00:01
Here, we’ll take a look
at Pick’s disease.
00:03
Pick’s disease really is a name
that’s falling out of favor.
00:08
The one that you
definitely want to know,
and the one that makes much more clinical
sense is frontotemporal dementia, FTD.
00:17
Rare, compared to Alzheimer’s disease.
00:21
Rare, but yet know everything
about F – Frontal lobe,
T – Temporal.
00:28
So, you tell me,
if you have problems with the frontal
lobe, how are you going to behave?
Like, Dr. Raj, crazy, insane,
mood, behavior, instability.
00:37
Right?
That’s frontal.
00:39
What about temporal?
We’ll see that in a second.
00:41
Think about temporal.
00:42
Language center?
There you go. Good.
00:45
Frontotemporal dementia.
00:47
And that’s what you’re going to predict.
00:48
Clinically, often have a combination
of frontal and temporal.
00:52
Frontal lobe includes personality
changes, mood behavior or disorders,
poor judgment,
disinhibition.
01:00
Does this sound like me?
Temporal lobe, we have disturbances
predominantly of the language.
01:06
Frontotemporal dementia, rare.
01:10
Frontotemporal Dementia or Frontotemporal lobar degeneration (FTLD)
is broken down into three major subtypes based on the dominant proteins found in brain inclusions.
01:21
The first subtype, FTLD-tau, represents about half of FTD cases. It's characterized by hyperphosphorylated tau proteins
that have become insoluble. Normally, tau proteins help
stabilize the cell's structure,
but when they're hyperphosphorylated, they lead to cellular
dysfunction.
01:40
The second subtype, FTLD-TDP, accounts for roughly 40% of FTD cases.
01:46
This subtype involves TDP-43 proteins that are also hyperphosphorylated and insoluble.
01:54
In healthy cells, TDP-43 is involved in regulating how genetic information is used,
but in FTD, the protein's abnormal form disrupts this process.
02:03
The third subtype is FTLD-FET, which includes 5 to 10% of FTD cases.
02:09
This subtype has inclusions of FET proteins,
which are associated with RNA and DNA binding and are essential for normal cell function.
02:18
Let me quickly go through this with you.
02:20
So grossly, what are you
going to find here?
Well, I told you this is a
differential of Alzheimer’s disease.
02:26
There is going to be --
as opposed to global atrophy that
we saw with Alzheimer’s disease,
with the frontotemporal dementia, you’re
going to find asymmetrical atrophy.
02:36
What does that mean?
It means that you’re not going to
have the same type of global atrophy.
02:40
You might find deepening of the sulci
in some places but not in others
And often, it will spare
the posterior two-thirds
of the superior temporal
gyrus, and that’s important.
02:50
So, there’re sparing here.
02:52
Severe atrophy results in gyri.
02:55
Well, what happens?
The gyri is going to thin,
and then you have a knife-like appearance
that you’re going to find because it
looks like you’re cutting right through,
cutting right through.
03:05
Microscopically,
severe neuronal loss as you can imagine,
especially in the outer
three layers of the cortex.
03:11
And you have these things
called Pick cells,
and this I would know.
03:16
These are neuronal swellings that you
find with frontotemporal dementia.
03:20
Remember, rare when compared
to Alzheimer’s disease.
03:23
So, if you’re suspecting frontotemporal
dementia, make sure that you’re darn sure
that this is what it is because they’re
going to give you specific information.
03:31
They have to.
03:32
So, there’s no really such
thing as your plaques,
things of that nature,
but you will find tau,
so be careful there.
03:42
The Pick bodies,
well, it's cytoplasmic,
round to oval,
filamentous inclusions, which
are very weakly eosinophilic.
03:50
What color is eosinophilic?
Pinkish.
03:53
But stain strongly with silver stain.
03:55
Now, be careful with that.
03:56
Last time we saw silver stain was
actually of the beta-amyloid plaque.
04:01
Composed of neurofilaments,
vesiculated type of
endoplasmic reticulum,
and paired helical filaments that are similar
to those found in Alzheimer’s disease
referring to the tau.
04:12
So be careful there, please.
04:13
You really, really want to pay attention
to that asymmetrical type of atrophy
that you find with
frontotemporal dementia.
04:20
In Alzheimer’s, it’s
more or less global.
