Dr. Zivadinov asks, is it time to redefine MS pathogenesis?

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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Tue Apr 24, 2012 4:37 pm

A new paper from BNAC on significant subcortical deep gray matter (SDGM) atrophy in early MS and CIS. Again, deep gray matter is showing signs of disease progression early in the disease.

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis.

Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.


http://www.ncbi.nlm.nih.gov/pubmed/22499842

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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Tue Apr 24, 2012 4:55 pm

Another new paper from BNAC suggesting that iron deposition in the subcortical deep gray matter (SDGM) shows up first, even before brain atrophy---

Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement, in the various SDGM structures, suggesting that iron deposition may precede structure-specific atrophy.


http://www.ajnr.org/content/early/2012/03/29/ajnr.A3030
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Wed Jan 16, 2013 2:53 pm

Update 2013--gray matter atrophy and iron deposition in the thalamus continues to grow in importance

New paper from Zivadinov, Frohman, Barnett, et al
The Thalamus and MS: Modern views on pathologic, imaging and clinical aspects

A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

http://www.ncbi.nlm.nih.gov/pubmed/23296131
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby HarryZ » Wed Jan 16, 2013 8:51 pm

Hi Cheer,

I can imagine the established world of MS medicine is already working on a way to try and discredit these findings. They've done in the past and they will do it the future. A lot of money is at issue here and any research that threatens this will be quickly attacked.

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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Thu Jan 17, 2013 10:18 am

HarryZ wrote:Hi Cheer,

I can imagine the established world of MS medicine is already working on a way to try and discredit these findings. They've done in the past and they will do it the future. A lot of money is at issue here and any research that threatens this will be quickly attacked.

Harry


I don't know about that this time, Harry....this recent paper includes some MS name researchers, including Dr. Eliot Frohman and Dr. Barnett. The evidence about the importance of gray matter atrophy is compiling. What will be interesting is how this will be explained--does the iron deposition come first, or is it initiated by the inflammatory process? Drug companies will go for the inflammatory observations, and start looking at cessation of gray matter atrophy as a marker of their products' efficacy.

The thalamus is located next to the third ventricles, and drained by the deep cerebral veins. We've been watching Jeff's gray matter for a few years now on MRI, and his thalamus looks normal again. In fact, his gray matter no longer shows any signs of atrophy. His retinas also look normal on OCT. OCT has been shown to be linked to gray matter health--since both the retina and gray matter are comprised of neurons, and mostly without myelin. That's the part that is concerning to pharma. I do believe that the rush to get the new oral meds to market and to get Tysabri approved as a first line medication is part of this.
more to come....
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby HarryZ » Thu Jan 17, 2013 10:32 am

I don't know about that this time, Harry....this recent paper includes some MS name researchers, including Dr. Eliot Frohman and Dr. Barnett.


Hi Cheer,

I sure hope you are right but pronominent names in the past haven't stopped the protective attacks that big pharma and associates have made against these people. Barnett has been looking to other causes of MS for a number of years now and is a good guy to have on your side. But big pharma has a lot of clout and they won't stand by idly if there is a threat to their revenue millions and this kind of research could make their immune system suppressive drugs extinct!

I'm really hoping for some new breakthrough in MS treatment that involes other avenues as opposed to what we have today.

Take care.

Harry
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby CureOrBust » Fri Jan 18, 2013 4:51 am

I use two different Neurologists, at two different locations. One of them is Prof John Pollard, who is very well respected within the "establishment" of MS treatment, worldwide; I think he also won an an award from the Australian Govt a few years back. When I first brought CCSVI to his attention, he quickly dismissed it because of its lack of backing within the (his) accepted group of respected neurologists.

What gives me GREAT hope here, is that Barnet shares an office with Prof Pollard and has shared credit on published papers, and now Barnet is obviously speaking with Zivadinov. I would be surprised if Barnet and Pollard do not speak about things like this "around the water cooler". Its not in your face CCSVI, but I think its small "leakage" like this that has a great potential to bring CCSVI research into the realm of the "respected" neurologists.
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby HarryZ » Fri Jan 18, 2013 7:11 am

CureOrBust wrote:I use two different Neurologists, at two different locations. One of them is Prof John Pollard, who is very well respected within the "establishment" of MS treatment, worldwide; I think he also won an an award from the Australian Govt a few years back. When I first brought CCSVI to his attention, he quickly dismissed it because of its lack of backing within the (his) accepted group of respected neurologists.

