Retinal thinning and MS. Why?

January 5, 2013 at 3:02pm

The OCT (optical coherence tomography) test for retinal thinning in MS is in the news again.  You may have seen the press releases on "the eyes have it" and MS.   OCT has been around for many years.  It is a test which uses light instead of sound waves to visualize an area of the body.  Because the eyeball can let light in, OCT scans are a great way to monitor what's going on inside and behind the eyeball.  The retina is made up of light sensitive neurons that form layers at the back of the eye.

The retina is a very important part of monitoring the MS process.  But something which is NEVER mentioned in this discussion is that, unlike the optic nerve,  the retina does not have myelin.  Myelination is rarely extended into the retina.  

If MS is an inflammatory disease which targets myelin, why is the retina being affected during an MS relapse?

Something else that is never mentioned in these MS OCT stories is that retinal thinning is seen in other diseases of neurodegeneration, including Parkinson's and Alzheimer's Disease.  Retinal thinning is not unique to MS.  The Michael J. Fox Foundation is looking at retinal thinning in Parkinson's, and there have been other "eyes may be a window" stories on OCT and Parkinson's

http://www.familypracticenews.com/news/print-friendly/retinal-thinning-may-be-a-window-on-parkinson-s/71227dfc82.html

+++++++++++++++++++++++++++++++++++++++

Here's the new study from Johns Hopkins MS Center:

Peter Calabresi, MD. and team recruited 164 participants from Johns Hopkins MS Center. They all underwent eye scans every six months to check for thinning of a part of their retinas. Repeat scans were carried out for an average of 21 months. Fifty-nine of the volunteers had no MS disease activity.

Here are some of the findings.

• MS patients with gadolinium-enhancing lesions (inflammatory lesions) had 54% faster thinning
• MS patients with new T2 lesions had 36% faster thinning that those with MS who did not have these features of MRI activity
• Participants whose level of disability got worse during the study had 37% more thinning, compared to patients whose level of disability did not change
• Participants who had the disease less than five years showed 43 percent faster thinning than those who had the disease more than five years

The editorial authors also noted that the study results provide indirect evidence that active inflammation — even if subclinical or occurring in a different functional system — is connected with greater rates of retinal neurodegeneration.

The more inflammation and swelling the researchers found in the retinas of the MS patients, the more inflammation showed up in their brain MRIs.

http://www.medicalnewstoday.com/articles/254469.php

So, optical coherence tomography appears to be a good test to monitor MS relapses, maybe better/easier/less expensive than MRI.

But some questions need to be asked-----

The retina does not have myelin.  Why is the retina thinning during an MS relapse?  What is happening?  Why is there retinal atrophy during an MS relapse?

Dr. Dake has written about this conundrum.  Why should the retina, which does not have myelin, be thinning during active MS relapses?  

CCSVI doppler diagnostics presented at vascular conference

January 4, 2013 at 2:09pm

The 34th Congress of the SIAPAV (Italian Society for Angiology and Vascular Medicine) http://www.siapav.it had an extensive review session of CCSVI diagnostics.  

There were three lectures presented by specialists in doppler ultrasound for CCSVI.  All of these specialists agree that CCSVI exists, it creates a delay of cerebral blood flow, hypoperfusion, and cerebral lesions, and there are very specific tests to measure this process.  

The specialists also stated that operators who are finding between 0-50% of CCSVI in people with MS are NOT utilizing correct doppler technique.  They stated that the SAME problem happened 35 years ago, when technicians began analysing the carotid arteries.  There is a very specific protocol that must be followed, or the results are inaccurate.  A lack of knowledge of the venous return system from the brain is part of this problem.

The fact that neurologists continue to ignore this clarion call from vascular specialists, and proceed with badly designed studies, is disturbing. There have been millions of dollars of wasted money and years of wasted time, pursuing studies that are of no value.

Below is the very specific review from this conference.

It is translated by google translate from Italian, and because if this, is not perfect.  But BNAC offers training for American doppler technicians, based on this protocol.  BNAC is the only center with a published US study that has worked with the experts in this doppler protocol.  None of the NMSS funded researcher utilized the complete and correct protocol.

http://www.siapav.it/angionews/updating-sulla-insufficienza-venosa-cerebro-spinale-cronica-ccsvi/

_______________________________________________________________

Refresher Course of the 34th Congress SIAPAV dedicated to CCSVI has provided an extensive updating on the diagnosis of chronic cerebrospinal venous insufficiency. The report that follows is intended as a reference for those interested in the clinical picture characterized by hemodynamic abnormalities and / or abnormalities of the refluxing veins from the Central Nervous System.

Three lectures were devoted to the physiology and pathophysiology of cerebral venous return (M. Mancini, Naples), which is essential for understanding the clinical phenomena, paintings echo-color-Doppler normal and pathological (G. Cacciaguerra, Catania), prerequisite for obtaining a correct diagnosis, limiting as much as possible the false negative and false positive and, finally, to the diagnostic protocol with the main criteria and / or accessories must be based on which the diagnosis (G. Arpaia, Vimercate).

