The autoimmune theory of MS; Doctors ask, "Have we got it horribly wrong?"

June 28, 2011 at 9:37am

Have we got it horribly wrong? 

 The fact that an opinion has been widely held is no evidence whatever that it is not utterly absurd; indeed in view of the silliness of the majority of mankind, a widespread belief is more likely to be foolish than sensible.

Bertrand Russell*

"The Pathogenesis of MS revisted."  

The Full paper is available here (this is one to print out and share.)

http://www.rcpe.ac.uk/journal/issue/journal_32_4/3_pathogenesis_of_MS.pdf                        

Here is a review of this critical paper in an issue of the New Scientist from 2002

New Scientist vol 176 issue 2369 - 16 November 2002, page 12 

It's not surprising there's no cure for multiple sclerosis. Researchers have been studying the wrong disease for over a century, argue a few rebels.  

THE century-old assumption that multiple sclerosis is an autoimmune disease is under attack. Treatments based on the autoimmune theory have failed so miserably, say a group of doctors, that it is time to look for other explanations.

In a lengthy review to be published next week in The Journal of the Royal College of Physicians of Edinburgh, the three neurologists dispute the received wisdom that the disease wreaks its havoc when immune cells attack and destroy myelin protein, which insulates nerves and helps them conduct signals. Instead, they back an emerging theory that MS is caused when support cells called astrocytes malfunction, perhaps as a result of genetic and environmental triggers.

 (NOTE:  One well-documented environmental cause of astrocyte malfunctioning is hypoxia, or low oxygen in the brain)

Many mainstream MS researchers contacted by New Scientist have poured scorn on the review. But a few agree it's time for a rethink.

Peter Behan and Abhijit Chaudhuri at the University of Glasgow and Bart Roep of the Leiden University Medical Centre pull no punches in their attempts to demolish the prevailing theory. They begin by attacking the animal experiments that have underpinned the autoimmune theory since the late 19th century.

Phlebology

June 26, 2011 at 3:08pm

Let's face it.  Phlebology, the diagnosis and treatment of venous disease, is just not as appealing as Neurology.  The word phlebology is hard to spell, hard to pronounce.  Reminiscent of phelgm, phlegmatic, other unsexy words that start with phl. 

The root of this word, phleb, is from the Latin fluere, meaning "to flow"

Truth is, phlebology is turning out to be a very, very important medical practice.  Veins, once thought to be uninvolved in disease, are turning out to be equally important as their brother arteries.  Maybe more so.

Veins take deoxygenated blood back to the heart.  If they are blocked, blood flow and hemodynamics are altered.  The influx of blood from the heart via the arteries is changed.   In the liver, in the kidneys, in the brain.  Any organ can be affected.  We think of varicose veins when we hear venous disease...again,  not sexy.  But veins run throughout the body, and if they are malformed, it can ruin our organs.

I got to meet and listen to a premiere phlebologist in Bologna in 2009.  Dr. Byung B. Lee was at the first symposium organized by Dr. Zamboni.  Dr. Lee talked about his introduction to venous disease as a liver transplant surgeon.    

Here are my notes from the conference.  Dr. Lee on venous malformations, in his own words.

Byung B. Lee- Georgetown University School of Medicine, Washington-Embryology of the venous system and origin of truncular venous malformations

Dr. Lee began as a transplant surgeon and admitted that his first liver transplant was a disaster. He learned the hard way that the vena cava is not just a single trunk, and a venous malformation was a most fearful thing, and a nightmare to a transplant surgeon. 

"We doctors have a tendency to specialize in our narrow fields, but I want to appeal to all of us to take a bird’s eye view. We need to look at the whole picture. We now understand the lower venous system, but it has taken us much too long to bring this knowledge all the way up to the neck and all the way to the junction of the superior vena cava.

Dr. Philip James on CCSVI

June 23, 2011 at 9:20am

Dr. Philip James has been studying MS for the past 30 years in Dundee, Scotland.  He has long been speaking out about the vascular connection to MS, and the importance of oxygenation of the central nervous system.  Here is a recent quote on his interpretation of where MS research "went wrong."