What gives me GREAT hope here, is that Barnet shares an office with Prof Pollard and has shared credit on published papers, and now Barnet is obviously speaking with Zivadinov. I would be surprised if Barnet and Pollard do not speak about things like this "around the water cooler". Its not in your face CCSVI, but I think its small "leakage" like this that has a great potential to bring CCSVI research into the realm of the "respected" neurologists.


While I can understand a doc's hesitation to endorse a procedure that is very new and does not yet have a lot of scientific backing to it, it's the "dismissal" or "bad-mouthing" attitude that gets launched immediately! Unfortunately new discoveries like CCSVI threaten the established theories on MS and a lot of money and personal reputations can hang in the balance. It would be nice if the "established" group would just say the new theory is interesting so let those who talk about provide the science to try and prove it.

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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Fri Jan 18, 2013 1:43 pm

CureOrBust wrote:I use two different Neurologists, at two different locations. One of them is Prof John Pollard, who is very well respected within the "establishment" of MS treatment, worldwide; I think he also won an an award from the Australian Govt a few years back. When I first brought CCSVI to his attention, he quickly dismissed it because of its lack of backing within the (his) accepted group of respected neurologists.

What gives me GREAT hope here, is that Barnet shares an office with Prof Pollard and has shared credit on published papers, and now Barnet is obviously speaking with Zivadinov. I would be surprised if Barnet and Pollard do not speak about things like this "around the water cooler". Its not in your face CCSVI, but I think its small "leakage" like this that has a great potential to bring CCSVI research into the realm of the "respected" neurologists.


Exactly, Cure! Barnett discussing the reasons for gray matter atrophy with Zivadinov is encouraging. The fact that Eliot Frohman, who was at the first CCSVI conference and collaborated on this gray matter study, is another interesting development. BNAC has been publishing some important research on the changes that happen after venoplasty---one presented at ECTRIMS showed increased cerebral spinal fluid flow in all pwMS treated with venoplasty. http://registration.akm.ch/einsicht.php ... KEN_ID=900
I'm sure they are monitoring gray matter, as well.
It was Dr. Frohman who mentioned how much normal pressure hydrocephalus (NPH) reminded him of CCSVI at that very first conference in Bologna in 2009. Stagnation of CSF is related to gray matter changes, indicated by the enlargement of the third ventricle.
And BNAC is at the forefront of looking at how gray matter is affected by the DMDs (supported by Biogen)--using 7 Tesla machines. http://cme.bnac.net/index.php?s=8

This studying MS pathogenesis as neurodegeneration, iron deposition, inflammation and deep gray matter loss, with myelin loss a secondary or concurrent event, is gaining more ground.
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby mmpetunia » Wed Feb 06, 2013 4:31 pm

Cheerleader,

you mentioned that you are keeping a close eye on the grey matter atrophy on your husbands MRI scans. i was under the impression that grey matter is not easily visible on MRI. how are you able to look at the grey matter? i would definitely be interested in keeping tabs on mine. also, the OCT eye scan, where/how are you getting this done? is this paid for out of pocket or can i request via my neuro?


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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Wed Feb 06, 2013 5:27 pm

mmpetunia wrote:Cheerleader,
you mentioned that you are keeping a close eye on the grey matter atrophy on your husbands MRI scans. i was under the impression that grey matter is not easily visible on MRI. how are you able to look at the grey matter? i would definitely be interested in keeping tabs on mine. also, the OCT eye scan, where/how are you getting this done? is this paid for out of pocket or can i request via my neuro?


Hi mmpetunia--
We asked our MRI techs to compare Jeff's previous MRIs (he had 3 done at the same facility, and 2 at Stanford.) They were able to view the thalamus, the width of the third ventricle and the brain stem. These gray matter structures are seen on regular MRI. By comparing the size of these structures, they were able to see a reversal of earlier atrophy, to his now normal appearing gray matter. This comparison method is not as detailed as the 7Tesla MRI technology used to see lesions in gray matter http://www.biomedcentral.com/1471-2377/11/153 but it gave us a good idea of Jeff's brain health. His white matter lesions are smaller, no new ones, and none have enhanced since his first MRI 6 years ago.

