Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the auto-immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Showing posts with label perivenous. Show all posts
Showing posts with label perivenous. Show all posts

Friday, September 20, 2013

The Central Vein Sign and New Research


September 20, 2013

It was 150 years ago, in 1863, when Eduard von Rindfleisch first peered through his microscope at an MS lesion and noted a vein inside the cerebral MS lesion.

If one looks carefully at freshly altered parts of the white matter ...one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood...All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation. 

Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.

We've known for over a century that MS lesions are perivenous, meaning lesions form around a vein.  There is a vein in the center of almost every cerebral MS lesion, and this makes the MS lesion unique.

So, it was interesting to see THREE brand new papers on this topic in 2013, coming from neurological research. 

Here's one from July 2013, published in "Frontiers of Neurology"--suggesting that these central veins and perivenous lesions, which are now very clear on 7Tesla MRI, might be helpful in making an MS diagnosis.

Venocentric Lesions: an MRI marker in MS?
In the past decade, numerous studies have explored a promising biomarker for MS: MRI-detectable veins within lesions. This biomarker is well established as detectable at 3 and 7T and efforts should be made to identify/optimize clinically practical methods for its evaluation. Prospective studies have shown that the presence of venocentric lesions at an early but ambiguous clinical presentation is highly predictive of future MS diagnosis. Work remains to be done to confirm or exclude lesions of common MS mimics as venocentric. Common imaging practice and lesion-rating paradigms should be adopted by scientists working in this field.

Here's another paper entitled "The Central Vein Sign: is there a place for susceptibility weighted imaging in possible multiple sclerosis." (Readers of this page know that CCSVI investigator, Dr. Mark Haacke, is the inventor of SWI.  He has noted these central veins and iron deposition in the MS brain for almost a decade now, and linked their presence to CCSVI.)

Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS).

The "central vein sign" was predominantly seen in MS lesions. The "central vein sign" helps discriminate between MS and non-MS lesions.

Here's yet another study published in the Journal of Neuroimmunology in May 2013 which notes the central veins visible in MS lesion.

Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions.
In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms
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These papers are no surprise--researchers have been noting these veins inside MS lesions for over a century.  But what continues to shock me is that researchers aren't asking WHY?

Friday, January 1, 2010

Let's talk about iron....


January 1, 2010 at 5:41pm

Now, let's talk about the iron issue. This has been Dr. Zamboni's "smoking gun." He wrote a paper on iron called "The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis"- in which he explicitly outlines the parallels between chronic venous insufficiency in the legs and iron deposition and what we see in MS brains. If you haven't read it yet, it's a must read-

http://jrsm.rsmjournals.com/cgi/content/full/99/11/589?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=zamboni&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

So, how long have doctors known about this connection of iron and the MS brain? 
Here is a paper from 1988- yes, that is over 20 years ago- discussing the cerebral vein walls and iron deposition in multiple sclerosis-

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1031540/pdf/jnnpsyc00537-0096.pdf

"C W M ADAMS
From the Division of Histopathology, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, University of London, UK

SUMMARY Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis. Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7 %), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. Occasional control cases showed haemosiderin deposition in the brain but, unlike the multiple sclerosis cases, these were diffuse and almost entirely related to coexistent cardiovascular or cerebrovascular disease. Haemosiderin deposition was common in the substantia nigra and other pigmented nuclei in all cases. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis."

Here we have a study in 1988 showing vein damage in almost half of the MS patients- and the researchers note hemorrhage, hemosiderin (iron storage) deposition, thickened vein walls and call it a form of "vasculitis."

"The results reported here reinforce the view that damage to the vein wall is an important aspect of the pathology of the multiple sclerosis plaque. The vasculitis caused is different from and of a more modest nature than that, for example, in systemic lupus or polyarteritis nodosa but is, nevertheless, enough to cause haemorrhage, and structural and permeability changes in the vessel wall. The term proposed by Lendrum for a wide range of vasculitic disorders is plasmatic vasculosis, and the damage to the vein wall in multiple sclerosis could be regarded as causing a minor degree of such plasmatic vasculosis. Inflammatory and reparative changes in the vein wall might be exacerbated by pulsations or surges in intracranial venous pressure and may result in increased permeability of the multiple sclerosis plaque, as shown at necropsy, by immunohistochemistry and by brain scan."

So, the researchers note that this is different than vasculitis- it's really about damage to the VEIN wall. They even posit that this damage may be caused by PULSATIONS or SURGES of intracranial venous pressure (like from venous reflux, perhaps?)
Let's just move ahead 20 years, thru the vast miasma of autoimmune research-

Here is Dr. Haacke's paper from earlier this year. This is research completed BEFORE he read Dr. Zamboni's research. After attending the first CCSVI symposium in Bologna in 2009, Dr. Haacke has since became so convinced that Dr. Zamboni's research provided the missing link, he is now covering the globe, opening research centers to diagnose venous stenosis and reflux.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650739/


Iron deposition in the MS brain is real, and we need to understand how it gets there, and what we can do to stop this injurious process.
Joan