All right, well let's talk about
and learn a little bit more
about the four common
and we're going to
review each of them.
First, let's start with
multiple system atrophy.
MSA is an adult onset sporadic,
rapidly progressive multisystem,
neurodegenerative fatal disease
that's characterized by
so bradykinesia, rigidity,
And it can also include
or just primary Parkinsonian symptoms.
We often see
as well as in some cases,
What's going on in MSA?
Well, what we see here is spreading
of aberrant alpha-synuclein.
MSA is an alpha-synuclein apathy
like idiopathic parkinson's disease.
There spreading of alpha-synuclein
deposits from neurons to glial cells.
This results in chronic
alterations in glial cell function.
There's impairment of the trophic function
between the oligodendrocytes and the axons,
as well as secondary axonal damage and
extensive demyelination that is occurring.
The glial and the myelin are both
involved in multiple system atrophy
and the pathology is spread
throughout the brain.
There is an inflammatory cascade that is
thought to be induced by this process,
and then subsequently secondary
neurodegeneration is thought to follow.
What are the clinical manifestations
what a patients present with?
Well, the history is important.
we see early autonomic dysfunction.
erectile dysfunction and incontinence.
We need to ask for those,
we need to interrogate those.
They're not always apparent
when evaluating a patient
and their key features to cue in on
in a test question or clinical exam.
On physical exam,
we're looking for Parkinsonian symptoms
as well as other
And there are three
types of the MSA.
MSA of the Parkinsonian type,
MSA of the cerebellar type,
and MSA that just involves
early autonomic dysfunction.
In Parkinsonian predominant cases,
we see akinesia or bradykinesia,
prominent axial rigidity,
We may or may not see tremor in the
vast majority of these patients,
we don't see tremor.
In contrast, a Parkinson's disease and
cognitive function is typically preserved
though we may see some subcortical
dementia early in the disease.
In the cerebellar predominant
cases, we see early ataxia.
We can see problems with equilibrium
and gait problems in those patients.
Dysdiadochokinesis or difficulty
with rapid alternating movements
is present on exam and we
really want to look for that
when evaluating patients with a
possible Parkinson's-plus syndrome.
And then dysarthria, as well as
ocular abnormalities can be observed.
The diagnosis is made
clinically we don't use imaging
to diagnose multiple
But we can see
and I'm demonstrating some of
the more severe and significant
in stage changes that
we can see on the brain.
Here we're looking at
MRI scans of the brain,
the far left is a T2 and the
others are sagittal T1 images.
All the way on the
right is normal.
And we're looking at that
midline, that parasagittal image,
we see the brainstem, a nice healthy
pons, midbrain on top of the pons,
and a dominant corpus callosum
with the cortex above it.
In moderate to
severe cases of MSA,
we can see atrophy of those subcortical
brainstem and cerebellar circuits.
Here you can see on the axial
section all the way to the left,
atrophy of the middle
There's prominent basal cisterns,
you see more spinal fluid
in those basal cisterns
than you would normally.
And this is
indicative of atrophy.
We can't see a lesion.
We see what's leftover from
neurodegeneration that's atrophy.
Similarly, on the 2 sagittal
images in the middle,
we see atrophy of the
olive and the pons
and the olivopontocerebellar
And you can see mild
atrophy on the left image
and then more severe
atrophy on the right.
And all of this gives rise
to Parkinsonian features
and likely prominent cerebellar
findings in these patients.
Now let's talk a little bit
about some of the MSA variants.
There's an MSAP or
a Parkinsonian type.
It was formerly called
and this is MSA with prominent
We may see tremor,
we see the typical Parkinsonian signs,
and early autonomic failure and that's
really what differentiates this from PD.
In the cerebellar type, this was formerly
called olivopontocerebellar atrophy.
And like the MRI scans we
looked at in the last slide,
we see prominent olive,
pons and cerebellar atrophy.
Here, the patients present with
prominent cerebellar dysfunction,
gait ataxia, limb ataxia, ataxic,
dysarthria, gaze-evoked nystagmus,
problems and dysmetria.
In the MSA-A type, this was formerly
known as shy drager disease.
This is MSA with prominent autonomic
features and patients present
with a predominance of
as well as potentially incontinence
and erectile dysfunction.
And this orthostatic hypotension is
very, very difficult to control.
Patients stand up and become
hypotensive and pass out.
And many of them develop
So they lay down and
They stand up and
And it's very difficult to control their
autonomic nervous system externally.
How about treatment?
How do we treat MSA?
Well, there's no definitive
disease modifying therapy.
We do think about
supportive care therapy.
Botox injections can be used for
focal dystonia is that can develop.
Orthostatic hypotension is the
most significant symptom we manage.
We think about using agents that
will increase blood pressure.
Fludrocortisone is first line and
midodrine is often second line
and occasionally we'll need third
or other fourth line agents.
And urogenital symptoms
are not uncommon
and we consider agents to
treat a neurogenic bladder.