So what's going on?
What causes weakness or
this junctional disorder
in patients with botox toxicity or
botulism, presenting with botulism?
Here we're going to look very closely
at the neuromuscular junction.
We see that the nerve is
ending on the top of the muscle
and as we zoom in we look at
the neuromuscular junction.
And we see the key pieces
that are that are required
Acetylcholine is contained
within the synaptic vesicles
and in order for muscle
contraction to occur,
it must move down the presynaptic
membrane down the nerve
bind to the presynaptic
terminus, release acetylcholine,
bind to its receptor
and this drives end plate potential,
muscle depolarization and contraction,
and there are key proteins that
are involved in that process,
and they're called the snap
and the snare proteins.
And you can see those
The snare and snap proteins help to move
the synaptic vesicle to the terminus.
They bind together,
bring the vesicle down to the terminus
and help it to bind to the presynaptic
terminus and release acetylcholine.
Botulism involves an impairment
in this signaling cascade.
So what happens?
Well botulism ,the botulism toxin is composed
of both a heavy chain and a light chain.
The heavy chain when ingested,
the heavy chain helps to bind
the toxin to the
As a result of binding that protein complex
is endocytosed into the nerve terminus
and we can see that happening
here in this figure.
The light chain then moves
out of the vesicle traffics
to where the snap and snare proteins are
and degrades the snap and snare proteins.
The presynaptic vesicle is
unable to bind to the membrane,
acetylcholine is not
able to be released.
Acetylcholine cannot drive end plate
potential and muscles cannot contract,
and patients present
with prominent weakness.
So here we see the treatments
for iatrogenic botulism
and there's four
things we think about.
The first and most important is withdraw
of the offending agent or ingestion,
that's what's caused this disorder and
the treatment of choice is withdrawal.
In some cases, we can think about
administration of the botulism antitoxin.
a symptomatic management,
which we can utilize in botulism
and can help in selected cases
and then really supportive care
is critical for these patients.