00:01
So let's walk through some of the
types of CNS inflammatory conditions
we can see the monophasic illnesses,
the recurrent illnesses.
00:09
And let's think a
little bit more about
the predominant cell type
that's involved
and the typical conditions
that we see.
00:16
Let's start with
monophasic conditions.
00:19
These are our
clinically isolated syndromes.
00:22
Patients present
with a single attack,
subacute onset of
neurologic deficits
that peaks over the course
of a couple of weeks
and then returns
typically back to normal.
00:31
We call these the
clinically isolated syndrome
because there is a isolated
syndrome that doesn't recur.
00:37
This syndrome can be categorized
based on the area of the
nervous system that's involved.
00:43
So clinically isolated
optic neuritis
is an optic neuritis that occurs
with one attack.
00:48
The patients develop new
vision changes or vision loss
often with red or color desaturation
and pain with eye movements.
00:55
Those are the classic symptoms
of an optic neuritis.
00:58
We may do an MRI and see
enhancement of the optic nerve
or an LP and see inflammation
within the nervous system.
01:04
Because again, the optic nerves
are an extension of the brain
and they're connected to
that same spinal fluid space.
01:10
In clinically
isolated optic neuritis,
there's one event
it's a monophasic illness.
01:14
We worry in a
patient's first presentation
that they could develop
new events and watch closely
for those and look for signs
of evidence of possible
or recurrence or
risk of recurrence.
01:26
When the brainstem is affected
is a clinically isolated
brainstem syndrome.
01:31
When the spinal cord is affected
is a clinically isolated
transverse myelitis.
01:36
And when there are no symptoms
and we see it just with imaging,
that is coined radiographic
isolated syndrome.
01:45
Those are the
clinically isolated syndromes
where there is a single area
of brain that is involved
and not a diffuse
or multifocal area that's involved.
01:53
We can also see monophasic
inflammatory disorders
where there's
dissemination of symptoms
over nearly the entire neuro
axis or central nervous system.
02:03
The most common of those
is the acute demyelinating
encephalomyelitis,
which is called ADEM.
02:09
This is a diffuse
multifocal process
that involves the brain
and the spinal cord.
02:14
That's why it's an
encephalomyelitis.
02:17
It's an inflammatory disorder.
02:18
That's why the name ends with itis.
02:20
There's inflammation
in the nervous system.
02:23
And there's demyelination.
02:24
We see demyelination
on MRI and spinal cord.
02:28
MRI of the spine and
MRI of the spinal cord.
02:31
We see increased protein with
the spinal fluid and with an LP.
02:35
And those are all suggestive of an
underlying
autoimmune condition
and demyelination.
02:40
It's follows a monophasic course
with sub acute onset,
peaking in several weeks, and then
often improving back to normal
and rarely recurs, but can
and in various rare exceptions.
02:52
And then there's a
second condition called
Acute hemorrhagic leukoencephalitis
or Hurst encephalitis,
which is just a hyperacute
and fulminant form of ADEM.
03:00
And again,
these are where there's an attack
all over the central nervous system
one time as a monophasic course.
03:09
Those monophasic
conditions are different
from the recurrent conditions.
03:14
And we can categorize recurrent
inflammation in the nervous system
based on the predominant
cell type that's involved.
03:21
There are recurrent T cell
predominant syndromes,
and this is where there's recurrent
episodes of relapses and remissions.
03:29
And the predominant cell type
that's involved
that we see is a T cell process.
03:33
Now when the
immune system is activated,
there's always some degree
of T cells and B cells
and a lot of other
things in between.
03:40
But the primary cell type that's
mediating this problem are T cells.
03:44
The classic example of
this is multiple sclerosis.
03:47
And there are a number
of types or categories
of multiple sclerosis
that we can see.
03:52
We can see relapsing remitting MS,
which is depicted on the
schematic on the left.
03:56
We can see relapsing
progressive MS,
where there's not
returned to baseline.
04:01
Patients develop persistent fixed
deficits during their remissions.
04:06
We can see secondarily
progressive MS,
which you see in the
depiction on the right,
where patients have
a period of relapses
followed by progression over time.
04:14
And that's where this
inflammatory disorder
is taking on a degenerative flavor.
04:21
And Primary Progressive MS
doesn't start with relapses
and remissions at all
it just progresses
steadily over time.
04:29
MS is driven by a
T cell activation,
and it is our produce a
prototypical T cell predominant
recurrent CNS autoimmune condition.
04:41
What about recurrent
B cell predominant disorders?
And again, these are primary
CNS neuroinflammatory disorders
where the problem is
really with the B cells.
04:49
B cells have to be
turned on by T cells
and they do interact
with the T cells
but we can measure the antibodies
and that's what gives
these conditions
their name and diagnostic testing.
05:00
There are two classic examples.
05:01
One, is NMO or
neuromyelitis optica.
05:05
And the second is MOG
antibody disorder.
05:08
We think about those and
some of the typical diseases
are NMO or Devic's disease,
which is another name
for that condition.
05:15
There is NMO spectrum disorders,
which are some of the secondary
CNS autoimmune conditions
that we'll talk about,
in MOG antibody disorder.
05:23
And these should be the
three things you think about
when we're thinking about
recurrent B cell predominant,
CNS autoimmune conditions.
05:31
And then there's also
another or also other
CNS neuroinflammatory disorders
that don't fall strictly
in those other categories.
05:38
There are some macrophage mediated,
macrophage predominant
conditions like neurosarcoidosis
Erdheim-Chester, Histocytosis,
and Rosai-Dorfman disease.
05:48
Here, macrophages are activated.
05:50
There's also T and B cells that
are a part of that process,
but the primary immune mediator
that infiltrates into the brain
are the macrophages.
05:58
We can also see some T cell variants
or variants of multiple sclerosis,
There's a Marburg, Schider's,
Balo's concentric sclerosis variant,
chronic myelopathy,
and progressive ataxia
that can also be observed.
06:11
And then some other conditions
that are CNS autoimmune condition,
Neuro-Behcet's,
and connective tissue disease
associated CNS-autoimmunity.
06:19
We can see some
mixed polyclonal B/T cell.
06:22
This disease is an example.
There is Castleman's disease
and primarily B cell
mediated disorders,
like a plasma cell granuloma
would also be a consideration.
06:31
And these are significantly less
common than the other disorders
that we discussed.
06:35
And I really encourage you
to focus on things like
MS, NMO, and MOG antibody disease
as well as the
clinically isolated syndromes.