00:01
How do we evaluate patients?
What do we do on exam?
How do we use provocative testing?
And what laboratory studies
should we consider
to work up a patient who were
concerned may have myasthenia?
Well, the first is we perform a
comprehensive neurologic exam.
00:16
Looking for signs of weakness
and fatigability.
00:19
If we see the presence of ptosis,
there's two really neat
examination techniques
that can evaluate that ptosis
and point to that problem being
from the neuromuscular junction.
00:30
And so these
tests are performed
when there is prominent
bulbar weakness
or prominent ptosis.
00:35
The first is the ice-pack test.
00:37
This is a really neat test.
00:39
And we're looking for
resolution of ptosis.
00:42
So we saw those images of patients
whose eyes were closed,
and we place an ice-pack,
and we see that the eye opens.
00:49
Why does this happen?
Well, it turns out when you cool
down the neuromuscular junction,
this improves neurotransmission.
00:56
And so we see better
acetylcholine quanta released
into the neuromuscular junction,
and better depolarization
of muscles.
01:04
To perform this test,
a patient is put at the bedside,
we get a cold ice-pack
and place it over the eye.
01:12
After about a minute, we look for
rapid resolution of ptosis.
01:16
And this occurs quickly and
needs to be evaluated quickly
after performing this test.
01:21
The second neat bedside test
that can evaluate
for the presence of
a junctional disorder
is the edrophonium test.
01:27
This is also called
the Tensilon test.
01:29
And again, we're looking
for resolution of ptosis.
01:33
This is a medication that
can improve transmission
at the neuromuscular junction.
01:37
And so we're also looking
for the presence of ptosis
prior to the test that
resolves immediately after.
01:44
What about
serologic testing?
What studies can we do to
evaluate for myasthenia gravis?
Well remember, myasthenia
is an inflammatory disorder.
01:53
It's an autoimmune condition.
01:55
And it's characterized by the
presence of autoreactive antibodies.
01:59
So we're going to look at those
in the circulating system.
02:03
The serologic studies
that are performed include
looking for acetylcholine
receptor antibodies,
anti-MuSK, the muscle specific
kinase antibodies.
02:12
And there are some other
increasingly described antibodies
that we'll talk about.
02:16
And we can categorize the myasthenia
as seropositive
in patients who have the
presence of one of those antibodies,
and seronegative in those
that have a clinical presentation
consistent with myasthenia
but the absence of antibodies.
02:31
So let's look
a little bit closer at the
postsynaptic
acetylcholine receptor.
02:36
Myasthenia is characterized
by antibodies
that bind to recognize an auto react
to this receptor.
02:43
And we can see antibodies that bind
to many of these areas.
02:47
Here you can see
the extracellular space,
the sarcolemma,
which is the cell membrane
of the muscle
and the muscle tissue itself.
02:55
The acetylcholine receptor lies
on this membrane
recognizes acetylcholine quanta
in the synaptic cleft,
and results in activation
of the muscle
as a result of bringing sodium
in to the muscle cell.
03:08
Acetylcholine receptor antibodies
bind to this receptor
and result in the
loss of function
inability to bring sodium
into the muscle
and activate the muscle
for contraction.
03:18
The second antibody that we see
is the antibody to MuSK.
03:21
And you can see the MuSK component
of this acetylcholine receptor here.
03:25
A docking enzyme that's critical
for its action.
03:29
So let's look a little bit closer at
the types of myasthenia
based on serologic testing.
03:33
And understand the features
of those antibody tests.
03:37
Well, acetylcholine receptor
antibodies are present
in the vast majority of myasthenics.
03:42
80% of myasthenics will find the
presence of acetylcholine receptors.
03:47
And there's a 20% remission rate,
which is great.
03:50
We also see acetylcholine
receptor antibodies
in patients with
ocular myasthenia.
03:55
That myasthenia that has a
predilection for the bulbar fibres
and really ptosis with an absence
of generalized weakness.
04:03
Anti-MuSK antibodies are the
second antibody that we test for.
04:06
And these we find in approximately
30% to 40% of patients
who don't have
acetylcholine receptors.
04:13
So our test initially is to look for
acetylcholine receptor antibodies.
04:16
And if positive a diagnosis of
myasthenia is made.
04:19
If negative of the physician or
clinician should consider testing
for MuSK antibody positive
myasthenia.
04:26
There's a smaller chance
of remission rate
with MuSK antibody myasthenia.
04:30
And patients often have more
prominent ocular symptoms
with a paucity of
systemic complaints
in some of these patients.
04:37
The last antibody that we can look
for is the anti-striational protein.
04:41
And this is present in 80% of
thymomatous myasthenia gravis
or myasthenia gravis that
occurs in a patient with a thymoma,
and 30% of nonthymomatous
myasthenic patients.
04:52
And these antibodies
are slightly less specific
than acetylcholine receptor
and MuSK antibody myasthenia.
04:58
About 15% of patient
will not have the presence
of circulating antibodies
and will be defined as seronegative
myasthenia gravis.
05:07
So we have to trust
our examination
Patients who present with typical
findings of a junctional disorder
and have other testing
that's consistent
with a junctional problem
can be diagnosed
with myasthenia
even in the absence
of circulating antibodies.
05:21
What other diagnostic tests
can be performed?
Well, one that we rely on
heavily in neurology is the
EMG nerve conduction study.
05:30
And this stands for
electromyography,
which is looking at the muscle
specifically with a needle
and nerve conduction
velocity testing,
which is shocking nerves to see
how they communicate.
05:41
You can see both
of these tests here.
05:42
The picture on the bottom
is demonstrating
a nerve conduction
velocity examination.
05:47
We take a probe and
put it where a nerve is
at the surface of the skin.
05:52
And we shocked both a sensory nerve
or a motor nerve
and see what happens.
05:56
For the sensory nerve,
we're looking at conduction
up that sensory nerve,
and seeing how fast
the conduction is.
06:02
And looking at the myelination of
the sensory nerve
and the number of axons
in the sensory nerve
to look for problems
in nerve transmission.
06:10
We can also look at motor nerves,
and we shock a motor nerve, and
look at contraction of the muscle.
06:16
And that helps us to look at both
the motor nerve,
the neuromuscular junction, and
the integrity of the muscle as well.
06:23
In the top picture,
we're looking at an EMG
or electromyography.
06:27
And this is where we take
a small needle
and put it into a muscle
and record the signal
around that muscle.
06:32
We can look for problems where
nerves are not innervating muscles,
or where muscles
could be damaged.
06:39
When we're evaluating a
neuromuscular junction disorder,
when critical EMG
nerve conduction test
is repetitive stimulation.
06:46
And this is a special technique
a way to do nerve conduction
to look at repetitive activation
of a muscle,
to see the problem in the
neuromuscular junction.
06:56
We see problems with
repetitive stimulation
about 90% of patients who have
a neuromuscular junction disorder
and specifically myasthenia gravis.
07:05
And the last test that we can look
at is called Single-fiber EMG.
07:09
And this was looking
very specifically
not at the entire muscle itself,
but individual
neuromuscular junctions
looking for problems with
transmission across the junction,
and that's called jitter.
07:20
And the presence of jitter
on a single fiber EMG
is highly specific for a
diagnosis of a junctional disorder
and is seen in patients
with myasthenia gravis
in up to 96% to 99%
of those patients.
07:33
So these are the tools
in our armamentarium
to evaluate patients
who have weakness
that appears to be from a
neuromuscular junction condition.