- [Announcer] And again, not to belabor the detail,
but they're actually able to identify
four different patterns.
So, this is the normal pattern of flow.
This is the heart, and the veins
draining blood from the jugular veins,
and the azygos vein, into the heart.
And, patients who had MS had different patterns,
but they all had abnormal flows or narrowings.
So, this was very, very controversial when it came out.
It was also very highly publicized,
patients heard about it,
and it was discussed a lot on the internet,
the blogs just went wild,
that Dr. Zamboni and his team had found
an important clue to the cause of multiple sclerosis,
and then of course, the hope was,
if you find these narrowings,
if you were to open up or unblock the veins,
that could theoretically be beneficial to patients.
But, it also caused a lot of consternation
in the medical field for a number of reasons,
a few of which I've listed here.
The fact that they found these abnormalities
by doppler, and 100% of patients with MS,
and 0% of people who didn't have MS
seemed almost too good to be true.
There's also the medical community who read research studies
know that it's never completely black and white like that.
So, that had people a little bit concerned.
These doppler tests are also very technically difficult,
and different people doing the different tests
may find different things, even in the same patient.
So, having uniformity from
individual from individual doing the test,
and from center to center doing the test is difficult.
It wasn't clear, when you read the research paper,
whether the person doing the test was blinded
to the fact that the patient had MS or not, or knew.
And that allows the possibility
of introducing some bias into the results.
If you're looking for a particular result,
and you know the patient, the person coming in for the test
has multiple sclerosis, you may be more likely to find
an abnormality, rather than if you
are completely blinded to that.
So, the question was,
to what extent were these findings real,
and what do they really mean?
They also, then, took that next step,
and the question was, if you find these blockages,
and undo them, what happens?
So, they took the patients that had multiple sclerosis,
and they did a procedure called angioplasty,
which means that they inserted a catheter
to the side of the narrowing,
and at the end of the catheter,
was a little balloon they could inflate,
and it allowed them to dilate the vein,
and open up the narrowing.
The idea was to undo the narrowing from within.
Unfortunately, the question was,
when patients were followed over time,
after the procedure, did it provide
any meaningful benefit to their condition?
Their vascular outcome was followed,
so, did the angioplasty procedure keep the blood vessel open
for a long period of time?
And their neurological outcome was followed,
so, did it lead to improvement
in their neurological function,
whether it be walking, or other functions.
And if you're already on treatment,
they decided to not to perturb the existing treatment.
So, this was done on top of treatment in some patients,
and in other patients who weren't on treatment,
they were left of the MS medicines.
One of the problems was, the patients all knew
that they had received a procedure.
You heard Dr. Barrie talk earlier before the break
about clinical trials, where we like,
in an ideal situation, to have a comparator group
against our intervention group.
So, we wanna know in a side-by-side comparison,
does an intervention, whether it be a drug,
or a treatment procedure like this, make a difference,
compared to people who don't receive the procedure.
And we also like it to be blinded,
meaning the patient, him or herself,
doesn't know whether they're getting the real treatment
or a sham treatment, and the people who do the evaluating
are also blinded, so they don't have bias
towards one conclusion or another.
So fortunately, the patients in this study
all came through without any complications
from the angioplasty procedure.
Remember, when you're blowing up veins,
there's always the risk that it blows the vein up too much,
and it causes a tear, and that leads to bleeding,
and could be catastrophic.
And then, what they found was,
when they went back and looked later,
that patients who had the angioplasty procedures
in the jugular vein, but about half of them,
actually, the narrowings came back.
So, the benefit of the angioplasty procedure was temporary.
It opened it up for awhile,
but then the narrowing redeveloped.
It was less likely to happen in the azygos veins.
But really, the main question was
what affect did these procedures have on the course of MS?
So, they reported that patients, prior to the procedure,
about half of them had had recent relapses,
and then following the procedure,
only about a quarter of them had relapses,
suggesting that there was some benefit.
And, when they did MRI scans on these patients
before and after the treatment,
these contrast enhancing lesions
that were talked about earlier this morning
were less frequent, compared to before the intervention.
And we use other rating scales,
quality of life rating scales,
to assess patients before and after an intervention,
and these were also performed in this study.
So, again, in this separate research publication,
in engendered a lot of conversation in the MS community.
They didn't have a control group,
so they didn't have a comparer group of people
who didn't receive the intervention,
or received a sham procedure.
They didn't have the physicians doing assessments
after the procedure be blinded,
and the possibility that the angioplasty procedure
was temporary made it a little bit difficult to know
how long it lasted, and whether the extent,
or the duration, of the opening
was variable from one patient to the next.
Again, there are lots of questions here about it.
Generated a lot of controversy,
but also got a lot of traction
in the medical community, in the patient community,
and really forced a careful reassessment
of our current knowledge, state of knowledge, of MS,
and how do we best move forward from these findings.
So, the possibility that the angioplasty procedures
were temporary, meaning the narrowing came back,
suggested to the treating physicians in this study
that instead of using a balloon to open it up,
they could put a little support mechanism
inside the vein, called a stent,
and keep it open permanently.
So, a logical alternative would be to actually
stent open the vein that was narrowed,
and that would be a more permanent procedure.
I talked earlier about how veins might be involved
in the pathogenesis of MS.
But, there are a lot of things that aren't
adequately explained, here.
We know that this is an autoimmune disease,
now how do we rationalize that to these vein findings?
How did we incorporate the fact that MS changes,
the prevalence of the disease, changes with age?
Some patients are genetically more susceptible
to coming down with MS than others,
and how does that explain,
how do these genetic differences link up
to potential vein abnormalities?
Furthermore, there are other diseases
that cause narrowings of veins,
and none of them are known to trigger MS-like illnesses.
So, things that block veins, or inflame veins,
in the neck or in the chest
don't lead to the development of multiple sclerosis.
So, it was really hard to put all this together
and understand what it meant.
But nonetheless, there was a lot of discussion
about Dr. Zamboni and his team had found a cure
for multiple sclerosis,
that we could treat these vein abnormalities,
and patients would be cured,
because 100% of patients had these abnormalities.