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Friday, October 21, 2011, 17:30 - 17:45
Anatomical and histological analysis of venous structures associated with chronic cerebro-spinal venous insufficiency

C. Diaconu, S. Staugaitis, J. McBride, C. Schwanger, A. Rae-Grant, R. Fox (Cleveland, US)
Background: Chronic cerebro-spinal venous insufficiency (CCSVI) is a new theory for MS pathogenesis. CCSVI includes alterations in cerebral venous outflow and is often assessed by ultrasound or magnetic resonance venography (MRV). No gross anatomical description of venous outflow in MS has been reported to date.
Methods: We harvested bilateral internal jugular (IJV), subclavian, brachiocephalic, and azygous (AZY) veins from 7 deceased MS patients and 6 non-MS controls. Veins were injected with silicone, dissected en bloc, incised longitudinally to expose the luminal surface, and fixed. All valves and structural abnormalities were characterized and photographed using a stereomicroscope. Vein wall stenosis was defined as a >= 50% reduction in cross-sectional area, defined from vein wall circumference and compared to a normal appearing region in the same vein.
Results: A variety of vein abnormalities were identified. The incidence of vein wall stenoses was similar in MS and controls: eight stenoses in 4 of 7 MS patients and five in 3 of 6 controls. Marked valvular and other intraluminal abnormalities with potential hemodynamic consequences were identified in 5 of 7 MS patients (7 abnormalities) and in 1 of 6 controls (1 abnormality). These abnormalities included circumferential membranous structures (1 MS and 1 control), longitudinally-oriented membranous structures (3 MS), single valve flap replacing IJV valve (2 MS), and enlarged and malpositioned valve leaflets (1 MS). In addition, minor anatomic variations without expected hemodynamic consequences were observed similarly in both MS and controls. These included valves with >2 leaflets, the presence of valves in the AZY, additional (duplicate) normal-appearing IJV valves, and small membranous septa.
Conclusion: Post mortem examination of the IJV and AZY veins of MS patients and non-MS controls demonstrated a variety of structural abnormalities and anatomic variations. Vein wall stenosis occurred at similar frequency in MS and non-MS controls. However, the frequency of intraluminal abnormalities with possible hemodynamic consequences was higher in MS patients compared to healthy controls, although the current sample size is limited. These results suggest that MRV (which predominantly evaluates vein wall stenoses) may be less effective than ultrasound in identifying venous abnormalities in CCSVI. In addition, examining only wall circumference in CCSVI ultrasound studies may miss some intraluminal abnormalities.
Claudiu Diaconu has nothing to disclose. Susan Staugaitis, MD,PhD, has nothing to disclose. Jennifer McBride, PhD, has nothing to disclose. Cynthia Schwanger has nothing to disclose. Alexander Rae-Grant, MD, presented a lecture for Teva Neuroscience and Biogen Idec with personal compensation. Robert Fox, MD, has received personal consulting or speaking fees from Biogen Idec, Genentech, Novartis, and Teva Neuroscience, and has served on clinical trial advisory committees for Biogen Idec. The current project is supported by the National MS Society (RC 1004-A-5).

Marked valvular and other intraluminal abnormalities with potential hemodynamic consequences were identified in 5 of 7 MS patients (7 abnormalities) and in 1 of 6 controls (1 abnormality). These abnormalities included circumferential membranous structures (1 MS and 1 control), longitudinally-oriented membranous structures (3 MS), single valve flap replacing IJV valve (2 MS), and enlarged and malpositioned valve leaflets (1 MS). In addition, minor anatomic variations without expected hemodynamic consequences were observed similarly in both MS and controls. These included valves with >2 leaflets, the presence of valves in the AZY, additional (duplicate) normal-appearing IJV valves, and small membranous septa.

I'm about to watch it. And I am sure that dehydration did not cause the luminal abnormalities found in this study!

This is excellent. Since we are looking at visible structural abnormalities, it is hard to argue with autopsy results.

They found more of the longitudinally-oriented membranous structures (aka septums) than what we usually hear about here. Perhaps these are underdiagnosed in patients? Could they be missed on IVUS?

A single valve flap replacing IJV valve might be how you'd describe my left jugular issue, unless it were better described as an enlarged valve leaflet. Finding only three valve abnormalities total in seven MS patients (14 jugulars) is fewer than what the IRs are seeing in living patients.

But this is clear support of the association between CCSVI intraluminal abnormalities and MS. It also helps clarify why there might be so much difficulty finding CCSVI, if the imaging studies are failing to differentiate between venous wall stenoses, which were found equally in both the MS patients and controls, and the intraluminal abnormalities, which were overwhelmingly found in the MS patients.

Here is Dr. Fox from ECTRIMS, doing a video interview for the MS Society, discussing his study....
this is big news, folks. A major neurologist from Cleveland Clinic finding venous malformations in autopsied jugular veins in pwMS, discussing the importance of correctly done ultrasound testing in CCSVI research. He has consulted with Dr. Zamboni and BNAC.

This may be the beginning of the tide turning....

http://www.youtube.com/watch?v=jSijkNDCotA


cheer

Hmmmm. One group sees 100%, the other 0%. In papers by Simka et.al. involving 000s of people we see a number north of 90%. And neurologists still think their opinion matters . . . . well I guess maybe to the MS Society.