An overview of the relevant aspects of the epidemiology, clinical presentation, basic disease mechanisms, diagnostic approaches and treatment options of the most common neurological diseases.
Module 3 Part 1: Overview and Electroencephalography
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Do curso por University of California, San Francisco
Introdução à Neurologia Clínica
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Epilepsy & Neurodegenerative Diseases
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Conheça os instrutores
Daniel Lowenstein, MDProfessor and Vice Chair, Department of Neurology
School of Medicine
S. Andrew Josephson, MDAssociate Professor
School of Medicine
Wade Smith, MDProfessor
School of Medicine
[BLANK_AUDIO]
Hello, everybody.
Welcome back to Introduction to Clinical Neurology.
I hope you've been enjoying the course thus far.
Today's class is going to be on seizures and epilepsy.
My name's Dan Lowenstein.
I'm a faculty member at UCSF and the director of the UCSF Epilepsy Center.
And it really is a pleasure to go over an important neurological disorder.
That is very com, common worldwide.
So we have quite a quite a bit of ground
to cover over the of the coming hour or so.
So lets go over the learning objectives.
You're going to see that they're pretty detailed.
And I'd like to make sure that you're aware of this.
Just so that you have a good sense of the, of
sort of the landscape on, on how to organize this information.
So, so here are the objectives.
First of all, I want to make sure that
you get a clear understanding of what the terms,
seizure, epileptogenesis, and epilepsy mean.
Next, we're going to talk about the properties of
the brain that give rise to the EEG.
And following that and with that understanding,
you'll be able to diagram out the basic
mechanisms that underlie an EEG spike, which
is one of the main features of seizures
that are generated in, in the cortex.
The, these objectives are particularly important to me because, one of the main
goals of the overall class today is that I'd like you to get
a really clear understanding, to be able to visualize in your mind, what
exactly is going on in the brain of someone who's having a seizure.
I imagine that most of you, since you're taking the class,
don't have that clearly in mind at the moment, but I think it's really
important because, for now it probably seems
somewhat mysterious, or strange, or difficult to understand.
But I, I'm, I'm, I guarantee that by the
end of our time together today, you will be able
to, to see in your mind precisely what's going
on in the brain of someone who's having a seizure.
Once we've done that, we'll move on to understanding the classification
systems for for seizures. Seizures come in many different types.
And it's important to understand those differences.
Because it has an effect on the way you approach
the patient from both a diagnostic and a therapeutic perspective.
Now, we'll then talk about the various
causes of seizures according to different age groups.
We'll just, just sort of superficially cover those because there are so many.
But, I'd like you to have an appreciation for
at least some of the causes.
And then we'll turn to how do you work up a
patient who comes in with a seizure and potentially has epilepsy.
So, first of all we'll we'll cover some of
the routine laboratory studies that, you'll do with the patient
with a first time seizure and what those results,
might mean, to you in terms of further work up.
And then, we'll just talk briefly about the main factors that we use in deciding
whether or not to treat a first time seizure.
After that, I'll talk a bit about antiepileptic drugs.
And again, briefly go over the molecular mechanisms that actions of those drugs.
And, I'd like you to focus on a few
of them and try to understand their mechanism of action.
And then we'll talk about some of the drugs that
are used specifically in first-line therapy for different types of seizures.
And then discuss the general approaches that we take in a patient that has
been started on an antiepileptic drug and then needs to be switched to another one.
Either because the first drug is ineffective or they're having side-effects
or other problems with the drug that they've been placed on.
And then I'll, I'll close with describing the characteristics of
patients with medically refractory epilepsy
that might benefit from surgical intervention.
Okay, so those are the learning objectives, it's a lot of ground to cover.
But we'll get going.
Before I do that though, let me just tell you what I'm not going to cover.
Because there's a lot of stuff to talk about,
and to understand in the world of seizures and epilepsies.
So I'm going to be skipping over tons of details about pathophysiology.
I won't go into virtually anything about the various epilepsy syndromes,
as they're called.
I won't go into details about the
mechanism of action of specific antiepileptic drugs.
Virtually nothing on, pharmacokinetics and drug,
drug interactions interactions and so forth.
Comorbidities of epilepsy, patients with epilepsy
actually often times have a number of
other issues and conditions and disorders that
are either equally or even more important.
But I won't describe them, discuss them today.