04:24
This is a photomicrograph of the anterior cingulate cortex taken from a patient diagnosed with frontotemporal dementia.
04:30
The tissue specimen has undergone a specific immunohistochemical staining process,
using an anti-tau protein immunostain, which appears brown, to label the abnormal tau proteins.
04:41
This has been counterstained with hematoxylin, which stains the cell nuclei and provides the blue background you see here.
04:48
As we look closer, you can observe many tau-immunoreactive dystrophic neurites.
04:54
These are characterized by the small, abnormally shaped
brown-immunostained extensions emanating from the neurons.
05:01
In the inset, a magnified view, we identify a distinct tau-positive neuronal cytoplasmic inclusion.
05:09
This structure, known as a Pick body, is indicative of the disease and can be seen within
what we refer to as a 'ballooned' neuron due to its enlarged size.
05:19
So, whenever you hear about tau,
top on your differential should be,
obviously, Alzheimer’s disease,
rarely could be
frontotemporal dementia.
05:31
Next, we move on to
movement disorders.
05:33
In other words, these are
subcortical dementia.
05:38
Let me stop there for one second.
05:39
What does cortical dementia mean to you?
Cortical meaning higher, higher type
of cognitive functioning, right?
We talk about language and
perception of language
and being able to do
those kinds of things.
05:52
Subcortical, you start getting closer
to what can make your life easier.
05:56
Basal ganglia, Parkinson’s disease.
05:59
What do you know about Parkinson's?
You lose the dopamine.
06:02
Multisystem atrophy.
06:04
Progressive supranuclear
palsy, we’ll talk about.
06:07
Corticobasal type of degeneration,
Huntington’s chorea,
and Wilson’s disease are movement
disorders that we’ll take a look at.
06:15
Our focus will be on basal
ganglia, for the most part.
06:20
Let’s first begin our discussion
by looking at Lewy body dementia.
06:25
Marked by progressive
cognitive decline.
06:28
I’m going to show you something here
that is a clinical pearl for sure,
that you want to pay attention
to with Lewy body dementia.
06:34
Memory and attention impaired.
06:37
Fluctuating course of good days.
06:42
This is what you’re paying attention to.
06:44
Your clinical pearl that you
want to know for sure here
with Lewy body dementia would
be visual hallucinations.
06:51
Ha-Lewy-cinations.
06:54
Can you do that for me?
Makes your life so much
easier, doesn’t it?
Ha-Lewy-cinations and delusions prominent
and early feature, early feature.
07:03
That’s a big deal,
and may present
with parkinsonism.
07:09
So, what are we looking
at in these pictures?
Is it Lewy body?
Specifically, they are in the middle.
07:14
Do you see that structure?
That looks rather eosinophilic and pink.
07:17
Perfectly, perfectly circular.
07:19
That is something called
a synuclein, synuclein.
07:23
I’ll talk to you about
that in a second.
07:24
It’s important that you pay
attention to synuclein.
07:27
Is it Lewy body dementia?
And we have another structure that
we’ll take a look at as well,
and this is quite indicative.
07:34
Can you see that
rod-like structure?
That’s all for Lewy
body dementia.
07:40
Cortical Lewy body must be present
to diagnose definitively.
07:43
So, what is Lewy body?
That’s what I’m showing you
on the picture on your left.
07:47
Lewy body is composed of,
that is what that circular eosinophilic
structure that you’re referring to.
07:53
That is synuclein.
07:55
Memorize that.
07:56
Be able to identify it, please.
07:58
And overall, that circular eosinophilic
structure that you’re finding in
this bigger structure is the Lewy body.
08:07
Plaques and tangles are frequently present,
identical to those seen
in Alzheimer’s disease.
08:11
Please be really careful.
08:13
What you will not find, obviously, in
Alzheimer’s disease will be Lewy body.
08:17
What are you paying
attention too clinically?
Ha-Lewy-cinations.
08:21
What is that that we
are seeing circular?
Synuclein.
08:24
What is the body?
The Lewy body.
08:27
Is this Parkinson?
Nope.
08:31
Vascular dementia, also known
as multi-infarct dementia.
08:35
What does that mean?
Number of blood vessels that
are undergoing compromise.
