Visualizing iron deposition in MS cadaver brains

[MSUK]

Abstract

Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI).

Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF.... Read More -
http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2944

[tsoft]

Only two brains and one with iron.
What will be happend with 100?

[Donnchadh]

Another intriguing clue; but not conclusive "proof" that iron plays a key role in MS.

Personally, I am convinced that CCSVI treatments should consists of two steps. Treat whatever underlying vascular disorders exist (stenosis, bad valves, etc.) and also attempt to remove the accumulated iron deposition.

Donnchadh

[tsoft]

Ok, but how can we remove the iron from the brain? Any ideas?

[oreo]

" ... how can we remove the iron from the brain? "

A large magnet perhaps.

Sorry, but every once in a while I feel the need to just let go and be a little silly.

[Rokkit]

A large magnet perhaps.

If that worked, one MRI should do the trick.

[cheerleader]

Here is the rest of the abstract. Note that Dr. Haacke was involved in this, as well as Stanford University--
link

Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent.

Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo

I've talked with Dr. Haacke regarding another mechanism for axonal death and immune activation, aside from iron deposition, due to venous stenosis: hypoxia created by slowed perfusion. Already Haacke and Dr. Hubbard are showing an increase in perfusion and oxygenation after angioplasty in patients with CCSVI.

I believe we are going to learn that this hypoxic injury is more related to RRMS, and the iron deposition is more related to progressive disease. Dr. Schelling linked Dawson's fingers lesions to venous reflux and a more progressive disease pattern. Indeed, SWI-MRI is showing that iron deposition is a bio-marker for progressive disease courses. My husband had more scattered, smaller lesions--and a flare after being at high altitude. He did not have reflux, but did have very narrowed jugulars with collateral drainage. He had slowed perfusion. He is also RRMS...

As far as removing iron... EGCG (green tea extract) is a terrific BBB permeable chelator, anti-oxidant and anti inflammatory supplement.
http://www.facebook.com/note.php?note_id=203333122210
cheer

[Bethr]

In a study I read (I'll try and find it) it said that people with "Iron-loading" genes, ie: C282Y and H63D being the most common, their MS progressed faster and was more severe, but was not a marker for getting MS.

People with just one "iron-loading" gene do not generally get hemochromatosis damage to organs, but they can have much higher levels of iron and transferrin saturation in blood. The prevalence of a "iron-loading" gene in Europeans is about 1 in 7-10 depending on who you listen to. If you have iron rich blood would the MS damage come quicker?

I think a normal iron level is an important thing for people, especially with MS.
The problem I see is,

What is a normal, healthy iron level?

Have labs set the safest ranges for people with MS?

Too many doctors I've seen dismiss a high iron level and some even think it's healthy!

Drinking green tea, or taking an extract will not help people with even a single "iron-loading" gene get rid of stored iron in their bodies, only phlebotomy will do that with any certainty. Genetically, your body will still keep loading mkore iron than you need.

[cheerleader]

Beth, I've asked Dr. Haacke about this. He personally doesn't believe that it's about iron "loading" or serum iron levels, but he admits it's still early in the research.... Here is his reply:

Iron has been implicated in multiple sclerosis for many years. It has been observed by MRI and has been seen in vessel wall for small venules. More recent work has shown that there can be iron build up around MS lesions and inside the lesions although not all lesions show an increase in iron content. Further, different parts of the brain associated with the medial venous drainage system also can show increases in iron content that appear to be affiliated with the draining veins. This iron is often not present MS lesions although in some cases it is and appears as either a uniform intensity or as a ring-like structure around the lesion. Iron in the pulvinar thalamus can increase and is seen in roughly 50% of MS cases especially for young people.

It is quite possible these increases in iron are related to the chronic venous insufficiency and may represent iron in one of three forms: oligodendrocyte ferritin after macrophage activity, iron from blood products or iron in the vessel wall or some combination of these. The iron that is measured here may represent hemosiderin which comes from the breakdown of blood not from other sources of iron. There is no evidence at this time that there are stray sources of iron causing this problem, not has that been proposed in this research. Further, it is unknown what role iron plays at this time and the main effect may remain the demyelinating inflammatory aspects of MS with iron representing either an outcome of endothelial damage or hemosiderin or as part of the inflammatory pathway. Iron has been implicated also in Zamboni's research; one explanation is that it come from a breakdown of ferritin because of a genetic problem related to the stability of ferritin. Much remains to be learned and it is possible that iron may serve as a biomarker for MS.