There are special issues related to women with epilepsy and pregnancy, and then
finally, unusually or abnormally prolonged seizures called
status epilepticus is a topic in itself.
I, should you have interest in this or more depth in the
things that I'm going to be talking about, I highly recommend these references.
This is just a start; there's a chapter
on seizures and epilepsy in Harrison's Principles of Internal Medicine.
I'm the author of that chapter so I'm a little bit biased but I do
know that there's a lot of detail in there that you, you might find interesting.
If you are more interested, or
equally interested in the underlying pathophysiology of
seizures and epilepsy, there's an excellent
chapter in Kandel's Principles of Neural Science.
And then for those of you interested in more
information about the pharmacology of antiepileptic
drugs, again, I think a very useful
chapter in Principles of Pharmacology by
David Golan and his coll, colleague editors.
Okay, so let's begin.
This, this is the way I've structured the presentation.
As you can see, there are five modules.
And you can listen to all five of them in succession over the next hour or so.
Or break
them up however you wish, but we'll start with focusing on how the EEG works.
Then in module two, going back to that really core issue that is so
important for me, in terms of what I hope you get out of this class.
And that is what's exactly happening in the brain of a person with a seizure.
Then, we'll talk about classification of seizures,
then we'll talk about the evaluation of
a patient with a first time seizures,
and then finally the treatment of epilepsy itself.
Okay, so lets lets start. Here is module one.
How does the EEG work?
Now, in order to answer this question, we have to back in history at least briefly
to the early part of the 20th century and it was this man, Hans Berger, a German
neurologist who was actually the first person to report an EEG in a human.
And you can see this is Burger patient over here on
the left wearing those strange looking electrodes emerging out of his
head, he's connected to a machine that's showing the,
electrical signals that are being produced by those electrodes.
And this is a more modern version rendition of what the EEG looks like.
But, here is actually what Burger reported.
In a very important paper in the mid 1920s.
And this represents the first recording of electrical activity directly
from a human being.
And, you know, if you sit back for a moment
and think about what that means historically, that was huge.
Up, up until that time people had known that
there was electrical activity coming out of the brain.
That had been thought about, discovered, shown, in different types
of models in the latter part of the 19th century.
But it took until this, this discovery, this report, to, to be able to
provide a, an actual reading, an actual measurement of
the function, of the output of the human brain.
And as you can imagine, probably wasn't very long after
when people decided, well now that we have this way
of measuring the brain activity of humans, lets see what's
going on in the brain of someone who's having epilepsy.
Okay, now let's discuss exactly
what is going on in the brain that gives rise to the
signals that, that, that, what was observed by Berger on that EEG.
So what I, what I've shown, what I'm
showing you here, is a, a cartoon, a schematic.
It's actually derived from Kandel's principles of neural science.
And what we're depicting here are some,
some neurons that are sitting in the neocortex.
And,
as you can see, here's the surface of the cortex.
And, I've drawn some two, two electrodes
that are actually right on the cortical surface.
In the EEG, they'd be much farther away on the scalp.
And in this, in this cartoon of a cortex, I've
shown two ensembles of large projection neurons.
These are the kind of neurons that sit in layer five of the neocortex.
And as you can see, there are three neurons
here, and they have axons that are coming from the
thalamus and those axons make synapses in the relatively
proximal part of the dendrites of these large projection neurons.
On the right you see another set of three neurons.
And here the axons are coming, say from the
other side of the brain, through the corpus callosum.
And those synapses are being made on the more distal part of the dendrite.
Now, looking at, looking at this cartoon, one thing, the first thing
you can appreciate is that these
large projection neurons have a similar orientation.
In other words, look at the way the dendrites are all oriented
upward, in this case, towards the surface of, of, of the cortex.
Secondly, let's consider the way the inputs
that come into these neurons, might arise.
So,
we'll look at an action, let's take an action potential.
So, here's your action potential, right here.
It's coming in from the thalamus, and it's going to move
down along the axon, and eventually reach the synapse of this neuron.
And when it does, it'll give rise to an excitatory postsynaptic potential.
Now, associated with that, is a flow of ions,
in this case, I'm showing sodium going into the dendrite.
That flow of ions
creates, in this case, a sink, because you have a
positive charge going from the
extracellular space, into the intercellular space.
So that region is going to be relatively negatively charged.
Of course wherever you have a sink you have
a source and that's creating flow of current, current.
