- Morning, my name is Dave Jung.
I'm one of the ear and lateral skull base
surgeons from Mass Eye here in Boston.
I'd like to thank the organizers
for giving me the opportunity to speak today.
Real honored to speak in front of this group.
I was asked to give a short talk about communication
options for hearing loss in NF2.
I have no disclosures to make.
Let me give you a quick overview of what I'll be speaking
about after I get these slides quickly.
There's been really excellent introduction
by both Dr. Evans and Dr. Blakely
so I won't have to rehash a lot of that.
I'm gonna be talking briefly about surgery.
Is there a role for surgery in hearing preservation in NF2?
The role of bevacizumab Avastin
in that in preserving hearing as long as possible.
Dr. Blakely just touched on that as well.
At the end I'll talk about a couple of rehabilitative
options including cochlear implantation
and auditory brainstem implantation.
So something that I think about every day,
this is a diagram of the ear, sound travels
in from the outside world goes through the ear canal,
vibrates the ear drum, and also the vibrates the three bones
of hearing which are the smallest bones in the human body.
Those sound waves then transmit through the stapes
into the cochlea where the hair cells convert those
vibrations into nerve signals, send them
to the brain through the cochlear nerve.
From the cochlear nerve they travel to the cochlear nucleus
and then up to higher order brain centers.
Those are where the two major rehabilitative
options that we currently use act,
number one, in the cochlea for a cochlear implant,
and here at the cochlear nucleus
for an auditory brainstem implant.
You've seen this picture already a couple of times today.
This is a classic MRI findings for NF2.
We see here bilateral vestibular schwannomas
and they arise right within the internal
auditory canal and affect hearing and balance.
It is and really does affect hearing in most patients,
really is the most common symptom in NF2 patients.
This is a diagram for the natural history
as it were of hearing in NF2 ears.
This appeared from Dr. Plotkin.
This maps out the decline, which is defined
as statistically a significant decrease
in word recognition score seen here.
This is a freedom from hearing decline,
everyone starts at 100% regardless of where you are.
That's just defined as your starting point.
Then people decline from there.
This is all ears here in the middle.
These are ears with the small tumors,
that is smaller than 1cc.
These ears with bigger tumors, larger than 1cc.
So you can see that the majority of ears
with vestibular schwannomas do decrease over time in NF2
but that larger tumors do tend to decrease
more quickly than do smaller tumors.
This will come up again in the section
that I speak about Avastin a little bit.
This really does affect NF2 patients quite a lot.
This is a NF2 specific quality of life
study that was developed in the UK.
I believe Dr. Evans was on this paper actually.
Higher numbers denote greater
influence upon daily activities.
You can see here that dizziness and decreased hearing
for NF2 patients is right at the top, particularly compared
to healthy individuals here on the right.
What are a couple of surgical approaches, or how do we think
about surgery, with respect to hearing preservation?
That is not rehabilitation but preservation in NF2.
This is somewhat controversial I'll say, right out
the onset, there are some proponents in our field
of removing tumors almost preemptively
via hearing preservation approach to try
to prevent a hearing loss in the future.
This is probably the largest series in that regard.
This is the patients from 1992
to 2004 from the House Ear Clinic.
These are 45 NF2 ears.
The mean age was 12.6 years, these are children
with standard deviation of 2.3 years.
You can see here that patients start out
with Class A hearing, that is essentially normal hearing
as defined by the American Academy of ENT.
After surgery, a little over half
ended up with the same class of hearing,
whereas a little less than half ended up losing
essentially all useful hearing on the operated ear.
That Class A or B hearing is considered
to be aidable, that is with a hearing aid.
The question arises as to whether this is over treatment.
We don't know upfront whether these tumors
would have grown or not, whether they would
have caused hearing loss in the future.
So this is somewhat controversial.
Moreover, if an ear is left with no service of hearing,
cochlear implant may not be an option down the road
because the cochlear nerve very well
might be sacrificed during the surgery.
Not always, but that is certainly a possibility.
There is another surgical technique
that is used in efforts to maintain hearing.
That is surgical decompression.
In decompression, the approach
is via middle fossa craniotomy.
So we'd be going above the ear.
We remove all the bone over the tumor.
The thought is to allow the tumor to decompress
and provide less tension on the nerve as it were.
