Death knells and coffins...

Death knell for CCSVI!---Another nail in the coffin---
Goodbye to all that; a short history of CCSVI---
CCSVI debunked!---The end for CCSVI

If all you read were the headlines, you might think that CCSVI was nothing more than a scourge, a fantasy, a vampiric spector that science has, thankfully, stabbed through the heart and removed forever.
It's over. Move along, people.  Nothing to see here.

But there is much more going on.

This week, a paper published in a neurological journal showed
"severe extracranial venous anomalies that signficantly impaired normal outflow from the brain" occur in some people with MS.
The full paper, in a provisional pdf, can be viewed here for free:
http://www.biomedcentral.com/content/pdf/1471-2377-13-151.pdf

These scientists do not think CCSVI is over.  They're still finding it.

Jeff and I know all about these extracranial venous anomalies that significantly impair the flow of blood from the brain to the heart.

Four and a half years ago, Jeff and I saw that very same problem happening in his body.  We were astounded at the MRV images on the computer screen in his doctor's office, which showed slowed collateral circulation and two malformed, stenotic jugular veins.

I put up an image from his magnetic resonance venography on an MS Forum.

And in doing so, poked a hornet's nest.

You can see in this MRV picture on the left from Stanford, Jeff had no jugular flow on the left side (right on pic), and reduced flow on the right.  This is evidenced by the collateral veins that are lit up like Satan's curly fries.  This is not normal.
What you should see are straight and open jugular veins, that look like drinking straws.  Like the picture on the right.  Can you see the difference???  Well, our doctor saw the difference, and we decided to treat Jeff's venous malformation.



In fact, both of the images were taken at Stanford University, by one of the premiere vascular specialists in the world.  He and his radiology team would later publish a paper on what healthy normal venous MRV looked like, compared to people with MS.  He believes that the kind of collateral circulation and pulsatility found in pwMS could well be damaging to the brain.  Here is one of his papers on this.
http://www.ajnr.org/content/33/8/1615.abstract


When Jeff's jugular veins were opened up, the collaterals went away, his cerebral blood flowed through his jugular veins in a timely manner, no more pulsatility.  And Jeff's brain has healed.  No MS progression.  His gray matter looks normal on MRI.

It's hard not to wonder what would have happened if I had simply taken the research to Stanford, where Jeff was treated, and then gone home to live out our days.  But I was part of an online MS forum, and we'd been sharing information between pwMS and caregivers.  In fact, that was how I first read Dr. Zamboni's published papers.

Maybe the research would have progressed more readily without patient involvement.  Maybe the scientific community would have been more accepting of Dr. Zamboni's research, without the media and patient spotlight.

But I doubt it.
And anyway, there's no going back.
I'm sorry for the way neurologists have used patient advocacy to prevail against the science.... but I'm also not sorry.  Because I got my energetic, brilliant husband back.  And he no longer has heat intolerence, sleep apnea, or crippling fatigue.  No MS progression.  He's still working more than full days, jogging, biking and living.

CCSVI exists.  It impairs blood flow from the brain.  It may not affect everyone with MS, and it may be present in normal people.  It's showing up in other neurological diseases.  There is great debate as to how it should be treated.  Jeff's doctor used stents, others have replaced veins, ballooned, used cutting balloons--others believe lifestyle and exercise may be enough, or antibiotics might help.  There is no agreement on the best course of treatment, and that has created confusion and controversy.

It's also clouded the fact that there are newly discovered and very obvious venous problems related to neurological disease.  

CCSVI exists.
How it is best treated will be debated, but this exploration is not even close to being over.
Joan

Restricted Blood Flow, Moyamoya Disease and MS

May 26, 2011

From my friend Mark--someone with MS who was treated at Stanford after my husband--a story in his local paper caught his eye this morning.

http://www.pe.com/localnews/corona/stories/PE_News_Local_W_wwedding26.3a17c61.html

When they first met in 1991, Corona residents Douglas Wang and Lizabeth Tso didn't know of the love and heartache that would follow them over the next 20 years.

Eight years later, they met a second time and fell in love.

In December 2001, Wang was diagnosed with multiple sclerosis. Nine months after that, at age 28, he suffered a massive stroke that left him paralyzed on his right side. He was then diagnosed with Moyamoya disease, a rare disorder that constricts blood flow to the brain.

Mark wondered, what the heck is Moyamoya Disease, and how is it like MS?  

Turns out, this disease, which restricts blood flow in the brain, is often MISDIAGNOSED as MS.

Moyamoya is a disease of the intracranial arteries which deliver blood inside the brain.  CCSVI is a disease of the extracranial veins.  But the mechanism of injury is hypoxia, not the immune system.

And to add another interesting layer to this tale...here is research from Stanford University, where Dr. Steinberg looked at pwMS and those with Moyamoya.

Misdiagnosis of Moyamoya Disease as Multiple Sclerosis Variants in a Case Series of Seven Patients

Omar Choudhri MD; Teresa Bell-Stephens RN; Robert M. Lober MD PhD; Nancy Fishbein; Gary K. Steinberg MD, PhD

Introduction

Multiple sclerosis is a relatively common demyelinating condition of the brain and spinal cord that can present insidiously with multiple neurological symptoms.Some multiple sclerosis symptoms could be mimicked by transient ischemic attacks in the setting of a vasculopathy such as moyamoya disease.