And if we look at that flow.
In this case we have positivity more in the distal region of the dendrite.
And negatively close, closer to the cell body.
And, if you can imagine, this electrode what it, what it is reading in
terms of voltage changes, it's, it's sensing
that there's more positivity closer to the electrode.
So, the actual readout of that electrode will show a positive charge.
In this case the deflection of the EEG is downward denoting positivity.
Okay, so the, the summation of the electrical activity
in the groups of neurons is what is exactly detected by the scalp electrode.
Now let's take a look at a different orientation.
In this case the EPS P's, and now I'm showing all
three at once because they're arriving close at the same time.
These EPS P's are all going to lead to a sink in the more distal part
of dendrite, right, and the source will be more proximal.
And in this case, as you can see, the EEG is detecting
a more negative charge and shows the upward deflection as depicted here.
So, it's the fact that there's the common
orientation of the dendrites in these large projection neurons.
The fact that there's production on a sink and a source, and
the relative distance of that form the electrodes that are summated by large
groups of neurons, that lead to the actual changes that we see on the EEG.
Now with that in mind, let's take a look at a real EEG.
This one is actually kind of an old fashioned
one, it's, it's was, was done on pen and paper.
But I think it's a great example of, of, of, of a typical EEG.
I want you to just take a look
at that for a moment.
Just think in your mind you know, what is it that you're seeing here.
I'll orient you a little bit.
You can see squiggly lines going across these eight traces.
You see this thing here.
This is, this is actually shows the montage.
It actually shows where the electrodes have been placed on this patient's head.
And in this particular case, you can see we've got lots of electrodes
on both sides of the brain.
And they can can be connected together electrically just
depending on how you want to switch the EEG.
but in this particular montage, the EEG that we're looking at here,
we're looking at the differences in potential that have been measured by the
electrodes between electrode 1 and 2, which is on the left side
of the brain in the front, then between this one and this one,
this one and this one, and this one and this one.
And on the other side of the brain you can see
the analogous align of electrodes that are that are being connected together.
So that means that these four traces are derived from
these four locations on the left side of the person's brain.
And similarly, these four are from the right side.
So now that you're oriented, let's take a look at what
the EEG shows.
So I, I, let me warn you, there's a couple of things here that are artifacts.
So, for example, this shown here and, and this thing.
these, as you can see, traces one and traces five,
this is in the front of the head, this is
actually close the eyeballs and whenever we blink because of
the movement of our eyes there's an artifacts that's produced.
And there's also some artifacts here some of these electrical signals
are just background noise but lets, lets consider
the, the EEG and look what's happening here.
What strikes, what stands out to me is for example,
what's going on here in trace four and trace eight.
So, let's look at this.
So here we go, we're going along and there's this kind of rhythmic
change and then it suddenly, it
sort of suddenly actually rel, relatively flattens.
Certainly compared to what follows, which is again, this rhythmic change.
And the same thing is happening here and here, in traces four and eight.
And where are those?
Well those actually are the electrodes that are in the
back part of the person's head, close to the occipital cortex.
And in fact, the thing that is creating this change, is
that the person has gone from having their eyes open, EO,
to eyes closed.
And in fact, this is what we would see on the
EEG of any of us if we have an EEG taken.
This is a normal response, it's the so called Alpha rhythm,
that is created, in the occipital cortex whenever we close our eyes.
Now this is pretty cool, right?
Because it's just showing just in the normal human brain, how measurements from
the scalp can sh, can, can reflect, pretty dramatic changes in electrical signal in
specific regions. So, let's then go on
now to look at an EEG from someone who's actually having a seizure.
As I mentioned before, this is what Berger and colleagues what their discovery
led to is the ability to actually record the EEG from people with epilepsy.
And if we compare the two EEGs that I've shown, this one,
given there's a bunch of different kinds of artifact in here.
But if you just look at this EEG, and compare it
to this one, I think you'll agree that there's quite a difference.
Again, the montage is similar.
But, what do you see? What do you see?
Mostly, lots of rhythmic activity. Rhythmic activity.
Right?
And in particular, there are these very, very spiky looking things shown here.
And it's the existence of these high-amplitude spike-like
activities that are really the essence of many forms of seizures.
And in the next module, we're going to
dive into trying to understand what is going
on in the region that is giving rise to this spiking activity in the human cortex.
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