00:01
In this talk, let's review some
of the Parkinson's Plus Syndromes.
00:06
These are Parkinsonian syndromes,
patients present with a Parkinsonism,
but they're not idiopathic PD.
00:15
First, let's talk a little
bit about Parkinsonisms.
00:17
There are two basic
Parkinsonisms.
00:20
One is a levodopa-responsive
Parkinsonism,
and that's idiopathic PD.
00:25
Those patients have bradykinesia, rigidity,
postural instability, often with tremor,
and they're readily responsive
to levodopa challenge.
00:34
The second is
levodopa-nonresponsive Parkinsonisms
and these are our PD-plus syndromes
that we'll review in this talk.
00:46
Let's start with an overview of some of
the common Parkinson's plus syndromes
and there's four that
I'd like you to know.
00:53
Lewy body dementia,
multiple system atrophy,
progressive supranuclear palsy,
and corticobasal or corticobasal
ganglionic degeneration.
01:03
And there are a number of things that I
want you to remember about these syndromes.
01:07
1. They're all Parkinsonisms.
01:10
So all four of these conditions
present with bradykinesia,
rigidity,
and postural instability,
that's really,
really important to remember.
01:19
However, there are also some unique
features of each of these conditions
that are unique to the condition and
help us to establish the diagnosis.
01:27
With Lewy body dementia,
we see early dementia as a
prominent feature in those patients.
01:33
So dementia begins within one year of
the development of Parkinsonian symptoms.
01:39
We can also see hallucinations
in these patients
and neuroleptics
sensitivity is common.
01:44
We use neuroleptics to manage
some of the symptoms we can see
when patients are
hallucinating or agitated,
and these patients will
develop severe sensitivity
and become agitated and confused
and may need hospitalization
as a result of initiation
of neuroleptics.
01:59
And those features are supportive of
a diagnosis of Lewy body dementia.
02:04
Next multiple system atrophy.
02:06
The key features to this syndrome
is early autonomic dysfunction.
02:11
So we think about orthostasis,
or erectile dysfunction and incontinence,
and early findings any
of those three findings
early in the course
of the Parkinsonism
should prompt the consideration
for multiple system atrophy.
02:26
Next, let's talk about
progressive supranuclear palsy.
02:30
The key things we see
there are twofold.
02:32
One is downgaze impairment.
02:34
So these patients have early vertical
downgaze palsy, they can't look down.
02:38
As a result they
have frequent falls
and we see falling
In Parkinson's
disease, falls or late.
02:44
In PSP, falls or early.
02:46
This is also an axial,
akinetic rigid Parkinsonism.
02:51
So patients have difficulty moving
and they are very, very rigid,
often in the axial musculature that
controls our posture and axial tone.
03:01
Patients may have other
brainstem symptoms,
dysphasia or oral
dyskinesias or dysphonia
and then lastly,
corticobasal degeneration.
03:10
This is a really unique
and kind of strange,
uniquely strange syndrome.
03:15
Here we see that it's
prominently asymmetric.
03:18
Patients begin with very
asymmetric symptoms.
03:21
And we see a few things, apraxia,
alien hand and cognitive deficits
and this owes to its predilection
for the parietal lobes.
03:29
Apraxia is motor planning,
so these patients are able to move,
but they just can't form the plan for
how to do it and what they need to do.
03:37
Alien limb is an
extreme variant of that
where a patient's limb
will be alien to them.
03:44
It will shave on its own,
it will cook on its own,
it will write things that the
patient doesn't want to write.
03:49
It literally is alien,
it does what it wants to do,
and the patient does not
appear to be in control.
03:55
Those findings of early
visual-spatial dysfunction
and early asymmetric
apraxia, or alien limb
should raise suspicion for
corticobasal degeneration.
04:07
Let's walk through each
of these and understand
why each of these Parkinsonisms
present differently
and look at the areas of
brain that are involved.
04:16
First,
I want to look at idiopathic PD.
04:18
And the problem that we think about is
in the substantia nigra pars compacta,
but it actually begins way down
deep in the brainstem early.
04:28
So the development of Lewy bodies
that degenerative pathology
that's developing in the brain
begins down in the caudal medulla.
04:35
And that early caudal
medulla dysfunction
likely leads to early
REM behavior disorder.
04:42
Slowly over time we see increase
in Lewy Body deposition,
further higher up in the
brainstem and the pons,
and ultimately in the
basal ganglia contributing
to the motor
development of symptoms.
04:54
And then over time, into the
cortex where patients will develop
late dementia, Parkinson's disease,
dementia and other cognitive dysfunction.
05:02
So again, early in the
disease for idiopathic PD,
we see REM behavior
disorder anosmia.
05:07
In the typical presentation,
we see the motor symptoms
as the subcortical basal
ganglia structures are involved.
05:14
And then late in the course of the disease
as Lewy bodies develop in the cortex,
we see dementia and other cortical
dysfunction in these patients.
05:22
This is different from
progressive supranuclear palsy.
05:26
And the distribution
of neurodegeneration.
05:29
It differs for PSP and helps us
to determine what symptoms we see
when patients present and
things we want to look out for.
05:37
PSP is a tauopathy.
05:38
So the structure that's
developing within the neurons,
the degeneration that's occurring
is a result of buildup of tau
and we see tau deposition
in the brainstem.
05:49
And you can see in the
upper diencephalon here,
there is frequent
deposition of tau
and this gives rise to the
vertical gaze dysfunction,
the vertical gaze center
is in the upper midbrain,
as well as prominent axial rigidity
that we see in this condition.
06:05
We can contrast that to
multiple system atrophy.
06:09
And you can see the brain regions
involved in multiple system atrophy.
06:13
It is many,
many multiple brain regions.
06:16
And we can see predominance
in one area or the other.
06:19
But we often see
in this condition,
deposition of abnormal protein in both the
subcortex, the brainstem and in the brain.
06:28
MSA is alpha-synuclein apathy.
06:31
And so the deposition that
we're seeing is alpha-synuclein.
06:35
In some cases, the alpha-synuclein
develops and builds up in the cerebellum,
and we may see an
MSA cerebellar type.
06:42
In other cases, it primarily affects
the subcortical basal ganglia,
and we can see an MSA
striatonigral or Parkinsonian type.
06:51
And lastly, we can see
problems in the deep brainstem.
06:54
And this gives rise to an
MSA a or autonomic type.
07:00
And then lastly,
let's look at corticobasal degeneration
understand the brain regions that
are affected by this condition.
07:06
This is also a tauopathy.
07:08
And so we're dealing with development
of tau protein and deposition of tau
and you can see here the prominent
involvement of the parietal lobes
giving rise to the the higher
level cortical sensory findings
in these patients including
that alien limb syndrome.