Search for tag: "epilepsy"

Interviewer: Focused ultrasound to treat essential tremor and how to decide if it's a good option for you. Dr. Shervin Rahimpour is a neurosurgeon who specializes in the treatment of essential tremor. Who is a good candidate to get relief if they have tremor symptoms using this treatment? Let's just start there.

Dr. Rahimpour: Essential tremor is the most common movement disorder and affects upwards of 10 million people in the United States. It's characterized by this either postural tremor when you try to maintain a posture with your hands or it can be brought about when you're trying to perform some kind of physical action with your hands. And it doesn't necessarily just affect the hands. It can affect people's voice, their balance, and other extremities.

While there are effective medications for essential tremor, some patients don't either respond to these medications or have bad drug side effects, and we have good interventions to try to treat this surgically.

Interviewer: And is there somebody in particular, beyond perhaps medications don't work or they'd react badly to them, that would be a good candidate for this particular surgery?

Dr. Rahimpour: Yeah, it could be the case that the medications work but just not enough. So you could imagine if your hands are shaking, whether it's affecting your work or just even trying to feed yourself, this can be really debilitating. So if the medications make the tremor a little bit better but not quite to where you need it to be, to be functional, that's where surgical intervention can play a significant role.

Interviewer: And if somebody comes into your office, what process do you go through to determine if they're a candidate?

Dr. Rahimpour: First, we make sure that they've actually exhausted their medical options. Obviously, we don't want to perform surgery on someone that could otherwise be treated with medications.

The next step is we assess their tremor. Sometimes patients are misdiagnosed, so we want to make sure they actually have essential tremor and not some other kind of movement disorder.

Once we've confirmed that, we assess their surgical candidacy. We look at their MRI imaging to look at their brain anatomy.

And then we discuss some of the options that are available to them. Currently, we have two different treatment options for essential tremor. Historically, the mainstay of surgical management of essential tremor has been deep brain stimulation, which involves placing electrodes in the sweet spot of the brain called the thalamus where we believe is a critical area for essential tremor.

This treatment involves two stages. One is placement of the electrodes in the brain during an awake surgery to make sure that we are providing adequate tremor relief, and then a second stage, which involves connecting those wires to a battery typically in the chest pocket, like you would for a pacemaker.

Now, this therapy is not necessarily for everyone. Certainly, for patients who don't want an open surgery, and also those that may not qualify as a good surgical candidate. And that's where I think focused ultrasound can play a significant role.

Interviewer: And how does focused ultrasound work then?

Dr. Rahimpour: Yeah. So focused ultrasound . . . similar to the way a magnifying glass focuses a beam of light to a point, acoustic lenses can be used to focus sound to a point. And so we use this principle to focus sound energy to that same spot in the brain, the thalamus, to try to disrupt the circuit that's causing a patient to have tremors.

Interviewer: This is non-invasive completely?

Dr. Rahimpour: Yeah, absolutely. So it involves a couple of things. One is to shave the head entirely, and other than that, there are no incisions, and typically, patients leave the hospital the same day.

Interviewer: Wow. And what about relief from the tremors? Does that develop pretty quickly as well?

Dr. Rahimpour: Yeah. That, we expect to be immediate. The caveat currently is that we can only treat one side of the brain. So for patients who might, say, be right-handed, treating their left brain for their right hand can mean a significant improvement in their quality of life.

Interviewer: And I've heard this procedure could also be used for Parkinson's. Is that true?

Dr. Rahimpour: Yeah. So for patients who have a tremor-dominant Parkinson's disease, focused ultrasound can also be an option. And then recently, as of last year, it's also FDA approved for other symptoms of Parkinson's, not just the tremor. Other symptoms include things like bradykinesia or rigidity, so difficulties initiating movement or moving.

Interviewer: If somebody is eligible for focused ultrasound, what considerations would a patient go through to determine if that's the treatment that they want to pursue?

Dr. Rahimpour: Yeah, so similar to deep brain stimulation, we want to make sure that the patient has the appropriate diagnosis for essential tremor, again, because a lot of things can mimic this disease.

So patients have to ask themselves whether or not they are willing to undergo an open surgery, which is deep brain stimulation. And if they're not, then this gives them a nice alternative option.

Patients who undergo evaluation for focused ultrasound should also consider potential side effects from this treatment. That includes temporary ones, like having some numbness and tingling sensations on the same side as their tremor, as well as potentially a brief period of time after the procedure of poor balance.

As the swelling develops from the treatment over the course of the next several days to weeks after the procedure, sometimes these symptoms can get a little bit worse before getting better. And by three months out to a year of follow-up, we don't expect these symptoms to persist.

Interviewer: Are there any long-term type symptoms that a patient should be aware of?

Dr. Rahimpour: Very rarely can these paresthesias or the sensation of numbness and tingling persist at a year's time, and the same goes for balance and abnormal gait.

One part of our pre-procedural evaluation involves an evaluation by our physical therapist, who assesses patients' gait and balance to ensure that we have a good adequate baseline before undergoing this procedure.

Interviewer: For somebody with essential tremor, when you use the focused ultrasound to reduce their tremors, how does that impact their quality of life?

Dr. Rahimpour: Treatment with focused ultrasound to reduce tremor can have a very meaningful impact on one's quality of life. It gives them the ability to do some of the hobbies that they enjoy and certainly some basic tasks like feeding themselves.

Interviewer: After somebody has had a focused ultrasound to treat tremor and, say, the tremor starts coming back after a period of time, the three years that you mentioned, can they get the focused ultrasound again?

Dr. Rahimpour: Absolutely. We can reevaluate them in clinic to see what their options are.

Interviewer: And if at that point they've also decided, "Well, maybe I want to try the deep brain stimulation at this point," is that another option?

Dr. Rahimpour: Yes, that can also still be on the table as an option.

Interviewer: Lifestyle changes that you can make to decrease the severity or number of seizures that you have. Dr. Sindhu Richards is an assistant professor of neurology at University of Utah Health. She specializes in treating epilepsy.

