This Is MS Multiple Sclerosis Knowledge & Support Community

We'd discussed some of this before, but I don't remember seeing the full text. I can't figure out how to link it, either. There's a link on the MS Society's webpage on CCSVI: http://www.nationalmssociety.org/resear ... index.aspx

Dr. Dake wrote:No matter where you stand on the recent controversy
surrounding the concept of chronic
cerebrospinal venous insufficiency (CCSVI) and
its proposed association with multiple sclerosis
(MS), it is increasingly clear that this theoretical
phenomenon challenges interventionalists
with far more questions then there are answers
readily available.

More questions than answers. Ok.

Whether an unconvinced
sceptic, open-minded observer, perplexed clinician,
hostile critic or convinced believer, no one
is dispassionate and all have to agree that
nothing in recent history has rocked our field
with the emotionally polarising force of CCSVI.

The open-minded observer sounds pretty dispassionate.... And terms like 'believer' aren't generally applied to other medical endeavors, such as varicose vein treatment, are they? Is the autoimmune theory of MS filled with believers and nonbelievers? Can I insult my neurologist by calling him a believer? Anyway. Yes, CCSVI has rocked the field of interventional radiology.

Currently, the themes of a myriad of big picture
questions concerning CCSVI can be consolidated
into three important considerations:
1. Does treatment of CCSVI cure MS?
2. Does CCSVI have a fundamental role in
causing MS?
3. Does endovascular therapy produce
objectively measured patient benefits
beyond a placebo effect?

Asking if treatment of CCSVI cures MS is looking for a yes/no answer. It seems unreasonable. Who can expect treating CCSVI to 'cure' a person with an EDSS of 9? Is stopping further damage a 'cure'? What does it mean to cure a disease, in other contexts?

Certainly, other equally important and more
detailed diagnostic, pathophysiologic, anatomic,
technical, and safety questions challenge us,
but as interested parties seek to embark on
collaborative controlled trials to study the
outcomes of CCSVI treatment, it is perhaps
prudent and beneficial to pause and examine
current snapshots of these three general issues.

Dr. Dake has a lot of words, and he knows how to use them.... Diagnostic questions, yes. Pathophysiologic questions? What would those be? Questions about the pathology of CCSVI, or its role in the pathology of MS. Anatomic questions, yes. Technical questions, yes, we discuss those in Dr. Sclafani's thread frequently. Safety questions, yes. We have Dr. Siskin and Dr. Simka's safety studies to show for the safety of the procedure, although we also have adverse events that have been shared and discussed in social media.

Interested parties are embarking on collaborative controlled trials to study the outcomes of CCSVI treatment! Yes, yes, yes.

Based on the initial clinical experience to date
and with some literary license, the following
comments provide perspectives that attempt
to summarise the contemporary opinions of
interventionalists actively involved in the
treatment of CCSVI.

Ok.

The present consensual view of interventionalists
and hopeful patients is resigned to the conclusion
that treatment of CCSVI is not a cure for
MS. Debates rage over what roles, if any, CCSVI
may play in conjunction with the genesis, progression
and symptoms associated with MS,
but even the most evangelical CCSVI advocates
understand that relief of extracranial venous ob -
struction will not magically re-myelinate com -
promised axons or reverse existing plaques.

There's that framing the conversation as involving evangelicals. If we get the word out, we are spreading knowledge of peer-reviewed published research. How is that evangelism? There are no flowers. Just research.

I think this is incorrect because a proper definition of 'cure' has not been established. If a patient with early-stage MS receives CCSVI treatment and no longer experiences MS symptoms or lesions, that may be a cure. If progression can be stopped, that may be defined as a cure. It has not been proven that this is what is happening to such people, but neither has it been proven that it is not.

The question of whether CCSVI has a function
in the genesis of MS is extremely contentious.
Perhaps, it looms as one of the most inflammatory
issues for many neurologists because it
challenges the widely held immune/auto-im -
mune paradigm that dominates MS research
models and clinical treatment concepts.

Neurologists, all inflamed! Yep.

The
influence of the doctrine that “establishes” the
immune basis for MS is profound, despite the
lack of a clear understanding of how an im -
mune mechanism is involved in the initiation of
disease and subsequently, its episodic course.

Do neurologists like being told by cardiologists that their theories lack a clear understanding of the etiology? Even when the cardiologists are completely right?

