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Pathological progression of MS documented for the first time

Posted: Wed Feb 11, 2015 4:37 am
by MSUK
In a paper published in the journal Lancet Neurology, an international team of researchers from Edinburgh, Cleveland and Vienna, under the leadership of Hans Lassmann, Head of the Department of Neuroimmunology at the MedUni Vienna, has for the first time documented the pathological progress of multiple sclerosis from its early to late stage and also shown that inflammatory and neurodegenerative processes have a role to play..... Read More - http://www.ms-uk.org/msetiology

Re: Pathological progression of MS documented for the first

Posted: Wed Feb 11, 2015 8:04 am
by vesta
MS-UK just posted (Feb 11, 2015) the following:

“In a paper published in the journal Lancet Neurology, an international team of researchers from Edinburgh, Cleveland and Vienna, under the leadership of Hans Lassmann, Head of the Department of Neuroimmunology at the MedUni Vienna, has for the first time documented the pathological progress of multiple sclerosis from its early to late stage and also shown that inflammatory and neurodegenerative processes have a role to play.

Until now, there have been two approaches to categorising the condition: the first approach regards MS as a disease of the nervous system that is inflammatory throughout, with the inflammation also being responsible for the subsequent neurodegenerative damage. The second approach postulates that the condition ultimately progresses from an inflammatory condition into a neurodegenerative one. In their current paper however, the team of researchers has demonstrated that MS is comprised of both factors - and that the inflammatory process acts as a "driving force" from the onset right to the end, and that neurodegenerative processes also occur in the so-called progressive, late phase that damage the brain.”


AND GUESS WHAT? I recently explained how and why. The early inflammatory phase is caused by the CCSVI “blood reflux” (that they haven’t got around to recognizing.) As the nervous system degenerates, the musculature goes into spasms, weakens and atrophies causing the body structure to collapse putting pressure on the spine. And now lesions on the spine lead the neurodegenerative processes of the progressive, late stage. Each inflammation “attack” stresses veins triggering the blood reflux which damages the nervous system which then damages the musculature, leading to another “attack”, a process of amplification I call the MS Positive Feedback Loop.


"MS POSITIVE FEEDBACK LOOP

The French Neurologist Jean-Martin Charcot, practicing at the Parisian la Pitié-Salpetrière hospital, first described Multiple Sclerosis (Sclérose en Plaques) in 1868. Among other things, he defined MS as a “rigidity disorder”. He thus set the tone in the Neurology profession of an unfortunate prejudice towards MS patients by claiming their “rigidity” symptoms were psychological in origin - signs of neurotic (usually female) hysteria. I now believe it is just this rigidity which is at the root of MS progression, but its origin is physiological, NOT psychological. Damaged nerves send “misfired” signals to the muscles which cramp and/or go into spasms. As the nervous system degenerates, the body becomes increasingly rigid, compressed as it is by muscles in spasm. And it is just this rigidity which triggers the process damaging to the central nervous system.

Let’s backtrack a bit.

As early as 1863 the Swiss pathologist George Edward Rindfleisch observed that MS lesions clustered around the brain’s draining veins. Disparate testimonies of this phenomena continued to surface thereafter, but it was only in 2008 that the Italian Professor Paolo Zamboni published a paper on the Internet offering an explanation. He described a condition he has named CCSVI in which venous blood “refluxes” into the Central Nervous System (CNS) owing to stenosed or damaged veins. These blood back jets injure the tissue which leads to inflammation of the myelin sheath and an immune system response. These early “attacks” describe relapse/remission MS (RRMS). Dr. Zamboni has thus discovered the origin of the “wound” which triggers the immune response.

Progressive MS presents the exception. My brief synopsis derived from MS UK’s site reads

“Primary Progressive MS (PPMS) concerns about 10 to 15% of MS cases. In contrast to RRMS (Relapse Remission) cases, the disease progresses continually without respite after striking an older population (age 40’ and 50’s). Unlike RRMS, there is little to no inflammation, there are fewer brain lesions, the lesions which do exist present fewer inflammatory cells, and more are found on the spinal cord than in the brain which leads to mobility problems. While PPMS cases exhibit less inflammation, there appears to be greater damage to the axons.”

