- Another test that helps us with the diagnosis
of multiple sclerosis is a spinal tap
where you remove fluid from around the spinal cord
and analyze it.
And what we look for in the spinal fluid
is a presence of certain proteins
that we call bands.
Actually the proteins are run out on a gel
and these certain proteins appear as these band-like strips
and we wanna see those bands in the spinal fluid
but not in the serum.
These proteins are
are substances that are produced by
inflammatory cells in the central nervous system
and we see them in multiple sclerosis.
You could also see them with other inflammatory conditions
of the central nervous system.
For example, sometimes the lupus affects the brain
and we can see these bands,
certain inflections like Lyme's disease
could result in these bands
but they're most common in multiple sclerosis.
The test is helpful but once again,
it doesn't indicate with a 100% certainty
whether or not someone has MS
not only because other conditions could lead to
the development of these bands
but because of the 30% of patients with MS
at the beginning do not have the bands
and most studies, approximately 80% of patients
will eventually develop them
but if you do not have this finding in the spinal fluid,
it doesn't rule out multiple sclerosis.
So, now I'm gonna talk about the different types of MS
and for decades we have been categorizing patients
into different subsets based on their clinical course,
the history of their symptoms.
As I mentioned earlier,
the relapsing remitting form is the most common form.
85% of cases of MS start this way.
And what this means is on these graphs,
we're measuring disability, neurological symptoms over time.
So these bumps represent episodes
when patients have MS relapses
or exacerbations as we call them
in which they develop new symptoms.
The symptoms I reviewed earlier could be optic neuritis
or decreased vision in the eye.
It could be a spinal cord syndrome
where there's numbness and weakness below the waist.
Early on though, most patients tend to recover.
It's often back to baseline, not always,
but they tend to improve
but if this is multiple sclerosis,
they will inevitably have another attack.
And the time between the attacks
could vary between three months and 30 years.
It's quite variable.
But over time, more and more attacks will occur.
Now in some patients over time,
the relapsing remitting phase of MS changes
and evolves into what we call secondary progressive MS.
And by progressive MS, what we mean is that
someone has a certain group of symptoms
that slowly get worse over time.
Often, this takes the form of weakness
on one side of the body or labored gait,
sometimes memory problems
but it doesn't occur as a discrete episode
like we see in the relapsing remitting stage.
These symptoms just very slowly and gradually get worse.
So you could see someone for example who may be
limping because of an MS lesion
and when ask them when that started,
it's hard for them to recall
because it happened very gradually.
They know that they're not walking as well today
as they did six months ago
or a year ago
but the timeframe is less clear.
So that's we call secondary progressive MS
and it follows a relapsing remitting phase.
It's secondary because it occurs afterward
that are secondary to the relapses.
There is a rarer form of multiple sclerosis
called primary progressive.
This accounts for about 10 to 15% of cases of MS
when an individual will not have any relapses
but will just go into a progressive phase from the get go.
And there's a lot of debate
over whether primary progressive MS
is actually a different disease from relapsing remitting /
secondary progressive MS.
So here's another illustration of the clinical course
of relapsing remitting MS over time.
Just as I showed you before these bumps represent attacks
of multiple sclerosis when patients develop symptoms.
In between the symptoms early on,
they may return to baseline
but inevitably will have more attacks
and some patients will at some point
go into this progressive phase.
So this a timeline.
Now this graph also illustrates a point
that I'd like to make
regarding the phenomenon of silent lesions or plaques.
These arrows are meant to represent
the appearance of new lesions on MRI scans
and you could see that they outnumber
the actual attacks of symptoms.
So it turns out that the majority of plaques
don't cause symptoms when they're forming.
In fact, 10 times or more plaques are what we call silent
as opposed to symptomatic.
Why is that the case?
Well, the plaques in multiple sclerosis aren't as large
as for example a big stroke.
They're relatively small
and often if some of their fibers are damaged,
other nerve fibers can take over the job and compensate.
Also, a lot of the lesions conform in areas of the brain
that have to do with intellectual functions,
the ability to calculate personality features
and a small lesion is not gonna be evident to a patient
or his or her family or co-workers.
So many lesions are forming sometimes when people feel fine
and that's why we regularly do MRI scans
even if a person believes that they're stable
because as these silent lesions collect
and accumulate over time,
there's less healthy nerve fibers to compensate
and ultimately, patients could enter a progressive phase.
I've had patients who, this is not typical,
but I'd had several patients who've had an episode
of optic neuritis as a teenager for example,
did not have another attack for 20 even 30 years
and then entered the progressive phase
because by chance, all of those plaques that were forming
were in areas that didn't cause symptoms
but then they built up over time and led to progression.
So the MRI scan allows us to get a more accurate idea
of what's going on with the disease in individual patients.
I mentioned primary progressive MS.
This is the type of MS where an individual
slowly accumulates disability over time
without having relapses.
This form of MS tends to present later in life,
often between the ages of 40 and 50
as opposed to the relapsing remitting phase
which occurs from in the 20s and 30s most typically.
Also in this form of MS, men are affected equally to women
as opposed to the relapsing remitting form
in which there's a two-fold higher incidence among women.
And there's less evidence of inflammation on MRI scans
during in this form of the disease.
They don't have as many of those plaques
that take up the dye which indicate inflammation.
So some people think this is a different form of disease
that doesn't involve so much inflammation,
that involves more of a dying of back of nerve fibers
with little inflammation.
A number of scientists who are my colleagues
and experts in MRIs
actually believe that it is indeed the same disease.
There's just the spectrum with regard to how it presents.
And sometimes within the same family,
we see individuals who have relapse and remitting
and who have progressive MS
and there are new gene studies that are coming out
that we've just published in fact over the last month.
These are studies in which hundreds of thousands of patients
have been analyzed to look for genes
that increase your risk of MS
and it turns out that the same genes
that increase your risk of relapse and remitting
overlap with the genes that increase your risk
of primary progressive.
So I'm beginning to think that they really are
the relapse remitting and primary progressive disease
are really the same entity but at different ends
of the spectrum.
This slide shows a series of MRI scans
done on one patient over six months
and the MRI scans were taken a month apart.
So there are six scans
and the scans were taken so that normally
you cannot see the lesions very well
but if you inject the dye, they light up.
So this just shows you how this person has lesions
which are coming and going over the course of the six months
and actually he didn't have any symptoms
during this time period.
So once again, to illustrate the point
that you can have these silent lesions develop.