Another brilliant article by Cheerleader..

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

Another brilliant article by Cheerleader..

Postby PCakes » Wed May 26, 2010 7:31 pm

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Postby jackiejay » Wed May 26, 2010 7:41 pm

yes, it is brilliant and very enlightening....in llight of this info and everything else we have learned about CCSVI...very unsure of continuing with immune modulating drugs.....what is the use?....but have read that people should continue taking them....very confusing....
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Postby cheerleader » Wed May 26, 2010 10:06 pm

Jackie--Dr. Zamboni recommends patients remain on their DMDs- even after angioplasty. The note I wrote is about how iron deposition measured on SWI MRI may very well be a better bio marker for MS progression rather than counting lesions--as Dr. Haacke has stated.

The immune system is activated in MS...there is no doubt about that. And if your DMD is keeping the immune system quiet, no need to change anything. Jeff remains on copaxone, even after his angioplasty a year ago. We don't know how long the immune system remains activated. More research is needed.
HTH,
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Not quite fair

Postby ScutFarkus » Wed May 26, 2010 11:15 pm

Isn't it widely believed that lesion size and location are at least as important as raw lesion count, and that this likely explains a lot of the variation in disability levels between people with similar lesion loads?

More importantly, the DMD drug effectiveness studies I have read used relapse rates as a key indicator of MS progression. In fact, my recollection is that the original studies that got the Avonex and Copaxone FDA approved, and from which we get the infamous 30% effectiveness numbers, used relapse rate as their primary measure. Point is, stating that "Pharma companies use the lesions shown on MRI as 'proof' that their particular drug is working" doesn't seem fair: that's just part of the evidence, and even if you reject that part, the relapse rate results are compelling.

My bet is that the drug companies would be absolutely thrilled to have a more sensitive measure of MS progression. A major impediment to drug development now is the size and duration needed in clinical trials to demonstrate benefits using today's crude measures. A more sensitive measure would allow company X to demonstrate their drug is, say, 3% more effective than company Y's, without requiring a 1000 subject trial lasting 5 years.

/Scut
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Postby jackiejay » Thu May 27, 2010 5:04 am

Thanks for clarifying, Cheer.....looks like we need big pharma after all...
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Postby patientx » Thu May 27, 2010 6:31 am

What is different in SWI-MRI, according to Dr. Haacke, is that brain damage shown due to iron deposition actually CORRESPONDS to disability in MS.

The more iron deposed in the brain, the more disability, the more progressive MS is. This is different than the usual measuring of hyperintense lesions on MRI, which have no specific correlation to disease severity.

Does anyone know if there are any studies that show this?

Scut, you're right. Most drug trials (even new ones, like for fingolimod and cladribine) use relapse rate as a primary endpoint. Reduction in lesion load is a secondary endpoint that they measure.
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Iron Deposition and Disability in MS

Postby Shayk » Thu May 27, 2010 7:55 am

Patientx
Quote:
What is different in SWI-MRI, according to Dr. Haacke, is that brain damage shown due to iron deposition actually CORRESPONDS to disability in MS.

The more iron deposed in the brain, the more disability, the more progressive MS is. This is different than the usual measuring of hyperintense lesions on MRI, which have no specific correlation to disease severity.

Does anyone know if there are any studies that show this?


I think the following research may be relevant to your questions--some more, some less. Several full articles are available if you click through to the abstract(s).

There has been a pilot study re: SWI, iron deposition and disability.

Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study
CONCLUSION: The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients.

In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.

Iron stores and cerebral veins in MS studied by susceptibility weighted imaging
CONCLUSION: Iron may serve as a biomarker of venous vascular damage in multiple sclerosis. The backward iron accumulation pattern seen in the basal ganglia and thalamus of most MS patients is consistent with the hypothesis of venous hypertension

Deep gray matter T2 hypointensity is present in patients with clinically isolated syndromes suggestive of multiple sclerosis
In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.

Transcranial brain sonography findings predict disease progression in multiple sclerosis
CONCLUSIONS: Neurodegenerative disease-like deep gray matter lesions can be frequently detected by transcranial sonography (TCS) in patients with multiple sclerosis (MS).

Findings suggest that TCS shows changes of brain iron metabolism which correlate with future progress of MS.

Quantitative assessment of brain iron by R(2)* relaxometry in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis
CONCLUSIONS: Quantitative assessment by R(2)* relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy.


Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging
CONCLUSION: The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics.

SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus


From Buffalo in 2009, Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis
CONCLUSIONS: Gray matter T2-hypointensity, suggestive of excessive iron deposition is associated with worsening disability in patients with MS.

Gray matter MRI assessment may be able to capture neurodegenerative aspects of the disease, with more clinical relevance than derived from conventional MRI measures

From Buffalo in 2002, T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study
CONCLUSIONS: Gray matter T2 hypointensity in MS is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional MRI findings.

While longitudinal studies are warranted, these results suggest that pathologic iron deposition is a surrogate marker of the destructive disease process.

Take care and hopefully others can add to this.

Sharon
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Postby ssmme » Thu May 27, 2010 10:23 am

patientx wrote:
Most drug trials (even new ones, like for fingolimod and cladribine) use relapse rate as a primary endpoint. Reduction in lesion load is a secondary endpoint that they measure.


I don't really feel that I've ever had what would be considered a classic textbook exacerbation. It's usually in hindsight that I begin to suspect that what I had been experiencing could have been one. I don't lose my sight then get it back, or experience the MS hug then get back feeling, sometimes my left hand and arm tingle sometimes it doesn't, L'hermitte's sign is there sometimes and sometimes it isn't. How can counting exacerbations be accurate? For the record, I don't believe lesion load is the answer either. There is not a simple way to measure new drugs with either of these methods. But I'm open to here suggestions?
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Postby jackiejay » Thu May 27, 2010 10:47 am

the gray matter associated with iron deposition in the brain....does this show up in a "normal" MRI or only with the SWI -MRI?...
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Postby ssmme » Thu May 27, 2010 11:21 am

I read some info posted by Cheerleader on Facebook about CCSVI and it mentioned that standard MRI does not see/show iron deposits.
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Postby cheerleader » Thu May 27, 2010 11:22 am

It was in hearing Dr. Mark Haacke in Bologna speak about iron deposition that I came home and wrote the Facebook note referenced at the top of the thread. He was fired up--finding correlation in what he had notice upon SWI MRI (which he invented) in MS brains and the Zamboni and BNAC findings. We've discussed iron on here quite a bit. If you search Haacke + iron in the forums, you'll find the threads. Thanks to Shayk for compiling a list of papers. These are my notes from Bologna--and why I came home all fired up.

Dr. Mark Haacke , the MRI Institute for Biomedical Research. Detroit, MI
MRI-SWI (susceptibility weighted imagery) cerebral veins and iron deposition-
Dr. Haacke developed SWI to see specific patterns in the venous structure. He states his findings in MS brains is consistent with everything presented today regarding venous structure, oxygen and iron deposition.

He offers thanks to the foundation and Bologna for the openness of discussion and the freedom of ideas. He asserts that CCSVI does not go against what we know about MS....however it will further define it.

In normal brain tissue, iron appears as ferritin 80% of the time and hemeiron 20%.
Iron can be visualized on SWI- it shows up at 3 tesla as dark gray. Capillary density absorbs most iron, and the basal ganglia is where it appears most.

In imaging MS brains, there is an increase in basal ganglia and thalamus iron, and this can serve as a bio marker for MS. Iron deposition progresses over time...the more iron, the worse the patient outcome will be.

Iron in the thalamus is a good bio marker for MS progression, without measuring brain lesions. Iron content and area of iron deposition increase with time.

There is a dramatic increase in iron in the brain in young people with MS as compared to controls, and this can be related to venous reflux. MS lesions show up on SWI as high in iron content.

Dawson’s Fingers enhance on SWI with LOTS of iron.....there is a uniform relationship between the veins and lesions.