Moyamoya disease is an idiopathic chronic cerebrovascular disorder, characterized by progressive occlusion of vessels comprising the circle of Willis and clinical presentation can vary depending on the ischemic territory. Here we present a series of patients managed as having multiple sclerosis for many years before being correctly diagnosed with moyamoya disease.

This study investigates the radiographic, laboratory and clinical overlap between the two clinical entities and outcomes after surgical revascularization.

Methods

Seven patients found in retrospective review of the 448 patients in the Stanford Moyamoya Database from 1991-2010 to have initial diagnosis of multiple sclerosis on presentation. MRI imaging, angiograms, CSF results and clinical follow-up data were reviewed.

Results

Male : Female ratio of our patients was 1:6 which correlates with female preponderence in both conditions. The average age of patientsmwas 35 years and duration of diagnosis for presumed multiple sclerosis varied between 6 months to 20 years. Extremity paresthesia was the most common neurological symptom in these patients. MRI periventricular FLAIR or T1 changes were the most common diagnostic clue to multiple sclerosis and a repeat MR angiogram or formal angiogram subsequently confirmed the diagnosis of moyamoya disease.

Greater than 60% of patients had improvement of their neurologic symptoms following cerebral

revascularization.

Conclusions

We believe that moyamoya disease should be considered in multiple sclerosis variants who present with paresthesias and do not respond to traditional immunosuppressive therapies.

Early diagnosis and revascularization procedures could help prevent further neurologic sequelae. Furthermore, subtle MRI findings should suggest obtaining a CTA/MRA or a formal angiogram to identify moyamoya vessels.

http://w3.cns.org/dp/2010CNS/1164.pdf

Given that Moyamoya is yet ANOTHER DIFFERENTIAL diagnosis for MS which involves the cerebrovasculature, I believe those with an MS diagnosis deserve to be tested with angiograms and MRVs, to learn if they have a vascular component to their disease.  The evidence continues to grow.

Joan

EAE in mice vs. the new Stanford animal model of CCSVI by Dr. Michael Dake

May 17, 2011 at 7:39pm

Here is part of Dr. Dake's lecture from the Hubbard Foundation conference:

http://www.youtube.com/watch?v=Xp2aWE7W8_w&feature=related

First, Dr. Dake explains how the current model of EAE is created in mice.  It is a rather convoluted procedure--

"There's an animal model, but it's not really, unfortunately, like most animal models, it's not really a human model.  Basically, you take like a mish of ground up spinal cord and brain from some other species, you mix it with some oily substance, some TB bacilli, and some bordadella pertussis, some whooping cough toxin, and inject into peridium,  and what you get is this whopping inflammatory response, and that's good because you get the accelerated disease process, but obviously in humans, it's a much more chronic and progressive thing.  

So, what we've done is taken mice and ligated (the jugular veins)  and we're going to move now up to marmosets, because that's the next level of the species, and marmosets you can actually partially occlude the veins and keep them open without totally ligating them.

 And these mice and their veins, we've got a recipe that we think is right where we want it.  We're starting to see not only clinical performance differences between mice that are ligated and mice that aren't  ligated, but now there's a way to tomographically, in a little mouse brain, to make these wafer thin micron sections thru the whole brain and we're learning a whole lot.  I think it's going to be very interesting as we move up to a larger model to really see....but we think that we're seeing an accentuation of the venous ligation on the disease process."

No words to describe how much I respect this man.  He listened to us and was interested, treated my husband's venous malformations,  and continues to speak out on CCSVI.  Thanks, Dr. Dake.

Dr. Michael Dake on CCSVI

November 19, 2010 at 11:26am

from the V-Aware November issue.

http://vaware.org/images/stories/pdfs/vaware_v2i3_lowres.pdf

Dr. Dake is the cardio-thoracic specialist I contacted with Dr. Zamboni's research in January 2009.  He was our local doctor at Stanford University.  The damage that Dr. Dake saw in Jeff's brain on MRI, and the damage he found in Jeff's jugular veins on MRV made sense to him.  As a vascular doctor, he understands the correlation of venous drainage and disease.

Important Points to note in this article:

1. CCSVI resembles a known venous disease, superior vena cava syndrome.  Symptoms related to this condition are similar to those in CCSVI.  Relieving CCSVI via angioplasty produces similar results in angioplasty for superior vena cava occlusion.

http://emedicine.medscape.com/article/760301-overview

2. CCSVI might account for the low flow states (hypoperfusion) found in pwMS.

3. Slowed blood flow changes the endothelial layer of blood vessels, allowing for a break in the blood brain barrier and immune cell penetration 

4. Inflammation created by disturbed blood flow in CCSVI continues to damage the vein lining.  Thus, CCSVI will progress with age of patient and length of disease.

++++++++++++++++++++++

Here is Dr. Dake on CCSVI---

Evidence presented recently in the medical literature proposes that patients with multiple sclerosis (MS) have a coexisting high frequency of obstruction to veins that drain the brain and spinal cord.

These data suggest that MS is associated with blockages in veins located in the neck or chest that alter cerebral venous hemodynamics, causing alterations in venous pressure and flow patterns. This venous obstruction is called chronic cerebrospinal venous insufficiency (CCSVI).