Dr. Richards, what are some of the recommendations you would give somebody who would like to make some lifestyle changes or look at their lifestyle as a way to reduce the number or the intensity of their seizures?

Dr. Richards: So one of the biggest things that can affect the seizure burden is the quality of sleep. So people who have sleep deprivation is a big trigger for seizures. So we say getting adequate amount of sleep every night, trying not to stay up late, having a regular sleep cycle will be really beneficial in terms of reducing the amount of seizures you have.

And in correlation to that, one of a common diagnosis of patients with epilepsy can have is obstructive sleep apnea. And so that's just where they're not getting good quality of sleep and might need a CPAP machine in order to do that.

And so people who get treated for sleep apnea tend to have a lower seizure burden as well, just because when they're treated for sleep apnea, they are getting better quality sleep. Even though they might be sleeping still a full eight to nine hours a night, but that quality is not great if they have untreated sleep apnea. So that's known to worsen seizures as well.

And then also, we also counsel people on alcohol use. So having an occasional glass here to there, or even a glass of wine a night is totally fine to do in patients who have epilepsy. We just get more concerned for like the binge alcohol use, because that is more so clearly linked with sleep deprivation as well. And then any significant alcohol use can actually provoke a seizure disorder itself. So we advise against a moderate to severe amount of alcohol use, but having a glass here or there or even drinking socially, occasionally is fine if you have epilepsy.

Another common thing that I get asked is any dietary changes and whether that can help with epilepsy. So in terms of in the adult population, there's not really clear evidence in sort of certain diets improving seizure frequency.

So in the pediatric population, there are certain seizure types that respond to the ketogenic diet. So if people with epilepsy really want to try a dietary measure to see if it reduces their seizure frequency, that is usually one I suggest just because it has good evidence in the peds world, but it doesn't in the adult world, but we know it doesn't do any harm in terms of seizure frequency. But in terms of like reducing other sugars or any other taking out any major dietary substance, we don't really recommend that in terms of in epilepsy.

Interviewer: So then to be clear, like the diet might not have good evidence behind it. Meaning I know physicians really like to have that evidence that shows yes, there is a direct link. That doesn't necessarily it might mean it might not help somebody. So if you want to talk to your doctor to make sure that the ketogenic diet is okay for you or some of these other dietary adjustments, that would probably be the first step to make sure it doesn't affect something else. But as far as epilepsy is concerned, it wouldn't impact that.

Dr. Richard: Exactly. Yeah. It wouldn't make it worse. So yeah, you would make sure to check with your like primary care doctor to see if that's an acceptable diet for you to go on.

Interviewer: Are there any other lifestyle things that somebody could look at or adjust or lifestyle things you've been asked about that we just don't know.

Dr. Richards: Those are the big ones I would say. We try to, you know, patients with epilepsy, we want you to live the best normal life you can. So continuing to be active, like exercising, that's all great in terms of any medical problem, but it's also great for epilepsy as well because that's another question we get.

We obviously don't want you to do any major exercise or activity where you would cause like serious injury to yourself if you were to have a big seizure. So certain restrictions we have in terms of that is if you go swimming, we say that you should have a one-on-one supervision. So like if you're at a beach and there's a lifeguard watching a bunch of people, that's not acceptable in terms of supervision. You should have someone on the beach watching you one-to-one directly. So that way, in case you had a seizure on the water, they could be able to pay attention and get you out of there. So that's one big thing.

And driving is a big thing, obviously, too that affects people's lifestyles because if you were having a seizure, you would lose consciousness, you would lose control of the car and not only harm yourself and the people in your car, but also other people on the road. So that's a really, really important precaution we like to stress in patients with epilepsy. So typically we ask them if, you know, they have a driver or take public transportation. It is one of the most difficult lifestyle changes that we find in patients with epilepsy, but it is an important one to follow. That way, you and others are safe.

And then other activities, you know, we kind of say, use your judgment. If you were to have a seizure and it would cause serious harm to yourself or others, you just should be cautious about. So like skydiving isn't one I usually recommend. You shouldn't be scuba diving. So things where, you know, if you were having a seizure, it would be really dangerous to yourself or others.

But the big ones we tell people are the no driving, the no swimming alone, you shouldn't be on heights and ladders, and you shouldn't be operating heavy machinery. Those are the big restrictions we give people when they're diagnosed with epilepsy.

If you have a diagnosis of epilepsy and you've been tried on different medications and are continuing to have seizures for at least more than a year, that you should be seen at an epilepsy center and seen specifically by epileptologists.

And we do have comprehensive care with neurosurgeons, radiologists, neuropsychologists, nurses, social worker. So you will get a lot of resources that you may not get otherwise in terms of other options for treating your epilepsy.

Interviewer: Someone's diagnosed with epilepsy, given medication for the seizures, and a year later still experiencing seizures. At what point do you go see a specialist?

Dr. Sindhu Richards is an expert in medically refractory epilepsy. Dr. Richards, when would somebody come and see you?

Dr. Richards: So we definitely say a year should be the general guidelines, but we try to be a little more proactive than that even. So, right now, the American Academy of Neurology has set out like a guideline saying that if a patient with epilepsy has been seen by the primary care provider and it's been three months where they're unable to treat the seizures effectively, they should be referred to some sort of neurologist, a general neurologist or an epilepsy specialist. And then, if a patient is seeing a general neurologist for a year with untreated seizures, those people should definitely be referred to an epilepsy center.

Interviewer: And after you reach that year, it's really not something that you should put off if you're still having seizures without medication. What are some of the dangers of doing that?

Dr. Richards: In terms of the biggest concern we get about uncontrolled seizures is there's a phenomenon called SUDEP, which stands for sudden unexplained death in epilepsy. And we really don't know the clear mechanism. We just know that people who have uncontrolled seizures are at higher chance of that. So that's the scariest thing we worry about for people who have uncontrolled seizures.