Jeff's OCT was requested by Dr. Dake, and was covered by insurance. It was done by our local retinal specialist. Jeff's retinas looked great...and they are a good indicator of gray matter health. Thinning retinas are correlated with gray matter atrophy. http://www.medscape.com/viewarticle/589462 His optic discs and nerve are not as healthy, since he has drusen. Your neuro can request the OCT test for you, which should be covered by insurance.
best of luck learning about your own gray matter--
cheer
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Fri Mar 22, 2013 8:08 am

New research presented at 2013 AAN meeting:
http://www.buffalo.edu/news/releases/2013/03/028.html

The five-year study, which covered 180 patients, also found that thalamic atrophy has p0tential as a way to evaluate novel therapies for MS, according to Eva Havrdova, MD, PhD, principal investigator.

“The thalamus is providing us with a new window on MS,” says Robert Zivadinov, MD, PhD, UB professor of neurology, BNAC director and leader of the research team. “In our recent studies, we have used large datasets to investigate the evolution of atrophy of the thalamus and its association with clinical impairment in MS, starting with the earliest stages of the disease. The location of the thalamus in the brain, its unique function and its vulnerability to changes wrought by the disease make the thalamus a critical barometer of the damage that MS causes to the brain.”

“Since progressive pathology of the thalamus has been shown in all different MS disease types, including in pediatric MS patients, we must look at the thalamus as a biomarker for assessing new therapies,” says Zivadinov. “Measurement of thalamic atrophy may become an ideal MRI outcome for MS clinical trials.

“Atrophy in MS patients happens in the thalamus more rapidly than in other brain structures,” Zivadinov continues. “It is detectable very early in the disease and it is less affected by fluid shifts in the brain, an effect of anti-inflammatory drugs used in MS. This feature in particular, makes thalamic atrophy an ideal candidate for assessing novel therapies.”
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby daniel » Fri Mar 22, 2013 8:42 am

Thanks for the update cheer! Does this also mean pathology of the thalamus is related to bloodflow/hypoxia?
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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby cheerleader » Fri Mar 22, 2013 9:31 am

daniel wrote:Thanks for the update cheer! Does this also mean pathology of the thalamus is related to bloodflow/hypoxia?

Hi Daniel--
always nice to see your teletubby baby....makes me smile!

Dr. Zamboni has shown how reflux in the deep cerebral veins affects the thalamus and sub-cortical gray matter of the brain-via iron deposition and hypoperfusion. http://www.nature.com/jcbfm/journal/v29 ... 180f6.html
But as of today, he is one of a couple of researchers noting this. BNAC will be looking at pharma solutions to thalamic atrophy, since pharma is giving them money to research this new biomarker for MS disease progression. I'm not sure if BNAC is monitoring the thalami of those they treated for CCSVI. It would make sense if they did, but much of MS research is not sense-based, but dollar based. (pun intended) My husband's thalamus is now "normal" on MRI.

Here, Dr. Zivadinov and Haacke note, via SWI technology, the correlation between iron deposition in the thalamus and severity of CCSVI-
http://www.ncbi.nlm.nih.gov/pubmed/20351672

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Re: Dr. Zivadinov asks, is it time to redefine MS pathogenes

Postby HarryZ » Fri Mar 22, 2013 4:58 pm

Dr. Zivadinov (a real neurologist) is asking if it's time to look at MS as a disease of the gray matter.
This is a radical shift, since, as Harry notes---the drugs on the market were not created to address gray matter degradation. It's as if Dr. Zivadinov is saying, we're back to square one...the days before EAE. That's pretty interesting.
cheer


Cheer,

It's so nice to hear that people like Zivadinov are looking outside the MS established box and attempting to approach the disease from another direction. But like I've always said before, the established world of MS medicine won't stand by idly and see their reputations and cash cows disappear. They will use whatever means they can to discredit people like Zivadinov and keep their domain solid. Let's just hope that he wins out in the long run.

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