You can see here these were 34 patients
who underwent the middle fossa decompression.
These were all patients in whom the ear was an only
hearing ear in a NF2 clinical situation.
That ear was rapidly declining.
So they said why not try middle fossa decompression.
These are the percentage of patients
who had some useful hearing preserved.
About half the patients had some useful hearing
preserved up to about three years out.
Some patients however did have useful hearing
preserved out to 10 years and still a little bit
of an open question as to why some patients
do better than others in this regard.
I'll only speak very briefly about
radiotherapy with respect to hearing.
Dr. Blakely's already touched on this.
As she mentioned, approximately 50% achieved
control of tumor growth, that is, size is a little bit
of a misnomer here, I apologize, at five years.
However long-term hearing preservation
is really quite poor in the 40% range.
There is a small but real risk of ration-induced
malignancy as Dr. Blakely mentioned.
However, the one advantage I would mention
with radiotherapy is that it quote, unquote
"preserves" the cochlear nerve for possible
cochlear implant down the road.
That is, the cochlear nerve is not
sacrificed in a surgical procedure.
There may be still some fibers that travel through the area
that can be stimulated with a cochlear implant.
I'll only touch very briefly on
Avastin bevacizumab for NF-2 tumors.
Dr. Blakely's already mentioned this.
It's not FDA approved for NF-2.
We never see a complete response for tumors.
However, this is the first study
of reporting this by Dr. Plotkin.
There really was a quite remarkable improvement
in hearing seen in some patients, not all,
after having received Avastin.
Interestingly, there really is not
any relationship between change in tumor size and hearing.
So this is something that still very much under
investigation or active clinical trials to look at this.
This just shows once again the plot that shows
hearing stability or improvement over time.
This is the percentage of patients,
everybody starts at 100%.
You'll recall that first slide that I told you
with all-comers and again we gotta realize these
are not tumors they're treating with Avastin.
Pretty much out here the percentage of people
with hearing improvement will be very, very low.
I'll move to the next section
of the talk which is describing a couple
of rehabilitative options for hearing.
What do we do when there's no useful
hearing left in the ear in NF2?
The first is cochlear implantation.
This is a widely circulated picture on social media.
Probably a lot of you has seen this.
This is a little girl who does not have NF2,
she was born deaf but her father got a little tattoo
to not make her feel as left out.
That tattoo shows a couple, one of the elements
of the cochlear implant, that is the sound processor,
looks like a big hearing aid, there's one on the outside.
This is the transmitter that connects
via magnet to the receiver stimulator
that is implanted during a surgical procedure.
You can see the newest cochlear implant designs have this
curved shaped to follow the turn of the cochlea.
So where does that act?
This is another version of that
picture that I showed you before.
Once again, sound comes in from the outside world.
Ultimately the sound waves reach the cochlea
and the cochlear implant, the electrode,
is inserted into the cochlea to stimulate
what remains of the auditory nerve, the cochlear nerve.
That's an important point to raise.
If the cochlear nerve has been sacrificed
previously through surgery or it's nonfunctional,
cochlear implant will not work.
Auditory brainstem implant, once again, acts here
at the next stopping point, the cochlear nucleus.
In other words, auditory brainstem implant
can work in a situation where there's no
functioning auditory nerve remaining.
Some NF2 patients with a "preserved"
auditory nerve can derive a very significant
benefit from cochlear implantation.
We can preserve the auditory nerve either after
decompression surgery after I mentioned before,
or nerve preservation attempt during tumor removal.
The other situation as I mentioned
before is radiation therapy.
There's a couple of small studies in this regard.
One is out of 2012, out of the Mayo Group.
They looked at 10 patients with NF2.
Five had had previous surgery with tumor
removal and nerve preservation.
Four that undergone radiation.
One has just undergone observation
with no previous treatment.
Nine patients had sound awareness.
Six had open set speech perception.
For those of you who are not aware of what that means,
there's closed set speech perception that's kinda like
a multiple choice exam, you know what the words are,
you're trying to decide from that set.
But open set speech perception is much more demanding.
They just play a sentence to you,
you don't know what it is, and you have to repeat it back.
Perhaps most compellingly, seven are daily users.
Meaning that they have enough benefit
from the implant to actually use it every day on their own.
