Agenesis Corpus Callosum: March 2011

Dr. Elliott Sherr is a Pediatric Neurologist at
University of California, San Francisco (UCSF).
Dr. Sherr is highly knowledgeable and an expert
on Agenesis of the Corpus Callosum. He sees many
patients, children, who have ACC and Dr. Sherr
is highly respected and well-liked by parents.
Dr. Sherr is on the Board of the National
Organization for Disorders of the Corpus Callosum
(NODCC) and he speaks at the annual Conferences.

Dr. Elliott Sherr is also involved in a very large
Brain Development Research Study on ACC.

I want to bring to your attention some excellent
resources that provide Dr. Sherr's knowledge
about agenesis of the corpus callosum. More
specifically:

At the 2004 NODCC Conference, Dr. Sherr gave
two presentations about Agenesis of the Corpus
Callosum. They are available as Conference
handouts [in outline form] to read below.

2004 Conference handout titled:
"ACC and Associated Features".

2004 Conference handout titled:
"How to Get the Most From Your Neurologist Visit".

In addition, both of the 2004 Conference Presentations
by Dr. Sherr, in their entirety, have been combined into
one DVD for viewing titled:

"Neurologic Issues in Disorders of the Corpus Callosum".
You can purchase the DVD from the NODCC store.

I own a copy of the DVD (recently purchased) and find
it to be very informative. My son, Matthew, who has
complete Agenesis of the Corpus Callosum was diagnosed
at four months and he is 17 years old.

The 2004 Conference DVD is divided into two separate
Presentations:

"How to Get the Most Out of the Visit/Relationship
with Your Neurologist"

and

"Agenesis of the Corpus Callosum and
Associated Features"

A few of the topics and information covered in
the "How to Get the Most Out of the Visit/
Relationship with Your Neurologist" 1st episode
of the DVD include:

Dr. Sherr says:

"I just want to say one thing: that there
are a lot of syndromes that are sometimes
associated with ACC where ACC is not
necessarily the principal issue. And that
doesn't mean that your child's not going to
have ACC related issues but it's important
to recognize that there's probably a lot
going on and ACC is a piece of that as
opposed to the primary driver of the issue."

Dr. Elliott Sherr was involved in an ACC Review
titled: "Agenesis of the corpus callosum: genetic,
developmental and functional aspects of
connectivity".

Genetic Syndromes occasionally and frequently
seen with ACC can be found on Page 8.

CHILD NEUROLOGISTS:

Dr. Sherr states that they should be board
certified in child neurology.

ADVICE REGARDING MRI FILMS:

He says:

"You should have the copy of the films with
you and in today's day and age you can have
a copy on CD. You can also, if you want,
have a film copy as well." (for yourself).

Dr. Sherr talks about asking for a film
copy of the MRI for you to have. Then you
are able to take the MRI film copy with
you to doctors and specialists that your
child sees.

Also discussed on the DVD:

What Type of ACC is this?

complete ACC
partial ACC-hypogenesis/dysgenesis
thin corpus callosum-hypoplasia

What are the associated CNS changes?
CNS = Central Nervous System
(in other words) - Dr. Sherr says:

"When you look at the MRI what other things
are there that can be seen?"

Is the MRI interpretation accurate?

Dr. Sherr says:

"I will tell you...so you know we're doing
research in my group on ACC and so we've had
families from around the country send us their
films and I can tell you that the accuracy...
the families always send us the films and
frequently the radiology report is included
in there."...

"for somebody who is not used to looking at
brains of children on MRI they're more likely to
make that mistake because they just don't have
the experience of looking at them. So the
people that I work with have probably looked
at in excess of 10,000 brain MRI's on children
and so they have a fairly strong wealth of
knowledge about what is what, what is normal,
what is abnormal and if it's abnormal, what is it,
and that is actually very important. And so when
we got the films--we've gotten over 100 set of
films--and I'll tell you that about 5 to 10% of
them were completely wrong"...

