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.

http://www.frontiersin.org/Multiple_Sclerosis_and_Neuroimmunology/10.3389/fneur.2013.00098/full

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.

http://www.ncbi.nlm.nih.gov/pubmed/23436147

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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http://www.ncbi.nlm.nih.gov/pubmed/23529352

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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?

Rindfleisch, with his microscope in 1863, was wondering why there was a change in the blood vessels in the MS brain.

Here is Dr. C.W. Adams in 1987, looking at autopsied brain tissue in the hopes of understanding the mechanism of lesion formation in MS.

The periventricular region was studied in the brains of 129 cases of multiple sclerosis, with the purpose of establishing the mechanism and order of events in the development of the periventricular plaque, and deciding whether there is any relationship between granular ependymitis and such plaques. Periventricular plaques were found in 82.2% of cases. Observation and computerized morphology showed that the early stage of the periventricular plaque is the formation of a lesion around a subependymal vein and that adjacent lesions later coalesce. 

(Subependymal means below the ependymal zone, in the lateral ventricles of the brain.)

http://www.ncbi.nlm.nih.gov/pubmed/3614542

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One cardiovascular doctor has asked why, and utilized Dr. Zamboni's research to explain the central vein found in MS lesions.

Here's Dr. Michael Dake's illuminating powerpoint presentation, explaining how CCSVI would create vessel wall breakdown, due to disturbed venous blood flow, microbleeds and perivenous fibrin cuffs, activating the inflammatory process. This would lead to adhesion molecule and cytokine expression, oxidative stress and reduced NOS activity--endothelial dysfunction and a breech in the blood brain barrier.  We know how this happens in chronic venous disease in other parts of the body.  Laminar, or smooth blood flow, maintains the endothelium.  Disturbed blood flow leads to a break down.

This would explain the central vein inside the lesion.

http://www.ucsfcme.com/2011/slides/MSU11003/14DakeCurrentStatusOfChronicCerebrospinalVenousInsufficiencyInMS.pdf

Perhaps neurologists do not want to ask why there is a central vein; because they know the answer points to a vascular connection to multiple sclerosis.  Their studies are looking at this central vein in MS lesions as purely a means to aid MS diagnosis, so they might begin disease modifying medications in their patients.  

But the looming question remains....why the central vein?

The answer will provide healing for those with MS.

Joan

PS--for those who wish to learn more about this history, Dr. Schelling has written the most comprehensive and thorough evaluation of the history of MS lesion studies.

http://www.ms-info.net/ms_040504.pdf