00:01
So let's start with a definition.
00:03
What is clinically
isolated syndrome?
This term is used to identify
a clinical event
that has characteristics
of a demyelinating episode,
such as a transverse myelitis
or an optic neuritis.
00:14
But MS cannot be formally diagnosed.
It's not recurrent.
00:17
There's not evidence
of other events.
00:19
So the definition of
clinically isolated syndrome
is the first clinical
and neurologic event
suggestive of a
demyelinating attack or MS,
lasting greater than 24 hours.
00:31
It's caused by inflammation
or demyelination
in one area of the nervous system
(monofocal)
or can be seen in multifocal
or multiple areas
of the nervous system.
00:42
And types of attacks include
optic neuritis,
spinal cord syndromes,
and brainstem syndromes.
00:48
Importantly, there's not
evidence of prior attacks
in these patients.
00:53
What are the types of
clinically isolated syndromes?
Well, inflammation can affect
anywhere in the nervous system
including the optic nerves,
spinal cord, brainstem,
and multiple areas in the brain.
01:04
And we can see the breakdown
of typical presentations
of clinically isolated syndrome.
01:08
Optic neuritis occurs in
somewhere around 20-21% of patients.
01:13
Spinal cord syndromes are common
and are termed
clinically isolated
transverse myelitis
where a single segment of
the spinal cord is affected
such as in our patient.
01:24
The brainstem can be affected
in a minority of cases
and some patients will present
with multifocal attacks in 23%.
01:33
Let's break down
some of these different
clinically isolated syndromes
and start with optic neuritis.
01:38
And this is very important
to understand.
01:40
It's a common presentation
for a CNS autoimmune condition
and we want to understand
the clinical presentation
and evaluation of these patients.
01:49
So some of the common features
that we see with an optic neuritis -
patients present with vision loss.
01:55
That is often
unilateral and monocular.
01:58
And that localization,
that presentation is critical
for localizing symptoms
to the optic nerve.
02:05
Vision loss, is the primary symptom
and patients report
decreased visual acuity.
02:10
The onset is typically gradual
with new onset vision loss
and reduced visual acuity
over three days to two weeks.
02:17
That sub acute onset.
02:19
Pain is extremely common,
and patients will tell you
that it hurts
when they move their eyes.
02:23
Pain with extra ocular movements.
02:26
And that is a sensitive
historical detail
for considering optic neuritis.
02:33
We look for an afferent
pupillary defect.
02:36
And this is evaluated by
a swinging flashlight test.
02:40
Looking at pupillary constriction
to a light stimulus.
02:43
When we do that, and we see dilation
to the light stimulus
that's abnormal.
02:48
And it is suggestive
of an afferent pupillary problem
or a Cranial Nerve II lesion.
02:55
And patients present
with a visual field defect
as a result of enhancement,
of irritation,
of inflammation,
of the optic nerve,
which we're seeing here on the MRI,
zoomed in on the right eye
orbit and optic nerve.
03:07
And we see contrast enhancement
in the optic nerve.
03:10
Active inflammation as a result
of this immune attack
that is contributing
to this patient's symptoms.
03:19
There are some neat features
that we see
with the vision loss
with optic neuritis
and when the early symptoms
that patients can report
as color desaturation,
which is evaluated by
the Ishihara plates
which you can see here.
03:31
We're looking at contrast
of the colors
and asking the patient
to count or report
the number that they see
on each of these plates or cards.
03:41
Patients with optic neuritis
will have desaturation of colors.
03:44
It's hard to see the contrast
between the two colors
and to report the numbers.
03:49
Whereas, normally,
they're sharp contrast.
03:51
And we can see
45, and 74, and 6, and 42
and report those numbers
on the Ishihara plates,
which will be difficult
to report for patients
experiencing an
acute optic neuritis.
04:06
There's some other features
of vision loss that help localize
the patient's symptoms
to the optic nerve.
