0:00

Dr. Laser,

0:01

this 63-year-old's main symptoms

0:03

are ataxia and memory loss.

0:05

So, we're into that neurodegenerative

0:07

group of disorders.

0:08

Before we start down the differential of

0:11

this case and point out some of the findings,

0:13

if we take the main dementias,

0:15

I use the clinical as well as the visual as

0:18

tip-offs to segregate into various diagnoses.

0:22

For instance, you know, movement disorders.

0:24

Most patients with ALZ,

0:26

at least in the early to mid-stage,

0:28

don't have a lot of movement disorder

0:29

associated with their syndrome.

0:31

So if they've got tremor and rigidity,

0:33

I'm in the Parkinsonian group,

0:35

whether it's multisystem,

0:36

atrophy or classic Parkinson's disease.

0:38

If they've got hallucinations,

0:40

granted hallucinations do occur with ALZ,

0:43

but prominent visual hallucinations

0:45

pretty early on in somnolence,

0:47

seen with dementia with Lewy bodies.

0:50

Then ALZ is really characterized,

0:52

not just by cognitive decline

0:54

and short-term memory loss.

0:56

The patients have enormous capacity to remember

0:59

back 30, 40, 50 years,

1:01

but short-term memory,

1:02

not so much.

1:03

Their daily function is impaired.

1:05

They can't remember what they said 30 seconds ago.

1:07

They have aphasia, paraphasia,

1:09

and they may even have semantic aphasia

1:12

where the meaning of words is lost.

1:14

Then you've got frontotemporal dementia syndromes,

1:17

of which Pick's disease was included in that in the past.

1:21

We don't use that name so much anymore.

1:23

There are heredofamilial types

1:25

and non-heredofamilial types.

1:27

But this disorder is characterized,

1:29

not just by frontal or frontotemporal involvement,

1:32

but by disinhibition, disexecutive behavior,

1:36

you know,

1:37

eating with your feet at the dinner table,

1:39

making weird and lascivious comments

1:42

early on in the disease.

1:43

So they lose their inhibitory capacity.

1:46

They are, in other words, unfiltered.

1:49

And then you've got vascular disease.

1:51

That one's a little bit easier,

1:52

that's kind of a stuttering decline.

1:54

But because there's vascular disease,

1:55

you may see macro infarcts or you may see,

1:58

as you've described before,

1:59

with the Fazekas scale,

2:00

multiple confluent areas of white matter

2:03

signal alteration,

2:04

commensurate with Binswanger syndrome.

2:07

So now let's scroll this case.

2:08

And we've got left greater than right,

2:11

both parietal and frontal cortical atrophy,

2:15

at least moderate in severity.

2:17

And then in the sagittal projection,

2:19

we've got some parietal occipital atrophy,

2:22

some occipital atrophy.

2:24

Here is the precuneus right here.

2:26

Also a little bit of atrophy,

2:28

some atrophy of the cingulate sulcus

2:30

going all the way forward.

2:32

And there's also some brain stem involvement.

2:35

You commented on this in the report,

2:37

the midbrain is atrophic.

2:39

It looks a little bit like a hummingbird.

2:41

The superior colliculus off to the side.

2:43

It's pretty good, actually.

2:45

It's pretty juicy in the midline.

2:46

It's a little small,

2:47

but they always are in the midline.

2:48

But that at least raised the possibility

2:50

of progressive supranuclear palsy.

2:53

So, ignoring the visual abnormalities that include

2:56

lens replacement and the patient's

2:58

been treated with a band

2:59

for I think possibly retinal detachment or nearsightedness.

3:03

I'm not sure which.

3:05

Tell us about the differential diagnosis of

3:08

ALZ and other disorders, including MCI.

3:12

And what is MCI?

3:15

Mild Cognitive Impairment Syndrome

3:17

is MCI.

3:18

Okay.

3:18

And that term is used a lot,

3:20

and we frequently use that term in place of ALZ

3:25

because if you put the term ALZ in a report,

3:27

it has emotional consequences,

3:29

it has insurance consequences,

3:32

and it has general relationship consequences.

3:34

I once did that in a report to a neurologist's

3:37

mother, and he came in.

3:37

He said, my mother is not demented.

3:39

He was absolutely incensed.

3:41

Turned out she developed dementia about a year later,

3:43

and she did have some cognitive impairment.

3:46

So what is cognitive...

3:48

Mild Cognitive Impairment Syndrome?

3:49

When do we use that term or pull that term out?

