The autoimmune theory --doctors ask, "Have we got it horribly wrong?"

Another interesting research paper dug up by Joan Beal:

Have we got it horribly wrong? 
The following is the quote which begins a critical paper from 2002.

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 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 breakdown of the 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 from Joan:  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.
Back then, researchers discovered that if they injected nerve or brain tissue into an animal, its immune system would attack the nervous system. They called this experimental allergic encephalomyelitis, and before long adopted EAE as the "animal model" of multiple sclerosis.

This, say the heretics, was a big mistake. In their view, EAE is completely different from MS. "There are huge differences, and they've been skipped over," Behan told New Scientist.

For instance, EAE either kills animals or leaves them with permanent disabilities. "It doesn't come and go like MS," he says. Animals with EAE also suffer severe nerve inflammation, whereas in MS inflammation is usually mild, if present at all.

Despite this, virtually all treatments for MS have been tested on EAE. Little wonder then, says Behan, that the treatments do not work for people. "Not a single human has been cured using these approaches," he says.

However, steroids and other immunosuppressants do work for a brain disease called acute disseminated encephalomyelitis, a rare result of infections. Behan thinks ADEM, not MS, is the human equivalent of EAE.
He also argues that the fact that traces of white blood cells are found at some sites of nerve and brain damage in MS patients does not prove they caused the damage. The same traces are found after strokes and neurodegenerative diseases.

 Israel Steiner, a neurologist at the Hadassah University Hospital in Jerusalem, agrees that EAE has blocked "effective progress" for decades. He thinks alternative theories should be put to the test. "I definitely believe it's high time to reconsider the entire field. It has not led us into understanding the disease or to a better therapy for patients," he says. "Many people in the community who do not have a vested interest in the autoimmune hypothesis share my views, but I'm not sure they would like to step out."

Almost 10 years since this review was written, and EAE is still used to create pharmaceuticals for MS.  When will this insanity end?

Information comes to light

I haven't posted in a while, as it seems hard to keep saying, yep I'm still feeling good. But that's the way it is.

Some days it is hard to remember what it was like to live with MS before my operation.

I still keep up with all the stuff that appears on the web, though, and thought it would be good to share information that appeared on Joan Beale's excellent Facebook page.

Research from the 1970s on spinal venous hypertension and myelopathies

by CCSVI in Multiple Sclerosis on Saturday, 04 June 2011 at 06:09

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 her 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

Acta Radiol Suppl. 1976;347:403-13.
[Cavo-spinal phlebography in myelopathies of venous origin. Application of the method in 115 cases].
[Article in French]
Aubin ML, Leriche H, Aboulker J, Ernest C, Ecoiffier J, Metzger J.
Abstract
The intraspinal venous stasis, described by ABOULKER as the cause of numerous myelopathies, is due to the addition of multiple venous abnormalities, demonstrated by cavospinal phlebography. The venae cavae and their major affluents and the prespinal system (lumbar and ascending lumbar veins, azygos, hemi-azygos, right superior intercostal and vertebral veins) are explored by catheterization. Cavo-spinal phlebography reveals multiple obstacles and the resulting stasis in the intraspinal plexus.
http://www.ncbi.nlm.nih.gov/pubmed/207126

------------------------------------------------------

The following quote is Mylene writing about her conversation with Dr. Garel, the IR who performed these procedures, and her translations from the research, originally written in French.

I spent 45 minutes on the phone with Dr.Garel from St-Justine Hosptial who was the IR who did the catheterization under Dr.Aboulker's study in the 70's. Interestingly enough. the results and the outcome of that experiemental treatment were exactly what Zamboni is finding. Here is a part of his work, translated from French to English from me. Note that : First : You should know that I do not know when to use the word " stenoses " vs " stenosis" 

The basis for surgical indication : To whom was surgery proposed ? 

Any patients who had a major cause of spinal cord problems of unknown origin resulting in progressive disabilities for whom no other therapeutic alternatives were available to them and whose cavo-spinal phlebography examination revealed multiple abnormalities of the major pathways of the caval and azygous system.

Note that it was a new and an experimental procedure proposed and well-explained to the patients at the time ( in the 1970's). Only those whose paraplegia were progressing and regularly worsening were offered the surgery.

