Once again, I’ll bring this
illustration to your attention
because I want you to know where we
are and what we’re dealing with.
So, we’re doing
and we spent an awful lot of time
with peripheral neuropathy and such.
And we talked about diseases of the
anterior horn, motor neuron diseases
such as amyotrophic
With peripheral neuropathy,
we went through plexopathies,
we went through mononeuropathy,
and walked through polyneuropathies.
And then what we have left now is going
to be neuromuscular junction diseases,
and then we’ll have our
myopathies including our,
what’s known as your muscular
dystrophies, Duchenne and company.
At this junction,
pun intended, it was the
With neuromuscular junction,
well, what are we looking at?
What if the problem
And that’s where
the disease was.
So, think about where you are first.
You’re going to release what
at the neuromuscular junction?
What does it bind to?
Your acetylcholine receptors,
a.k.a., nicotinic receptors.
These are ligand-gated.
This then opens up your sodium
channel, and in comes the sodium, right?
But in order for you to
release that acetylcholine,
what do you need to bring in
presynaptically so you can release it?
Ah! Voltage-gated calcium channel.
So, presynaptic disease,
Lambert-Eaton myasthenic syndrome.
We have already talked about this
as being possibly paraneoplastic
with small cell lung cancer.
Botulism, what does that do?
Well, if you’re injecting
Because you heard Botox, right?
That’s amazing to me.
But you’re trying to
iron out the wrinkles
by inhibiting the release of
And something called tick
infamous myasthenia gravis.
That’s where we’ll begin
is myasthenia gravis.
Clinical features: What happens here?
Well, most likely, an autoimmune
disease automatically puts you
into to the gender or
sex of females, right?
In addition to that, what
else might you find here?
The thymus in a
Well, normally, it
should be non-existent.
But then they give you a chest x-ray
or you’ve been shown a chest x-ray,
and then all of a sudden,
in this 40-year-old female,
you’ll find a thymic shadow.
A thymic shadow in a 40-year-old?
Why in the world was there
a thymoma to begin with?
Well, maybe because this
female had myasthenia gravis.
And what happened?
Well, she had fatigable weakness.
What kind of muscles?
The proximal versus the distal.
And you have different types
of muscles, don’t you?
You have type 1 and type 2.
The fast-twitch will be type 2, that you’ll
have to memorize in your own special way.
But type 2 will be the fast muscle fiber.
They require quite
a bit of energy,
so therefore, think about the
So, your patient is now complaining of,
“Hey, doc, I wake up in the morning.
Hey, I feel great
and I go to work.
And man, around lunchtime, I’m
having a hard time seeing.
And by the time four o’clock rolls out, I
am barely able to get out of my chair.”
So, prominent ocular involvement,
because the first type of muscle fibers
that would be affected will be fast-twitch.
Ptosis and diplopia.
Pupils never get involved, because why?
This is neuromuscular
junction, is that clear?
It has nothing to do with
ocular motor parasympathetic.
Bulbar musculature frequently involved, and
deep tendon reflexes usually preserved.
Around four o’clock, why does the
patient feel so incredibly tired?
the pathogenesis, which we’ll
talk about in a second,
the acetylcholine receptors, type 2
hypersensitivity, had been destroyed.
If you don’t have these receptors, it
might be difficult for you to move, huh?
How in the world are you supposed
to have an action potential
in the neuromuscular junction if
your receptors are obliterated?
The pathophysio, what is it?
Antibodies directed against the
postsynaptic acetylcholine receptors.
On the muscle fiber.
Hence, the oculomotor
was not affected, right?
What was affected?
Oh, the muscle, that’s right,
the type 2 muscle fibers.
with thymic hyperplasia.
Stop there, absorb that.
I told you about this female who had
a thymic shadow at the age of 40.
Remember, the thymus is responsible
for educating our T-cells.
And once the T-cells are educated and
then the soft T-cells undergo apoptosis,
then really, the thymus
undergoes involution itself.
the thymomas, older onset,
which may need to be removed,
and that’s what I
was referring to.
The thymectomy on your chest X-ray
would then reveal a thymic shadow.
Next, well, what happens on
your nerve conduction test, NCS?
Decremental response with low
frequency repetitive stimulation.
Increased jitter on single fiber EMG.
So, what do you think you
might want to do in which
you can increase the
strength of the muscle?
If the problem is that the acetylcholine
receptor is never worked,
why not increase the
concentration of acetylcholine?
“That sounds like a
fantastic idea, Dr. Raj.”
It is, because if you do increase the
concentration of acetylcholine, guess what?
You might actually get a response where the
muscle fiber might increase in strength.
You’re going to use this for
your diagnostic purposes,
and actually, long-term
management of your patient.
Are you having fun yet?
Let’s do this.
Now, myasthenia gravis,
what do you want to do?
Increase the concentration of
acetylcholine in the synaptic cleft.
Can you picture that?
Are you there?
A wonderful place to be.
You inhibit the
Think about drugs such
And steroids-sparing agents.
And so here, immunomodulators, right?
Azathioprine, if necessary,
methotrexate and company.
IVIG and plasmapheresis,
especially if there’s a crisis.
Remember, this is an
autoimmune disease, huh?
And so therefore, attacking
the acetylcholine receptors,
and if you start getting to a point where
it’s refractory and it’s
really not responding,
then you’re really not left
with much of a choice,
and then it is shown that
by removing the thymus,
this hyperplastic thymus or a thymoma,
that the patient’s symptoms might subside.