PPMS patients are not included in MS drug research and treatment because both target the myelin damaging inflammation of RRMS. Now, if an entire subset of patients is excluded from research because they do not conform to the auto-immune theory of MS, maybe the theory itself is suspect.

Eventually RRMS may evolve into Secondary Progressive MS, meaning it resembles the primary form. I repeat. “there is little to no inflammation, there are fewer brain lesions, the lesions which do exist present fewer inflammatory cells, and more are found on the spinal cord than in the brain which leads to mobility problems. While PPMS cases exhibit less inflammation, there appears to be greater damage to the axons.”

What does this imply to me? It implies that the driving factor in progressive MS is no longer centered in obstructed venous blood flow but in a damaged spine and obstructed cerebro-spinal fluid circulation.

And here we can understand the MS positive feedback loop.

MS venous blood circulation is deficient for any number of reasons. A stress attack can trigger the blood “reflux” into the central nervous system (brain/spine) which inevitably damages the nerves. When the nerves are damaged, muscles cramp up, perhaps go into spasms. As the body freezes up, fluid circulation (blood/cerebrospinal fluid) slows setting the stage for the slightest stress event to trigger another “attack”. Thus each “attack” triggers muscle cramps and body rigidity which in turn sets the stage for more attacks. (I include ANY illness and/or toxicity as stress events. Also, poor blood circulation in the brain persists apart from occasional relapses so constant effort must be made to release body tension and blood/cerebrospinal fluid circulation.)

Eventually the body rigidity/muscle spasms deform and damage the spine. As muscles weaken and atrophy the entire body structure is compromised leading to obstructed cerebrospinal circulation and direct pressure on the spinal cord. At this point it is no longer the blood reflux inflammation which “wound” the nerves so much as lesions and cerebrospinal fluid obstructions which impact the spine. We now have SPMS and increasing issues with mobility. Ideally MSers should turn to functional healers who can manipulate the head/cervicals/spine to relieve pressure on the spinal cord and free the spinal fluid – Osteopaths and Chiropractors. Physical Therapists and Massage Therapists can provide fluidity and movement so vital to overcoming the natural tendency to rigidity.

Obviously this implies that at the onset of RRMS one should make every effort to enhance blood/cerebrospinal fluid circulation through the brain/spinal cord in order to stop the blood “reflux” and the attendant muscle spasms/rigidity. I can see that had I known about CCSVI and followed the advice on this site 25 years ago, I wouldn’t need a cane today and needn’t worry now about the increasing rigidity in my spine.

I can also understand why “liberation therapy” (angioplasty) works best in the early RRMS phase when stenosed veins are the primary problem and treatment “liberates” the blood flow. One has thus prevented the wound. Once Progression sets in, there is little to no inflammation which implies that the veins are no longer the primary issue. In that case attention should focus on treating lesions on the spine. And since drug therapy focuses on the inflammation, none is proposed for Progressive MS."

Positive MS Feedback Loop previously published on my site MS Cure Enigmas.net

<http://www.mscureenigmas.net/>

Re: Pathological progression of MS documented for the first

Posted: Wed Feb 11, 2015 4:04 pm
by 1eye
Sorry, wrong forum, wrong paper. This post refers to the right one. This paper is worth reading, and the PDF ends up to be 11 pages.

This paper is free.

Re: Pathological progression of MS documented for the first

Posted: Thu Feb 12, 2015 7:35 am
by vesta
1eye wrote:Sorry, wrong forum, wrong paper. This post refers to the right one. This paper is worth reading, and the PDF ends up to be 11 pages.

This paper is free.
Please post the link. Thanks

Re: Pathological progression of MS documented for the first

Posted: Thu Feb 12, 2015 8:24 am
by 1eye
http://www.thelancet.com/pdfs/journals/ ... ogRequest=

They will let you access it if you do their free registration. All they ask is your email.

Re: Pathological progression of MS documented for the first

Posted: Thu Feb 12, 2015 8:33 am
by 1eye
This paper and others non-MS related discuss the use of non-haem iron in oligodedrocytes and myelin and free iron accumulation due to age in the brain. I don't see a discussion of iron which comes from abundant red blood cells which pass the blood-brain barrier. This must occur, and microbleeds have been seen on 7-Tesla MRI. Would these not be a significant contributor to mitochondrial damage, more even than clonal expansion of mutated mitochondria? After some interaction involving free iron from blood and mitochondria, might not iron-damaged mitochondria still clonally expand as well?

