0:00

If you take all comers who demonstrate white

0:04

matter lesions, we would have to say that

0:07

vascular etiologies are the most common.

0:10

And the two most common would be

0:12

microangiopathy and migraines.

0:15

By microangiopathy, we mean those small white

0:18

matter lesions that occur in the periventricular

0:20

and subcortical region in the elderly

0:22

patients who have atherosclerotic disease.

0:26

And it used to be that I would dictate

0:28

these as multiple periventricular

0:31

and subcortical white matter lesions,

0:33

associated with small vessel ischemic disease.

0:36

However, in the era of Epic and MyChart,

0:40

I found that the patients were calling

0:43

the clinicians and inquiring about what it

0:45

means for small vessel ischemic disease.

0:48

By saying the word ischemic,

0:50

you're implying that the white matter is

0:52

not getting enough blood supply.

0:54

And the patients were, you know, disturbed

0:57

by this and calling their clinicians.

0:59

And then, of course, the clinicians would call me and say,

1:01

"Do you have to use

1:02

that term small vessel ischemic disease?"

1:05

So nowadays, I kind of use the term

1:08

microangiopathic white matter changes

1:11

rather than ischemic disease.

1:13

And then, I usually use the caveat,

1:15

age-appropriate or greater than expected for age.

1:20

If I say that it's greater than expected for age,

1:23

these little white matter lesions,

1:25

then I usually will follow it by saying,

1:28

recommend clinical correlation for risk factors of

1:32

smoking, hypertension, hyperlipidemia, diabetes,

1:37

family history, and sedentary lifestyle.

1:40

So, those are the typical risk factors

1:42

for these little small vessel,

1:44

white matter, focal lesions that occur in the

1:48

periventricular and subcortical region.

1:51

They may occur in and of themselves

1:53

without any deep gray matter involvement.

1:56

Once you have deep gray matter involvement

1:58

then I will use the term lacunar disease in

2:02

the basal ganglia for the same entity of

2:05

Small Vessel Microangiopathic Disease or Leukoangia.

2:09

Leukoaraiosis is another

2:12

term that sometimes is utilized.

2:14

But I had to make a change in using that term,

2:17

Chronic Small Vessel Ischemic Disease,

2:19

once we had the MyChart with

2:22

patients looking up their own MRI reports.

2:26

So that's the, sort of the, the

2:27

elderly population, if you will.

2:29

By elderly, uh, you know, we usually say

2:31

that we will grant one white matter lesion

2:34

per decade of life and call it normal.

2:37

Which means that if you're in your forties, we'll say,

2:39

"Well, you can have up to 4 or 5 small white matter

2:43

lesions that we would say are within the

2:45

usual standard of the patient's age."

2:49

60 years old, six or seven of them.

2:52

So, if you see more than that,

2:53

it's when I start to blow the whistle and say,

2:56

"Recommend correlation for risk

2:57

factors of atherosclerotic disease."

3:00

In the younger age group, we're usually

3:03

concerned about white matter lesions

3:05

that are in the periphery,

3:07

just in the subcortical region, and those are

3:10

manifestations of migraine headaches.

3:12

So, small dots of high signal intensity in

3:15

the periphery without involvement of the

3:17

periventricular white matter is more commonly

3:20

seen in the patients who have migraines.

3:23

When you have florid involvement of the white

3:25

matter in a more confluent fashion, as well as

3:29

diffuse deep gray matter lacunar infarctions,

3:34

we may think of the entity of subcortical

3:36

arteriosclerotic, sclerotic encephalopathy.

3:39

This is obviously a syndrome in

3:41

which there is cognitive change.

3:43

This is usually elderly patients who

3:45

have hypertension, often with smoking.

3:48

And the term that is also used for

3:49

this is Binswangers, or we use SAE

3:53

for Subcortical Arteriosclerotic Encephalopathy.

3:57

So, this is microangiopathy gone

4:01

wild with diffuse confluent disease.

4:05

These are usually patients who have,

4:07

indeed, lacunar infarctions of the basal

4:09

ganglia or the striatocapsular region.

4:12

And finally, the other vascular etiology

4:14

which we'll talk about is CADASIL,

4:16

which I'll describe in just a moment.

4:19

What are we thinking about with regard to migraines?

4:21

In general, the patient who has

4:23

migraines are these tiny little dots

4:25

out in the periphery of the brain that

4:28

are seen in patients with migraines.

4:31

So usually, we're seeing them a little

4:33

bit more peripheral than this, usually

4:36

not affecting the periventricular zone,

4:39

but off in the periphery of the brain.

4:42

And this is a pattern which is

4:45

seen in patients with migraines.

4:48

However, there is a differential diagnosis for this.

4:51

So, we would probably include the so

4:54

called small vessel ischemic disease.

4:56

even if, in the absence of the

4:59

periventricular white matter lesions.

5:01

The other thing that can be do,

5:03

can lead to a similar appearance, is repetitive trauma.

5:08

So, in those patients who are athletes or have

5:12

repetitive trauma, they do tend to get little

5:15

white matter lesions out in the periphery.

5:17

They may also see something in

5:19

the central white matter,

5:21

for example, in the corpus callosum.

5:23

But this would be our chronic traumatic encephalopathy.

5:26

Most patients with CTE, Chronic Traumatic Encephalopathy,

5:30

have nothing on their MRI scan.

