Can multiple sclerosis be treated by endovascular means?

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Michael Dake, Stanford, California, USA told delegates at the Society of Interventional Radiology’s 35th Annual Scientific Meeting in Tampa, USA, about the initial observations recorded after endovascular treatment of venous stenotic lesions implicated in multiple sclerosis (MS).

“I would like to introduce you to a hypothesis that is not exactly new, but that is getting a lot of high-profile exposure in the lay press. It has to do with the potential association between MS and extra cranial venous obstruction. This is not yet a comprehensive understanding, but this is truly a work in progress that is being played out in real time across the world right now,” said Dake.


What is the rationale that supports the association between multiple sclerosis and venous obstruction?


Dake said it has long been known that MS plaques are venocentric as the lesions have been found to extend counter to normal venous flow direction. Also, the distribution of lesions is often peri-ventricular, and peri-venous cuffs similar to the appearance noted in chronic venous disease are seen.


“The blood-brain barrier breakdown is also at the core of our current understanding of MS whether you consider a vascular pathogenesis or an immune reactive autoimmune basis, which forms our current understanding,” he said.


Dake pointed out that the new conceptual framework was based on the understanding that the vessel wall responds dynamically to changes in flow and pressure (pulsatile shear stress and cyclic strain).


“Alterations in venous flow and pressure may elicit inflammation, thrombosis and tissue injury. Anatomical anomalies in cerebrovenous drainage alter cerebrovenous flow patterns and pressure.These alterations cause increased expression of endothelial adhesion molecules, chemokines, cytokines, and prothrombotic factors; increased smooth muscle 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; and parenchymal injury due to inflammation and oxidative stress with demyelination, resolving with fibrosis and plaque formation,” he said.


Referring to the preliminary outcomes from endovascular management of extra-cranial venous insufficiency, Dake said, “This remains to be seen, but clearly global symptoms attributable to MS, but not referrable to a neuro-anatomic loci, such as fatigue, headache, heat sensitivity,‘brain fog’ and urinary urgency, show short-term improvement and in some cases complete resolution. This suggests that these particular MS symptoms may be more accurately categorised as related to venous obstruction.”


Dake told delegates that it was important to remember that lesion sites appeared to be non-specific (dural sinus, jugular, brachiocephalic, azygous veins alone or in combination) and also that lesion etiology is non-specific (congenital/hereditary, osseous impingement, arterial compression, post-inflammatory, arachnoid granulation, etc., alone or in combination).


Chronic cerebrospinal venous insufficiency (CCSVI) is characterised by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins and the azygous vein. It is strongly associated with MS.


Paolo Zamboni, University of Ferrara, Italy, has been evaluating the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. He presented the rationale and preliminary results of an endovascular treatment for MS at the 31st Charing Cross International Symposium, London, UK in 2009.


He said that though MS is an inflammatory neurodegenerative disease of the central nervous system of unknown origin − widely considered to be autoimmune in nature−it is strongly associated with chronic cerebrospinal venous insufficiency. He has emphasised the need for more research in the area and noted that it is still not proven whether CCSVI is a cause of MS, or a product of MS.


Zamboni’s study with 65 patients found that percutaneous transluminal angioplasty of venous strictures in patients with CCSVI is safe, and the clinical course positively influenced clinical and quality of life parameters of the associated MS.


Based on the results of this pilot study, the Italian investigator has recently called for further study that CCSVI may be corrected by endovascular means. He has suggested that if further evidence supports the link between MS and CCSVI, endovascular treatment of the latter may ultimately add to the arsenal of therapies available for MS.