The paper in J Neurochem. 1997 Aug;69(2):443-54., Transport of iron in the blood-brain-cerebrospinal fluid system, by Bradbury MW. contains
"Transferrin in CSF is fully saturated, and the excess iron may be loosely bound as Fe(II). Brain iron is regulated in iron depletion, suggesting a role for the blood-brain barrier (BBB). Iron crosses the luminal membrane of the capillary endothelium by receptor-mediated endocytosis of ferric transferrin. This results in an initial linear uptake of radioactive iron into brain at an average rate relative to serum of about 3.3 x 10(-3) ml x g of brain(-1) x h(-1) in the adult rat. This corresponds to about 80 nmol x kg(-1) x h(-1)."
It also says
"From interstitial fluid, ferric transferrin is taken up by neurones and glial cells by the usual receptor-mediated endocytosis. Calculations of the amount of iron leaving the system with the bulk flow of CSF indicate that most iron entering brain across the capillary endothelium finally leaves the system with the bulk outflow of CSF through arachnoid villi and other channels. A system in which influx of iron into brain is by regulated receptor-mediated transport and in which efflux is by bulk flow is ideal for homeostasis of brain iron."
For free iron to accumulate, this iron homeostasis must be broken, I think by red blood cells passing the damaged BBB and then being digested by phagocytes, freeing the iron ions.

Are we not seeing blood carrying gadolinium in lesions, and will it not carry iron bound to red blood cells as well, if the barrier is damaged enough? What happens to these cells? Don't they play a role in free iron accumulation? The red blood cells do not locomote themselves, and would this not result in the clotting cascade?

If anyone is confused by the numbers, the English translation of
3.3 x 10(-3) ml x g of brain(-1) x h(-1) in the adult rat. This corresponds to about 80 nmol x kg(-1) x h(-1)
might be 0.0033 millilitres per gram of brain per hour, corresponding to 0.00000008 nanomoles per kilogram per hour. A very small amount.

These moles are not very small mammals in the family Talpidae, nor are they very small espionage agents, nor are they very small persons named Adrian. Molarity is concentration, not humourousness of books by Sue Townsend.

Re: Pathological progression of MS documented for the first

Posted: Fri Feb 13, 2015 2:02 am
by NHE
1eye wrote:If anyone is confused by the numbers, the English translation of
3.3 x 10(-3) ml x g of brain(-1) x h(-1) in the adult rat. This corresponds to about 80 nmol x kg(-1) x h(-1)
might be 0.0033 millilitres per gram of brain per hour, corresponding to 0.00000008 nanomoles per kilogram per hour. A very small amount.
80 nmol is 10-8 moles or 0.00000008 moles, but not "0.00000008 nanomoles."

Re: Pathological progression of MS documented for the first

Posted: Fri Feb 13, 2015 1:39 pm
by 1eye
Good catch. Coincidentally I was re-reading this and spotted that and was just about to edit the error out when I scrolled down and noticed you had pointed it out, so I'll just leave it in. It's still nano-scopically small, although it's really a ratio, so scaling based on a measurement is fair. It's the rate of iron uptake they are talking about.

Re: the non-Adrian type of mole:

Incidentally Wikipedia sez
In honour of the unit, some chemists celebrate October 23 (a reference to the 1023 part of the Avogadro constant) as "Mole Day". Some also do the same for February 6 and June 2.
and:
the Avogadro constant, which has a value of 6.02214129(27)×1023 elementary entities of the substance
Just realized June 2 is also my nephew's birthday. He has a doctorate in Chemistry. non-sequitur: And my wedding anniversary is on Friday 13, too.

Re: Pathological progression of MS documented for the first

Posted: Mon Feb 16, 2015 2:50 am
by Leonard
1eye wrote:http://www.thelancet.com/pdfs/journals/ ... ogRequest=

They will let you access it if you do their free registration. All they ask is your email.
these people should look at this page:

http://www.thisisms.com/forum/general-d ... 8-660.html

it brings together many of the pieces of the puzzle, some of which they mention in their article. :smile: