69 – SYNGAP1 and Epilepsy Surgery: Is It Time To Consider A Different Toolbox?

Taylor Abel, MD & Monika Jones, JD

All children with drug-resistant seizures should be referred for a surgical evaluation after failure of two appropriate and tolerated anti-seizure medications. In this webinar, our speakers will discuss the wide array of tools available in the epilepsy surgery toolbox today, including various neuromodulation devices.

Links: 

Pediatric Epilepsy Surgery Alliance

Stopthedelay.org: Our awareness campaign around when it’s time to be referred to a surgical evaluation. Includes relevant articles re delay to evaluation.

Let’s Talk About Epilepsy Surgery: YouTube playlist with heavy hitters in the world of epilepsy surgery. Starts with barriers to evaluation through making the decision.

These are our introductory comments:

Monika Jones is Founder and Executive Director of the Pediatric Epilepsy Surgery Alliance (formerly known as The Brain Recovery Project). She is also the principal investigator of the Global Pediatric Epilepsy Surgery Registry, the only patient-powered (by parent proxy) study to understand the developmental trajectory after epilepsy surgery.

Dr. Taylor Abel is a pediatric neurosurgeon specializing in epilepsy surgery. He is surgical director of the Pediatric Epilepsy Surgery Program at UPMC Children’s Hospital of Pittsburgh and is a highly-published researcher on epilepsy surgery, including neuromodulation. He also sits on the scientific advisory board for the Pediatric Epilepsy Surgery Alliance.

THIS IS A TRANSCRIPT ONLY:


0:06
hello everyone and welcome to today’s webinar my name is Olga Bode and I’m a student Gap parent and part of the team
0:11
here at uh Syndicate research fund our presentation today is singap one and
0:17
epilepsy surgery is it time to consider a different toolbox and I have the pleasure to introduce
0:24
today’s speakers Monica Jones JD and Dr Abel Taylor
0:30
Monica is founder and executive director of the Pediatric epilepsy surgery Alliance formerly known as the brain
0:37
recovery project she is also the principal investigator of the global pediatric epilepsy surgery
0:43
registry the only patient powered by parent proxy study to understand the
0:49
developmental trajectory after epilepsy surgery Dr Taylor Abel is a pediatric
0:55
neurosurgeon specializing in epilepsy surgery he is surgical director of the Pediatric epilepsy surgery program at
1:02
UPMC Children’s Hospital of Pittsburgh and is a highly published researcher on
1:07
epilepsy surgery including neuromodulation excuse me sorry he also sits on the
1:15
scientific Advisory board for the Pediatric epilepsy surgery Alliance uh recorded version of this webinar will
1:21
be available on the srf website under webinars on the family menu and by the end of this presentation you
1:28
will have the opportunity to answer your questions we’d love to hear from you and if you can put those questions in the Q
1:34
a and for those of us just joining you welcome and again our speakers today are
1:40
Monica Jones and Dr Abel Dr Taylor Abel their presentation today is syngap1 and
1:48
epilepsy surgery is a time to consider a different toolbox it’s now my pleasure to turn things over
1:54
to Monica thank you thank you very much let me get my presentation up I didn’t quite
2:01
cue it appropriately here I hope you can all see it can you see the presentation
2:06
thank you yes great terrific I’m Monica Jones I
2:11
just wanted to say how fortunate we are to have Dr Abel with us he is a highly
2:16
trained epilepsy surgeon you know I I like to say there are neurosurgeon and and then there are highly trained
2:23
pediatric epilepsy surgeons and that’s who Dr Abel is we’re very spoiled that he’s on our scientific Advisory Board
2:30
and very excited that on really short notice he decided to join us for this webinar
2:35
um I’m a hemispherectomy mom my son has had the left half of his brain removed to stop seizures and I’m very passionate
2:44
about making sure that parents understand that surgery is a treatment
2:50
for drug resistant seizures that they should be considering at least when we think about epilepsy treatments
2:57
we have to think about them as being in three different tool boxes the first
3:04
toolbox that your doctor your doc your child’s neurologist will go into is obviously the medical toolbox the
3:11
medicines if medicines don’t work then you’re supposed to be referred to go to
3:17
see if one of the tools in the surgery toolbox works and then if you’re not a
3:22
candidate for one of the respective surgeries the surgeries where they remove or destroy part of the brain then
3:30
we would look at neuromodulation devices which we’ll talk about today or Diet
3:35
the international league against epilepsy which is really the premier Global body of neurologists and
3:42
neurosurgeons who set these standards that our doctors followed published a
3:48
very important paper last year and where they said really anyone up to
3:54
about age 70 every single patient as soon as they’re drug resistant regardless of how long they’ve had the
4:01
epilepsy regardless of how much money they have the type of insurance that they have regardless of their seizure
4:08
type regardless of any of these things they should be referred for a surgical
4:14
evaluation so then the question is well then what is drug resistance that is a
4:20
really easy formula to remember a child is drug resistant if they have failed
4:25
too appropriate and tolerated anti-epileptic drugs if your child gets
4:30
a rash from an anti-epileptic drug they’re not considered tolerated so you wouldn’t count that medication or if
4:37
they have a drug that’s not really appropriate for the type of epilepsy your child has let’s say they’re having
4:44
absent seizures and they’re given a medication that’s not really indicated for absent seizures they wouldn’t count
4:50
but otherwise when they have failed to you’re supposed to be referred for a
4:55
surgical evaluation and that generally doesn’t happen often I’m sure there are a lot of parents out there who are
5:01
experiencing yet another medication a third a fourth being thrown at them and
5:06
no discussion about surgery has been made yet so we just want to open up that door for you to start considering
5:13
opening up that surgery toolbox to see what’s in there that might help your
5:18
child epilepsy surgery is not a last resort you’ll see this on our Twitter you’ll
5:24
see me talking about this does this mean that I’m saying today you need to go in and make sure that your child gets
5:30
surgery no all I’m saying is get a referral for a surgical evaluation so
5:37
that together with your team you can open up that toolbox and have the
5:42
evaluations needed to see which tool might be able to help
5:48
So today we’re just going to briefly talk about what epilepsy surgery is I like to think of them as going into
5:55
four different buckets surgeries that remove part of the brain destroy part of
6:01
the brain disconnect part of the brain there are also surgeries that technically are not considered epilepsy
6:08
surgery but we put them into that uh overall toolbox and there’s a lot of
6:13
literature that starts to say well yeah I guess this is kind of epilepsy surgery and these are these neuromodulation
6:19
devices so VNS DBS RNs Dr Abel will introduce us to those and these are what
6:25
we talk about when I say open up that surgery toolbox to see what’s in there
6:32
I’m going to pass it off to Dr Abel now who will introduce us to what a comprehensive pre-surgical evaluation
6:39
means in the non-invasive phase which is phase one
6:47
sorry I’m muted thank you Monica and thank you for that wonderful introduction
6:54
um it’s uh it’s really an honor to be able to talk about epilepsy surgery today
7:00
uh I I’m a pediatric epilepsy surgeon at the University of Pittsburgh in our
7:06
children’s hospital and I do about 120 epilepsy surgeries a year
7:13
and um so in preparation for this talk I actually sent an email out to all of our
7:20
neurologists uh to get their view on
7:25
um epilepsy surgery for syngap and one of the things that I thought was really
7:31
interesting is that one of them responded by saying we’ve probably done
7:37
uh more epilepsy surgery on patients with syngap than we realized but maybe we don’t realize it because we haven’t
7:43
done genetic testing in all of our patients um so anyway we’re going to talk a
7:49
little bit about evaluation for epilepsy surgery and
7:54
um when this slide here goes over the phase one evaluation which is a when
8:00
we’re evaluating for epilepsy surgery one of the most important things for us to do is to sort out if epilepsy is
8:07
coming from one part of the brain or is coming from the brain more broadly what we would
8:13
term uh generalized epilepsy and often these genetic epilepsies like syngap are
8:20
generalized epilepsies but it’s really important to establish that definitively before we plan an
8:28
epilepsy surgery and so what this typically involves is uh you can see on the left we do EEG and
8:35
and many of you are all of you are familiar with EDG we do a really detailed MRI study where
8:42
we look at the brain in really uh high definition to try to see if there’s an
8:48
abnormality in the brain that’s causing seizures we do expect in Pet Imaging when it’s
8:54
available um there are many centers where most centers that are a level four Epilepsy
9:01
Center will have a pet and then some centers will also have a MAG and a speck but that pet is really
9:09
important whereas the mag inspect are not always necessary but can sometimes add some information
9:16
but um it’s really important to go somewhere where you have these evaluation tools
9:22
available so that you can get a complete evaluation we can go to the next slide
9:31
um and uh so just because I think the point here is that just just because you
9:37
have a genetic epilepsy does not mean that you are not a candidate for epilepsy surgery
9:45
and there are many examples of this there are some types of genetic epilepsies that are actually associated
9:52
with focal abnormalities and just because you have for example syngap does not mean that there’s not a
10:00
focal abnormality causing seizures which is why the phase one evaluation is
10:05
really important but also genetic generalized epilepsies can also
10:12
be successfully treated with different epilepsy surgery strategies which we can
10:18
talk about I think in some of the upcoming slides Monica is there anything else you’d like
10:24
to add with the slide we just looked over we did a presentation with the Deep
10:29
connections group recently about surgeries for rare genetic epilepsy and I think that’s why I put it in the in
10:36
the slide at the bottom that please go over there to also look at that webinar because it will share some of the data
10:43
around surgeries for rare genetic epilepsies as well that’s it
10:48
great um and so there are several different types of
10:56
epilepsy surgery like Monica mentioned earlier and I think I think when people think of
11:03
epilepsy surgery they typically think of a traditional type of epilepsy surgery where
11:09
we’re doing a craniotomy meaning we’re removing an area of bone over the brain and then we’re removing an area of the
11:16
brain sometimes a lobe or disconnecting or removing a hemisphere
11:21
or sometimes we’re removing a brain tumor or something like that
11:26
and that’s traditionally what people think of when they think of epilepsy surgery and that’s what that those are
11:32
some of the most common epilepsy surgeries that we still do today um there are other situations where we
11:41
are just disconnecting that part of the brain so rather than removing it we’re just disconnecting it so it’s
11:47
functionally removed but not actually removing it for abnormalities that are small we can
11:55
place a laser probe without doing a craniotomy to destroy that tissue that’s
12:00
called laser ablation or in some countries and also sometimes the United States
12:06
we do thermocoagulation which is where is just another way of heating the brain
12:12
to destroy it but what’s really important to recognize in is in the last uh 30 years but
12:19
especially the last uh 10 years there’s really been an explosion in the
12:26
availability of neuromodulation technology and so these are Technologies
12:31
where rather than removing or destroying a part of the brain
12:36
we stimulate a nerve in the neck or we stimulate the brain itself
12:43
to try to decrease seizures and um I’m speaking about this in very broad
12:49
terms which we’ll we’ll talk a little bit more in subsequent slides but some of these strategies are associated with
12:56
seizure freedom and other strategies are just associated with decreasing seizures but these different neuromodulation
13:04
strategies can also be very effective
13:12
so sometimes the goal of epilepsy surgery is to achieve seizure freedom in
13:19
other times the goal of epilepsy surgery is to reduce seizures and improve
13:26
quality of life but really the bottom line is that
13:31
um we really want to focus especially these days on improving quality of life
13:39
and improving a child’s development and uh and thinking and cognition and so
13:47
um one of the jobs of the epilepsy team and epilepsy surgery team is to assess patients holistically and
13:56
so we we don’t want to just consider someone’s how many seizures someone’s having but
14:02
how they’re affecting their quality of life and what the patient and their
14:08
family’s goals are and so sometimes I’ll meet someone where their goal really is to be able to drive a car
14:15
and there’s some surgeries that are not compatible doing that and so we try to consider all of those things together
14:23
um when we’re making decisions with uh with families
14:29
so and with syngat there are three main seizure types I cleared my Colonia
14:37
absence seizures and also tonic clonic or drop attack seizures
14:44
drop attack seizures are particularly important to talk about because they can
14:50
be associated with um with head injuries uh and uh the need to wear a helmet
14:58
sometimes even use of a wheelchair um or anxiety about having another drop
15:05
attack seizure and so there are there are certain epilepsy surgery strategies that we think about in particular with
15:12
with these types of seizures and so um Corpus callasotomy is a fancy term
15:19
for one particular surgery that we use to treat drop attacks in particular and and
15:27
what this consists of is traditionally making a small opening in
15:33
the bone and then going between the two hemispheres of the brain
15:39
to uh do you see my mouse probably not
15:44
but to disconnect this structure in the middle of the two hemispheres fears here
15:49
which is called the corpus callosum and the reason for doing that is that by
15:55
disconnecting the corpus callosum there’s about a 60 to 70 percent chance that drop attack seizures will go away
16:04
um some other seizure types will also improve after a corpus callisotomy um but but the main goal is often to
16:11
treat drop attack seizures and so um there are now mult even though this
16:18
traditional way of doing a corpus call sodomy has been around for a long time and you can see that approach on the
16:25
left side of the screen here this craniotomy there are now multiple different ways to do a corpus
16:31
callosotomy that are less invasive and so one method is the endoscopic
16:36
calasotomy that was pioneered by some
16:41
some people in Detroit Sandeep sued and also Sandy lamb in Chicago but that’s a way where rather than doing
16:49
the traditional larger type of craniotomy a smaller opening is made in a camera is placed in that camera is
16:56
used to disconnect the corpus callosum and then um more recently we’ve begun using laser
17:05
ablation methods where rather than even doing a small craniotomy we just Place
17:10
three or four laser ablation probes into the brain using a special robot
17:17
and without doing a craniotomy we’re now able to do a corpus callosotomy
17:23
um and so that’s uh that’s also now been quite common and these less invasive
17:29
techniques are probably just as effective as the traditional technique
17:34
Monica am I going way too slow or are we doing okay on time
17:40
I think we’re okay you’re doing great okay um this is a this is data from a review
17:48
article by George ibrahim’s group George is a neurosurgeon at the University of
17:54
Toronto the hospital for sick children but it Compares corpus callasotomy with
18:01
vagus nerve stimulation which are two different strategies for treating drop attack seizures
18:07
and what this shows and what other models and other reviews have shown
18:14
are that Corpus callisotomy is more effective for treating drop attack seizures so here it’s associated with
18:22
about 70 percent seizure freedom from drop attack seizures whereas VNS
18:28
is associated with about 28 seizure freedom from drop attack seizures
18:34
and this data is very similar to what’s also been seen in the adult systematic
18:41
review where it’s about 70 percent for Corpus call sodomy in 20 for vagus nerve
18:48
stimulation and so important to note though that these
18:53
treatments are often used in combination and so for somebody with someone with
18:59
really severe drop attack seizures we’re often using Corpus callosotomy but then
19:04
often using DNS and we’re often using them together so even though we’re presenting comparing the effectiveness of these
19:11
strategies they’re not mutually exclusive meaning we don’t have to choose between them we
19:17
can use both and in some many patients we do use both
19:22
um VNS and Corpus callosotomy are associated with different rates of
19:29
complications and so um for vagus nerve stimulation
19:35
you can get infection infection is probably the most common complication which occurs in about three percent of
19:41
patients um a small subset of patients will need
19:46
additional surgery but then common complications or Adverse
19:52
Events are throat pain or coughing or drooling those are things that can happen because
19:58
we’re stimulating the vagus nerve and because we’ve done a surgery in the neck that are really common after DNS
20:05
but that are not usually um don’t usually stop patients from using
20:12
the therapy um Corpus callasotomy
20:18
is associated with a higher rate of complications about 13 in this series
20:23
had temporary weakness there’s a high percentage of patients that have What’s
20:30
called the disconnection syndrome which is where your personality is blunted for
20:35
several months and your personality is just really off for a while but then typically recovers
20:42
um and in about two to three percent of patients that are permanently affected
20:47
by this disconnection syndrome now it’s important to note that these
20:53
less invasive approaches like laser ablation or the endoscopic approach may
20:58
be associated with lower rates of these calcotomy complications but um until we have more data we won’t
21:06
be able to describe that uh very well
21:12
um vagus nerve stimulation is one of the most traditional forms of
21:18
neuromodulation to treat epilepsy and what it is as you can see in this
21:24
picture is that we make a small opening in the neck where we place these stimulator leads on
21:30
the vagus nerve and then we tunnel those leads and connect them to a battery or
21:35
pulse generator that’s implanted on kind of below the clavicle in the chest
21:41
it’s always placed on the left side and um when I I do about 50 of these
21:47
procedures a year and when I’m talking to families what I usually say is that
21:53
um the most common risk of this surgery
21:58
is there’s about a 30 chance that it won’t be effective for you in a way that’s appreciable
22:04
but what that means is there’s about a 70 percent chance that you will appreciate a benefit
22:09
and for about [Music] um for about 60 percent of patients there’s about a 50 reduction in seizure
22:16
frequency and so 50 so cutting the seizures in half is typically what the studies that
22:23
have studied DNS have considered as their as their outcome and so there’s
22:29
about a 60 chance that you’ll cut your seizures in half and about a 10 chance
22:35
of reducing them by about 90 and then there’s about a five percent chance of becoming seizure free but but it’s
22:42
important to note that that’s about the same odds that you’d become seizure free even without an epilepsy surgery
23:03
responsive neurostimulation is a relatively new strategy for treating uh
23:10
drug resistant epilepsy and the advantage of responsive
23:15
neurostimulation is that there are two advantages one is that we’re stimulating the brain directly
23:21
and the other Advantage is that the electrodes that are implanted can
23:27
actually sense when a seizure is starting and then the device which is implanted in the skull close to the brain
23:34
senses when the seizures are starting and can deliver therapeutic stimulation in response to the seizures starting
23:41
and so um this has become a really powerful method for reducing seizures
23:47
in different types of epilepsies where uh for example if the seizures are
23:53
arising from motor cortex or the the part of the brain that controls motor function or the part of the brain that
23:59
controls language function and we can’t remove those areas this is a strategy where we can put
24:05
electrodes directly on those areas and stimulate them to reduce the
24:11
seizures and so um there have been a number of studies now that have studied RNs in children
24:18
and have found that it’s safe and effective
24:24
um with acceptable rates of Adverse Events
24:29
um now for generalized epilepsy
24:35
groups are also using responsive neurostimulation but rather than
24:40
implanting it on the surface of the brain where the seizures are starting they’ve been implanting the electrodes
24:46
uh deeper in the brain in the thalamus which is the brain’s Grand Central Station
24:52
and that’s a way where RNs can detect seizures coming from anywhere in the
24:57
brain and deliver a stimulation to a part of the brain that can then stop the
25:03
seizure from spreading and so um that type of treatment is the topic
25:09
of a of a large clinical trial right now but but preliminary Studies have shown
25:14
that this is maybe a an effective treatment for generalized epilepsies
25:24
that’s a good segue into discussing deep brain stimulation which is a similar
25:30
strategy to what I was just describing where um
25:35
we’re stimulating the brain’s Grand Central Station and so when we when
25:40
seizures are generalized and can come from anywhere in the brain the strategy often rather than trying to
25:47
stimulate the brain surface itself is to place electrodes into the thalamus which
25:54
is the brain’s relay station and by doing that we’re modulating we’re
26:00
changing brain activity globally which um Can can reduce seizures and this has
26:05
been shown to be effective in Lennox Cousteau type epilepsies and other
26:11
generalized epilepsies and so this is a um becoming a more and more commonly
26:17
used strategy for treating generalized epilepsy and some types of focal epilepsy also
26:31
I just wanted to chime in if you go to our YouTube channel we have two other
26:36
excellent videos that Dr Abel has shared with us actually their sessions from our
26:42
family conference he did a terrific one in 2019 with Dr George Ibrahim who whom
26:48
he mentioned earlier and then he did a kind of a follow-up to that this summer and then there’s also a great session on
26:55
minimally invasive surgery with Dr Sandy lamb whom he mentioned earlier as well and Dr David Adelson so please feel free
27:02
to go to our YouTube channel to learn a little bit more and then also like I certainly don’t um
27:09
and I’m not endorsing the accuracy of any statements in these groups but there are two big groups for Pediatric
27:16
epilepsy surgery as well as RNs DBS and VNS and Fa on Facebook if you pop into
27:22
those groups and just want to see what some of the conversations are you you might be able to find some good
27:27
information there we should open up for questions for Dr Abel
27:35
super thank you both thank you Dr Abel thanks Monica um I know Lauren had a question and then
27:41
I’ve my I’ve been exchanging a lot of texts so uh srf people if you want to just talk just message me I can put you
27:48
on or if you prefer to type put it in the Q a but Lauren do you want to go first
27:53
yeah so um my son is 12 he’s about to turn 13. he had a VNS placed when he was
27:59
four so he’s had it almost this is going into his ninth year
28:05
um he had intractable epilepsy and was failing drugs all kinds of things just
28:10
having drop seizures like crazy he had like 100 in a day in the morning um it was really bad and they offered
28:18
you know other things whatever drugs weren’t working so we decided to go with the VNS and
28:25
um like it cured his drop seizures I know and he hasn’t Gap won a lot of kids
28:31
within Gap one aren’t having as good of luck I don’t think with it but for some reason he is it’s been like a miracle
28:38
honestly because he was dropping so much um so now that the VNS is getting older we need to replace it and they have been
28:46
getting pushed back there’s impedance on it I guess uh whatever it’s this time like it’s getting old we’ve had it for
28:51
so long but getting pushed back that it’s elective surgery and
28:57
he’s starting to drop again and he weighs 175 pounds like his drops are
29:02
much different than they were when he was little um so I don’t know I think it’s weird to
29:08
me that they’re considering an elective but then they also I did finally meet with his neurosurgeon two weeks ago and
29:14
they actually just called me yesterday to schedule the VNS replacement which is good but in the meantime I’ve been
29:20
stressing out about it mostly um like why can’t we replace this thing and then uh
29:26
now they’re telling me maybe we should do the CC instead like that was an option and
29:33
family I was really not my question is it’s weird I guess I’m just commenting that so
29:39
um they won’t be saying that to me yeah go ahead a couple couple things
29:45
um and I’ll speak in general terms so that I’m not providing any specific medical advice but I’ll speak in general
29:52
terms and say that um first I think that VNS sometimes is
29:58
considered elective surgery but but I think we need as a field we need to be a
30:04
little bit careful about that because there’s data now that shows that
30:09
um having VNS reduces the risk of sudden unexplained death and epilepsy
30:14
and so there’s large population data that shows that VNS reduces the risk of
30:20
death in epilepsy yeah and um and we also know that
30:27
um or we have a pretty good idea that when a VNS battery begins to get low it’s not as effective as when the
30:34
battery is high and so um this is speaking in general terms but if I had a
30:39
patient who um had a really good benefit from the VNS
30:45
I would I would make sure to replace the battery before considering other strategies
30:52
and and it could be so it’s also important to recognize that it’s I think
30:57
it’s good that um I think it’s always good to make sure that other strategies can also be
31:04
considered because because epilepsy is a progressive illness and um so I I should say some types of
31:12
epilepsies are are progressive and um
31:18
and so sometimes VNS is enough for a while but then you have to consider something more like DBS or RNs
31:25
or a calcotomy um we think based on just looking here
31:32
and looking at one other Center that we do collaborations with that probably 60
31:37
percent of of kids that get a VNS or excuse me that get a calcotomy have a
31:44
VNS first so VNS is typically the first step
31:49
but but I think I I would uh in a situation where VNS worked really
31:55
well it may be good to see how the VNS works again after a battery change before
32:01
considering other steps okay that’s what I’m leaning towards too thank you
32:07
I appreciate that that’s general advice thank you I appreciate that for sure
32:14
it’s a really good what you said about the VNS and the batteries because we do that is definitely the first step for a
32:21
lot of our parents um I’m not sure if so Sydney in the Q a
32:27
said can you share more about DBS age restrictions conditions for which it’s on label how hard is it to get access to
32:35
the surgery if it’s off label or if the kiddos on the underside
32:40
okay this is the question from Sydney yeah
32:46
um so so I think
32:52
the youngest I’ve ever heard of someone getting DBS and it was not for epilepsy it was for
32:58
dystonia is 18 months of age wow so you can do
33:04
DBS in a child that’s very young but the but this is tricky for a few
33:11
reasons one being that the skull is thin which makes placing the electrodes a little bit more difficult
33:18
um I’ve not placed DBS in a child that young the youngest I’ve done is three years
33:24
um but um so placing the electrodes can be a little bit more difficult but also the head is still growing and
33:31
so it’s possible that the electrodes can migrate and so I think DBS should be
33:37
considered in young children but but certain extra
33:43
discussion needs to be had about what to do if the electrodes migrate some of the
33:49
challenges with placing the device some of the increased risks I think all of
33:54
those things need to be considered carefully and also weighed against some of the other potential treatment options
34:01
that are available for younger children for example we we’ve studied our series
34:08
of children who have had VNS at younger than age six and these children do have more
34:15
complications than the older children that have had VNS I know this question
34:21
is specific to DBS but probably some similarities between those two and just having some more risks at a
34:27
younger age and I think the it is
34:33
um technically not FDA approved for for children
34:39
but um but that doesn’t mean that it it
34:45
shouldn’t be part of the armamentarium because often when we get to a point when we’re considering DBS
34:53
um we often don’t have other options and so this is something that we are very direct with families about
35:01
um but we still need to consider it now that does make it more difficult to get
35:07
approved by the by the insurance companies yeah so the pre-approval process can be
35:15
really difficult um for whatever reason we’ve we’ve we
35:21
haven’t had too many issues here in Pittsburgh but
35:27
um but I’ve certainly heard of other groups where this has been an issue and so from
35:32
a health policy State this is for VNS DBS RNs laser ablation all these different
35:38
strategies that are novel and I think it’s up to us in the medical community
35:43
and also the health policy Community to show that these are
35:50
cost-effective strategies because um because they probably
35:57
some we need to figure this out but they probably are cost effective when we’re considering the how they change
36:04
emergency room visits how they change medication the need for medication changes and things like that
36:10
and so um but this is something we need to we need to figure out because it is a major
36:16
issue yeah I’m going to move uh Sydney up to panelists to hit you with our next
36:21
question and then I have a couple for you um actually I’m gonna that Sydney I’ll
36:26
let you go and then and then I have it and then I have a question can I answer Nancy Kessler’s question
36:32
sure it’s pretty it’s uh so um so long-term VNS you can have a CAT scan
36:40
in an MRI the more recent and more the more recent bns’s are MRI compatible
36:45
and Cat Scan is no problem um so battery Replacements happen once
36:54
every about three to ten years that’s a huge range in which you would need a battery replacement the battery
37:00
replacement surgeries are not as big as the initial surgery to place the leaves in the neck but um but there’s still a
37:07
surgery where you’re placed under anesthesia and um and there can be infections from
37:13
those um so that is part of the long-term care
37:19
um and I I
37:24
pushing on the neck that’s tricky I would just try to discourage it and keep the neck padded if you can but but I
37:30
also have a lot of patients that have struggled with this and it has been okay
37:36
so anyway I I hope that answers your question Sydney
37:44
hi everybody hi Dr Abel um my kiddo and it’s actually a patient
37:50
of Dr sigal was at UPMC um so coming to you from Pittsburgh today
37:56
hey there um I wanted to ask a second question um to the first one about the DVS
38:03
um in it so my kid is five and he’s um severely refractory until every
38:10
single medication we’ve ever tried um he has a VNS but we’ve actually never
38:16
had the spect the pet or the Meg just a ton of eegs um in an MRI which was you
38:23
know kind of unsurprisingly clean um as a lot of our singapians are so I’m
38:29
curious should I be asking for all of these other um studies because surgery is going to
38:35
always be on the table for us I think I I think it depends on what
38:41
your EEG results showed and what the MRI showed and so if it’s really clear that
38:47
um in in the genetic in the exact genetic testing results
38:52
sometimes those results would be clear enough that those other tests may not
38:57
add much but it really depends on your specific case um but it’s something I would ask um you
39:05
could always ask Dr sugawa about it um since you’re in Pittsburgh I’m happy to look at those things for you also
39:12
um but but but sometimes those things are not necessary
39:18
no that’s great I think that’s what I was looking for which is confirmation that we haven’t accidentally left a
39:24
stone unturned and that I’ve gotten you know good advice so far even with a kid
39:29
so complicated um by not having these things and I guess I always kind of took it as yes
39:36
the seizures are really bad and so we don’t need any more we don’t need to look at anything else to know that he’s
39:41
a candidate for surgery I have I have two questions for you Dr
39:48
Abel and and I and I want to say that um this is such a valuable talk and even
39:53
though we only have you know about 20 of us here I know this webinar will be
39:58
watched many many times because when parents get the genetic diagnosis they get a bunch of drugs and then some
40:04
doctor suggests surgery and they promptly freak out and call me so now I’m so grateful to you and Monica
40:10
because I will Point them to this webinar and then tell them to call me back but what I’ve observed and this isn’t in the literature yet but I expect
40:18
it to get there is some of our singapians who don’t suffer
40:23
from tonic clonics around 18 tend to progress and and suddenly I I I’ve lost track of
40:30
how many families told me at 18 they started having drops right and then so what happens is
40:36
in at least one case I’m familiar with that’s when they got a VNS and um
40:43
and now that the seizures are progressing and the VNS keeps getting turned up and it’s like a bad race right
40:48
but the VNS isn’t and so I guess two questions on that one is an
40:55
easy one is when I just described that to you you know genetic epilepsy relatively
41:01
manageable seizures until 18 suddenly radical progression lots of drugs not helping advs but not not making a
41:09
difference and the kids on a lot of drugs is that where you go to a cc or
41:14
something that’s question one but then question two is there’s there’s some interesting
41:20
research out right now I think Juliet Knowles wrote a paper last year about elliptogenesis and what goes on in the
41:26
brain and over time does the brain learn to seize and
41:32
tell me if I’m just being too random here but is there a case to be made when
41:37
you start thinking about okay what’s going on in this brain and why does seizures progress over a lifetime in in
41:43
getting some kind of neuromodulation DNS RNs DBS whatever in sooner rather than
41:50
later like in the kit in that in that hypothetical case we have an 18 year old and now we’re in a race what if we put
41:57
in a VNS much sooner I think I think no one knows the answer to that question okay because the only
42:05
way to have the answer to that question would be to uh to do a study where
42:11
you did that where you took patience and you put in vns’s early
42:16
maybe earlier than you would normally and then compared them to patients that didn’t but that would be uh the reason you
42:23
couldn’t do that is um there there’s some ethical issues with doing that right and it would just be a
42:29