3:53

So, typically,

3:54

the way I do it is I look at all the scales that

3:56

we've discussed prior,

3:57

the global cortical atrophy scale,

3:59

the medial temporal lobe atrophy scale,

4:01

the Fazekas scale,

4:02

the codom scale.

4:03

And I try to form a picture of what's going on

4:05

with the patient.

4:05

I try to grade it subjectively,

4:08

but with those scales in mind.

4:09

So I look at the hippocampi,

4:11

which is probably the most important scale

4:14

to look at, and the degree of atrophy,

4:16

the degree of volume loss of the hippocampi.

4:18

In this case,

4:19

as Dr. Pomeranz is pointing out on the left,

4:21

the medial temporal lobe atrophy scale would be

4:24

a two to three, almost a three in this case.

4:26

So, there's profound left hippocampal volume loss.

4:29

And let's redefine what that is.

4:30

The choroidal fissure is big.

4:32

The temporal horn is big,

4:34

and there is at least moderate to

4:36

severe hippocampal atrophy.

4:38

All these structures that live in here,

4:40

the dentate gyrus, the amygdala, and others,

4:45

nice and juicy on the right,

4:46

very small and lobulated on the left.

4:49

And as you and I have discussed before,

4:51

the number one biomarker for ALZ is hippocampal

4:55

volume loss, and this patient has it.

4:58

Now, in somebody where you want to suggest

5:00

the diagnosis of ALZ,

5:02

but they don't give you a strong

5:04

cognitive decline history,

5:06

one way to say it in code is findings are highly

5:11

suggestive of Mild Cognitive Impairment Syndrome,

5:14

or progression thereof.

5:16

Which is your way of saying,

5:17

I'm worried about MCI progressing to ALZ.

5:21

Now, what percent of patients that don't have a florid

5:24

ALZ go on to MCI that have perihippocampal

5:28

or hippocampal involvement?

5:30

It's about 12% per year.

5:32

If they've got some cognitive decline that's mild,

5:34

will go on to flat-out ALZ.

5:36

And over five years,

5:38

80% will end up with ALZ.

5:40

So this patient, you know, is a big candidate,

5:43

a strong candidate for ALZ

5:44

if they don't have it already.

5:46

We haven't physically examined this individual.

5:48

And this patient also has a fair

5:51

amount of frontal involvement,

5:52

which makes the case a little more challenging.

5:55

Right?

5:55

The left is involved more than the right,

5:57

so you might consider a more

5:59

atypical form of frontolobar dementia

6:02

or frontotemporal dementia with parietal extension back

6:05

rather than ALZ with extension forward,

6:08

except there's no behavioral disturbance.

6:10

The patient only has memory loss.

6:12

So that really clinically favors ALZ over FLD,

6:16

Frontal Lobar Dementia,

6:17

But there is involvement of the olfactory area,

6:20

which at least raises the possibility

6:23

of a frontolobar dementia.

6:25

So, we've got a pretty broad differential here.

6:27

Any other comments before we exit this case?

6:31

I would.

6:31

One other thing that you could show is if

6:34

you show the FLAIR sequence,

6:35

that there is very little white matter disease

6:38

for a 63-year-old.

6:38

He has some punctate white matter lesions,

6:42

but the degree of white matter is essentially

6:44

normal for a patient of this age.

6:46

That's a very good point.

6:47

You know, his Fazekas scale is one.

6:49

And one of your charges, one of your jobs,

6:52

is to try and tease out what kind of dementia

6:54

you're dealing with.

6:55

And if you can exclude vascular disease...

6:58

And by the way,

6:58

vascular disease and neurodegenerative disease combined,

7:01

account for 15% of all dementia.

7:03

So, it's pretty common.

7:05

15% are purely vascular.

7:06

So now you've got 30% are attributable

7:09

to vascular disease.

7:10

So if you've got vascular disease

7:12

that's very prominent,

7:13

you may want to treat that patient with, say,

7:15

a statin,

7:16

very aggressive statin therapy to try and halt the

7:18

progression of microvascular

7:20

or macrovascular dementia.

7:22

So, very little white matter disease makes this

7:25

unlikely to be a vasculopathic dementia and more

7:28

likely to be a primary neurodegenerative disease.

7:31

And some of the ones we were

7:32

considering here were PSP,

7:34

which we eventually excluded because

7:36

of the collicular plate,

7:37

even though there is a hummingbird sign,

7:39

frontolobar dementia

7:40

or related Picks disease and ALZ

7:44

or MCI Alzheimer's disease

7:45

or mild cognitive impairment syndrome.

7:48

Any other comments before we quit?

7:49

Nope.

7:49

Okay, P and Laser out.