5:32

However, you may see, in some patients,

5:36

these tiny little dots.

5:37

So, traumatic injury.

5:40

This may be elicited by a patient

5:44

history of a previous concussion from

5:45

a motor vehicle collision, for example.

5:48

And that may explain some white

5:50

matter lesions in the periphery if

5:52

the patient does not have migraines.

5:54

and does not have any vascular risk factors.

5:58

Continuing on the theme of vascular

6:00

etiologies of white matter disease.

6:03

I come to CADASIL, and a CADASIL refers to

6:08

cerebral autosomal dominant arteriopathy with

6:13

subcortical infarcts and leukoencephalopathy.

6:18

So with CADASIL, we find a characteristic

6:22

location of the white matter disease.

6:25

And that characteristic location is

6:27

in the anterior aspect of the temporal lobes

6:30

with subcortical white matter changes

6:32

that you see here bilaterally.

6:35

The second most common characteristic

6:37

location is in the external capsule

6:40

where you see here bilateral high

6:42

signal intensity on the FLAIR images.

6:46

That combination, which may occur in addition

6:50

to periventricular and subcortical white

6:53

matter changes, but that combination of

6:56

external capsule and anterior temporal lobe

6:58

involvement is sort of classic for CADASIL,

7:02

cerebral autosomal dominant arteriopathy

7:08

with subcortical infarcts

7:10

and leukoencephalopathy.

7:12

CADASIL is an entity that can

7:15

be a source of cognitive change.

7:22

It may be a lesion that has a predilection

7:26

for migraine headaches and can lead to

7:30

patients with episodes of stroke-like illness.

7:33

So, CADASIL.

7:36

CADASIL differential diagnosis includes

7:39

Binswanger's disease, or that SAE

7:41

we mentioned before, the subcortical

7:43

arteriosclerotic encephalopathy.

7:48

So, on the top, we have the examples of CADASIL,

7:53

on the bottom, we have examples of Binswanger's.

7:56

What's the difference?

7:57

CADASIL has, in particular,

8:00

the anterior temporal lobe involvement,

8:02

which as you can see, is not present.

8:05

on the patients with Binswanger's disease.

8:07

Binswanger's generally has more in the

8:10

way of lacunar infarctions in the basal

8:14

ganglia, which you see relative sparing of

8:16

the basal ganglia in patients with CADASIL.

8:19

Both of them can have fluffy

8:22

confluent white matter disease.

8:24

And as you can see, the patients

8:28

with CADASIL, typically have

8:30

that external capsule involvement.

8:32

However, in this particular case of

8:34

Binswangers, you also see the involvement

8:36

of the external capsule bilaterally.

8:39

So, that is not as specific as the

8:42

anterior temporal lobe involvement.

8:44

And CADASIL generally can go out even to the

8:47

deep white matter of the subcortical U fibers.

8:50

This is a differential diagnosis.

8:52

CADASIL patients may not have hypertension,

8:55

but almost all Binswangers or SAE patients

8:58

have hypertension, and quite often

8:59

these patients, as I said, are smokers.

9:02

CADASIL is a younger age group, and as I said,

9:05

it's osmo dominant for this notch gene that

9:09

we search for in serology, and usually

9:13

a younger presentation than Binswanger's.

9:18

This is a patient who has

9:21

a brain that shows high signal intensity in the

9:25

periventricular and subcortical white matter,

9:27

associated with volume loss.

9:30

So here, you see that white matter in

9:31

the periventricular is somewhat fluffy-looking,

9:34

and out in the periphery,

9:37

you see the subcortical white matter or deep white

9:41

matter involvement that is also confluent.

9:44

So, this patient is a patient who

9:46

has atherosclerotic risk factors and

9:48

this is an example of a relatively

9:51

fulminant case of what I would call

9:53

chronic small vessel ischemic disease.

9:57

And because of this diffuse involvement,

10:00

no matter what this patient's age,

10:01

I would say, greater than expected for age.

10:05

Recommend clinical evaluation

10:07

for atherosclerotic risk factors.

10:09

That's how I handle this type of involvement.

10:13

There are different grading systems,

10:15

so-called Fazekas, F-A-Z-E-K-A-S,

10:18

for the involvement of the white matter disease,

10:21

if you want to give a scale for the

10:25

involvement, depending upon whether it's just

10:28

solitary or multiple areas, or more confluent

10:31

areas or extension out into the peripheral

10:33

white matter.

10:35

This would be the different grades of

10:37

white matter disease by the FAZEKAS scale.

10:41

Of the other vascular etiologies of

10:44

white matter demyelination,

10:45

one can have numerous vascularities that can

10:48

cause focal white matter lesions.

10:50

These are almost all of the collagen

10:52

vascular disease and mixed connective tissue

10:54

diseases, et cetera, rheumatoid, et cetera.

10:56

You can also see this with Sjogren's

10:58

syndrome, with lupus, generally on the basis

11:01

of the antiphospholipid antibody syndrome,

11:04

which the patient is hypercoagulable

11:06

and can have small ischemic infarcts.

11:09

You can have granulomatous,

11:10

primary angiitis of the central nervous system.

11:14

This is probably the most common of the vasculitis.

11:16

And then we have more of a,

11:18

sort of infectious etiology with Behcet's syndrome.