"Even the best radiologists are going to make
mistakes."

"So how do you address that?"

Neuroradiologist and
Pediatric Neuroradiologist

"Who's reading the film? Is it a Neuroradiologist?

So there are Radiologists, people who are board
certified in radiology, but then there are people
who do an extra two years of additional training
and all they look at are images of the brain and
the spine and the nerve roots throughout the body
so they're more likely to be experts in reading
brains."

"And then there's another level. It's not
a level that you can get a little certificate for
but there is another level of specialization where
they're Pediatric Neuroradiologists, where all they
do all day long is look at MRI's and other imaging
modalities of kids' brains and kids' spines and the
reason that's important is that the developing brain
looks a lot different on MRI than the mature brain.
There's a lot that's going on obviously inside of
your child's head when they're developing and that
is actually seen to some degree when you take
pictures. when you take this MRI and somebody who
is an expert in that knows about what a brain is
supposed to look like at 3 months and how it's
supposed to look at 3 years, cuz those are very,
very different. And how you interpret the results
is based on your knowledge of knowing how the brain
looks as it progresses during development. So this
would definitely be one of those cases where if
only a local radiologist has looked at it, you
should request that the MRI be reviewed by a Pediatric
Neuroradiologist. And there are ways to have your
local doctor send the films to another radiologist
[Pediatric Neuroradiologist] for a second opinion
and I would pursue those."

Dr. Sherr says:

"Have your Neurologist show you the films and go
over the films with your Neurologist."

He says to question the Neurologist about the
indecipherable terms on the MRI report and have
them explain each finding to you.

MRI's in Children

Dr. Sherr says:

"There are certain things that we can see at
3 years we can't see at 3 months and so if your
child's first scan was at 3 months of age I
would recommend getting a second scan when
they're 3 or 4 years of age."

He provides more detail about this topic on
the DVD.

Preliminary Findings of ACC:
White Matter

Dr. Sherr states:

"Is there a correlation between what we see on
their MRI and how they're doing clinically?"
We did find something preliminarily. We found
that the clinical score correlates with the
amount of white matter and white matter is
insulation in the brain."

"So the more insulation [white matter] that
you're missing the more severe your clinical
condition was. And if the brainstem was
involved that was also correlating with
severity."

Dr. Sherr further states:

"Knowing more about the MRI is going to
provide you additional information about how
your child is likely to do. And I say likely
because this is just a rough correlation. It's
not a guideline. It's not an absolute-ism."

MRIs and ACC

Dr. Sherr says:

"Everybody should have one MRI at diagnosis
and, unless the diagnosis was made later in
life, should have a second MRI."

The DVD includes many other topics and
information about ACC.

At the end of the DVD Dr. Sherr took
questions from the audience. One
question was:

"Why do some people who have ACC function
fairly normally and live a relatively
normal adult life?"

Dr. Sherr replies:

"Some of that might have to do with other
places that fibers cross...so there's
something called the anterior commissure
and it's a place that fibers cross and it's
in front of and a little down from where the
corpus callosum is."

"And actually when we reviewed some people with ACC
we noticed that they had big anterior commissures,
suggesting that maybe fibers that should have gone
through the corpus callosum crossed through there.
So that's one possible explanation."

note: Anterior commissure. Small band of approximately
50,000 axons that connects the cerebral hemispheres. The
anterior commissure connects the temporal lobes and is
located at the base of the fornix.

A few of the topics and information covered in the
"Agenesis of the Corpus Callosum and Associated
Features" 2nd episode of the DVD include:

MRI features that can be associated with ACC:

*COLPOCEPHALY:

"This is a posterior enlargement
of the lateral ventricles that results from the
absence of the corpus callosum."

"Similar phenomenom is the 'steer-horn' shaped
lateral ventricles seen more anteriorly."

