- So I think in the medical community,
the first order of business was to really dig deeper
and try to understand whether
these findings could be reproduced.
So that generated interest at other centers.
So these were a series of papers
that came out of an Italian multiple sclerosis center.
So other centers sought to try to reproduce
Dr. Zamboni's teams findings.
So here are a couple of studies.
One here in the United States and the State University
of New York in Buffalo.
They had 500 patients and this was a study
where they used the Doppler test
to try to find vein abnormalities in MS patients.
People with other neurological diseases
and people without known diseases.
These are the proportion of patients
that they found the abnormalities with.
So suggesting an increased frequency in MS
but not the dramatic 100 percent versus zero percent
findings that the Italian group had reported.
Here's another study in Europe that studied 76 patients,
again with the ultrasound test and they couldn't
find blockages in any of their patients.
So was this variability in the test
from one center to the next?
Was this variability in MS from different countries
in Europe versus North America?
How could this be explained?
And it's continued to be the subject of investigation.
So Dr. Zamboni's team suggested that this variability
was the result of the fact
that different centers were using different techniques
to find these blockages.
So colleagues also in Italy decided to use
the very same techniques that Dr. Zamboni
and his team had used.
So in essence to try to fully reproduce their findings
using the exact same methods and criteria and strategies
so that we couldn't really have discrepancy
about different results based on different techniques.
So they studied MS patients, 84 people and control 56 people
and did not find any differences between the two groups.
And amongst the MS patients,
about half of them were found to have abnormalities
and half of them didn't.
They were followed over time and the important thing
from this paper which was actually published last month
in the medical literature in a prominent neurology journal.
There was no difference between the CCSVI positive MS
patients and the CCSVI negative MS patients
in terms of their future clinical course.
So it didn't mean that if you had vein blockages
your MS had been there longer or is more severe
or is more likely to deteriorate over the coming months
than if you didn't have these blockages.
So I think we're in a situation now where a number
of groups have independently been unable to reproduce
Dr. Zamboni's findings.
And I think that leaves us with some unanswered questions
about the relationship between the CCSVI abnormality
and multiple sclerosis.
So there have been centers that have actually gone ahead
and started to put stents into narrow veins.
And this was a prominent vascular, interventional
vascular specialists at Stanford
that was doing this a few years back.
And unfortunately there were a couple of adverse
events that came out from their experience.
So sometimes when patients get the stent,
they're put on a blood thinner for a period of time
after the stent is done to prevent it from clotting up.
And unfortunately, a patient had a fatal bleeding event
inside the brain because of the blood thinner.
And in another patient the stent that was put
into the jugular vein actually slipped out of position
and it migrated into the heart.
And it forced the heart surgeons to have to go in
emergently to fish it out.
So there was an unexpected complication
that required heart surgery.
So the university at that point decided
we don't really know what's going on here,
the procedures look risky.
And they halted the procedures being done at Stanford.
So I think these kind of experiences
and the fact that other centers have not been able
to reproduce Dr. Zamboni's findings
has forced a little bit of rethinking
about the CCSVI.
And at the end I'll come back to some
of my thoughts about that.
I did want to take on the somewhat controversial subject
of the use of medical marijuana
for treating MS related symptoms.
I get asked about this in the clinic
quite a bit by patients.
As many of you are aware, it's been approved,
medical marijuana's been approved for medical use
in the state of Michigan since it was approved
on a ballot initiative in late 2008.
And it's a very common and obviously controversial
subject in our field.
So cannabis is a plant and commonly
referred to as marijuana.
And the flowering petals of the plant are
what is usually smoked recreationally
and therapeutically for many many years.
And it turns out that the bio-chemists have found
many different compounds in marijuana
that are in this cannabinoid family.
And the one that people may have heard of most commonly
is this compound called THC or tetrahydro cannabinoid
which is the main psychoactive substance,
the substance that makes you quote high
when you smoke marijuana.
And actually chemists have synthesized this molecule
and it's available as a therapeutic agent.
So this is also known as dronabinol,
people know it as Marinol.
Here's another cannabinoid that's called Sativex
and the extract of the plant Cannador.
These are all commercially available preparations
of derivatives of marijuana.
So they've been used therapeutically for pain relief,
for appetite stimulation in patients with cancer
and for other indications for some time.
So the question is what effect does using the natural
plant product or synthetic product
have on multiple sclerosis?
So it's been described for many years by MS patients
that people who use marijuana find
that many of their MS symptoms are made less severe.
So there's word of mouth reports
that it helps a variety of different symptoms.
It's really to hard to know the extent
to which it's being used in the MS population
but I found a little bit of literature to suggest
that a small proportion of patients in the UK
admit to smoking marijuana for their MS symptoms.
And in a group of MS patients in Canada,
the use actually is relatively high.
So I think it's fairly common and the fact
that I get asked about it regularly in the clinic
means that it's something that's on people's minds.
Now none of the synthetic compounds that I mentioned
are licensed for use in MS.
So you can get a prescription for the drugs I mentioned
on the previous slide but it's not approved
by the Food and Drug Administration for multiple sclerosis.
Although last year it was approved in the UK,
one of these preparations for treating
muscle stiffness or spasticity.
So there are now medical studies that are being done
to suggest that these synthetic compounds
may be useful to treat symptoms.
So anecdotal evidence, widespread reported benefits.
There have been mail surveys that are done anonymously
so that people get sent a survey,
they don't put their name on it.
And if they're willing to discuss their marijuana use
relative to their MS related symptoms suggests
that in a high proportion of patients,
symptoms of pain, symptoms of muscle stiffness,
tremors and even mood disruption anxiety and depression
are benefited subjectively by the use of marijuana.
Other symptoms that may perhaps less commonly improved
with cannabis use include fatigue,
sexual dysfunction, weight loss.
There are even some people but a fewer proportion of them
that think it helps bladder symptoms.
Dr. Braley introduced you to the concept of clinical trials.
There are different ways to evaluate
the rigor of clinical trials.
Class I evidence is the most rigorous
so it's a placebo controlled blinded study.
And there have been studies with the compounds
in small groups of patients that suggest
that it's beneficial for some symptoms of MS.
Less rigorous evidence suggests
that it helps bladder symptoms.