00:01
So how do we think about
neuroinflammatory disorders?
What is the classification?
I like to think about
classifying them in three ways.
00:09
The first is whether they're
primary or secondary.
00:14
The second is by the type of
the dominant immune population
that's involved.
00:18
And we'll talk a little bit
more about what that means.
00:20
And then last, I differentiate
the isolated single events
from recurrent or
multiple events over time.
00:26
And this helps us to understand
the types of neuroinflammatory
disorders we can see,
and the ones that
we're going to diagnose in patients
and on test questions.
00:37
First, let's start with step one.
00:38
Let's understand
the difference between
a primary CNS
neuroinflammatory disorder
and a secondary CNS
neuroinflammatory disorder.
00:48
Primary neuroinflammatory disorders
are ones that
were the autoimmune attack
is only in the CNS.
00:54
There's not a systemic
immune disorder,
there's not
systemic autoimmunity,
this is autoimmunity to the brain
and to the brain only.
01:02
Examples of this include
multiple sclerosis,
neuromyelitis optica,
and MOG antibody disorder,
which we'll talk a
little bit more about.
01:10
Here, we need to evaluate
inflammation within
the Central Nervous System.
01:15
We're looking for activation of
the immune response in the CNS.
01:18
We can do a lumbar puncture
to look for elevated protein
and possibly mildly elevated cells.
01:24
We're looking for that
immune infiltration into the CNS,
or neuroimaging
showing an immune attack
on the brain or spinal cord,
which is evidenced by increased T2,
signal, swelling
in the central nervous system
and often with the
presence of enhancement.
01:39
That enhancement is indicating
breakdown of the
blood-brain barrier,
which is how the
immune system is infiltrating
into the central nervous system.
01:48
There's often not evidence
of systemic inflammation.
01:51
We don't see elevation
on ESR or CRP, or ANA's,
or rheumatoid factors,
or other evidence of an
underlying autoimmune condition.
01:59
The primary process
is in the brain or CNS.
02:04
That differs from secondary
CNS neuroinflammatory disorders,
where the immune attack occurs
in the systemic system,
and then it flows into the brain
or central nervous system
as a result of the underlying
systemic autoimmunity.
02:18
Examples of this include
systemic lupus erythematosus,
Sjogren's syndrome,
rheumatoid arthritis, and others.
02:26
And here the patient
has an underlying
systemic autoimmune condition
that can involve the brain.
02:32
Our evaluation here involves
a twofold evaluation,
both looking for evidence
of CNS immune attack,
as well as the underlying systemic
activation of the immune system.
02:43
And we can do that by investigating
the CNS with a lumbar puncture.
02:46
We're looking for increase
in CSF protein,
and potentially mild elevation
in cell counter pleocytosis.
02:53
The neuroimaging
showing an immune attack
on the brain or spinal cord.
02:58
In addition, these patients
require systemic evaluation
for an underlying
autoimmune condition.
03:03
My typical screen includes an ESR,
CRP, ANA, and rheumatoid factor,
but we may need to dig deeper
based on the history and the
examination of the patient,
if we're concerned about
one of these conditions.
03:15
We may look for double stranded DNA
testing in patients
who may have systemic
lupus or sjogrens antibody,
SSA, SSB,
or RO or LA antibodies in patients
with sjogrens syndrome,
or rheumatoid factor
and patients with
rheumatoid arthritis,
digging for that underlying evidence
of a systemic autoimmune condition.
03:39
Step two in evaluating
these patients
is to determine
whether this is
a monophasic illness
or recurrent illnesses.
03:45
because there were
recurrent attacks,
immune attacks that could
occur in the nervous system,
or is this a single one time event.
03:52
So, monophasic illnesses
and recurrent illnesses.
03:57
The classic monophasic course
you're seeing here
in this schematic graph.
04:02
And we see evolution over time
and patients with
a monophasic illness
have a single attack.
04:06
They begin normal.
04:08
There's onset of disability,
which typically occurs sub acutely.
04:12
So over the course
of a couple of weeks,
patients will develop
weakness in the arm or leg,
they'll develop a paraparesis.
they'll develop vision loss,
and that sub acute onset is common
in patients who have
inflammatory disorders.
04:24
This peaks often over the course
of a couple of weeks
and then gradually improves.
04:30
With patients typically
returning to normal,
as you see in this graph
with no long term disability.
04:35
Now patients can be left
with long term disability
as a result of this
monophasic illness.
04:41
And certain conditions will result
in a monophasic course.
04:46
And that's different from
the recurrent course.
04:48
And here we see
a good example of the depiction
of what a recurrent
autoimmune condition will look like.
04:54
These patients have
periods of relapse
where there's
a new disability and remission,
which often returns to normal.
05:01
Here we have
sub-acute onset of symptoms
in each one of these relapses.
05:05
So patients develop new symptoms
over the course of days, to weeks.
05:09
And again, this may be
hemi body symptoms
or paraparesis,
or new vision changes,
as a result of wherever
the lesion is occurring.
05:16
The immune attack is
occurring in the brain.
05:18
This peaks over the course
of a couple of weeks,
and then there's
spontaneous improvement
or improvement more quickly
with treatment.
05:25
Patients often returned to normal
without disability,
but we can see persistent disability
after each one of these episodes.
05:32
And again with recurrent conditions
patients are at risk for relapses
for new episodes
or recurrence of symptoms.
05:40
with each one of these episodes.
05:43
And this relapsing remitting course
is highly suggestive
of a CNS autoimmune condition.
05:49
We think about
autoimmune conditions,
paraneoplastic conditions,
sometimes infections can have this
relapsing remitting course
and occasionally toxic exposures.
05:59
Those four
pathophysiologic processes
are the ones we should consider
with this type of a course.