*UPWARD DISPLACEMENT OF LATERAL VENTRICLES

Dr. Sherr says:

"The first two [colpocephaly and upward
displacement of lateral ventricles] are
almost always seen with ACC...not always
but almost always...and it's just what
happens to the brain in the absence of
the corpus callosum."

"So it's not a separate diagnosis
all by itself. It [colpocephaly]
is intrinsic to the diagnosis of
ACC."

He also states:

"So it's like if you're building a building
and you take out scaffolding in one of the
main areas of the building then the
building's going to look different. It's
going to have support structures in
different places and so that's what's happening
to the brain."

"But it's not a separate diagnosis. It's
just what happens when the scaffolding,
which is the corpus callosum in a way, is
missing. The ventricle's going to bulge out."

"So colpocephaly and what radiologists
call steer-horn shape ventricles are a
consequence of the absence of the corpus
callosum."

*PROBST BUNDLES

The corpus callosum is made up of 200 million
axons (also referred to as fibers).

Dr. Sherr says:

"Axons are like the telephone wires that are
connecting all the phones together and they are
these wires and they go from one side of the brain
and they cross over to the other side of the brain.
And if they cross over to the other side of the brain
then the corpus callosum is formed and if they don't,
then where are they going to go...

So in certain individuals those fibers go to the middle,
they can't cross, presumably because the structure that
needs to be made in development, (what's called a callosal
sling) is not there and so instead they turn to the left
or they turn to the right and they go alongside the edge
of the callosum (or where the callosum would have been)
and form the Probst bundles. And it's unclear what this
means.

Some people think that if you have Probst bundles that
it correlates with a better diagnosis [outcome]. We
don't know that yet but that's hopefully one of the
things we'll be able to answer more definitively."

Dr. Sherr (in the DVD) goes on to point out visually
on an MRI image where the Probst bundles are.

He then says:

"Not everybody with ACC has Probst bundles but a lot
of people do have Probst bundles but we don't know the
significance of that yet."

*INTERHEMISPHERIC CYSTS:
*a. type 1 - communicate with ventricles
*b. type 2 - not communicate with ventricles
*c. continuum with lipoma

Dr. Sherr says:

"These cysts are fluid filled structures outside
of the brain matter proper."

"So actually when the brain is formed there
actually is a space between the two hemispheres
so it's not within the brain proper...it's sort
of like in between the two sides."

"And the current thinking is that cysts develop
in lieu of the corpus callosum."

*LIPOMA:

Dr. Sherr says:

"One thing that happens instead of a cyst
forming is that a little structure, that's
basically a fat collection, which is called
a lipoma, will form instead.

ACC Brain Images

In the DVD, Dr. Sherr also speaks in detail
about other brain anomalies seen with ACC.

Dr. Sherr said:

"If you just look at the number of people who
have just ACC and nothing else that's a smaller
percentage than the total, so most kids with
ACC are going to have ACC and something else."

Dr. Sherr explains the different views of
the brain on MRI films and shows examples.

Dr. Elliott Sherr advises:

"When you get an MRI scan you need people to do
Axial, Coronal and Sagittal views to get a true
picture of the structure of the brain."

Also discussed:

Can My Child Have ACC and:

Autism
Attention Deficit Hyperactivity Disorder
Obsessive Compulsive Disorder
Cerebral Palsy
Mental Retardation

Dr. Sherr says:

"The short answer is yes."

However, in the DVD he goes on to answer
in more detail.

ACC Syndromes with Molecular Genetic
Testing:

Dr. Sherr says:

"So these are examples where the gene is known
and it causes ACC."

Andermann Syndrome
Mowat-Wilson
ARX related syndromes
L1CAM

He also says that in his experience they are
very uncommon causes of ACC.

The DVD covers a lot more topics and
information about ACC.

At the end of the Presentation Dr. Sherr
took questions from the audience.

(a few of the questions are):

Question:

"Is it acceptable to request a typed up
copy, in layman's terms, of what the MRI
interpretation is?"

