I hesitate to do this, there are many links I did not include (like all the ones related to perfusion of the brain and mean transit times and all the venous ulcer material) that are of interest for the person interested in this idea, but I wanted to mine the thread for the links to the really essential materials. If we ever get a forum of our own this will be a sticky at the top.........as it is I will update it from time to time and repost it I guess
Please don't let this be an excuse to not read the thread, it is full of really great discussion and other materials!
The Zamboni et al Materials
Zamboni presentation 2006 The Big idea: iron dependant inflammation in venous disease an proposed parallels in MS
There are a variety of materials in that link related to venous cause of MS, the Zamboni paper is the second one down and it outlines the hypothesis of how MS might be caused by venous insufficiency. This paper starts the journey for the Ferrara team forming the basis for the idea that MS might be related to venous issues and setting the stage for later research to see if that is correct or not. The other materials on that "lab project" paper are worth reading as well.
Zamboni et al 2007 Intracranial Venous haemodynamics in MS
This paper is the first doppler studies of 89 MS patients and 60 controls.
All MSers had at least 2 venous abnormalities; 100% concordance.
Menegatti, Zamboni, '08 Doppler Haemodynamics of cerebral venous return
This paper describes how to do the tests and suggests parameters for normal findings.
Zamboni et al 2009 The value of cerebral doppler haemodynamics in the assessment of ms
Though this paper was published in January of '09 the research was actually done before that of the Dec '08 paper: it was the second large doppler study.
It used 109 MS patients and 177 controls including people with OND and other vascular diseases, thus giving the opportunity for the controls to have issues that might make them prone to have problems with the venous system. Again, all MS patients had 2 abnormal findings and controls had one or less. Because the controls were people who we might suspect could have issues with venous drainage and it remained true that MSers were the only ones that had 2 or more abnormalities, and because this was a large study, it becomes more likely this is a pathognomic pattern for MS; unique to MSers.
In fact the total number of tests performed on normal people, 5 tests times 177 people=871 normal and only 24 abnormal findings. The test totals on the MSers were 288 normal and 257 abnormal tests. Huge differences in venous function overall wsith the MS population failing test after test while it was rare for others to have an issue
Zamboni et al Dec 2008 "Chronic cerebrospinal venous insifficiency in patients with multiple sclerosis"
By the time they did this research, the team was finally permitted to do venograms in any patient with MS who again showed the 2 abnormals.
All 65 patents did, so all had venograms after the dopplers to assess the actual stenoses. This paper includes picture of the stenoses, twisted veins, etc that were seen on venogram in addition to showing that 100% concordance with the 2 abnormalities on doppler.
Dopplers are sort of like taking a blood pressure; they are an indirect but noninvasive and safe way to get a hint of blood flow. Venograms are like an x-ray; you insert dye into a vein and watch it with an x ray type mahine as it goes through the vein. You directly visualize the vein by this method. The fact that this research has venograms that showed actual stenoses, and that these stenoses showed up in 4 distinct patterns is very very important. it is direct evidence of an abnormality not a hypothetical speculation that there "might" be one. There is a stenosis in these people. For those individuals it is proven. However it remains to be seen if removing these results in better MS outcomes ie do they get better.
After this research the Zamboni team enrolled 100 people with MS in a new study. This time, every patient will get not only dopplers and venograms, they also have their stenoses repaired with the Liberation Procedure--an endovascular procedure to relieve the stenoses. They will be followed for one year to see how they do with regards to MRI findings EDSS etc. That study began in Oct '08 for enrolling assessment etc, and the surgeries were done in January '09. Comments on how this is going by Dr Zamboni are below in the cxsyposium interview.
Simka comment on the Zamboni Dec'08 paper
Dr Simka comments on the work with some very thoughtful observations.
presentations with slides by Zamboni
Charing Cross 2007 Presentation by Zamboni
Don't yet have the '09 one with the results of the Liberation proceudre hinted at, but here's an interview with Dr Zamboni from that symposium
'09 Charing Cross Interview with Dr Zamboni with comments on his Liberation procedure
The Schelling materials
F. Alfons Schelling "Multiple Sclerosis: The Image and its message"
Video clips of the venous abnormalities, pictures etc by Schelling
Other Supportive Abstracts/Papers
Chih-ping Chung et al Jugular venous reflux
Simka, Rybak 2008 "Hypothetical molecular mechanisms by which local iron overload facilitates the devel. of venous ulcer and multiple sclerosis
Dr. Simka Website
7 tesla MRI:a new vision of microvascular abnormalities in MS
Raised venous pressure as a factor in mutiple sclerosis