And then, in terms of like other complications, so people, you know, having ongoing seizures can really affect daily life. So when you're having seizures, you're unable to drive. You can't operate heavy machinery or be on heights. So it depends on your work situation as well. But the biggest one that impacts people is the driving aspect. So it can really affect your quality of life in that sense.

And then, also depending on where the seizures are coming from, most people kind of developed some memory problems in terms of ongoing seizure activity. So that's a common complication we see that we try to avoid, if we can treat them early.

Interviewer: At this point, they walk into your office. Walk me through the diagnosis process that you use to get to a diagnosis of medically refractory epilepsy. And from what I understand, one of the first things you might look at is, "Was the initial diagnosis of epilepsy correct?" Because I guess it's like 13% to 15% of people that are diagnosed with epilepsy actually have something else.

Dr. Richards: Yeah, exactly. So that's a really important step to clarify too. And one of the ways we do that is, obviously, getting a very good history in terms of what exactly they're doing from the patient. But also a really important aspect is getting a history from the bystanders because they're the ones that are seeing what the patient's actually doing.

A very common diagnosis that epilepsy can be confused with is what we call psychogenic non-epileptic spells. So some people, due to like stress or anxiety, their body can react in a way where it looks like they're having a seizure when actually they're not. Like, we look at the brain activity, it's actually completely normal during that time. So if we're uncertain about the diagnosis, that's definitely the first step to try to confirm that. And one of the ways we typically do that, that is available at epilepsy centers, is that we bring people into the hospital and monitor them on the EEG, which is the brainwave study. And we try to capture their typical episodes so that we can see exactly what's going on in the brain. And if they do have epilepsy, it helps us see where it is coming from in the brain. So that's usually the first step we do to kind of clarify the diagnosis.

And then, after that, in order to be diagnosed with medically refractory epilepsy, you have had to have an adequate trial of two anti-epileptic drugs and are continuing to have seizures. So in terms of what we mean by adequate trials is a lot of people stop medications because they have side effects from them, and so that wouldn't mean an adequate trial. So if you stop a medication because of side effects and you're still having seizures, you still have to have a good trial of two drugs before you can be considered medically refractory epilepsy.

Interviewer: So, at this point, if you do then come to the diagnosis that it is medically refractory epilepsy, what are the steps at that point?

Dr. Richards: When you see a patient who's diagnosed with epilepsy and you start a new medication, so an anti-epileptic drug, about 50% of patients will become seizure-free on that. So that's a really good amount of people who will be seizure-free. Once you get to the second drug, an additional 13% will be seizure-free.

So then you're kind of left in this third category of patients who are not seizure-free on medications. And you usually tend to try different trials, but they continue to have seizures. So it's that third of patients who are diagnosed with epilepsy that are considered the medically refractory.

And so, you know, like I said, the main concern for these people are the long-term side effects of having seizures, the risk of sudden death. So we really try to offer other options. And one of the biggest options we have to offer is surgery. And so there's a lot of workup to be done before we consider surgery because, you know, that is a very big step and it's a big deal for us and for patients too to go through potential brain surgery.

So the very first step, in terms of treatment of medically refractory epilepsy, is bringing someone into the hospital where we try to capture their seizures. Because, in order to see what surgical options a patient has, we need to know where the seizures are likely coming from. And so what we'll do is we'll bring the patient in, we'll stop all of their anti-epileptic drugs because we want them to have a seizure when they're in the hospital. And then, once we've gotten about two to three seizures and they're reliably from the same location or let's say they show us that the patient has seizures coming from several different locations, we'll know what the next step could be. So that would be the very first step.

And then, after that, we typically try to do some non-invasive evaluations to help us pinpoint even more where the seizures are coming from. So this includes different type of imaging. So patients will definitely get an MRI because we try to see if there's a reason or a lesion or a structural cause as to why they are having seizures.

And then we'll also do some more advanced imaging. So we'll do what we call a PET scan, which is a nuclear scan. So we inject dye and we look at the areas of activity in the brain. And usually, in patients with seizure, the activity of the brain is decreased in their seizure focus. So that helps us kind of guide us towards where we think the seizures are coming from as well.

And then we'll typically send them to a neuropsychologist. And the neuropsychologist will look at their memory, their language, and other important functions of the brain so we can figure out where these important functions are and to make sure that they aren't affected when we consider surgery.

And then, lastly, to kind of do that as well, we do what we call functional MRI, where we ask them to do some different language tasks and some different motor tasks because then we can see exactly where in the brain it lights up and we know where those tests are coming from so we avoid those areas in surgery as well. So there's quite an extensive workup to do before you even consider the surgical options for a patient.

Interviewer: And after you do all of these tests, you have a much better idea then of what you're dealing with, where the surgery needs to focus on. At that point, is the type of surgery that the patient will get really based on what those tests indicated, or are there some choices the patient will have to make in surgical procedures?

Dr. Richards: Yeah. So there are definitely choices that we can make, whether like how invasive the patient is willing to go versus like if they want to be a little more conservative, because we have options where we can actually take out the brain. But we also have a lot of neuromodulation, which are devices which wouldn't require any major, you know, removing of the skull in terms of brain surgery and things like that. So it's a ongoing discussion with the patient about what we think would be the benefits versus risks and what they feel like would be an acceptable surgery and things like that.

So after those initial testings are done, we'll typically put EEG electrodes directly into the brain. So it's a minor surgery, where we drill a hole in the skull and we put electrodes right into the brain. And so that gives us an even more precise localization of where the seizures are coming from. So that's typically a step we will do even before we consider surgery.

Interviewer: And you mentioned some of these outcomes are like a 50% reduction. Generally, what is the reduction in seizures that a surgical procedure can offer? And then, you know, if there still are seizures, how are those addressed going forward in the future if, you know, an individual is resistant to medication, is not able to control it with medications?