Dr. Sherr replies:

"The answer is absolutely yes."

Question:

"Symptoms that might trigger you to get
another MRI?"

Dr. Sherr replies:

"I think that the symptoms that would trigger
somebody to get another MRI down the road
would be a significant worsening. So if a child
is developing at his or her own rate and then
all of a sudden they stop developing or they
decline in development, that would be a reason
to get an MRI. If there's new symptoms that
are significant and not sort of part of things
that they're already doing, you need to
potentially get another MRI, and the last one
would be something that might need to be
discussed with your doctor, depending on what
they are."

Also available from the NODCC is Dr. Sherr's
presentation at the 2008 Conference on podcast, at
no cost, which includes some of the same information
on the DVD from the 2004 Conference plus even
more information. In my opinion, the DVD and the
2008 Conference podcast are BOTH excellent
resources about ACC.

note: The DVD from the 2004 Presentation
gives the advantage of being able to see the exact
area of the brain Dr. Sherr is talking about (because
he uses a red light pointer to visually point to the specific
brain structure in the picture that he is discussing).
The 2008 Conference podcast displays still frame pictures
of the brain and you only hear Dr. Sherr talking about
specific areas of the brain, but do not get to visually
see them being pointed out.

note: you will need to download the TechSmith
Screen Capture Codec (TSCC) to view the podcast:
download here.

2008 Conference podcast with Dr. Sherr

(a few interesting highlights are):

3 family generation of complete ACC and
partial ACC in one family. Dr. Sherr discusses
one family where ACC and partial ACC is seen
in a grandfather, children and grandchildren.

seen at time frame 12:44-15:26

Dr. Sherr states:

"All of these individuals with a corpus
callosum disorder did well or average in
school and the adults have jobs. So these
are folks who are functioning at a very
high level."

ACC and Heart Defects:
seen at time frame 32:53-33:49

Dr. Sherr says:

"Almost 1/4 of the kids had heart problems.
Now these are not innocent murmurs that then
go away. These are actually kids who have real
heart disease. So my recommendation on any child
with ACC is that they get a comprehensive heart evaluation."

Colpocephaly is discussed:
seen at time frame 38:52-40:29

Dr. Sherr says:

"And so if doctors say your child has hydrocephalus
you want to be very careful to ask them, well does
the child have hydrocephalus or does he or she just
have colpocephaly?"

Interhemispheric Cysts discussion
and other ACC features
seen at time frame 43:20

Question regarding Interhemispheric Cysts:

"Do they enlarge or do they stay the same?"

seen at time frame 49:09-50:44

Dr. Sherr's answer:

"I don't think I have good enough numbers yet
but I would say that the short answer is most
don't change in size and a few will change
in size.

"If a cyst enlarges it will result in the
symptoms of hydrocephalus and so usually what
that will mean is that the child will present
with some sort of symptoms...usually it could
mean things like vomiting, particularly vomiting
when you first wake up in the morning, if a child's
eyes seem to be pointing down too much instead of
being right in the middle of the eyelids, if the
child seems to be too sleepy (lethargic) that
could also be a sign of hydrocephalus."

"So for my patients in my clinic who have an
interhemispheric cyst, when they're little I'll
get an MRI every year for the first three years
of life and if there's no growth after three years,
then I'll do one more when they're 5 years of age and
then after that I won't do anything unless they have
symptoms. But that way...I think most of the kids that
have cyst enlargements, it happens early on."

It's definitely worth exploring these valuable
ACC resources mentioned in more depth for yourself.

You can also find additional resources about ACC
(including Conference handouts, podcasts, and other
items) available at the NODCC website.

Do you want to enroll in the ACC Research Study at
UCSF where Dr. Sherr and his colleagues are involved?
Please contact: Brieana Fregeau at 415-502-8039.

Agenesis Corpus Callosum

Monday, March 14, 2011

Dr. Sherr talks about ACC

Saturday, March 5, 2011

Got an Idea?