A Neurologist's Point of View on the New Research suggesting that MS is a Vascular Disease
Just a little preface here before presenting the writing of Doctor Nitin Sethi. We have been talking a lot this week about something called Chronic cerebrospinal venous insufficiency (that sure is a hard phrase to spell!) and the latest research of a Dr. Zamboni who claims that MS may really be a vascular disease instead of an autoimmune one. If you haven't already read about this, here is my introductory post about this topic and how some MS patients have actually had surgery to clear blockages in their veins in the hopes that this procedure will actually cure their MS symptoms.
In addition to interviews with two MS patients who have gotten this surgery I have also invited Doctor Sethi, neurologist and blogger, to give his perspective of this radical new theory. I hope that he will bring a balance to our discussion through his questions and healthy skepticism.
Remember that you call the shots as to your treatment. Always research for yourself what things you may hear. It is good to ask questions and to be cautious. Ask for second and even third opinions. Do what is right for you... is the bottom line.
I now present to you...Doctor Sethi!
Nitin K. Sethi, MD
Assistant Professor of Neurology
New York-Presbyterian Hospital
Weill Cornell Medical Center
New York, NY 10065
Chronic cerebrospinal venous insufficiency in multiple sclerosis: Is it a cause effect relationship? What we now and what we don't know
Merely me recently wrote to me asking me for my opinion on the presence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). She said that CCSVI and its association with MS was a "hot" topic of debate on MS related websites and blogs. Most of the buzz has been generated by an article which first appeared in the online edition of the Journal of Neurology Neurosurgery and Psychiatry (JNNP) dated December 2008. This article by Zamboni et al and the accompanying editorial by Claude Franceschi seems to have generated more excitement in the online MS community as compared to physicians and researchers involved in this field 1, 2.
So what did Zamboni et al. exactly say that has created all this excitement? Well put simply they found significant obstacles in the main extracranial (meaning outside the brain) cerebrospinal veins (namely the jugular and azygous system of venous drainage) in their group of 65 MS patients as compared to controls (the controls were patients who were either healthy subjects matched for age and gender with MS patients, others were patients affected by other neurological diseases such as Parkinson's disease and amyotrophic lateral sclerosis and yet others were patients not affected by neurological diseases but scheduled for venography for some other pathology).
They further found different patterns of CCSVI (meaning different patterns of stenosis) in their MS patient group. Patients who had relapsing remitting and secondary progressive course of MS disease had different patterns of CCSVI as compared to patients with primary progressive MS. So what was Zamboni et al. final conclusion? Simple they said and I quote "that MS is strongly associated with CCSVI and that the location of the venous obstructions plays a key role in determining the clinical course of the disease".
Well before we dwell into this further it may be wise to attempt to understand how CCSVI may cause damage in MS. The hypothesis is that the venous obstruction leads to accumulation of metabolic wastes leading to injury of central nervous system (CNS) tissue. The slow venous flow leads to iron deposition and this may be toxic to the neurons.
"Elementary by dear Watson" as Sherlock Holmes might say sitting in his lodging at 221B Baker Street, London. Why did not someone think of this before? Someone has finally cracked the case. We finally know what causes MS, not all that hue and cry about auto-immunity and possible viral etiology. It is CCSVI that causes MS. And if it is CCSVI which causes MS, all we have to do is open these blocked veins to let the blood flow freely again. No need for those pesky interferon shots and other drugs with equally hard to pronounce names (Copaxone, Tysarbi etc etc!!!).
"Not so quick by dear friend" says the good Dr. Watson. Medicine is not all black and white. In fact it is shades of grey and the field of MS is littered with the ghosts of previous promising research and** wonder drugs** which did not go anywhere. Before I accept your theory Holmes I have some questions which need to be answered.
If CCSVI is indeed the cause of MS, then why do many patients of MS have no evidence of CCSVI?
Are these venous obstructions the cause or the product of MS (meaning what came first the MS or the venous obstruction-kind of chicken and egg question)
If CCSVI is indeed the cause of MS in at least some patients, would opening these blocked vessels lead to improvement? Will the disease progression stop or will the venous blockages come back again.
Do these venous blockages lead to some kind of sterile inflammatory process which responds to the current line of MS drugs?
Is it possible that these venous obstructions are infact related to the side-effects of MS drugs on the venous walls?
- Does every patient with MS need to be tested/ investigated for these venous obstructions (meaning should all MS patients undergo venography or extracranial color doppler examination?)
The ever wise Holmes takes a long puff of his pipe. Patience my dear Watson. Patience. The game is afoot!!! The interesting research of Zamboni et al. is just another piece of the intricate puzzle which is MS.
- 1. Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'Ara S, Bartolomei I, Salvi F. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr; 80(4):392-9.