The other study, looking at cochlear implants in NF2,
this is 2014 out of the Manchester group.
Six patients with NF2, the small case series, all had
previous or concurrent hearing nerve preservation surgery.
They looked at something called cochlear
promontory stimulation, that is while they're in there,
they stimulate the cochlea directly to see if a nerve signal
can travel through the auditory nerve.
Five out of the six developed sound
awareness and speech perception.
Four are daily users.
One had no responses at all
and received an ABI down the road.
The other emerging, or actually I would say
it really established at this stage,
rehabilitative options, auditory brainstem implantation.
Once again here is that diagram
showing you that the advantage
of the ABI is that it can work here
at the cochlear nucleus in the complete
absence of a functioning auditory nerve.
ABI design really is a modified cochlear implant.
It was developed first at the House Ear Clinic in the 70's.
You see again here the sound
processor with the transmitter coil.
This is the implanted portion
that stays underneath the scalp.
The electrode array, which in this case
is a flat array, is placed within
the fourth ventricle over the cochlear nucleus itself.
What are the FDA criteria for ABI surgery?
First is the NF2 diagnosis.
You have to be above 12 years of age.
They do require a fair amount of,
they do have a medical and psychologolical evaluation.
ABI should be placed during first or second
tumor removal or after both tumors have been removed.
But interestingly there's no strict
audiologic criteria for ABI placement.
Of course the main question is does
the ABI actually improve hearing?
Well it clearly does, I think the data shows,
provide sound awareness and helps in lip reading.
It does also provide some benefit
in closed set word recognition.
But open set word understanding,
really that's pretty much the minority,
at least for NF2 patients, at this stage.
The House Ear Clinic having developed the ABI
as the most experience in this regard.
The first patient was implanted in 1979.
So far they've done 92 NF2 patients.
85% of those patients get some auditory stimulation.
In most cases this is an aid to lip reading essentially.
93% have better sentence understanding
in the context of improved lip reading.
But only 12% have limited speech understanding.
That is, in the absence of lip reading.
The latest of ABI results that have
been collated and reported from
multiple groups, these are really worldwide.
This was reported in 2014.
Once again this is an analysis of best outcomes.
They only looked at these 26 out of 84 patients
who had better than 30% open-set speech recognition.
In this analysis it appears that better word scores
are obtained with a shorter period of deafness.
That kind of stands to reason in the nervous system
in general, it's sort of use to lose it,
and more active electrodes being placed within
the cochlear nucleus or on top
of the cochlear nucleus rather.
Tumor size/volume and patient age
did not negatively or positively affect incomes.
Once again, there is a lot of things
about this that we don't understanding.
Interestingly there is a very small number of patients,
these are not NF2 patients, but who are born without
an auditory nerve, and for some reason these
ABI patients perform significantly better.
This is a paper that came out in 2000, I can't read that.
But recently in non-NF2 patients, that is children
who are born without an auditory nerve, actually achieve
open set sentence recognition 65% of the time.
But in this study, only 12% of the time in NF2 patients.
I would be remiss in a surgical talk
if I didn't show you at least one short movie.
So I'll show you, this is once again not
an NF2 patient but this is a child undergoing
ABI placement for a cochlear nerve aplasia.
So what we see here is the flat electrode being placed
within the 4th ventricle over the cochlear nucleus.
Here we're using an endoscope to visual
a cerebellopontine angle as Dr. Blakely mentioned.
Here's the seventh nerve exiting the brain stem.
Here's the ninth, 10th, 11th, the cranial
nerve complex, the lower cranial nerves.
You can see the electrode going in
to the fourth ventricle there.
I'll just skip ahead here.
It shows the child did achieve some sound awareness.
This is her mom speaking behind her and she turns around.
But you'll see that she does still primarily communicate
via sign language, so still not perfect.
So in conclusion, observation I think
just goes right along with what Dr. Blakely mentioned,
of non-growing tumors optimal for hearing.
Nothing can improve upon or really
simulate the natural hearing.
There is an emerging role for Avastin
although still a fair amount of work
needs to be done in that regard,
and there's ongoing active clinical trials for this.
Surgical decompression may be considered to stave off
hearing loss as long as possible,
perhaps in conjunction with Avastin.