very difficult thing to do um so
42:35
now there is some evidence that um that the longer you’re treated with
42:40
neuromodulation the more effective it is and so there’s this idea that
42:46
that maybe the brain even learns in response to getting the neuromodulation and
42:51
and that changes the behavior of the epilepsy I’m I’m speaking in very broad terms yeah
42:58
um but but I think these are these are like questions that are on the frontier that
43:05
that I hopefully we have better answers to in the next like 10 20 years
43:11
but in a sense like you’re right we couldn’t ethically do the study prospectively but we could look
43:16
retrospectively at say I think Lauren getting an EEG at four was was pretty rare for our community pardon me of ens
43:23
at four is pretty rare for our community and that seemed to keep the seizures at Bay the battery dies the seizures come back we’ll see what happens when we put
43:30
the battery back maybe anyway I’m now in riffing um but it’s hard to be a it’s hard to be
43:36
a rare disease Advocate and not wish you hadn’t gotten an MB PhD at some point in the progression
43:42
um I don’t know if that resonates with Monica but um Nancy also asked a question about is there a long-term
43:48
effect to having the VNS in without a battery can I can I interject real quick just from a parent standpoint just this
43:56
whole issue of the eventually what did the seizures do to the brain and you
44:01
know there’s there is literature on with something called kindling which is if you keep seizing or you then seize are
44:08
you then teaching the good neurons to C’s as well I know with removing half my
44:14
son’s brain by the way that was done in three surgeries the first one he was three months old the goal was to stop
44:21
the seizures the second goal was we did not want the bad deformed hemisphere to
44:28
teach the good hemisphere how to see that was kind of the two things that we
44:35
talked about with his surgeon was stopping the seizures but also we wanted to keep the good half that he did have
44:42
that wasn’t deformed as healthy as possible so that you know
44:48
that uh it wouldn’t learn how to seize as well
44:56
got it um Dr Abel there’s a bunch of questions in the Q a uh there’s the Nancy question
45:02
about leaving it in yes um so leaving if if uh
45:12
long-term effects if the VNS is left in but not kept up so generally if a VNS is runs out of
45:21
batteries and is not effective and we don’t want to replace the battery we typically would just leave it in place
45:27
because there’s no increase not necessarily any increased risk to leaving it there but the surgery to remove a VNS is is a
45:35
lot bigger than the surgery to put it in and that’s because of all the scar tissue that develops around the VNS
45:41
leads so typically when I remove VNS leads I do it I recruit one of our head and neck
45:48
surgeons and it’s a bigger surgery than just implanting it in the first place so that’s why we generally try to leave
45:54
them in unless there’s a good reason to remove it I hope that answers your question
46:06
yep and then this next one from Simon Volta Minnie’s again
46:17
so the question here is just most of our kids the phenotype especially when they’re young as you’ve pointed out in your presentation upside some myoconia
46:23
but large clusters and it could a VNS be helpful with these if they haven’t yet
46:29
gone to drops yes I think so yeah I think I would talk specifically
46:34
with your neurologist about it but I but in some cases certainly
46:40
and then Christy Burns one of our parents she points out her son had a cc at two and
46:47
guessing before this and get diagnosis and she’s she wonders what not having a complete callosum will have any
46:54
disadvantages with future brain development or cognition so this is a really good question
47:02
um there may be some subtle issues
47:07
um but I think it really depends on on a lot of different things like what is
47:13
what is otherwise Baseline function was and uh and those sorts of things I have
47:19
an 18 year old um who
47:24
who has epilepsy syndrome very similar to syngap who actually had a calcitomy at 18 and it did not affect her
47:32
significantly um uh so even even as an adult
47:40
sometimes you can have a calcotomy that will not have a a major effect on cognition
47:47
we have a we have a VIP guest Heidi G is making an observation I’ll let you
47:52
comment other things to consider or how surgical interactions impact the network and progression puberty and hormones
47:58
also have an impact on seizure increases how do we how does one and I agree I
48:06
mean I see all of our kids when puberty hits it gets the the syngap is a strong behavioral phenotype too so you got the
48:12
behaviors and the seizures both can get a little crazy with puberty is that something to think about as you
48:18
time um a potential surgical intervention or any other comments on Heidi’s thought
48:26
I I think it’s an important thought um and uh I I’m I’m not certainly not as
48:33
much of an expert as my neurology colleagues on this aspect
48:38
fair enough Christy says thanks um so Ginny asks the question is this is
48:45
the surge or the surgery we were talking about also effective for generalized surgery generalized epilepsy
48:53
yes of course I’m assuming he’s talking
48:58
about the surgery the surgeries we’ve just discussed yes so in general for
49:03
generalized epilepsies um Corpus calisotomy is generally considered for generalized epilepsies
49:09
that include drop attack seizures but Corpus call sodomy can also be effective
49:15
for generalized tonic clonic seizures and and bilateral tonic seizures
49:22
um so it can be effective for different seizure types um VNS is also we’ve looked at that in
49:30
our data here at Pittsburgh but other centers have as well is also effective for generalized epilepsies and that’s
49:36
typically what we use it for um deep DBS specifically Central median
49:44
DBS which is just one of the Targets in the thalamus is used for generalized epilepsy and the
49:53
and also Central median RNs and so each of those neuromodulation strategies
49:59
is typically used for uh generalized epilepsy
50:04
great and when people are considering this
50:10
I mean you there there could not be many people at your level Dr Abel like do you
50:15
encourage patients to go out and consult with other neurosurgeons I mean how did people
50:21
how many of your patients are local versus people who reach out to you for a sec second opinions or assessments if
50:27
they don’t have access this level of care at home I think
50:33
I think this is this is tricky so so a lot of level four epilepsy centers have
50:40
the capability to do these things but I think um like one of the one of the first
50:46
questions on the chat from Ed talks about surgery should be available and what are
50:53
the restrictions part of the restrictions are just getting a referral and and I think there
51:00
are multiple levels of how this can happen there are some some patient specific variables where
51:08
you might just live really far away from a level four Epilepsy Center like when I was in Iowa we we just
51:14
didn’t have many pediatric neurologists and so there were children with pretty severe epilepsies that were being
51:20
treated by pediatricians um out in the community and may have just not gotten referred