 "The recent publicity given to the work of Professor Paolo Zamboni has highlighted a growing disaffection with the concept of ‘auto’ immunity which has dominated MS research and treatment for more than half a century. Zamboni trained as a vascular surgeon specializing on problems of leg veins, which often leak as we age, allowing red blood cells into the surrounding tissues. When the red cells break down they liberate iron which causes damage to the walls of veins and the surrounding cells. Similar damage was found in the veins in the centre of the typical ‘plaques’ of multiple sclerosis as long ago as 1863.

However, the use of an animal model for MS research after WW2 led to the concept of auto immunity where, it is claimed, the immune system attacks normal tissue. Despite sixty years of research there is no evidence of this and it remains just a theory. What is certain is the damage in MS involves veins and inflammation and Professor Zamboni has focused on these proven observations. He noticed, when using ultrasound scanning of the neck in a Multiple Sclerosis patient, that blood flowed the wrong way in a vein and also that the vein appeared to be constricted.

After more investigations he has used the same procedure used to stretch arteries in the heart to relieve the vein constrictions. Several patients have found the procedure beneficial, greatly reducing their symptoms although stretching the veins will not affect existing scarring. There has been no indication of why the veins constrict, although increased ‘reactivity’ of blood vessels has been reported before in MS patients.

Professor Zamboni’s work has highlighted the importance of the blood-brain barrier. Oxygen is responsible for the genetic control of inflammation and lack of oxygen has been shown in affected areas in MS patients by brain imaging. Neurologists are likely to remain sceptical of vein stretching until a ‘controlled’ study is done in which a sham procedure is used and compared to a group of matched patients who have the real procedure undertaken."

- Philip B James MB ChB DIH PhD FFOM

Emeritus Professor of Medicine University of Dundee

Honorary Medical Adviser MS Therapy Centres.

Vascular aspects of multiple sclerosis

June 21, 2011 at 1:35pm

I have the complete review paper from Lancet Neurology.  It is a review of recent research in MS and is a compilation of the many studies we've linked on this page.  The endothelium, hypoperfusion, ischemia , CCSVI and the many terms we've learned over the past two years are all mentioned.  I do not want to violate copyright laws,  and can't copy and paste the full paper, but I'll give a brief breakdown.  You'll see text from the paper in italics, and then my comments.  

Note the word "might" is used extensively.  They review the research connecting the vascular system to MS.  While this is not earth-shattering to those of us who know CCSVI, up close and personal--it is encouraging to see this review in a neurological journal.  

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70105-3/abstract

Abstract:

Vascular aspects of multiple sclerosis

Miguel D’haeseleer, Melissa Cambron, Ludo Vanopdenbosch, Jacques De Keyser

Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial dysfunction secondary to inflammatory disease activity and increased plasma homocysteine concentrations. Second, patients with MS have global cerebral hypoperfusion, which might predispose them to the development of ischaemic stroke. The widespread decrease in perfusion in normal-appearing white matter and grey matter in MS seems not to be secondary to axonal degeneration, but might be a result of reduced axonal activity, reduced astrocyte energy metabolism, and perhaps increased blood concentrations of endothelin-1. Data suggest that a subtype of focal MS lesions might have an ischaemic origin, and there seems to be a link between reduced white matter perfusion and cognitive dysfunction in MS. Third, the pathology of MS might be the consequence of a chronic state of impaired venous drainage from the CNS, for which the term chronic cerebrospinal venous insufficiency (CCSVI) has been coined. A number of recent vascular studies do not support the CCSVI theory, but some elements of CCSVI might be explained by slower cerebral venous blood flow secondary to the reduced cerebral perfusion in patients with MS compared with healthy individuals.

#1   People with MS have ischemic stroke more often than healthy people.