Dr. Richards: Yeah. So this is why we like to get to people early because the data has shown . . . so let's say you have a patient with medically refractory epilepsy and you continue to try to treat them with different medicines. Only about 8% of those people will become seizure-free. Versus with surgery, about like 65% may become seizure-free. So that's a great difference in terms of seizure freedom. And you can even imagine, if people don't become seizure-free, they'll at least have a significant seizure reduction.

So the big thing to know is that people who go through epilepsy surgery, it's not an alternative for medicines. So these people will, generally, remain on medicines to make sure that we control the seizures. It just means that they might be on less medicine, which is great because medicines can cause side effects, it might not need as much. So that's an important thing to clarify for people because people think they can just get surgery and come off everything. But we do have to keep people on medicines to give them the highest chance of seizure freedom.

Interviewer: And I'd imagine it varies from all the different types of surgeries because, you know, you mentioned some actually require the skull to be open, which I even have a hard time even saying. That sounds a little scary. And then there's some of the more non-invasive procedures. What type of recovery could a patient look at after receiving surgery?

Dr. Richards: Yeah. So for the invasive ones, where you have like either . . . the invasive one is really like the lobectomy. And for that one, I would say, you know, in terms of like people who are in the hospital, they're only in the hospital for a few days, but usually it takes like about a month, I'd say, to fully recover from that surgery. In terms of for the neuromodulation procedures, the patients usually go home the next day and there really isn't that much of a significant recovery, people do really well.

Interviewer: I don't know if a question is going to come out of this or not, but listening to you talk about just the process of diagnosis and then the process of treatment, just how incredible is all of it that we can do any of it, right? That you have the equipment and the expertise and the training to be able to go in and pinpoint where this problem might be in the brain and then be able to go in and do something about that. I mean does that resonate with you on any level whatsoever or is it just something you do at this point?

Dr. Richards: Yeah. So that's why I fell in love with epilepsy. You know, going through neurology residency, we do deal with a lot of different devastating conditions. But for epilepsy, I really felt like there was something we could do and something we could offer. And the surgical options for epilepsy is really what brought me into this field because I felt that it was just amazing that what we could do and the different devices, and I think we're continuing to kind of develop more and more things that are going to be on the horizon. Like, 10 years ago, it wouldn't have been an option for this patient to have gotten that surgery and she still would have been having seizures. So I'm continuing to be hopeful that, down the line, we're going to have a lot more options, especially for our generalized patients because these people don't have a lot of surgical options at this point.

Interviewer: New surgical procedures can potentially change the life of children that suffer from epilepsy. We'll talk about that next on The Scope.

Announcer: Health tips, medical news, research, and more for a happier, healthier life. From University of Utah Health Sciences, this is The Scope.

Interviewer: New advances in surgery for drug-resistant epilepsy have the potential to improve many children's lives in a lot of different ways, but yet many kids who would benefit don't get it. Those that don't get these treatments oftentimes get worse. In this episode, we're going to find out more about new evidence and benefits of pediatric epilepsy surgery. And to find out more, we're talking to Dr. Matthew Sweney, he's the Medical Director of the Epilepsy Program at Primary Children's Hospital, and the Surgical Director of the program, Dr. Robert Bollo. Thank you very much for joining us today.

This is exciting stuff. So the first statement that really kind of intrigues me is, when it comes to surgical options to help children with epilepsy, many kids that would benefit from it don't get it. Why is that?

Dr. Sweney: Well, there's an entity in pediatric epilepsy that we call the treatment gap, and that is the gap from getting kids the appropriate care that they need for the severity of their epilepsy. And the treatment gap is a global phenomenon and one that we deal with locally, and it's held to a very specific standard as to when you become drug-resistant in dealing with your epilepsy. And that's a global standard in which two to three typical seizure medications are failing and you continue to have seizures.

Interviewer: And what's happening? So people are going beyond that?

Dr. Sweney: Yeah.

Interviewer: They just keep trying other things as opposed to going to the next steps?

Dr. Sweney: Yeah, there's a sense of somewhat of despair in which medication after medication is tried. And statistically we know, as epilepsy care providers, that when you fail two, sometimes three medications, the likelihood of any of the additional medications, which currently is around 12 to 15, the likelihood of any of them doing any significant benefit in regards to seizure control is low single digit probability. So it's a global standard set by the International League Against Epilepsy, which is kind of the international governing body in epilepsy management that says, if you fail two to three medications, you should seek more advanced care through a dedicated epilepsy program.

Interviewer: And this isn't happening. People aren't seeking more advanced care. Why is that?

Dr. Sweney: Well, there's a disconnect. A lot of care is provided by folks that aren't necessarily familiar with the details of epilepsy care and the different tools available. And so those outside of the area of a large center, like our own, might find that their doctor is telling them to just continue to try seizure medications one after the other, so that five, six, seven are tried and failed, and they just assume that this is the best that it's going to get.

Interviewer: And then after some medications are tried, there's like a process that you go through to help treat children with epilepsy, right? It starts out least invasive and then builds up to surgery, which can be very beneficial and we'll talk about here with Dr. Bollo in a second.

Dr. Sweney: Yeah, absolutely. It's a fairly set approach to what you do under the circumstances of drug-resistant epilepsy. There's cornerstones to the evaluation that consist of a really long EEG, which is a brainwave test used to characterize where the seizures are coming from. There's imaging that's involved to identify any structural abnormalities to the brain. And from that point, we can then determine what are all the options available in dealing with that epilepsy.

Interviewer: And there's new evidence out there that actually says that surgery is a really effective option, like you've known that it has been for a while, but just within the past month of the recording of this. Tell me about that new evidence, Dr. Bollo.

