Summary of the Second Annual CCSVI meeting
(from my perspective)
To sort of organize my thoughts I will proceed chronologically.
First of all, it was very interesting to be at this meeting. I had attended Dr. Hubbard's meeting this spring and it was nice to see him and his lovely wife again.
I did miss the patient day due to work issues, but i understand that that went off well and that the patients who came felt it was valuable.
So, from a radiologist's perspective, all of the "rock stars" in the field were present with the exception of Dr. Zamboni ( which was unfortunate but we all wish him a speedy recovery). I wouldn't call this meeting a "love-fest" both the people present were for the most part already doing the procedure, or planning on doing the procedure. By and large, the sense from most everyone present that I could glen was that CCSVI is associated in some fashion with MS ( weather causative to concomitant or as a result of the disease) but that the overlap needs better definition. The most controversial part of the conference seemed to be Dr. Zivadinov's call to make sure that our studies address an outcome that is focused on reducing or treating MS like a new drug would, with similar types of primary endpoints.
Dr. Sclafani made the point upfront that he doesn't treat MS, he treat CCSVI in the hope that it reduces MS symptoms.
Beggs presented a very good series of talks that simplified the fluid dyanamics in CCSVI essentially arguing that what goes in, must come out. He postulated that narrowing at the final outflow of the jugular veins MUST cause some dilation of the parenchymal veins and that the compensator for a block or reduction in jugular outflow had to be chronic dilation of the parenchymal veins or increased reliance on CSF mechanisms to maintain the outflow. He correlated this to perfusion where essentially more stenosis = less brain perfusion. when increase blood volume is in the cranium, brain tissue must be getting compressed.
This got me to thinking about CSF flow and if a study correlating ventricle size and aquiduct size might have some relevance in diagnosing or predicting who might get MS (I.e. If you have a small aqueduct, maybe you can't compensate for venous stenosis and your MS risk of exacerbation of symptoms might go up?). If we follow the reasoning of Dr. Beggs it would seem that relieving CSF pressure would provide some more reserve for venous stasis, so would a Ventriculo-Peritoneal shunt reduce exacerbations of symptoms by relieving pressure? Didn't get to ask that question.
Dr. Salvi's presentations on hydrocephalus and neurodegenerative disease and clinical presentations of CCSVI were interesting in the fact that there seems to be some parallels with normopressure hydrocephalus (NPH) and MS type symptoms which would fit in with what Dr. Beggs was talking about.
I found the attempt at correlating MS with other venous symptoms not fully presented. Dr. Salvi showed a picture of someone with sever edema in the lower extremities that looked just like venous stasis and claimed that they had a complete reduction in the LEG swelling after jugular treatments for CCSVI. This seems hard to explain and I would have liked to see any data to support this.
Ms. Marr presented a quick overview of ultrasound imaging. Nothing earth shattering, just how to do an ultrasound.
A few points that I did find useful, keep the head in a neutral position. I know from experience that most monographers I have seen will have the patient turn their head opposite the side being scanned to open up the vein. Ms. Marr suggested that turning the neck would alter the flow and confound the results.
Also interesting was her call to use warm gel. The claim is that cold or room temperature gelling can cause jugular venous spasm. No sure if this is true or not, but warm gel does seem more courteous. I will switch to ensure this immediately.
Other recommendations that she had:
Drink 16 Oz of water within the 2 h of exam to ensure proper hydration and thus the veins will be enlarged.
No steroids within 30 days of the exam.
No air travel during the previous 24 h before the exam. Contending that it takes the body 24 hours to reset to baseline after flying ( would like to see the data to support this).
Dr. McDonald did a nice literature review and kept pointing out the folks before us that thought MS was strictly venous flow related. There was some discussion about how and when to follow patients that live close enough to be followed.
Diane Driscoll ( doctor of optometry) gave a very interesting introduction into the role of MAST cells and the immune system, essentially stating ( if I understood it correctly) that mast cells hang out in the choroid plexus - glands that make CSF. When they go into circulation for whichever reason activated them, they can exacerbate MS symptoms. She discussed treatments with acetazolamide which had apparently shown some promise. This looks like another area ripe for research. I wish I was smarter.
End Day 1
I think I did a pretty good job of summarizing this as it was occurring.
Highlights included being admonished by Dr. Zivadinov and the basic discussion about weather it is premature to proceed with randomized studies. The point to do it is to try to establish if dilating veins does any good at all. The point that it was too soon revolved around us not having enough experience to even have a consensus on what should be dilated and by how much. Until we know how we are going to treat, it is too soon to do the randomized stuff. Specifically, what protocol do you use on the treatment arm? What do you treat and how much - how large? Remember, if this part is flawed and the vessels go undertreated, then the results from the "First randomized study" will show that dilating the jugular veins is not useful at all - when it simply might be that they didn't dilate enough, etc. Zivadinov is a smart guy who is on the ball, so I am sure that this part will be addressed, but that is essentially the arguments in the pro and con camps.
The disclosure part was a bit preachy. I can tell you that every doctor there already knew what it meant to be be involved with CCSVI. After telling folks about CCSVI in my own facility I can tell you how verbally aggressive some of the nay-Sayers can be. The only neurologist I could find to work with me on these folks is outside the hospital system. Good for us he is an excellent Doctor. I sent my own father in law to see him ( and I LIKE my father in law too). Dr. Zivadinov did have a point that some folks were now basing a carreer on CCSVI treatments, but disclosures in this setting don't really pertain to that as I understand it.
I do agree at some point the CCSVI data will have to address the overall treatment of MS like reduced placque burdens, etc.
The work in Poland and Bulgaria has been prolific and useful. Dr.s Simka and Petrov have done alot of work oversea and have been ahead of the treatment curve so to speak. It was interesting to see the significant reduction in the amount of stenting that went on as experience increased. At this point it seems stenting is only used for severe lesions that do not respond at all to plasty, or as a bailout for vessel wall repair.
We got a glimps of the Hubbard data from Dr. Ponec which uses the MSIS-29 data. It was very favorable and exciting to see.
We got a look at the study design for the PREMISe study by Dr. Zivadinov
We got a look at the Albany study design by Dr. Siskin
Of note - rapid clearing of contrast from the jugular veins seemed to hold some importance for diagnostic purposes from the presenting Doctors. It seemed like clearing of contrast in less than three seconds was important to show lack of stenosis. The volume of contrast and rate of injection was not discussed in this. Also, no one discussed using pull back pressures where pressures are measured across a narrowing as a way to determine significance. I have done that on all of my patients trying to reduce the gradient to 1mmhg which is within the margin of error for the electronic sphygmomanometer. Anything greater that 2mmHg Medes to be treated in my opinion. It will be interesting to see if future studies include this data.
All in all it was a very interesting conference and I am glad that I attended and know that it has furthered my own resolve to be active in this fascinating and underserved corner of medicine.
Stuff to follow -up on:
Question correlation between heart disease, infective mononucleosis, irritable bowel or crohns and increased risk of CCSVI. Use of Ginko Biloba may reduce Symptoms?
Investigate: does placement of IJ catheters in MS patients increase MS symptoms?
Articles to pull and review:
Kitano et al, journal of nuclear medicine 1964
Doepps, et al. Meir radiology 2004
Centonez -Ann neurologist 2011