Clearly, a genuine collaboration that respectfully
encourages involvement of all interested parties could lead to the most objective, efficient
and conclusive scientific investigations of
CCSVI, but make no mistake; this will require
the successful tackling of many tough challenges.

Respect! Such as by not framing the discussion with religious talk!

Daunting impediments include: vested
interests, silos with different cultures, hidden
agendas, and diverse levels of understanding,
strong egos, messenger killers, entrenched
dogmatists, sanctimonious pontificators, cynical
nihilists, and a whole range of biases.

Add Dr. Freedman to the list too....unless he was covered by the 'strong egos,' or maybe the 'sanctimonious pontificators'?
It would be foolish to ignore the presence of vested interests, but we get painted as foolish for anything that seems paranoid about Big Pharma.

Obviously, no one denies that interventionalists
are ill-equipped to exclusively shepherd
clinical treatment trials aimed at providing
meaningful results informed by prior experiences
that refined safety and efficacy metrics
to objectively investigate new drug therapies.

How are interventionalists ill-equipped? Interventional radiologists are the best. Interventionalists are quick learners. Give them funding, and see what they can do.

Yes, ideally there would be neurologist and IR collaboration, in any trials. But last I checked, we are not living in an ideal world. And I don't want our researchers to have to wait while neurologists come around. Full steam ahead.

On the other hand, what has been learned
from the initial observational phase of CCSVI
treatment is informative and should not be
wholesale discounted.

For example, it is now apparent that after
endovascular therapy, certain constitutional or
general symptoms common to MS patients,
such as fatigue, heat intolerance, clouded cognition,
urinary problems, cold distal extremities
etc., respond in a tempo that ranges from
hours to days rather than the usual weeks or
months typically necessary to achieve full benefits
and clinical stabilisation with pharma -
cological disease-modifying therapies.

I experienced this. And it is a bit overstated to say that the pharmacological disease-modifying therapies could achieve the same symptom abatement that endovascular therapy achieved. Nothing has ever been offered to me that improved my symptoms the way CCSVI venoplasty did.

It is in everyone’s interest to contribute to the
development of new therapeutic concepts
capable of delivering improved treatments that
yield greater benefits for MS patients and their
families.

This should seem obvious, yet it would seem that it needs to be stated. CCSVI research needs intellectual contributions, not roadblocks.

In terms of CCSVI, this involves the
performance of high-quality randomised controlled
trials incorporating objective analyses of
results using standard measurements of outcomes
established in the MS literature while
taking into account other potentially positive
responses related to the endovascular
management of venous obstruction.

Ok, I had to read that one twice. Did I mention that Dr. Dake owns a lot of words? The standard measurements of outcomes established in MS literature would be reduction of relapses, QOL questionnaires, and white matter lesions as measured on MRI. But what would be the other potentially positive responses related to the endovascular management of venous obstruction? A color hue test would've worked for me! As would a vision test, since my vision improved to the extent of needing a new prescription for my contacts.

Perhaps, there are unrealised synergistic opportunities
with the combination of therapeutic
modalities. It is conceivable that disease-modifying
drugs, together with endovascular treatment
of CCSVI, working through different
mechanisms to manage the disease process,
have the potential to incrementally benefit
patients beyond what can be achieved with a
single approach.

Synergistic opportunities! And I don't think that's a hidden ad for Synergy.
CCSVI + a DMD = "cure" ?

After all, it is not far-fetched to
expect that combination therapies targeting
different aspects of a progressive disease
process might improve upon the relatively
modest therapeutic advantages realised with
current therapies.

Relatively modest advantages with the current therapies? As far as I understand it, the DMDs have no impact on progression. That is modest indeed.

Indeed, recent publications in the medical literature
have questioned the exaggerated cost/
benefit ratio for patients administered current
disease-modifying therapies. The wisdom and
value of sustaining therapeutic approaches
that cost more than $800,000 per quality adjusted
life year (QALY) – about 10 times as expensive as what is generally considered cost effective
– may undergo further scrutiny in the
future (1).

Our DMDs are unbelievably expensive and, by-and-large, barely work.

Similar studies that detail benchmarks
for therapeutic effectiveness in other
important diseases have informed and ultimately
guided decisions by insurance organisations
and government healthcare agencies
responsible for healthcare payments.

If the government and/or insurance companies catch on, they won't even want to fund the barely effective DMDs, and we won't even have that.

I'm getting depressed, Dr. Dake! Give me some good news.