04:11
And in general,
we think of vision loss
and peripheral field loss
is as either
pre-chiasmatic or post-chiasmatic.
04:19
And this is an important feature
to localize
where in the nervous system
the lesion may be to contribute
to vision symptoms.
04:27
Homonymous visual field loss
and homonymous visual field defects
as you see on the left here
with this left homonymous hemianopia
are suggestive of
post-chiasmatic disorders.
04:37
And this occurs from
CNS brain pathology.
04:40
Posterior to the optic chiasm
a tumor, or a stroke,
or other lesion in that area
of vision information.
04:50
And that compares
to monocular vision loss.
04:52
As you see here
where there's vision loss
and the entirety of the left eye
really sparing the right eye
which is suggestive of
a prechiasmatic problem
and point squarely to optic nerve
pathology and optic neuropathy
and potentially to inflammation
of the optic nerve
and optic neuritis.
05:10
And when we think about monocular
vision loss or an optic neuropathy,
we can categorize that
as painless or painful.
05:18
And pain in the presentation is
important in driving us towards
potential differential diagnoses.
05:24
Painless vision loss is supportive
of a diagnosis of optic neuropathy.
05:29
A problem with the optic nerve
that is not from inflammation.
05:32
And we think about arthritic causes
or vasculitic causes,
and nonarteritic causes
of optic neuropathy.
05:39
In contrast, painful vision loss
should point towards
the consideration for a
diagnosis of optic neuritis.
05:46
Inflammation of the optic nerve
contributing to this
patient's symptoms
and it may have various causes
either associated with a
systemic inflammatory disorder
like Sjogrens or lupus,
or a primary CNS
autoimmune condition like MS
or a clinically isolated
optic neuritis.
06:05
What are some uncommon
features of optic neuritis?
Occasionally we will see
bilateral onset of vision loss
and optic neuritis.
06:13
And you can see that in the
MRI here with avid enhancement
of both optic nerves that
you can see in the green arrows.
06:19
And this can be seen with a variety
of CNS autoimmune conditions
other than MS.
06:26
Bilateral optic neuritis
is uncommon in MS,
but more common in a condition
called neuromyelitis optica
and occasionally in
MOG antibody disorder.
06:36
Painless optic neuritis is uncommon
and should point towards
a possible other diagnoses
which should be evaluated.
06:43
We can see
painless optic neuritis in MS
and clinically isolated syndromes
but should undergo a thorough
evaluation of those patients.
06:51
Severe vision loss
with no light perception
is uncommon in
inflammatory conditions
and really should warrant
exhaustive workup for neoplasms
or other potential causes.
07:02
Though occasionally we can see
very severe vision loss
in optic neuritis.
07:07
And moderate to severe
disc swelling, and hemorrhages,
and retina retinal exudates
should also point towards
other potential etiologies.
07:15
We can see papilledema
or swelling of the optic nerve,
and in some cases
of optic neuritis.
07:20
But the swelling is really behind
the optic nerve head
and in the vast majority of patients
presenting with optic neuritis.
07:27
We don't see abnormalities
on the fundoscopic exam.
07:33
In patients presenting
with optic neuritis,
we see reduced visual acuity
which is evaluated with the
Snellen card or Snellen chart.
07:40
In general,
patients are treated
and we'll discuss the treatment
in just a minute.
07:43
But we expect improvement
both spontaneously and
more rapidly with treatment,
and in general for patients who
have vision worse than 20/50.
07:52
Acuity will improve more than
three lines on the Snellen chart
over the course of six months.
07:57
And this helps us to prognosticate
and guide patients
as they present with an
acute optic neuritis.
08:05
How about other clinically
isolated syndromes?
Let's talk a little bit about
spinal cord syndromes.
08:09
And here we can see a
representative MRI of the spine
showing an area and a lesion,
an area of acute edema within the
spinal cord contributing to symptoms
and suggestive of a
autoimmune attack in the C spine.