These are all things that
are actively undergoing development.
Cochlear implants, there's no question
that if it's possible to place a cochlear implant
provides the better rehabilitative outcome.
Auditory brainstem implants provide sound awareness
and aids the lib-reading in most NF2 cases.
Some NF2 patients can achieve open set speech recognition.
That certainly is not the expectation
with auditory brainstem implantation.
So clearly the need has been touched on before
for improved therapy and rehabilitative options.
With that, I went through the slides pretty quickly.
I'll end and we'll be happy to take questions.
Thanks very much.
(audience applause)
- Thank you for sticking so well to time.
Do you want to just stay here?
Well, no actually, we could probably take the mic down.
Do you have a reason, do you think,
why people who were born congenitally deaf
with no functioning cochlear nerve
do better than people with NF2?
Do you have a sort of idea why that might be?
- That's a really interesting question.
The top performers for cochlear implants
are also kids who are born deaf
and who are implanted very, very early.
So that certainly plays a role.
There's a lot of research both at the Eye and Ear,
where I work, and at other places, looking at other
things that the tumor might secrete
that are quote, unquote toxic to hearing.
There are some evidence there may be some inflammatory
protein such as TNF-alpha that might have
a negative impact upon the hearing nerve itself.
These are all things that are under active investigation.
- Questions.
- [Audience Member] Is there ever any reason
to put in a cochlear implant before the nerve is damaged?
Because I know it won't work if the nerve is damaged,
so why not just put it in before the tumor grows?
- I'm sorry if I didn't mention this.
The disadvantage of the cochlear implant
is a sacrifice of all residual normal
acoustical hearing in the ear.
That being said, people are actively putting in cochlear
implants as quote, unquote sleeper devices.
So if you have a patient in whom
you know you're able to preserve
the cochlear nerve the best you can,
and you've confirmed that with stimulation in the surgery,
they'll actually put in, and they have no residual hearing,
no useful hearing in that ear, they'll go in and put
the implants in in a situation in which
there's a tumor on the other side with a very, very high
likelihood of losing hearing on the other ear over time.
- We've done that in Manchester.
In fact we had a lad who used his cochlear implant
alongside his normal hearing ear for many years
and got amazing benefit from that.
Occasionally you get these super users
who are able to use it and don't need it to be a sleeper.
Any other questions?
- After a neural, what is it, the acoustic neuroma,
I'm sorry, with all the terminology.
(man speaking off microphone)
Once the hearing nerve is severed,
is there any studies about reconnecting it?
- That's a good question and there
has been some work in that area.
David, you're probably best placed.
- It's a really interesting question.
For some reason, the cochlear nerve is actually exquisitely
sensitive to being severed in that way.
For example, I'll give you a counter example.
For motor nerves, for example, the facial nerve,
we reconnect that through nerve grafts and conduits
all the time, with variable results,
but so far none of that has really been shown
to be effective for the auditory nerve.
There's something about the incredible
fine tuning of signals through that nerve
that makes it really incredibly difficult.
People are working hard on it,
but it's just a very difficult problem.
- Any other questions?
Yup.
Will I get in the US relay team?
- [Audience Member] Thank you. (laughing)
Actually I'm not sure if this is right.
I was writing so fast that I may have this wrong, but--
- I was going fast too.
- [Audience Member] I know, we were both going fast,
and you were going fast too.
(audience laughing)
I believe on one slide you showed
that after tumor removal with surgery
about half of the persons lost hearing,
what happens if they weren't removed?
- [Dave] So that's why that's a little
bit controversial, right?
Because you're taking a situation where we don't know
what that particular tumor would have done.
Would it have grown?
We don't know, and that's why I think
it's hard to propose to a patient,
or a patient's family, or parents, really in that situation,
we're willing to go in and perform a surgery
in which today there's a 50% chance you're going to lose
all useful hearing in that ear.
Then the question becomes how well can you map out
the future behavior of that particular tumor?
Like Dr. Blakely mentioned, that's really
where future biomarkers, tumor markers,
are really gonna be important.
- [Man In Grey Suit] Great, anyone else?
Well I think we're just about on the coffee break.
So thank you all and thank you for coming
and listening and sorry we did go
a bit quickly with too many slides.
Okay, thanks.
(audience applause)
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