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Here are couple of other related, non-Zamboni Pubmed abstracts:


Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis.

Arch Neurol. 2008 Jun;65(6):812-6.
Comment in: Arch Neurol. 2008 Nov;65(11):1547-8; author reply 1548.
Ge Y, Zohrabian VM, Grossman RI.
Department of Radiology, Center for Biomedical Imaging, New York University School of Medicine, 650 First Ave, Room 615, New York, NY 10016, USA. yulin.ge@nyumc.org

BACKGROUND: Although the role of vascular pathology in multiple sclerosis (MS) lesions was suggested long ago, the derivation of these lesions from the vasculature has been difficult to assess in vivo. Ultrahigh-field (eg, 7-T) magnetic resonance imaging (MRI) has become a tool for assessing vascular involvement in MS lesions owing to markedly increased image resolution and susceptibility contrast of venous blood.

OBJECTIVE: To describe the perivenous association of MS lesions on high-resolution and high-contrast 7-T susceptibility-sensitive MRI.

DESIGN: Case study.

SETTING: University hospital.

PATIENTS: Two women with clinically definite relapsing-remitting MS.

RESULTS: We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI.

CONCLUSIONS: These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response.


Raised venous pressure as a factor in multiple sclerosis.

Med Hypotheses. 2008;70(6):1112-7.
Comment in: Med Hypotheses. 2008 Oct;71(4):619.
Talbert DG.
Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Du Cane Road, London W12 ONN, United Kingdom. d.talbert@imperial.ac.uk

It is hypothesised that the inflammatory condition seen in MS and the progressive myelopathy that is being successfully halted by obliteration of dural arteriovenous fistulas (DAVFs), may actually be two sides of the same coin.

Excessive venous hypertension can stretch vein walls sufficiently to separate the tight junctions between endothelial cells forming the blood-brain-barrier (BBB). Colloids, etc., but not necessarily erythrocytes, could then pass through the exposed porous basement membranes. The resulting changes in osmotic pressure, etc. would disrupt the axon and dendrite internal transport systems, leading to their disintegration. The normal inflammatory processes which would follow, might be indistinguishable from those associated with autoimmune disease.

Ascending progressive myelopathy and disablement are associated with an intracranial DAVF when its outflow enters the spinal venous system and descends past the cervical region. This can be arrested, and some degree of recovery produced, if the DAVF can be successfully eliminated or blocked. However, if the DAVF outflow is entirely into the spine, intracranial venous pressure may be normal and so there is nothing to alert the clinician to the presence of an intracranial DAVF.

It is suggested that where spinal MS has been diagnosed from clinical observations, patients should be referred for angiological investigation to search for DAVFs within the head to identify any treatable subjects.

My question is... what could twist a vein? Did you see that thing?
I am not feeling good about this. I hope I am looking at this all wrong.
Terry

Terry wrote:My question is... what could twist a vein? Did you see that thing?

pretty wild looking, huh Terry?? "Tortuous" veins and arteries can be genetic or caused by blood backflow (exactly what Zamboni found)

Thanks for the non-Zamboni vascular studies, Dignan. I am now your #1 Fan....but not in a creepy, stalker way.
AC

I also thought apart from the 100% MS patients vs. 0% controls, the differentiation in location of venous insufficiency in RRMS vs PPMS was very interesting.

I am going to ask my neuro in April....only 18 weeks or so....if I ask my new GP I know he will put me into the looney tunes category. I can see that look in his eye because I give the impression of being so well.

SO....if it IS venous insufficiency what's next? What could treat this? - apart from the partial treatment we are trying out with herbs/vits?

gotta answer more questions to deal with that i think. figure out what's causing the backup. is it something about the blood. what is it about the blood. are the veins just skinnier and easier to block. is there a gene partially responsible. if it's a property of the blood, what makes the blood like that. will any single treatment make us feel a little better, or stop progression, or heal existing damage, or slow progression down a bit, or what. can we do something about the general blockage issue from the liver. does the liver function need a boost. if so, why are we taking meds that impair the liver. where are we going to get the funding for all this research. hehehe

WW...maybe print out a copy of the research and pop it in the mail with a simple letter to your neuro. Just so he has it in advance. That's what I've done. Like Cure said, our doctors are used to reading medical journals. This research comes with a seal of approval from a respected journal. It's not like we're completely whacko on this one.

JL-everything you ask will be asked (and answered) in the future. You're so right about the meds and liver. The reason I went down this path was because Jeff had outward physical signs of a blood disorder when he was diagnosed, before any treatment. He was jaundiced, had sky high liver enzymes and petechiae on his legs. His neuro said it was not related to his MS, but I couldn't understand that. He'd never been so sick before. Neuros wouldn't consider a vascular connection. Maybe now they will.

Many different molecules can leak from blood vessels. T cells, B cells, iron, you name it. Jeff's on copaxone, because his t-cells were getting into his brain tissue, creating inflammation and degeneration. That's calmed down for now...but what else is still going on in there? It seems an easier concept to fix the levees, rather than pile up sand bags around the house and hope not to flood.

Zamboni does not define these blockages, or posit what these "venous obstructions" are, but they are in the blood vessels, and they are hampering the correct flow of blood in people with MS.

I offered that one idea was intravascular plaques from CPn causing this.

But another thing I thought of--I did read both papers-- was whether or not it is possible the tortuous veins and insufficiency is SECONDARY to the sclerotic area in the brain.

thought based on this; If an alcoholic gets cirrhosis of the liver, the liver gets physically sclerotic and hard. One consequence of this is the veins that lead to the liver from the gut become distended and vericose because the blood can't get through the narrowed and inflexible veins in the liver, and this damage leads all the way back to the esophogus where the vericosities can rupture, possibly killing the alcoholic person if it is not caught in time. But the hardened nature of the liver is the cause; it squishes the vessels so they end up being narrow, hard and inflexible so blood trying to get through there backs up like water behind a dam, stretching and damaging the vessels behind that area. The problem with the esophogeal vericies is not a vessel problem, it is a hardened liver problem.

However you could open up the vessels in the liver so the blood could flow well there reducing the esophogeal verices, which would be an important improvement, but it would do nothing for the cirrhosis.

Is it possible that MS plaque areas are hard enough to do the same things to the cerebral veins? I don't know, but the venous insufficiencies would be an effect not a cause then, just as they are in esophogeal vericies.

OTOH the Shelling theory is that pressure itself causes the damage to the brain tissue. I hope they can prove that it comes before the MS damage, like people with optic neuritis getting a full cerebro spinal vein workup and seeing if anyone has this venous issue before they have symptomatic MS . If the venous issue is there even in the earliest stages that would help identify it as causitive rather than secondary, especially if it is bad right from the beginning before the lesion is large.

The final lines of the Schelling paper outlines his simple approach to cure MS if it is caused by these venous malformations: simple vein procedures to prevent the reflux. Wouldn' that be great?

I am very drawn to this theory in particular in the way Schelling sees the status of current MS research. He simply says the current paradigm ignores way too much fact about the disease, creating thoeries based on misguided dogma not supported by the known pathology.

I could not agree more with this assessment, If MS were autoimmune we would be able to control it much better than we can with current therapies.
Good grief, we can give novantrone that is causing people such suppressed immunity that some get AML, and the MS still progresses? Immunity so suppressed it ignores cancer but it still chews on your brain for fun? Illogical, esp when shutting down autoimminity is so easy when we KNOW it IS "autoimmunity" we are dealing with, like in EAE.

They keep telling us "more complicated than we thought...." Yes, it's very complicated when you are trying to force something that doesn't fit ....

mrhodes40 wrote: But another thing I thought of--I did read both papers-- was whether or not it is possible the tortuous veins and insufficiency is SECONDARY to the sclerotic area in the brain.

Could be a possibilty, Marie...comparing the doppler results with MRI would confirm location of lesions vs. venous insufficiency. Following CIS patients would show which comes first, veins or lesions. Most tortuous veins are congenital (like in Ehlers Danlos and other connective tissue disease), but these might be caused by MS lesion activity. One thought....patients with Alzheimers brain lesions didn't show reflux or tortuous veins. If the lesions caused the veins, wouldn't they show a similar process? This process is unique to MS. Further studies needed.

Glad you read thru Schelling. I was interested to read your observations of pressure creating damage to brain tissue. Yes, wouldn't it be wonderful if treating the misbehaving veins could stop the MS process. I'm just gonna imagine that!

If MS were autoimmune we would be able to control it much better than we can with current therapies.
They keep telling us "more complicated than we thought...." Yes, it's very complicated when you are trying to force something that doesn't fit ....

I agree, Marie!!! I'm a fan of Ockham's Razor...I couldn't believe the convoluted logic of MS treatment. That's why I went off on the vascular route...I could see physical signs of Jeff's blood not working. Yet no neuro considered high liver enzymes, petechiae, coagulation issues, SED rate and jaundice as part of the pic. Suddenly his T-cells were in attack mode, for no apparent reason, and his blood was just, coincidentally, funky.

AC

Just really trying to get my mind around this. Does this bring us back to the autoreactive memory T cells getting through the BBB and into the CNS? Could this study have identified the method that our BBB fails and allows the whole process to continue?

So how would they treat something like this. What does this all actually mean? Good find everyone.

to follow up, i had a more detailed look at this on the other thread and my questions from earlier would be different now. originally i had thought the blockage might match up with spatial distributions of brain lesions, but from the abstract i only got a sense of blockages in the cerebrospinal "out door" vein. will have to read the full text to see if one type of azygos vein damage correlates with dawson's fingers and such.

Every MSer tested had blockage in the jugular vein or the azygous vein. Most had blockage in both veins. Both veins take blood back to the heart.

the azygous vein in the MS group was affected in 86% of cases.Most cases involved membranous obstruction of the junction with the superior vena cava, twisting, or, less frequently, septum and atresia as can be seen in the x-rays in Figure 2a; in 12 cases the azygous system presented stenoses at several points up to even atresia of the lumbar plexuses

The azygous vein is one of a system of veins that drain the thoracic and abdominal walls; it runs up the right side of the thoracic vertebral column, rises as a continuation of the right ascending lumbar vein and terminates in the superior vena cava. It was shown to be mostly twisted, with some instances of stenoses.

As for the jugular veins, they were found to be stenosed unilaterally or bilaterally in 59/65 patients (91%). The stenoses were frequently annulus and septum, followed by atresia; no twisting was observed.

The jugular veins are veins that bring deoxygenated blood from the head back to the heart via the superior vena cava. The stenoses were ring-shaped, divided, or closed up. The jugular veins were not twisted.

I will have Jeff's azygous vein and jugular vein checked for blockage when we get back home in Jan.
AC

weird i thought i had gathered from the abstract that most blockages were in the CS azygos vein. will have to spend more time with that and the full text. once i'm properly graduated ;)

For people who are asking what can be done about all this, I have no answers, but Zamboni had an idea in his original paper (page 5 of this document: http://www.physics.ubc.ca/~rauscher/labproject.pdf):

Although investigations on the role of iron in MS are
still few, some evidence supports a pivotal role for iron in
MS inflammation. The effect of manipulation of iron level
was investigated in EAE, a form of induced autoimmune
encephalomyelitis in mice used as an experimental model of
MS.31 The incidence of EAE was 60–70% in mice with a
normal iron level and in iron-overloaded mice, but 0% in
iron-deficient mice. The findings suggest that iron
deficiency provides protection from the development of
EAE31 and also challenge traditional views on what
constitutes a normal level of stored iron.14 The authors31
noted that, ‘The failure of iron-deficient mice to develop
EAE is impressive. Many of the pharmaceutical approaches
to inhibiting EAE are less effective than iron deficiency.’
Another group32 investigated the serum concentration
of soluble transferrin receptor (sTFR) in a group of MS
patients. The levels were found to be significantly higher in
patients with active MS, either in progressive or relapsingremitting
clinical form, than in controls. Serum ferritin
levels were also significantly elevated in patients affected by
the active and progressive form.32 Both findings support the
hypothesis above described, which proposes local iron
overload as the initial signal of the inflammatory chain in MS.
Although the primum movens of MS is still elusive, these
studies suggest that iron-dependent mechanisms of inflammation
seen in CVD could be relevant to MS. Future work
on MMPs and on iron/macrophage interactions appears
especially promising. However, because of its relevant
epidemiology and its easily visualized lesions, CVD is an
ideal model for investigating iron mediated mechanisms of
tissue injury of venous and inflammatory origin, as well as
the use of deliberate induction of iron deficiency as a
treatment modality.

Didn't realize there is actually a 7 tesla MS study open and recruiting now. Looks like its in Maryland.

Magnetic Resonance Imaging to Detect Brain Damage in Patients With Multiple Sclerosis