Mancini has outlined the salient features of venous hemodynamics in the brain, illustrating the intracranial circulation time measured with echo contrast (landmarks carotid artery, jugular vein and thyroid) that are significantly delayed in CCSVI. From the point of view  the speaker presented the map of cerebral perfusion and the prevalence of MS plaques in the hypoperfused areas in the form of clinical progressive MS,  while the prevalence in areas hypoperfused would be greater in relapsing-remitting clinical form. This could explain the greater effectiveness of the correction hemodynamics in relapsing-remitting MS, compared to progressive MS.

2013--The 150th anniversary of MS as a vascular disease

December 31, 2012 at 9:33am

What's old is new.

2013 is the 150th anniversary of Eduard Rindfleisch's publication describing MS as a vascular disease.  

Rindfleisch, a German pathologist, studied post-mortem brain samples from people with MS.  He noted that inside all of the lesions he could clearly see an enlarged blood vessel.  He believed the inflammatory response seen in the MS brain was created by hypereremia, or engorgement, due to blocked blood flow.

It's now 2013.  150 years is a long time.  Too long.

Here is what Rindfleisch noticed in the MS brain in 1863.

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.

http://www.ms-gateway.ie/understanding-ms/research/eduard-rindfleisch-1836-1908-107.htm

Unbelievably, in 2012 researchers begin to look at the cerebral veins of people with MS while they are alive, using MRI venograms.  And they notice what Rindfleisch saw---engorged penetrating veins in active, or newly-formed lesions.  

They conclude that the cerebral veins in people with MS are not normal----149 years after Rindfleisch said this.

http://www.ncbi.nlm.nih.gov/pubmed/22968782

++++++++++++++++++++++++++++++++++++++++++

Here is a timeline which outlines the history of the study of MS as a vascular disease.

http://www.ccsvi.org/index.php/the-basics/history-and-timeline

When you read this timeline, notice how the researchers asserting the vascular connection used actual autopsied brain tissue from people with MS.  These are not manufactured mouse models of MS. Notice how many times the words perivenous, veins, blood and fibrinogen are mentioned, thoughout the decades of research.  

An inflammatory process is activated whenever there is a break in the blood brain barrier in humans.  The idea that MS is created by a rogue immune system-- crossing the blood brain barrier and attacking myelin-- is STILL only a theory.  The break in the blood brain barrier precedes demyelination in MS.  Why does this happen?

Dr. Zamboni showed how extracranial venous malformations could lead to cerebral hypoperfusion. A process that would lead to a hypoperfusion/reperfusion injury to the brain. 

http://ccsviinms.blogspot.com/2013/09/multiple-sclerosis-hypoperfusionreperfu.html 

A process that would explain what Rindfleisch noted 150 years ago and researchers see today.  And despite what some neurologists are claiming, Dr. Zamboni's theory has not been disproven by their research.  Because they are not looking at collateral circulation, hypoperfusion and mean transit time.

When MS specialists claim that "we've investigated the vascular connection to MS, and there's nothing there" they are usually referring to Dr. Tracy Putnam's research and trials of newly discovered blood thinners in people with MS.  This happened in the 1940s, when Dr. Putnam was modeling MS lesions by blocking the venous sinus of dogs.  Dr. Putnam was just beginning to understand the implications of blocked venous flow on the brain, when Thomas Rivers created the EAE model of MS. People wanted a cure for MS, and looked to the creators of the polio vaccine for the answers.  Vascular research was abandoned.  For those interested in more of this history, here is the story of TJ Putnam.

http://ccsviinms.blogspot.com/2012/06/dr.html

The following paper was published by researchers at the Royal Free Hospital of Medicine in London. It is available online, in toto, for free.  The reason it is important is that researchers examined actual autopsied brains from people with acute MS, and studied the lesions on an immunohistochemical level.  This paper was published in 1994.

Immunohistochemical study of vascular injury in acute multiple sclerosis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501826/?page=1

AIMS--To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.

METHODS--Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.  

RESULTS--Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.

CONCLUSION--It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

++++++++++++++++++++++++++++++++++

Why is there so much reticence by MS researchers to truly collaborate wih vascular doctors, to understand Dr. Zamboni's discovery of truncular venous malformations in the extracranial veins of pwMS?

Cleveland Clinic/Case Western studied post mortem jugular veins from pwMS and found the presence of a novel venous valve that had not been described in anatomy textbooks.  Just as Dr. Zamboni said, pwMS have truncular venous malformations.  Yet there has been no more investigation into this phenomena.  Why not?  

It is now four years since the first group of patients and caregivers began discussing Dr. Zamboni's research on This is MS.  And so far, only BNAC has collaborated with Dr. Zamboni to study his doppler protocol.  Millions of MS Society dollars are spent on a variety of diagnostics--without looking at the deep cerebral veins, with utilization of valsalva manuever, without consulting phlebologists on the nature of truncular venous malformations.  All of the wasted time and money, in an attempt to quell vascular research, and assert the dominance of immunomodulating drugs.  

Let's celebrate 2013 as the 150th anniversary of Rindfleisch's observation.

We call for collaboration.   It's time.

Happy New Year!!

Joan