08:39
And the number of blood vessels
that undergo compromise
will then cause decreased
cognitive functioning.
08:44
Vascular, multi-infarct
dementia.
08:47
Risk factors are those for any
type of vascular disease.
08:50
Maybe seen with large artery stroke
or severe subcortical disease,
this is known as Binswanger’s.
08:57
Abrupt onset or more
commonly, clinical pearl,
step-wise progression is
the key to diagnosis.
09:05
It’s slow.
09:07
But here, we have blood vessels
that are being affected.
09:09
So maybe atherosclerosis resulting
in stroke, hypertension.
09:13
If you go down into the subcortical
region penetrating deep arteries,
then you’re worried about things
like Charcot-Bouchard aneurysm
and lacunar infarcts.
09:24
Focal deficit on neurologic
exam suggests the diagnosis.
09:28
Vascular dementia, a.k.a.,
multi-infarct dementia
and step-wise progression are the key
points on this particular slide.
09:38
We’ll move on to normal
pressure hydrocephalus.
09:42
Okay.
09:42
Slow down here for one second.
09:44
There are couple of things that I want
to make sure that we’re clear about.
09:47
Hydrocephalus has been a topic that
we’ve covered in great detail.
09:49
We have talked about communicating
hydrocephalus, which means what?
Communicating.
09:54
You’re thinking about the flow or
the path of cerebrospinal fluid.
09:59
You’re moving from lateral ventricle,
third ventricle, fourth ventricle,
bathing the spinal cord up
through the subarachnoid
and then going into the
arachnoid granulation, right?
Communicating, example
would be post-meningitis,
when you have scarring or fibrosis
of the arachnoid granulation.
10:14
Maybe tuberculous meningitis.
10:16
If it's obstructive, or your
non-communicating hydrocephalus,
a list of differentials
or large and wide,
in which we have Arnold-Chiari
or you have Dandy-Walker,
you could have medulloblastoma.
10:28
We'll talk about a bunch of these
causing obstructive.
10:30
But in those cases, what happens?
You have increase
in intracranial pressure.
10:34
Now, we talked about
Alzheimer's disease
in which we then have
global atrophy of the cortex
resulting in a compensatory
ventricular enlargement
or we call it
compensatory ventriculomegaly.
10:47
Actually, I didn't even
make that up. I kid you not.
10:50
It's called ventriculomegaly.
How beautiful is that name?
Yes, I'm a dork. But the point is
that hydrocephalus ex vacuo.
10:57
In that case, we have
intracranial pressure
that is normal.
11:01
And here we have
normal pressure hydrocephalus.
11:06
How is this possible?
First, please be able
to identify your patient.
11:10
Dementia, gait difficulty,
and incontinence.
11:15
Please know the triad.
No doubt, please now the triad.
11:18
Gait difficulty,
incontinence,
and this dementia
is actually reversible.
11:24
So why is it normal pressure?
Well, the concept is
over a long period of time
chronicity maybe there is adaptation
that is taking place in the brain.
11:35
And with that type of adaptation,
maybe the pressure now
in the intracranium has
actually become normal.
11:42
Lumbar puncture may reveal
elevated opening pressure.
11:44
Now, you want to be really,
really careful with this, right?
Because if your pressure,
intracranial pressure is elevated,
you never do a lumbar puncture,
you're going to kill your patient.
11:54
But here, if you know for a fact
that there is no signs or symptoms
of increased intracranial pressure,
well just keep this in mind.
12:02
Prolonged CSF monitoring may reveal
abnormal what's known as B waves.
12:08
Imaging will reveal
enlarged ventricles,
it looks like it's hydrocephalus,
and your treatment is with shunting.
12:15
Okay, so even though you call this
normal pressure hydrocephalus,
there could be
increased accumulation of fluid,
so shunting is necessary.
12:23
And excellent success.
And this is important,
because you're able to
then drain the fluid
from your ventricles and such,
you actually would be able to
reverse the dementia,
the gait difficulty.
12:37
That is quite rare.
12:38
So now, apart from the
reversible type of dementia,
as we've talked about, such as:
B12 deficiency, hypothyroidism,
Wernicke-Korsakoff,
and so on and so forth.
12:46
There's every possibility that
this could also be reversed,
in normal pressure hydrocephalus
with simple shunt placement.