08:22
Typical symptoms
of spinal cord syndromes
are a partial myelitis.
08:26
We can see symptoms of weakness,
hemibody weakness, or numbness.
08:29
Sensory symptoms are common.
08:31
We can see Lhermitte's sign.
08:32
And this is when the patient's head
is flexed or extended
and this results in the
sensation of electric shock
that extends down the arm and legs
as a result of
ephaptic transmission,
demyelination of the nerves
in the C spine
results in the potential
for automatic transmission
down those nerves.
08:51
And it's bending of the neck,
activates the nerves,
and results in
an electric shock like sensation,
which is relatively specific
to a CNS lesion,
in the C spine or spinal cord.
09:03
We can see paraesthesia,
as again sensory symptoms
are common,
erectile dysfunction.
09:07
Bowel and bladder dysfunction
can be present
in patients with lesions
in the T spine
may report a band like sensation.
09:15
Something wrapping around
or hugging their chest
as a result of a lesion
in the thoracic cord.
09:20
And since sensory symptoms
predominate in many patients
and often symptoms are asymmetric
resulting from the eccentric
location of the lesion
within the spinal cord.
09:32
We can also see
some uncommon features
which again support a workup
for other potential etiologies
before making the diagnosis
of a transverse myelitis.
09:41
Complete acute
transverse myelitis is uncommon
in clinically isolated
transverse myelitis or MS
and should prompt a workup for
other potential inflammatory
and non inflammatory etiologies.
09:53
Radiculopathy is uncommon
and this is really a peripheral
nervous system problem
and transverse myelitis is a
central nervous system disorder.
10:01
So evidence of radiculopathy
should warrant a workup
for alternative causes.
10:07
Areflexia is uncommon.
10:08
We really see hyperreflexia
from spinal cord conditions
and should see that in patients
who present with acute or
subacute transverse myelitis.
10:16
And segmental loss of pain
and temperature sensation
that does not fit
a spinal cord level
should warrant evaluation
for peripheral nervous
system conditions.
10:25
Rapid progressive
symmetrical paraplegia
should raise the consideration
for Guillain-Barré
that we can also see that
rapid ascending paraparesis
in patients with
transverse myelitis.
10:39
And then what about
brainstem syndromes?
Here we're looking at atypical
lesion in the brainstem.
10:43
And patients presenting with
brainstem syndromes though uncommon,
should warrant consideration
for an autoimmune cause
or a clinically isolated syndrome.
10:54
Some of the symptoms
that we can see
in patients presenting
with brainstem syndromes
include diplopia or
6th nerve palsy or 3rd nerve palsy
problem with a yoking
of eye movements.
11:04
We can see an
internuclear ophthalmoplegia
and that's where the patient
is looking/gazing to one side.
11:10
And the affected eye
is unable to adduct,
unable to medially adduct
towards the nose,
and that's termed an
internuclear ophthalmoplegia,
results from a lesion in between
the 6th and 3rd nerve nuclei
in the brainstem
and a suggestive of a lesion
in that area
and not uncommonly,
an inflammatory lesion.
11:33
Ataxia is a symptom that can occur
from brainstem syndromes.
11:36
Nystagmus is a result
of interruption
of cerebellar circuitry and fibers.
11:41
Facial numbness can be seen.
11:44
Unilateral internuclear
ophthalmoplegia.
11:47
So other problems
with eye movements.
11:49
Facial palsy,
a weakness of the face
either central or
peripheral facial palsy
owing from the exiting of the
facial nerve within the brainstem.
12:01
Trigeminal neuralgia
can be seen
and this is not an
uncommon presentation
for a brainstem syndrome.
12:07
So, all of these are symptoms
of brainstem lesions
affecting either
the white matter tracts
or the cranial nerve nuclei
as they exit the brainstem.
12:18
Then deafness.
12:19
Deafness is rare to be seen
with the brainstem syndrome
but is not impossible
in these patients.