

this was the thread that revisited lesion types and prineas right? i hadn't seen this interesting item, for the mention of edema VS demyelinating lesions.

this was the thread that revisited lesion types and prineas right? i hadn't seen this interesting item, for the mention of edema VS demyelinating lesions.

JL, what? I'd answer, I own a copy of Prineas and Barnett, but don't understand the question.

Yes I have vertebral vein reflus it is relieved when lying down because the jugulars take the flow then, when upright the VV's are the main course.

I'd wonder about inversion and suspect that if Zamboni is right and we all have these venous issues that it would probably not be the best choice to be upside down. if you thinka bout venous ulcers int he foot the biggest thing that they make people do is keep them up so the blood does not pool in there and make the area too congested. People who are succesful in that do much better than those who do not.

oh whoooops! looks like i forgot to paste in the link .. i can't find it again in a hurry sorry. it wasnt' a question about the prineas paper, just trying to confirm if this was the thread where lesion types etc recently resurfaced.. to place the link in the right thought process. but it's long gone now sry

Skip the inversions.

Tilt the bed and be patient. I have spent 15 years of my life researching this and amassed a huge amount of input from people with ms and other neurological conditions who have reported phenomenal results from simply tilting the whole bed to a five-degree head up angle.

If you really want to experiment with inversion over a prolonged period, perhaps you should do some research using contraindications, head down tilt, sleep. This should give you a good understanding of what happens to the body when we are the wrong way up in relation to gravity. But what you won't learn there is that you will get diarrhoea, produce urine free of toxins, develop heart and muscular atrophy, osteoporosis, increase your risk of paralysis and spasm, raise the pressure inside the central and peripheral nervous system, damage your kidneys, experience visual disturbances.

Horizontal bedrest is used by the vast majority of people. No controlled study has been conducted to state it’s safety, so presumably we sleep flat because the bed we sleep in is flat. Not very scientific IMHO.

Inclined bed therapy on the other hand has been tested and a huge amount of data from people with ms has shown it is a useful paradigm for people with neurological conditions.

Solutes alter pressure inside vessels as gravity pulls them through the vessels. Ever thought that injecting a dye in the vessels might contribute to the circulation and could be responsible for causing a back flow depending on the density of said solutes?

There is a lot of data relating to epidurals altering the way the nervous system functions. Arachnoiditis being one such condition directly attributed to the introduction of foreign substances into the spinal cord. Could those injections have reversed the flow of cerebrospinal fluid and introduced reflux damage? Absolutely according to my own research with solutes!

IBT increases the density of urine! Head Down tilt does the opposite! This should tell us something about how solutes arrive in the bladder!

Don’t make the mistake of thinking something that costs nothing and is simple to use is not going to make much difference to people with ms.

Don’t make the mistake of thinking that because the medical profession have not stamped an approval based upon credentials required, that it invalidates the reports from many people who have been sleeping on an incline for many years and have reported many symptoms being totally reversed.

Do keep a journal and report back to the forum regularly about any changes good or bad that you notice after your bed has been elevated at the head end.

Andrew

skydog wrote:Without getting too technical could gently simulating the cvs with Andrew's inclined bed and daily inversions on a inversion table help strengthen the now open bbb. Has there been any prior discussion related to what this could do? Keeping it simple… Mark

JL, this thread??

http://www.thisisms.com/ftopict-6851.html