51:27
and then even even at a uh a busy level sometimes even a level four Epilepsy
51:33
Center um because because a large proportion of pediatric neurology is um is epilepsy
51:40
there are some non-epilepsy experts that treat pediatric epilepsy and they just might not refer for
51:47
surgery and so there are a number of different layers of barriers that can contribute
51:56
um but I think it’s one of those things where I think I think I think webinars like
52:02
this are actually make a huge difference because anyone can get on Facebook and see this
52:08
and can then advocate for themselves just to make sure that these things are considered
52:14
yeah that paper I mentioned in the beginning that is a power paper I mean that is
52:20
from the international league against epilepsy saying once you’re drug resistant which is failing to appropriate and tolerated medications
52:27
you are supposed to be referred for a surgical evaluation and doesn’t mean you’ve decided to have
52:33
surgery it just means you are now ready to open that toolbox and work with a clinician a surgeon to try to figure out
52:39
which one might work then you can go back with your family the people who are close to you and have a discussion about
52:45
it but not even referring over to be able to take a peek into that toolbox I
52:50
have a huge problem with that I really do it’s unfair to our families that that you’re not even being told
52:57
about the toolbox in the first place or allowed to take a peek inside
53:03
speaking of the toolbox and gets people are texting me and I’m telling them just come and ask
53:09
um but so let me just I’m just trying I’m trying to triage the Q a here so Ginny
53:15
responds sun is 19 syngap diagnosed two and a half years ago with onset of grandma and his tonic clonic seizures
53:21
have increased to more than weekly over the past six months since VNS placement or not October he is now so he’s now also
53:28
having clusters of partials
53:34
so I’m not sure that’s a that’s a complicated case um I’m not sure if there’s a question there
53:41
and then the other thing in here that’s interesting um and I think Germaine to all these ndds Sandy says
53:48
sister had a DBS as an adult she’s able to communicate so her doctors are able to tweak the DBS based on her
53:55
Communications but with these non-verbal singapians who have varying levels of intellectual impairment
54:00
how do you tweak these neuromodulation devices yeah this is this is a really good
54:07
question and we have to we have to do this with uh with really
54:13
careful observation so um this comes up a lot with dbs4
54:18
dystonia for example where um the Globus pallidus which is where the part of the brain where we put the
54:24
electrodes um stimulating around it can cause different side effects and in really young children when we’re
54:32
slowly ramping up the stimulation we watch carefully for whether or not their mouth is switching
54:38
so a grown-up would be able to tell us that their mouth is twitching and that something’s off but instead we watch for
54:44
it really carefully and I think we would use a SIM we use a similar approach in in patients that are not able to
54:51
communicate as well okay so Sydney you have a question and then oh guys see your hands up Sydney do you want to go
54:59
yeah just one more um I know that like a lot of our doctors give us this progression especially for
55:05
the ones who have so many seizures it’s meds and then more meds and then keto
55:11
and then VNS and then other forms of surgery right that I mean that’s what I’ve been told Monica do you want to
55:16
jump in and correct me because I think in your head go for it I’m going to stick my neck out
55:22
if you read through the literature it’s two meds and then a referral for a
55:28
surgical evaluation and then if your child is not a candidate then Keto that’s the progression I think a lot of
55:35
so this is where we’re talking about barriers a lot of neurologists see the look on the parents face and said oh
55:40
well let’s try diet or let’s try VNS or and obviously I’ve come from when
55:46
we’re looking at a spectrum of surgeries there’s a VNS and then there’s all the way to removing half of your child’s
55:52
brain so please be mindful that my personal experience is also bringing a bias to this
55:57
but that is the progression that is the step that you’re supposed to go in and that barrier to surgery and I mean it’s
56:04
a big problem it’s a big problem if you live in an area as Dr Abel said where you’ll maybe you only have one surgical
56:10
facility nearby uh if you’re poor if you don’t have the right kind of insurance if you don’t speak English well just all
56:17
of these barriers that start to be put up so I think it really becomes from a parent standpoint you have to be an
56:23
advocate you really have to be a a strong advocate for your child and push for that that referral
56:29
I’m really glad that you said that because I would dare to Guess that most of us do not get a um
56:35
a surgery consult after we fail to meds like very few of us probably
56:41
um but my I was um wanting to kind of ask like what I’ve told you is I think
56:47
the progression that a lot of us are given um for treatments and I’m wondering like
56:52
if we’re talking about like surgery specifically um is there a kind of like progression
56:59
that you would go through with regards to invasiveness so like I’m thinking it
57:05
might be VNS RNs DBS Corpus callosodomy are we gonna be asked to go through a
57:12
progression like that or will our team be looking more at like our child individually their aging of course all
57:18
of that stuff and then placing them into the surgery that they think is best so this is a really good question and
57:25
this also is kind of a similar question to uh one of the anonymous attendees asked given the heterogeneity and
57:32
neuromodulation options how do you choose between VNS RNs and DBS and how
57:38
heavily does the type of seizure impact the decision-making process and so
57:44
um I think the bottom line right now is that this is something we’re figuring
57:50
out and so we don’t know for sure yet because
57:57
um I think one thing I try to stress to families is that each of these different
58:02
procedures are safe and they all have what would be considered
58:08
acceptable rates of Adverse Events um
58:14
and so they’re all safe and um and so I think sometimes it’s just a
58:19
matter of discussing the pros and cons I think at this point most families in
58:25
most of the epileptologists I work with still would consider VNS
58:31
before RNs or DBS for a generalized epilepsy just because that’s what we
58:37
have the most experience with but then in the next 10 years that might change one time I also took care of a
58:44
child a child of a neck doctor an ENT and they said that because they were an
58:52
ENT they’ve seen they’ve seen problems with vns’s and so they just didn’t want a VNS
58:58
and so we did RNs instead and that was what the family was most comfortable with and and and
59:05
um and the child had good benefit from it and so um I think I think with limited
59:11
uh information there has to be shared decision making and then also just being very direct and
59:18
and transparent about what we know as a field and what we don’t know
59:23