Dr. Bollo: Yeah, so thank you. There was a new study published in "The New England Journal" about a month or so ago that is really the first class one evidence we have for pediatric epilepsy surgery. And it was a large center in India actually, where they typically have a long waiting list for surgery, and they randomized children with all different types of epilepsy. So a very real world type study, all different types that might come into a center for either surgical treatment or to continue medications for 12 months, which had been their standard of care. And they found a significant difference in not only seizure freedom but benefits to children across multiple domains, including quality of life, behavioral health, and cognitive function, who got surgery. And in general, patients who continued on medications either got worse or stayed the same. At the end of the study, they had about 77% of patients who met the criteria for seizure freedom at a year in the surgery group compared to 7% in the medical group.

Interviewer: Wow. And if you're a parent with a child with epilepsy, that's significant.

Dr. Bollo: Yes.

Interviewer: Or if you're the child with epilepsy, right?

Dr. Bollo: Absolutely. And children who had surgery, their quality of life improved, their behavior health, their conduct, all of these things tended to get better across that population. So I think that's a very important study that sort of reinforces what we've known for a long time but really shows a significant degree of clarity and resolution that not only is continuing to have seizures bad for the developing brain, and surgery is certainly scary, but it's actually quite effective.

Interviewer: So surgery could lead to a much better life for that child, but not getting surgery could actually be bad as well. I think we tend to think not doing something means status quo, but that's not the case with epilepsy.

Dr. Bollo: It's not, especially in the developing brain, so especially in a child. There's clearly loss of function across those same domains of behavioral health, quality of life, and cognitive function with persistent seizures. We often talk about epilepsy as a disease that's bimodal. It's the old and the young, and it is much more common in children than in adults. And in children, it's much more common in very young children compared to older children. So it's really a disease affecting the brain that's trying to develop.

Interviewer: So coming back in a real world situation, if you have a child that has epilepsy and you've gone beyond this treatment gap you talked about, if you've gone beyond the two or three medications, which research shows after you've tried two or three, is that correct, that odds are the other 18 or whatever else might be out there is not going to be effective, that that could be a detriment if you then decide, "Well, let's try some more medications."

Dr. Sweney: That's true. We know it's almost like a glass ceiling when it comes to epilepsy therapy that, two-thirds of the time, a combination of two to three medications can stop seizures. That leaves a third of the time that's not going to stop, despite any attempt at further anti-epileptic medications. So, I mean, the treatment gap, from our standpoint, for practitioners out there and families out there who are dealing with epilepsy early in the stages of the disease, to know what the resources available are and to know what the next steps should be and to not be complacent and to not just accept the status quo.

Dr. Bollo: And I would agree with that and I think we need to acknowledge that surgery is extremely scary. All of the time, families come to us and they say, "But I don't want memory loss, and I don't want the prospect of visual loss or a loss of an essential function like motor function." And that's very important, and I think a big part of the psychology that has led to this treatment gap and leads to long delays in getting access to surgery. And so I think we see it as our responsibility to come up with better and better ways to do surgery, less and less invasive ways, in order to do it in a way that is less risky, less morbid, gets kids home, back to school, and back to regular life as quickly as possible.

Interviewer: Yeah, because that could be scary, right, thinking about your child having their brain operated on, that's a terrifying thing. And some of this new technology, it's very high-tech, robots, lasers. I was reading a description of one of the procedures, image-guided endoscopic surgery, which is that surgery that needs just a small little hole that you can perform complex brain operations for the treatment of epilepsy. And that's what you do. Talk about some of these treatments, help us feel more comfortable with them and where they've come.

Dr. Bollo: Yeah, no, thank you. So I think if you think about 10 years ago how we did things was we would often do very large craniotomies, very large exposures of the brain. And there are three kind of main reasons to do that. Number one is, because oftentimes, an EEG, a regular EEG that you think about on the scalp doesn't have good spatial resolution. It's hard to target the structures and figure out exactly where that seizure is starting in the brain. So oftentimes, we have to put electrodes in the brain or on the surface of the brain to get better spatial resolution, better maps.

Another reason might be to map the functional cortex, where is motor function, how does my hand move, where is sensation, where is vision, where is language function within the brain in this child. And especially if the seizure's coming from areas that are close to that, we need those different maps to do things safely.

A third reason is obviously resecting the epilepsy focus or removing the cause of the seizures. So to take the first one, we've gone from doing large operations and putting large electrode arrays on the surface of the brain to robotically placing depth electrodes that are very carefully targeted to different areas of the brain and different functional circuits within the brain, all through tiny little stab incisions. So we can put up to 18 or 20 electrodes, each of which has about 10 contacts on it, through these methods, using computer technologies and robotic technology very safely and very quickly. And then when we take those out, the kids can go home the same day.

Interviewer: Isn't that kind of amazing?

Dr. Bollo: It is amazing to see.

Interviewer: I mean, really?

Dr. Bollo: Yeah. I think families are blown away when they go through it. And I'm like, "Okay, you can go home," and they're like, "Really? How long do I have to stay out of school?" I'm like, "You don't."

Dr. Sweney: Families are routinely kind of astounded with what we tell them is kind of the expected recovery with these. They're expecting weeks to months of being incapacitated, just because surgeries 30 years ago would have that. But, you know, this isn't 30 years ago.

Interviewer: And things are only getting better. I remember when I had my tonsils out a long time ago, I was in the hospital for a couple of days, right. And I don't know if that's still the same but that just is amazing, compare and contrast that.

Dr. Bollo: Yeah, so a large, big opening on the side of one's head to multiple, just little incisions closed with a single stitch that'll absorb over time and right back home and right back to school.

Interviewer: And with pinpoint accuracy, being able to know exactly where you need to target the surgery and where the trouble spots are to avoid them so you don't cause no harm, yeah.

Dr. Bollo: Absolutely.

Interviewer: What's the next step for somebody that wants to learn more? I think that hopefully this conversation has maybe helped people overcome a couple of things. One, the treatment gap, realizing there is a set continuum of treatment, steps that you take, "If this one doesn't work, we're going to move to the next one, we're going to move to the next one." If you don't move down that, it could actually negatively impact your child. If you move along it, it could make things much better. And then the other thing is just becoming more comfortable with the technology and surgery, that it's maybe not the scary thing.