Inflammation is widely accepted to play an integral part in the pathogenesis of atherosclerosis.18,19 Endothelial dysfunction is an early step towards overt atherosclerosis and the immune system seems to be highly involved in both processes.20 Endothelial dysfunction has been described in the very early stage of rheumatoid arthritis, probably as a result of inflammatory disease activity.21 Rheumatoid arthritis is an autoimmune disease22 in which increased cardiovascular morbidity and mortality has been noted.23 Alterations in endothelial function, as well as platelet activation and thrombophilia, have been reported in MS.24–26 Moreover, oxidative stress contributes to the development of endothelial dysfunction.27 Higher amounts of systemic and CNS oxidative stress have been reported in patients with MS than in healthy controls.28–30

The concentration of plasma homocysteine, which is believed to be an independent cardiovascular risk factor,31 is also raised in patients with MS.32,33 The cause of the increase in homocysteine concentration is unknown, but it occurs independently of serum concentrations of vitamin B12, vitamin B6, or folate.34 There is evidence that hyperhomocysteinaemia can cause endothelial dysfunction, even at moderately increased concentrations of homocysteine.35,36

The above evidence suggests that the increased frequency of ischaemic stroke in MS might be mediated through converging inflammatory pathways, oxidative stress, and raised homocysteine concentrations leading to endothelial dysfunction.

What this section is saying is that oxidative stress, endothelial dysfunction, endothelin-1 levels and homocysteine levels are higher in pwMS, and may contribute to higher stroke levels.  (We've talked about this on here for awhile, it's why I created the endothelial health program for Jeff--I noted this connection in his serum numbers, and tried to help him thru diet, supplements, exercise and lifestyle.)

The researchers are positing that this is all due to inflammation and the immune system in MS. They believe it all begins there.   But they have no proof of this.  It's just their theory--their way of looking at the evidence thru their prism of MS as immune.  But what we've discussed on here is that all of these factors are also found in diffuse cerebral hypoxia, or low levels of O2 in the brain.   We don't need to involve the immune system in this theory if we look at it thru the prism of reduced oxygenation in the brain due to slowed blood flow.

Research from the 1970s on spinal venous hypertension and myelopathies

June 3, 2011 at 10:09pm

Thanks to  Mylène Therrien for the following info on research from the 1970s on myelopathy of the spine due to venous hypertension and malformations in the veins surrounding the spine.  The 80 patients tested and treated in these studies had paraplegia and injury of the spine due to venous malformations.  

They were treated for venous stenosis in the 1970s.  Dr. Zamboni has referenced this research in his publications, but I hadn't seen these abstracts or understood the history.

Here are the abstracts and links I found from the info given in Mylene's posting:

Acta Radiol Suppl. 1976;347:395-401.

[Intraspinal venous hypertension due to multiple anomalies in the caval system. A major cause of myelopathies].

[Article in French]

Aboulker J, Aubin ML, Leriche H, Guiraudon G, Ancri D, Metzger J.

Abstract

Increased venous intraspinal pressure is described as a venous system disease, resulting in numerous unexplained paraplegias and tetraplegias. The chronic venous stasis in the intraspinal plexuses, into which the circulation of the spinal cord is drained, is due to the association of multiple abnormalities (stenoses, compressions, thromboses) on the major pathways of the caval and azygos system. The abnormalities, most of which are not known, are demonstrated by a special procedure, the cavo-spinal phlebography, and some of them are subjected to surgery.

PMID:

 207125 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/207125

 Acta Radiol Suppl. 1976;347:415-7.

[Cavo-spinal phlebography in myelopathies. Stenoses of internal jugular and azygos veins, venous compressions and thromboses].

[Article in French]

Leriche H, Aubin ML, Aboulker J.

Abstract

Increased intraspinal venous pressure, resulting according to ABOULKER in numerous spastic paraplegias and quadriplegias is due to multiple venous abnormalities demonstrated by cavo-spinal phlebography. The most frequent are stenoses of the internal jugular veins, the left renal, the left iliac veins, the azygos veins and compressions of the innominate venous trunks. These abnormalities cause a permanent stasis in the intraspinal plexuses through excessive supply or insufficient drainage. Out of 80 patients, 60 per cent had at least 2 abnormalities, 38 per cent at least 3 abnormalities.

PMID:

 207127 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/207127