Is this a form of demyelination? Microbleeding? Perhaps it is hemosiderin?

BOLD technology- a means to measure blood oxygen levels. SWI is sensitive to local iron content- but neuros weren’t interested in this, no one has cared about output function.

In 7 Tesla MRIs, you can see venules. We can see the microvascular response to iron deposition. Perfusion weighted imagery gives us the complete picture.

Progressive MS shows a loss of oxygen in the brain. A complete change in cerebral hemodynamics, it is much worse the RRMS.

SWIM technology- is an attempt to quantify the de-oxyginated saturation of the veins. Iron builds up counter current to the flow, it gets much worse with time.

Dr. Haacke wonders if in Sturge Weber syndrome there is a venous obstruction? No one has ever looked....neuros focus on the brain to the exclusion of the rest of the body. SWI technology will provide new and accurate markers for studying abnormal iron content in the MS brain.

Iron acts as an inflammatory agent in he brain. There is a microvascular breakdown and ischemic areas lose cerebral bloodflow.

The pieces of the puzzle fit when considering how CCSVI can do this to the MS brain.

Can SWI be used as a bio marker in early MS? Should we be treating MS with chelating agents and antiinflammatories?

MS patients have an increased amount of iron in the basal ganglia- and this may very well be from venous obstruction. There are 1000 systems in the world that can do SWI technology. There is now spin software available on line- so that anyone can use SWI capabilities
www.MRimaging.com

The technology exists- we need to create a complete MS protocol...one that considers oxygen saturation, iron deposition, and perfusion time.


Dr. Haacke's site has a new paper (pre-publication) lots more papers-
http://www.ms-mri.com/presentations.php
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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cheerleader

Postby blossom » Thu May 27, 2010 10:48 pm

cheerleader, have you ever heard if dr. haacke or anyone is studying or trying to come up with a safe way to get rid of the iron once a person is liberated? or, do they feel once proper flow is restored it will help get rid of it. i have read that most people with ms have very high aluminum in them. i for one do. have you ever heard if that is in the picture? probably the wrong time and place to get into this but thought i'd ask. thanks
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Re: cheerleader

Postby cheerleader » Fri May 28, 2010 8:51 am

blossom wrote:cheerleader, have you ever heard if dr. haacke or anyone is studying or trying to come up with a safe way to get rid of the iron once a person is liberated? or, do they feel once proper flow is restored it will help get rid of it. i have read that most people with ms have very high aluminum in them. i for one do. have you ever heard if that is in the picture? probably the wrong time and place to get into this but thought i'd ask. thanks


hi Blossom-
Dr. Haacke is an imaging researcher, so this wouldn't be his area. He was just positing this as a possible treatment. I know that Dr. Zamboni was looking into this, but he is so busy with his CCSVI work I haven't heard any more from him regarding chelation. I believe the thought is that once correct blood flow is restored, the endothelial lining of the BBB is strengthened and iron deposition is halted. Dr. Haacke's SWI MRI testing will be following up on patients once they have had angioplasty, to see if this is true.

There have been a few clinical trials on EGCG (green tea extract) and MS--big one in Berlin.
link
EGCG is a wonderful anti-inflammatory chelator that permeates the BBB. Jeff takes it as a supplement. Might be worth it to look into it until the doctors sort out chelation therapies.
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: EGCG

Postby silverbirch » Fri May 28, 2010 4:18 pm

cheerleader wrote:
blossom wrote:cheerleader, 2007/deutsch/PJ/PJ28373.html] link [/url]
EGCG is a wonderful anti-inflammatory chelator that permeates the BBB. Jeff takes it as a supplement. Might be worth it to look into it until the doctors sort out chelation therapies.


cheerleader could you please breakdown EGCG into its full meaning please I would also like to buy a good one

Thank you for your thread - its again very interesting

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Postby patientx » Fri May 28, 2010 5:05 pm

Thanks. Sharon. That's a pretty exhaustive list. I'll give them a read (though I will have to do most at work, since that's only where I am able to get most of the full articles.)
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