my my son was super refractory as an infant we had to put him into a coma
59:29
Sydney nothing would stop his seizures when I think back to the decision making
59:35
both in the literature as well as how we made a decision as a family it’s what what is our end goal
59:42
do I want to do a surgery that has a 70 chance of stopping his epilepsy type or
59:51
do I want to try something that has a 20 chance when we know nothing no medication is
59:57
going to stop it so I think perhaps parent to parent stepping back and first really defining
1:00:04
what your end goal is what is the seizure type you’re trying to stop how
1:00:09
is it affecting your child and then looking at the tools in the toolbox which surgery is the one that is going
1:00:19
to give them the most relief and that’s the one we chose
1:00:28
um so we got the so the thanks are starting to pour in Nancy said thank you
1:00:34
um I can answer uh obvious question yeah please
1:00:40
um so focused ultrasound is potentially a viable option for certain types of epilepsies
1:00:46
but um there be and I know this because there was just a early stage clinical trial that was published in epilepsia
1:00:52
but but um still a lot of a lot we don’t know about it and are figuring out
1:00:59
got it um and Jenny just Echoes the point previously made eight meds in her kiddo
1:01:06
before VNS yeah um Heidi shared a cool paper I think we’re that I think we got through the Q a guy
1:01:13
Olga did you have a question yeah go for it yes thank you Mike uh thank you Dr Abel
1:01:19
uh just a quick question my son we’ve been very fortunate in seizures have been controlled with medication however
1:01:25
he’s been on uh anti-epileptic since he’s been three he’s probably biased
1:01:30
third or fourth one Lamictal works pretty well then at the age of eight he started having drop seizures so we added
1:01:37
on fee and have to continue and that has helped with the drop seizures but we have to continually increase that as he
1:01:44
gets older and bigger and I’m just wondering he has a neurologist and then he has an epileptologist but uh if we
1:01:51
should consult with neurosurgery I’m concerned about the long lasting side effects of all these anti-epileptics and
1:01:59
if you know it’s progress epilepsy Progressive what can is that something we should consider or I know it’s a
1:02:06
case-by-case basis but it’s never been offered to us to consult with
1:02:11
neurosurgery or look at any other type of um you know um procedures yeah I think absolutely I
1:02:19
think those things it’s good to discuss those things and know what the options are for sure right where do you live
1:02:27
I’m in Houston so I was wondering is Texas Children yeah or Howard Winer yeah yeah okay yeah Dr
1:02:35
Warner World experts yeah okay good that’s good to know thank you
1:02:40
because I haven’t made it that far yet I’ve we that’s where our neurologist and our epileptologist is but okay thank you
1:02:47
so much so so I have I have one last one for you Dr Abel um one of the questions I get from
1:02:54
parents because we are singap is very fortunate in the you know I say this to
1:02:59
parents sometimes I say it to them too early I say congratulations on getting a diagnosis and they look at me like I’ve
1:03:04
got two heads because they’re like I just got a lifelong diagnosis for my child I said yeah but now you know exactly what letter is wrong and there
1:03:12
are genetic therapies under development and then I get questions like hey I might have a chance to get access
1:03:18
to this drug but there’s an ASO that’s a couple years away should I wait for the ASO and as a rule I say if you have a
1:03:25
chance to help your child reduce seizures today you should pursue it so with that as a setup
1:03:31
where’s the discussion in the epilepsy surgery Community with regard to those of us in the genetic epilepsy Community
1:03:36
like how how do we say to a parent looking at a x-year-old where X is a
1:03:42
single digit who’s holding hope for an ASO or a gene therapy but has a chance to pursue an epilepsy
1:03:49
surgery it’s a kind of hard question but it can’t be the first time you’ve heard some version of it yeah I think it
1:03:56
depends I think um a lot of a lot of the epilepsy surgeries
1:04:01
that we really are talking about today are things where we are where the surgery we’re doing
1:04:07
does not make in does not make what we would think of as like an irreversible change
1:04:14
and so like VNS or RNs um certainly you can’t undo a surgery
1:04:20
once you’ve done it and so there’s that aspect of it that has to be carefully considered but um but it’s not it’s not
1:04:28
a hemispherotomy or a lesionectomy or a lobectomy right and so
1:04:34
um so I I think that the pros and cons of these approaches just need to be
1:04:39
weighed and and um and I think for my child I think if
1:04:45
there is a risk of death from epilepsy and and there was a
1:04:50
treatment like VNS that could reduce that risk um I would want it as early as possible
1:04:56
yeah yeah I’m always whenever people say sudip I’m always I always feel compelled to say that we have not had it to our
1:05:02
knowledge because we’re radically under-diagnosed we’ve not had to sing happy and suffer from pseudot but it is
1:05:08
still a serious thing and but I I think a lot of families as the seizures progress which they tend to do struggle
1:05:15
mightily under the burden and I I’m glad we’re having this conversation I also like your answer in terms of framing a
1:05:21
number of these interventions the neuromodulation especially is not irreversible and and
1:05:27
maybe exclude inclusion on inclusion exclusion for a trial but would probably not prevent getting dosed with these
1:05:34
Gene therapies when they’re available right it’s hard to answer but one thing that I think is going to be
1:05:41
really important is as we become more aware of genetic epilepsies we need to uh and we need a lot more data but we
1:05:49
need to start stratifying our outcomes of surgeries based on what the genetics
1:05:54
were yeah I mean is it standard practice for you to do exomes on all your patients when you operate probably not right
1:06:01
so that’s usually something that if we have any suspicion we try to do it before surgery
1:06:07
because also there are some things we can find that are associated with focal epilepsy and have us look even harder
1:06:12
for a focus right but uh but then there are also barriers
1:06:19
like Insurance barriers and things like that to getting genetic testing or just personal belief
1:06:25
cultural barriers so um those are all things that
1:06:31
come up great thank you we’ve gone over time grateful to both of you any last words
1:06:41
thanks a lot for having us and thanks to Monica for inviting me and thank you for to you for inviting me
1:06:47
it was our it was our privilege and we we we love Monica someone I
1:06:54
I I ask her for advice sometimes oh my goodness no no it’s been an honor to be
1:07:00
with your group and anything we can do as an organization to further collaborate with you all please let’s do
1:07:05
it great and I and people who come to me with hard questions I will just send you to Monica
1:07:11
if you want to skip the step just call Monica she’s fabulous and a lot of getting a lot of messages of thanks so
1:07:17
thank you both thanks everybody have a great day take care