[Cece]

I believe we are going to learn that this hypoxic injury is more related to RRMS, and the iron deposition is more related to progressive disease.

Would secondary progressive be a case of iron deposition finally catching up to us?

This seems a workable theory. It fits my anecdotal evidence point (RR with flairs repeatedly after altitude). Fatigue would also fit with hypoxia rather than with iron deposition and I have fatigue!

[cheerleader]

I believe we are going to learn that this hypoxic injury is more related to RRMS, and the iron deposition is more related to progressive disease.

Would secondary progressive be a case of iron deposition finally catching up to us?

This seems a workable theory. It fits my anecdotal evidence point (RR with flairs repeatedly after altitude). Fatigue would also fit with hypoxia rather than with iron deposition and I have fatigue!

Cece---this is just my theory...and I am by no means a doc, but what I think happens is that the hypoxic injury caused by venous insufficiency leads to axonal death and immune activation. RRMS patients might have hypoxic events (virus, high altitude, stress) that compound venous insufficiency, and this creates a flare. Compound these flares over time, you have axonal death which leads to iron deposition into brain tissue from oligodendrocyte destruction. This iron buildup eventually overwhelms the immune system, and MS then moves into the progressive phase.

Dr. Dake told us that he thought Jeff's relief from fatigue, heat intolerance, spasms, urgent bladder and cog fog were do to relief from venous insufficiency. And Jeff went skiing and snow shoeing at high altitude last winter, no problem since angio.
interesting,
cheer

[jimmylegs]

hmm, ms lesions correlated with absence of zinc? interesting.

Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus.

FYI for newer members, if you have not come across the following on your own:

http://www.thisisms.com/ftopicp-49483.html#49483
Posted: Fri Jan 02, 2009

-Zinc deficiency changes your iron metabolism.
i found an in vitro study; will look for more:
http://www.jbc.org/cgi/content/abstract/283/8/5168
Zinc Deficiency-induced Iron Accumulation
snippets:

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations... The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression...

http://www.thisisms.com/ftopicp-57772.html#57772
Posted: Mon May 18, 2009
http://www.jbc.org/cgi/content/full/283/8/5168
Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins

http://www.thisisms.com/ftopicp-70068.html#70068
Mon Oct 05, 2009
beating the dead horse some more:

Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins*
Abstract
One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 μm zinc), zinc-supplemented (S, 50 μm zinc), or control (C, 4 μm zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

HTH,
jimmylegs

[shye]

are we missing, ignoring an important statement in the above abstract?

To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF.

Need the full article to get its conclusions re: zinc. Since all the trace metals are needed, and are needed in a certain ratio (ex: Too much Zinc interferes with Copper uptake and can cause verious cytopenias; Copper is needed for Iron transport and uptake, etc etc.),we cannot just focus on Iron. The reason we are possibly depositing Iron might have nothing to do with the amt of iron we have, but on the relative deficiency of another trace mineral such as copper or zinc.

(I say this as someone who is heterozygous for hemochromatosis H63D mutation, and who got incredible energy when did first phlebotomy--will do second one in two weeks to see if this continues. But I also take supplements of trace elements copper and zinc, as well as others.)

[shye]

Hi Jimmylegs--we both were working on same at same time! I decided to post, then go look for the Zinc references--now see you did that legwork (again)!!!! and not a dead horse at all--very much an important link in the aspect of iron deposition in MS I think.

[silverbirch]

Do you think a regular visits to the Hyperbaric chamber are also benifical to MS ? Ive been toying with this for some months reading the above looks like a visit maybe worth while -

I have RR (14 months) Ive had to stop giving blood (uk guide lines) plus I had hysteroctomy 3 yrs a - a good drop of green tea

Locally we have one of these chambers and MSERS get it very cheap rate

I attended an MS ball and one girl has been going to the chamber for 10 years her MS is stable and has remained at RR although I do not know of drugs she may / may be taken. Plus her ms maybe the stable one alot of things to factor in ......

I wounder if type of bloods come into MS Im rhesus neg ? ive not seen anything about blood groups and MS

I would very much welcome your views