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Michael R. Jaff, DO Conflicts of Interest • • Consultant – Abbott Vascular (non-compensated) – Arsenal Medical – Becker Venture Services Group – Boston Scientific (non-compensated) – Covidien (non-compensated) – Harvard Clinical Research Institute – Medtronic (non-compensated) – Micell, Incorporated – Neocure – Nexeon Medical Systems – Primacea Equity – Access Closure, Inc – Embolitech, Inc – Hotspur, Inc – Icon Interventional, Inc – I.C.Sciences, Inc – PQ Bypass, Inc – Primacea – Sadra Medical – TMI – Vascular Therapies, Inc • Board Member – VIVA Physicians (Not For Profit 501(c) 3 Organization) • www.vivapvd.com February, 2011 1 CRT 2011 Washington, DC Venous Angioplasty for Multiple Sclerosis: Sounds Like Voodoo and Not Worth Investigating Michael R. Jaff, DO Associate Professor of Medicine Harvard Medical School Medical Director, Vascular Ultrasound Core Laboratory Massachusetts General Hospital Boston, Massachusetts Voodoo—Not sure what the CRT Organizers Meant by Voodoo… 3 Multiple Sclerosis • Chronic demyelinating central nervous system disorder – Four Courses • Relapsing/Remitting • Primary Progressive • Secondary Progressive • Progressive/Relapsing 4 Concept of Venous Stenosis and MS • Not a new concept 5 Concept of Venous Stenosis and MS • Not a new concept 6 • Tracey Putnam, Boston City Hospital, developed an experimental dog model of venous obstruction to study MS. • At the end of his paper, he stated: • “The similarity between such lesions and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction |is the essential immediate antecedent to the formation of typical sclerotic plaques.” Putnam (1935). Studies in multiple sclerosis: encephalitis and sclerotic plaques produced by venular obstruction. Arch. of Neurol. and Psychiatry. 33: 929-940. Congested Vessels Surrounded by Demyelination Ann New York Acad Sci 1954 58:582-594 7 CCSVI and MS: A New Conceptual Framework • • • • • Anatomical anomalies in cerebrovenous drainage (IJ, VRT and or AZG VV) alter cerebral venous flow patterns and pressure. These alterations cause: • Increased expression of endothelial adhesion molecules, chemokines, cytokines, and prothrombotic factors. Increased vsmc injury response and generation of oxygen-derived free radicals Adherence of immune cells and their infiltration into the surrounding tissue. Infiltrating immune 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. Parenchymal injury due to inflammation and oxidative stress with demyelination, resolving with fibrosis and plaque formation. J Vasc Surg 2009;50:1348-58 8 Venous Obstruction: Where Does It Occur? • High Jugular Lesions • Mid Jugular Lesions • Low Jugular Lesions • Azygous 9 Venous Obstruction: Where Does It Occur? • High Jugular Lesions • Mid Jugular Lesions • Low Jugular Lesions • Azygous 10 Venous Obstruction: Where Does It Occur? • High Jugular Lesions • Mid Jugular Lesions • Low Jugular Lesions • Azygous 11 Venous Obstruction: Where Does It Occur? • High Jugular Lesions • Mid Jugular Lesions • Low Jugular Lesions • Azygous 12 Venous Obstruction: Where Does It Occur? • High Jugular Lesions • Mid Jugular Lesions • Low Jugular Lesions • Azygous 13 Reduction in Venous Pressure following Venous PTA… J Vasc Surg 2009;50:1348-58 14 …results in an improvement in function J Vasc Surg 2009;50:1348-58 15 So Far, Seems Like This is the Real Deal • However, I have a lot of concerns… – Does CCSVI occur more often in MS than in normal age/sex matched controls? – How can this be reliably diagnosed today? – If you successfully repair the stenosis (es), does the patient get better? • If so, for how long? 16 In the Meantime….. 17 And Physicians Have Jumped on the Bandwagon…. 18 Patients Can Go Anywhere for This… 19 So, I Am Not Convinced That This is Voodoo • However, we owe it to ourselves and our patients to really figure this out before offering this therapy outside of clinical trials to (often) desperate patients • We need to figure out how often CCSVI occurs in MS patients and in the general population • We need to standardized an effective, reliable, reproducible diagnostic algorithm • Then we need to study the efficacy of therapy in an organized, safe, prospective fashion 20