Aboulker and al., were investigating the multiple abnormalities ( stenosis-compression-thrombosis) which reduce or block the circulation in the large veins of the caval system, resulting in spinal venous stasis as a result of excessive supply and inadequate drainage. That would result in impairment in function of the cord, just like any organ when return circulation is chronically impaired. 

HERE ARE THE RESULTS of the cavo-spinal phlebography done on 80 patients who experienced unexplained spastic paraplegias and quadraplegias. 

Out of the 80 patients, only 21 patients had the left renal vein investigated. 

INTERESTINGLY ENOUGH, ABNORMALITIES WERE FOUND AT ALL LEVELS OF THE VENOUS SYSTEM. The left primitive iliac vein was found to be among the most frequent abnormalities observed. The other ones were stenoses of the IJVs, the left renal vein, the azygous veins and the compressions of the innominate venous trunks.

Out of the 80 patients, 60% had at least 2 abnormalities and 38% had at least 3.

FREQUENCY OF THE ABNORMALITIES:

LUMBAR LEVEL: 

ILIAC VEIN 
- left primitive iliac vein showed recanalized old thrombus in 5% of the patients.
 - 48% of the patients showed a stenosis of the left primitive iliac vein. 
(Note that an upstream stasis were always found with those obstructions.) 
 - 34% of the patients had an abnormality of the intraspinal dorsal and lumbar plexuses and an abnormality of the azygous system as well.. 

 RENAL VEIN: - Note that only 21 patients out of 80 patients had their left renal vein investigated. 
 -47,6% of those 21 patients had a compression of their left renal vein. 
-30% of the 21 patients had an abnormality in the intraspinal dorsal and lumbar plexuses and in the azygous system

DORSAL AND AZYGOUS LEVEL:

-12% of the patients had either a stenosis or a compression of the arch of the azygous ( " crosse de l'azygos ") and hemiazygous. Those abnormalities resulted in all those cases in a distal stasis in the intraspinal plexus. 

AT THE CERVICAL LEVEL:

-A venous abnormality at the cervical level was found in 77% of the 80 patients. 
 - 65% of the 80 patients had a stenosis of the IJV ( again here , don't know when to use stenosis or stenose) 
( 16% = bilateral stenosis ; 49% = unilateral stenosis where 33% were mainly found on the left side whereas 16% were found on the right side). 
 -12% were found to have a bone or arterial compression of the innominate venous trunks. 

ALL PATIENTS WHO HAD AN ABNORMALITY AT THE CERVICAL LEVEL ( IJV stenosis or compression of the innominate venous trunks) HAD AN ABNORMAL SUPPLY OF THE CERVICAL INTRASPINAL PLEXUS WITH GENERALLY IMPORTANT DILATATION OF THE VERTEBRAL VEINS.

SUMMARY:

Out of the 80 patients :

-15% had a normal venous cavo-spinal phlebography.
-25% had one abnormality
-21% had 2 abnormalities
-26% had 3 abnormalities
-12% had 4 and more abnormalities.

Note that those percentages are lower (less important ) than reality because the roots (" les racines") of the azygous were seen only 41 times out of 80 and because the left renal vein was investigated in only 21 patients out of 80 patients. So when the roots of the azygous and the renal vein were investigated, abnormalities were found in 50% of the cases ( one time out of two).

TO CONCLUDE: 

PERMANENT STASIS IN THE INTRASPINAL PLEXUSES THROUGH EXCESSIVE SUPPLY OR INSUFFICIENT DRAINAGE CAUSED BY ABNORMALITIES WERE FOUND AS FOLLOW: 

- Out of 80 patients, 60% had at least 2 abnormalities whereas 38% had at least 3 abnormalities.
--------------------------------------------------------------

thanks, Mylène .  I'm floored.  This is not new...
The researcher, Jose Aboulker (1920-2009) was a pioneer of neurosurgery and neurology in France and a renowned anti-Nazi partisan.
http://resources.metapress.com/pdf-preview.axd?code=h23w2x34q73kt946&size=largest

Dr. Laurent Garel is a research and interventional radiologist in Montreal (he must have been a student in the 1970s!)
http://www.chu-sainte-justine.org/research/chercheurs.aspx?ID_NOUVEAU=2394215&id_page=2432&id_menu=2429&all=y

wow.
Joan