Currently, the long-term results of endovascular treatment of patients with CCSVI are unknown.

Agreed. And I would hope research is underway that will change that 'unknown' to 'known.' We need answers.

Although it is estimated that 15,000 patients
have been treated worldwide, many have not
received adequate follow-up surveillance. This
is often due to the lack of local or regional op -
portunities for undergoing the initial procedure.
In many cases, this results in patients tra -
velling long distances to undergo therapy, but
subsequently leaves them without any continuity
in medical care for follow-up at home.

He's talking about you, Canada....

Without the ability to capture the important
necessary data for longitudinal follow-up evaluations
in a large percentage of patients, the
reports to date of early treatment experience
have focused on detailing the safety of the procedure
and immediate responses.

The initial experiences of endovascular treatment of
CCSVI published in the medical literature are
consistent in documenting the safety of balloon
angioplasty (PTA), (and in smaller groups,
stent placement following failure of PTA) and
lack of associated serious adverse events (2-4).

Safe and lacking in associated serious adverse events. That would make a nice headline in CTV or WSJ.

The frequencies and range of procedure-related
complications is similar to those established
for endovascular interventions involving other
venous territories, including substantial
experience in iliac veins, vena cavas, and
brachiocephalic veins.

CCSVI procedure-related complications are similar to those in other established endovascular interventions. That would make a nice headline too.

Many prominent neurologists have dismissed
the concept of CCSVI as totally implausible and
absolute lunacy; at best, an annoying distraction
that steals attention from promising new
drug therapies and at worst, a simplistic farcical
ruse conjured to trick susceptible patients into
chasing an expensive illusion.

Hostility, misrepresentation or misunderstanding of CCSVI, and extreme closed-mindedness.

Proponents of CCSVI contend that its relevance to the location
of typical peri-venous plaque in MS is supported
by the presence of documented correlates
elsewhere in the body.

We do? It's not exactly our rallying cry. 'Documented correlates elsewhere in the body.' That might mean plaques in leg chronic venous insufficiency or the damage to the liver in Budd Chiari.

I would contend that outflow obstructions obstruct flow from an organ that is damaged, and that organ is the brain, and it is an important one.

Let's see what else he has to say about our contentions.

They argue that the histological
appearance of peri-venous cuffing
evi dent in MS plaques is similar to the perivenous
tissue reaction observed in a variety of
other anatomic territories where there is chronic
obstruction of a venous bed – such as, leg
veins in the setting of chronic deep venous
thrombosis (post-phlebitic syndrome), and
hepatic veins associated with an obstructive
venopathy like Budd-Chiari.

Yes, ok, I should've read ahead. This is the same as what was presented in Dr. Zamboni's 'The Big Idea' paper.

When presented with this notion, many neurologists
are in disbelief that such a ludicrous idea
could be seriously entertained. “Prevalence
studies would indicate that chronic venous
insufficiency of the legs and MS are as far apart
pathologically as possible.”

I am not sure why acquired leg venous insufficiency would be expected to occur in the same patients in which congenital CCSVI abnormalities occur. The issues in the legs may occur after a thrombosis creates an insufficient valve, unable to pump blood upwards. The issues in CCSVI occurs after birth defect of the IJV valves blocks the passage of blood flow. These are not the same patients.

Underappreciated in the midst of these clashing
positions is one other example of a similar
venous lesion with potential relevance to MS –
sheathing of retinal veins.

Yes! I am so interested in this.

This cuffing or
sheath ing of veins can be appreciated on fundoscopic
examination of the eyes and may be
associated with retinal vein thrombosis, optic
neuritis and vision loss. In the majority of cases
when it is diagnosed during an evaluation of
disturbed vision, it occurs in patients with MS.

Studied extensively at the Mayo Clinic, it is not
however singularly associated with cases of
established MS. Its frequency among MS
patients is estimated to range from 11% to
42%.

After fluoroscein dye administration, it is
possible to observe leakage of dye around the
retinal veins and histologically, the veins
display a thickened wall similar to appearances
observed in other chronically obstructed
venous territories.

This is what Dr. Diana has been talking about as well. You can see the effects of venous obstruction in the fundi of our eyes, in 11% to 42% of people with MS. I do not know if I am among those numbers, but I would be surprised if I was not, because of my pars planitis and optic neuritis and improvements in vision after the CCSVI procedure relieved any venous obstruction.