Dr. Bollo: Yeah, I think that our responsibility as providers, and our team takes that very seriously, that we need to make surgery safer, less risky, and easier on kids, and this new technology that we have facilitates that. And so we try to bring it together in a synergistic way and offer as minimally invasive a surgical treatment as we could have for any given child in any given situation.

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Interviewer: Coming up next on The Scope, a few of the latest and most important changes for how epilepsy is treated and managed in kids for pediatricians and parents. You're both going to get value out of this next.

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Interviewer: Dr. Matthew Sweney is from University of Utah Healthcare. He's presenting at the Pediatric Academic Society's conference and he's here to fill us in on what we know about treatment for children with epilepsy. There is a pretty clear treatment pathway we're discovering, even though maybe a lot of people don't realize that, so let's talk about some of those things.

Dr. Sweney: Recently the International League Against Epilepsy has standardized the definition of drug resistant epilepsy in kids. It's fairly straightforward that if you have failed two anti-epileptic medications that were appropriately selected and tried for an adequate duration, if they don't work, then you are a candidate for other options. That was part of the purpose of the talk, to highlight what the treatment algorithm and the different management options are for kids with epilepsy.

Interviewer: Yeah. Give me kind of a brief overview of this pathway of treatment.

Dr. Sweney: Well, in kids, the definition of epilepsy is when you have two unprovoked seizures. If that's the case, we talk about initiating medication, hopefully with the goal of eliminating the seizures. The first medication, no matter what you choose, it's interesting how we've been in this game for 100 years as far as having anti-epileptic medications and we have had difficulty moving the needle because no matter what medication you select, it gives you about 50% of kids with seizure freedom.

So in other words, you stop seizures with the first medication half the time. If you add a second medication, you get another 10%. If you add a third medication, you get another 5%. If you add a fourth, fifth sixth, seventh, eighth, ninth, tenth through fifteen, you get low single digits with each one.

Interviewer: Not all at the same time, but trying each one to see which one works.

Dr. Sweney: Each one sequentially.

Interviewer: For that particular child.

Dr. Sweney: Yes. So the International League Against Epilepsy has said, well, the statistical benefit of additional medication trials is so low that you should look at other things. That's where the term drug-resistant epilepsy comes in and then the menu options include in some cases surgical resection, which often gives you the best chance of actually curing epilepsy because all of our medications don't unwire a brain that's wired to seize, they just treat the symptom of the seizure.

So we look at epilepsy surgery as an option in some of our more severe cases where there is a target that can be safely removed. If not, then we look at other options like neuromodulation which involves implantable devices, dietary modification, which surprisingly has been in effect for thousands of years with humans, but we've just kind of medicalized it in the past 30 years and that's with a ketogenic diet. And then of course sometimes medications are the best bet. Unfortunately it's usually not the greatest statistical chance, but we take what we can get when all other options don't work.

Interviewer: What would surprise . . . are parents surprised that surgery is actually an option that works as well as it does? Does it work that well?

Dr. Sweney: Yeah. Some surgical scenarios can give you up to 80 to 90%, let me rephrase that, 80 to 90% of kids undergoing that surgery may be seizure-free in five years, which is kind of our yardstick for measuring how well it works. That's not perfect and they've attempted to look at it even longer term, like decades, but there are some barriers to getting good data on those kinds of studies.

So when you look at the prospect of 80 to 90% seizure freedom five years down the road versus low single digits with additional medications, families are often really surprised to hear that we feel that surgery is a good option. There's a lot of anxiety generated about taking your kid into surgery and have somebody cutting on their brain, but the whole idea with surgery is you have the same child going into surgery coming out, just without seizures.

Interviewer: And then after surgery for those that are cured, for those that it's alleviated symptoms, then do you move onto the dietary aspect or is that one of the first things you do?

Dr. Sweney: It depends on the circumstance. The ketogenic diet in some epilepsy syndromes is actually the preferred treatment of choice. That's where you trick the body into thinking its starving when it's not. You still meet other nutritional needs that are required, but you shift the fuel source from the preferred fuel source of the brain, which is sugar and you go to the second most preferred, which is the breakdown products of fat.

Sometimes we even do something called the modified Atkins which has a little bit more publicity and it's a better target maybe for older kids. It's the same premise where you trick the body into thinking that it's in starvation mode and that's what we found over the past hundreds of years, folks with epilepsy, when they get sick and they don't eat, sometimes their seizures get better.

Interviewer: When you give your talk at the Pediatric Academic Society's conference, what else will you be addressing?

Dr. Sweney: In addition to highlighting the epidemiologic burden and the medication management issues, we'll talk about some of the new surgical alternatives, which reduce the invasiveness and alleviate some of the morbidity or issues generated by the surgical process itself, ideally making shorter stays in the hospital and having kids go home quicker. And then also to kind of talk about in addition to dietary modification, the increasing use of genetic testing over the past five to ten years, which should down the road ideally provide the possibility of a tailored management approach for kids with epilepsy.

Interviewer: Is that something you'd recommend to anyone with a child with epilepsy is to get some sort of genetic testing done at this point or is it really you as a specialist can target, "This might be advantageous for you?"

Dr. Sweney: As epilepsy care practitioners, we're in the process of figuring that out. I would not make it a blanket recommendation because the results don't justify the cost at this point. There are specific scenarios where there are well-defined epilepsy syndromes where I think it's a little bit higher yield or in cases where there's clearly a family predominant effect where it might have a bearing on family planning and information that you or your children might need to know down the road.

So no, it is not a one-size-fits-all at this point. But genetic testing is becoming more and more reasonably priced and we're getting a better idea of what to do with the information. So I see it becoming a heavier component of the diagnostic workup in the next five years.

Interviewer: Would you have a final thought for pediatricians or parents on this topic? Is there a takeaway that they should . . . ?

Dr. Sweney: Well, one of the biggest things that families say is that they feel lost early in the course of their epilepsy care identifying a practitioner that's familiar with what they're dealing with and has a clear idea of what the next should be. My goal would be to emphasize that that's out there and that you just need to basically know what doors to knock on and know what care pathways to pursue. But there is help and that's what we're here for.

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Female Voice: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Julie: The anticonvulsant drug development program at the University of Utah has been instrumental in bringing an amazing 16 epilepsy drugs to the clinic. My guest, Dr. Steve White, is director of the program. Dr. White, I understand there are some impressive statistics associated with your program.

Dr. Steve White: Yes, Julie. Since the inception of this program in 1975 there have been approximately 31,000 investigational new drugs that have been through the doors here at the University of Utah. Of those 31,000 about 16 new drugs have come to market since 1993. The Utah program has actually been responsible for the early identification of anti-seizure activity for six of those compounds.

Julie: What do you think it is about the program that has made it so successful?

Dr. Steve White: One of the important aspects of this program is it really is a partnership between the National Institutes of Health, the academic and the pharmaceutical sponsor, and the University of Utah. The way the program works is that it is a free service to the sponsor. Anyone worldwide who thinks they may have a drug that could be useful for the treatment of epilepsy can submit their compound to the National Institutes of Neurological Disorders and Stroke, or the N.I.N.D.S., and then that compound is actually sent to Utah. We do the initial testing in a series of animal seizure and epilepsy models which over the years have proven really predictive efficacy in the patient population with epilepsy. The other important aspect of it is that success breeds more success. As new drugs come to market that show promise more sponsors come to the table, and because this is a service provided free to the sponsor there's really no reason for someone not to submit their compound.

Julie: Yeah. So a sponsor could be a researcher or, say, a company?

Dr. Steve White: Absolutely. The sponsor could be an academic chemist next door, or it could be someone in Europe or China or India, and indeed we see compounds coming from all over the world.

Julie: I imagine you test them on many types of epilepsy, because there are many causes of the disease.

Dr. Steve White: Indeed. One of the things that makes epilepsy so challenging to treat and to understand is because there are so many causes. The common causes that we think about of acquired epilepsy would be traumatic brain injury, stroke in the elderly patient, C.N.S. or brain infection in the younger patient. In addition to that, you have many of the genetic causes of epilepsy that are being identified today, and with every passing month or year more and more genetic mutations are being identified that can lead to epilepsy. By profiling a drug that a sponsor might submit to the program in these various models of epilepsy that are intended to model the different human epilepsies or at least that particular class, we provide the sponsor with sufficient information for them to move forward and be thinking about a clinical development program.

Julie: How long might it take for a compound to come to you and you either to say okay this isn't going to do anything or to ultimately get it perhaps to market in the best cases?

Dr. Steve White: If a compound came in, and we had enough compound, and we could move it all the way through, and it was showing efficacy or effectiveness at each of the various steps, it could move all the way through our program in about a year very effectively. Then, it would go onto the toxicology studies, and then it would go into the clinical testing. That overall program is estimated to take about eight to ten years. It's a long process from beginning to end.

Julie: What different directions do you envision the program taking?

Dr. Steve White: Over the years we've learned that epilepsy is more than about a patient's seizure control. One of the things that we have been doing recently in the last two years with the support of the N.I.H. is developing models of learning and memory and testing drugs in animals to see whether the most promising drugs actually do affect cognitive processes. It's not only about the drugs, but it's also trying to understand the effect of the epilepsy on learning and memory and affect. We're constantly developing those models to try and study that particular aspect of epilepsy.

Julie: Looking to the future, how might your program be changing?

Dr. Steve White: Take for example the patient with traumatic brain injury. We know that about 20% of those patients are high risk for developing epilepsy within the next 24 to 36 months. Imagine a day if we had biomarkers which could predict which of that 20% patient population would develop epilepsy, and imagine our ability to identify a neuro- protective drug that the patient could be treated with for a short period of time during the remodeling of the brain that leads to epilepsy to prevent that. This whole area falls under the idea of disease modification, and this is something that our program is certainly very interested in and the entire epilepsy research community is involved in.

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Julie: For nearly one-third of epilepsy patients, currently available medications simply do not work to control their condition. Dr. Karen Wilcox is investigating the biological basis of epilepsy, with a goal of finding new therapies. Dr. Wilcox, how common is epilepsy?

Dr. Wilcox: Well, Julie, epilepsy afflicts between 1 to 3% of the population. It's known that nearly 16 million people worldwide have epilepsy and that probably roughly one-third of those patients have very difficult-to-control seizures, even with existing drug therapies.

Julie: What are some of the major challenges that people with epilepsy still face?

Dr. Wilcox: Patients with epilepsy have a lot of issues still today with stigma. It can impact their ability to hold down jobs, and they aren't allowed to drive often if they're still having seizure activity, and certainly it can impact learning and memory in the developing brain for young patients. Some of the other things that people are unaware of are the high rate of sudden, unexplained death in epilepsy, or SUDEP. It turns out that epilepsy is responsible for more deaths a year than breast cancer.

Julie: So since some patients respond to drugs and others don't, does that mean there are different types of epilepsy?

Dr. Wilcox: Oh, that's a fabulous question, Julie. We know that probably about two-thirds of all epilepsies are the result of genetic mutations in a variety of genes. Over 120 genes to date have been identified that have mutations that can sometimes lead to epilepsy. So there's a genetic predisposition in some people. We also know that in about a third of other epilepsies, they result from traumatic brain injury of some sort, or an insult to the central nervous system, be it infection, traumatic brain injury, status epilepticus, which is a state of constant seizures. So there are a lot of reasons that people develop epilepsy, and these complex reasons and the complex genetics underlying it can really make it difficult to understand why some patients respond quite well to anticonvulsant drugs while others do not.

Julie: This has been a subject of research in your lab for a little while. What have you discovered so far?

Dr. Wilcox: One of the things that my laboratory is particularly interested in trying to understand is what is it about the one-third of those patients who still have their seizures despite taking many medications. And we're trying to understand the biology of these pharmaco-resistant seizures, trying to understand the pathophysiology of these pharmaco-resistant seizures, and trying to identify new therapeutic approaches. One of the areas that my laboratory particularly focuses on, which is a little bit unique, is the role of astrocytes in neuronal function. So astrocytes are a very specific type of cell in the brain. In fact, they outnumber neurons in the brain . . .

Julie: Oh, really?

Dr. Wilcox: . . . quite considerably, and these astrocytes have always been thought of as sort of the housekeeping genes, or housekeeping cells, of the brain. They do a lot of important maintenance of activities in the brain. They take up neurotransmitters, they balance the ions that are in the brain, and they can help dampen excitability. But we now know that following an insult to the brain, there are dramatic changes in astrocytes that really have not been thought about all that much in the literature. And so our laboratory is very much focused on trying to understand structure and function of astrocytes that might change as a consequence of brain injury.

Julie: Now I'm guessing that most people haven't heard of astrocytes. Why is that?

Dr. Wilcox: Well, neuroscience has focused on neurons.

Julie: There you go. It's not astrocyte science, I guess.

Dr. Wilcox: Or glial science.

Julie: Yeah, um-hum.

Dr. Wilcox: We like to call ourselves a glial science lab. The astrocytes are a form of glial cells, and glia is actually a Latin term for glue, so people thought that astrocytes were the glue that held the brain together, and, in fact, they do impart structural integrity to the nervous system. However, it's recently become well understood that they're not passive at all, and, in fact, astrocytes are now known to release a number of signaling molecules that directly interact with neurons to change the neurons behavior. And so that happens normally during normal neural function, and now we're beginning to understanding that those functions change dramatically following an insult to the brain.

Julie: What happens to neurons during epilepsy, and how might astrocytes feed into that?

Dr. Wilcox: Oh, that's a very good question also. So neurons absolutely are required for epilepsy. Neurons are firing action potentials all at the same time during a seizure, so a seizure is really defined as a hypersynchronous activity of a population of neurons in the brain. But what astrocytes may or may not be doing correctly during that seizure activity is the focus of my laboratory. And so we're trying to understand if perhaps there are different proteins on astrocytes that could actually serve as therapeutic targets for novel drugs, and whether or not we can interfere with astrocyte behavior so that we're not interfering as much with the actual neuronal behavior that's so important for other functions that the brain is responsible for, emotions and cognition, and things of that nature.

Julie: Do you know, are astrocytes triggering the neurons to have this epilepsy response, or are they just sort of passing the message along to other neurons?

Dr. Wilcox: Well, those are great questions that we really haven't had the tools to understand until very recently. So now we're beginning to develop the appropriate tools to look scientifically, to be able to look at the function of astrocytes before a seizure, during a seizure, and after a seizure. And this results from collaborations that my laboratory has with others here at the university, with Dr. John White in bioengineering, and Drs. Peter Taverdek [SP] and Mario Capecchi in human genetics. In work that we've been doing with them, we've been developing new, novel mouse models that will enable us to directly visualize, using very sophisticated microscopy, the activity patterns of astrocytes, because they're going to now express a protein that will fluoresce when the astrocytes become activated.

Julie: But basically your idea is that astrocytes play an important role in some types of epilepsy but not other types of epilepsy, or . . .

Dr. Wilcox: Well, that remains to be seen.

Julie: Okay.

Dr. Wilcox: One of the interesting things that we've noticed in a couple of our animal models is that, even in some of the genetic models of epilepsy, you can engineer mice to have the same mutations as humans do that then results in epilepsy. And what we found there is even in the lack of obvious neuronal damage or cell death, we do see changes in these astrocytes, so they do become inflamed, or what we refer to as activated. They go into their activated state. Just by virtue of having a seizure, even if you don't have epilepsy, it can cause an inflammatory response in the brain, and this is something that's really just beginning to become understood, because for many decades it was not recognized that the immune system was actually involved in brain function. And so we're all starting to recognize that this pathology, which wasn't really appreciated before, might actually contribute to all sorts of seizure activity.

Julie: And so with new information, it possibly could give you new targets for controlling epilepsy.

Dr. Wilcox: That's our thoughts exactly.

Julie: Yeah.

Dr. Wilcox: And that's our hypothesis, is that if we can enhance the things that they do well, so, for example, it can help to dampen excitability in the brain. So perhaps we could find therapies by exploiting the good or diminishing the bad activities that occur as a consequence of activation of these astrocytes.

Julie: Now something that's been in the news lately is the use of cannabinoids, which comes from marijuana, as a way to control epilepsy in some patients. Is this something that might also work for those patients that don't respond to currently available drugs?

Dr. Wilcox: As recently shown on T.V. specials by Sanjay Gupta at CNN, we know there are some patients, in particular, for example, Charlotte Figi, who has a type of epilepsy called Dravet syndrome, a very severe type of epilepsy that results as a consequence of genetic mutations in a variety of different genes that encode for ion channels, and she has reportedly responded very well to a very specific type of extract from marijuana called Charlotte's Web, named after Charlotte. This has offered a lot of hope to families. Here in Utah recently, a new bill is being passed to deschedule extracts from low THC-containing marijuana plants so that these families can maybe try these compounds. I think the epilepsy community is very cautious whenever a new therapy is identified, or a new approach is identified, and what we'd like to see is research to be done. And the research has been hampered over the years because of marijuana's scheduling as a schedule one compound, which makes it very difficult for researchers to get it, makes it very difficult for the science to be done. And so what we'd like to see is more rigorous clinical trials, that are double-blind, placebo-controlled trials, in the right patient populations. It may work in some patients. It may not work in all patients, like just about every anticonvulsant agent out there. And so what we'd like to see is, moving forward, the ability to do the science to really confirm that treating with extracts from marijuana plants or medical marijuana do no harm and actually are efficacious.

Woman: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences radio.