Dr. Ponec discusses a meeting of eleven leading researchers in CCSVI during his Hubbard presentation. This multidisciplinary consensus panel was put together to come up with a research agenda, to move CCSVI investigations forward around the globe.
The FULL MEETING and DISCUSSION are published here:
From the Journal of Vascular and Interventional Radiology May 2011 Issue
http://www.jvir.org/article/S1051-0443(11)00759-7/fulltext
On October 18, 2010, the clinical trials division of the Society of Interventional Radiology (SIR) Foundation commissioned and convened a multidisciplinary meeting of physicians and scientists with expertise in clinical management of MS, basic sciences, neuroradiologic imaging, and vascular and venous interventions. The purpose of the meeting was to review the existing data linking CCSVI with MS and establish a research agenda for the evaluation of imaging and interventional therapies in the treatment of patients with MS.
Present at this meeting were Gary Siskin, MD, Ziv Haskal, MD, Gordon McLennan, MD
Michael Dake, MD, E. Mark Haacke, PhD, Sandy McDonald, MD, Walter Royal III, MD, Suresh Vedantham, MD, David Hubbard, MD, Salvatore Sclafani, MD, R. Torrance Andrews, MD and Heidi Sauder, PhD
More from the paper. NOTE: This panel understands the connection of MS and Venous Disease. It is real, and has consequences.
Venous Disease and MS
A relationship between the brain lesions of MS and cerebral veins has been suspected since the time of Charcot (5). Postmortem studies have demonstrated that periventricular plaques appear to extend along cerebral veins (26, 27), and that other plaques arise from segments of large epiventricular veins and extend into the cerebral hemispheres along cerebral veins (6). In light of this relationship, Putnam (7) noted in 1935 that “the conclusion appears almost inevitable that venular obstruction is the essential antecedent to the foundation of typical sclerotic plaques.”
When significant extracranial venous disease is present, collateral vessels often develop to prevent the development of intracranial venous hypertension (28). However, even with these collateral pathways in place, venous drainage can potentially be insufficient and the transit time prolonged, as confirmed by MR perfusion studies (29, 30, 31). This can lead to several problems. As normal cerebrospinal fluid circulation depends on efficient venous drainage from the CNS, insufficient venous drainage can lead to lower net cerebrospinal fluid flow (32); this is supported by the increases in the volume of the lateral and third ventricles in MS (33). It can also cause retrograde venous flow and chronic reflux into the CNS (28), which can ultimately increase the resistance to flow and transmural pressure (34, 35). Even before the recent description of CCSVI, venous hypertension was thought to play a role in the pathogenesis of MS (36, 37).
The theory of CCSVI suggests that increases in venous pressure lead to venous dilation, which can potentially increase the permeability of the blood-brain barrier (38). It is possible that alterations in venous hemodynamics could increase the expression of endothelial adhesion molecules, chemokines, and cytokines that ultimately alter endothelial adhesiveness and permeability. Such alterations in vascular homeostasis permit the infiltration of immune cells into the surrounding tissue. These cells elaborate cytokines and oxygen-derived free radicals that further increase vascular permeability, leading to insudation of plasma proteins and, in some cases, red blood cells. Red blood cell extravasation with subsequent perivenous iron deposition can result in significant inflammatory change (8, 34). Iron is known to be important for CNS physiology, as it is a cofactor for neural metabolism and adenosine triphosphate production and because it is involved in myelination and oligodendrocyte development (39, 40). Limited studies have supported the contribution of local iron overload to the inflammation associated with MS (41, 42).
As to the importance of TREATMENT TRIALS---
There was near-universal agreement that randomized trials would be required to confirm the role of venous interventions in MS. However, it was equally clear from the discussion that several factors could be better understood before large-scale randomized trials are initiated. Among these are the aforementioned confirmatory prevalence and diagnosis data, but also the need to define the appropriate study population, the need to optimize the interventional techniques for diagnosis and treatment, and to agree on appropriate endpoints for primary and secondary endpoint analysis. The panel, therefore, encourages the performance of investigator-initiated single-center and multicenter studies so safety and outcome data can be reported. In this way, a foundation of knowledge in these areas can be gathered. This knowledge will help provide the information necessary to appropriately power a prospective randomized trial.
In addition, it is critical to support and continue the basic science work under way to better understand the relationship between venous stenoses and hypertension and the subsequent contribution of CCSVI to patients with MS. Animal models will likely prove useful, though inflammatory mediators may be assessed with serum sampling in the context of human trials.
As the rhetoric from the pharma sponsored press and their sponsored MS specialists heats up, rest assured, the scientists who understand the connection to venous disease and MS are NOT BACKING DOWN. You will not read about what is going on in the vascular research world, it will not get big, splashy press coverage with controversial headlines. But we'll continue to disseminate it here. Feel free to print out the research, bring it to your doctors, continue to press for treatment trials, speak out. CCSVI research is not going away.
Joan