Infantile Spasms – PediaCast 507
- Infantile spasms are a medical emergency! Symptoms can be subtle, and quick diagnosis and treatment are essential for preventing lifelong consequences. This week, we raise awareness and explore the details of this serious type of seizure. We hope you can join us!
- Infantile Spasms
- COVID-19 Vaccine
- Infantile Spasms Program at Nationwide Children’s Hospital
- Infantile Spasms Awareness Week
- Infantile Spasms Action Network
- TSC Alliance (Tuberous Sclerosis Complex)
- Epilepsy Foundation
Announcer 1: This is PediaCast.
Announcer 2: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike.
Dr. Mike Patrick: Hello, everyone, and welcome once again to PediaCast. It is a pediatric podcast for moms and dads. This is Dr. Mike coming to you from Nationwide Children's Hospital. We are in Columbus, Ohio.
It's Episode 507 for November 30th, 2021. We're calling this one "Infantile Spasms". I want to welcome you to the program.
So, Infantile Spasms Awareness Week is upon us which takes place every year during the first week of December, specifically December 1st through the 7th every year. I think this is the seventh year actually for it.
And so, our goal today is to raise awareness about infantile spasms. And in doing so, we'll explain what they are, why it is so very important to recognize and diagnose and treat them as quickly as possible. Because the longer they go unrecognized, the more likely they're to cause significant lifelong developmental and intellectual disabilities for those who are affected.
Now, fortunately, infantile spasms are relatively rare, but it is important that all parents have a basic working knowledge of what they are, because even though your infant may not have infantile spasms… Ends up being about 1 in 2,000 live births, those babies are going to go on to have infantile spasms. So, 1 in 2,000, it's rare but it's not unheard of, either. I mean, I'm sure there are at least 2,000 live births in your community every year, probably more than that.
And so, this may be something that affects someone you know, maybe a friend, a family member, a colleague, and you may be the one to say, "Hey, that sounds like it could infantile spasms." We want to be able to recognize this in the community, and so that's why it is important that all of us have awareness about infantile spams.
The symptoms can be mild and subtle at times. Parents may not know if those symptoms are significant and it's possible that their medical provider could be taking a wait-and-see approach at the time when action is needed. And so, in order to be a terrific advocate for babies, we need to know about these things and really push to make sure that they're getting evaluated and diagnosed and treated as quickly as possible.
And we'll talk more during this episode about exactly what this looks like, what are infantile spasms. So that you'll have some awareness and know what we're all should be on the lookout for as we really try to identify babies who are affected and impact their future life and development by getting them the help they need when they need it. Because we really can make a difference by urging these parents to persistently seek help.
And in our usual PediaCast fashion, we have some really terrific guests joining us as we consider infantile spasms. Dr. John Mytinger is a pediatric neurologist at Nationwide Children's Hospital. Dr. Martina Bebin is a pediatric neurologist at Children's of Alabama, and Kari Rosbeck is president and CEO of the TSC Alliance, which is helping to sponsor Infantile Spasms Awareness Week. And much more on that to come.
Before we get to them, as you probably know, COVID-19 vaccine is now approved for all children from the age of five years and on up through adulthood. It's been approved by the US Food and Drug Administration and the US Centers for Disease Control and Prevention. And it is recommended starting at age five for all children by the American Academy of Pediatrics and the American Academy of Family Physicians.
It's also recommended by Nationwide Children's Hospital and by all of us here at PediaCast. In fact, every member of my family, young and old is fully vaccinated against COVID-19.
The biggest concern you may be reading about or hearing in your social media feeds regarding the COVID-19 vaccine in children is the possibility of myocarditis, which is a fancy way of saying inflammation of heart muscle. You may have come across that. There have been rare cases of myocarditis associated with COVID-19 vaccine particularly among teenage boys and young men.
Again, this is a very rare event. And when it occurs with the vaccine, the cases tend to be mild and short-lived. However, did you know that infection with COVID-19, so natural infection with the virus, is actually much more likely to cause myocarditis than the vaccine?
And also, a syndrome that can follow COVID-19 infection in children, sometimes weeks after the infection is gone, it's called MIS-C or multisystem inflammatory syndrome in children. And this syndrome is only caused by infection with COVID-19 virus. So, this does not happen from the vaccine. And that too, this MIS-C that you can get following COVID-19 infection in kids, is also associated with myocarditis which can be very severe.
So, yes, the vaccine has been associated with rare and usually mild cases of myocarditis. However, remaining unvaccinated is a much bigger risk because natural COVID infections in kids and this multisystem inflammatory syndrome, it's a tongue twister, in children, this MIS-C, that can also result in myocarditis more frequently than the vaccine and with the greater risk of severe myocarditis.
So, as we consider all the risks and benefits of the COVID-19 vaccine in kids from age five and on up through adulthood, the benefits of vaccination clearly outweigh the risks. And that is why, these vaccines are recommended by the Food and Drug Administration, the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American Academy of Family Physicians, Nationwide Children's Hospital, and all of us here at PediaCast.
So, if you have been waiting to get your kids get vaccinated, I would say now is the time before the holidays and all the family gatherings that go along with the holidays. For more information regarding the COVID-19 vaccine in children, Nationwide Children's Hospital has a landing site called COVID-19 Vaccine Information for Parents. We'll put a link to that in the show notes so you can find it easily.
And then for information on the science behind COVID-19 vaccines, including what they are and how they work, be sure to check out COVID-19 Vaccines, PediaCast Episode 485. And in previewing that episode, let me just say this, COVID-19 vaccines are not based on a new technology, and in that episode, we talked about exactly where the technology came from, sort of the history of it.
They do not contain magnet particles or computer chips and they do not alter your DNA. And again, we talked about all of these things in Episode 485 COVID-19 vaccines. Again, I'll put a link to that in the show notes.
All right, before we turn our attention to infantile spasm, let's run through our usual quick reminders. You can find us in all the places where podcasts are found. We're in the Apple and Google podcast apps, iHeart Radio, Spotify, SoundCloud, Amazon Music, and most other podcast apps for iOS and Android.
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And then, I want to remind you the information presented in every episode of PediaCast is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for specific individuals. If you have a concern about your child's health, be sure to call your healthcare provider.
So, let's take a quick break. We'll get our expert guests connected to the studio and then we will be back to explore infantile spasms. It's coming up right after this.
Dr. Mike Patrick: Dr. John Mytinger is a pediatric neurologist at Nationwide Children's Hospital and an assistant professor of pediatrics at the Ohio State University College of Medicine. Dr. Martina Bebin is a pediatric neurologist at Children's of Alabama and the professor of neurology at UAB School of Medicine. And Kari Rosbeck is president and CEO of the TSC Alliance which we will learn more about as we continue our journey through Infantile Spasms Awareness Week.
But right now, at the beginning of our time together, let's take a moment to warmly welcome our guests. Thank you all so much for being here today. We really appreciate you taking time out of your busy schedules.
Dr. Mytinger, I wanted to start with you. What exactly are infantile spasms? It maybe a term that parents haven't heard before.
Dr. John Mytinger: Yeah, Mike. Thanks. I can provide an overview of infantile spasms, but the infantile spasms are seizures occurring in children between the ages of two months and two years. Unfortunately, seizures are associated with poor developmental and epilepsy outcomes, with some children experiencing lifelong epilepsy.
Fortunately, we can improve the outcomes for many children with rapid and effective treatment. More than 90% of the time, infantile spasms occur within the first year of life, most often between about four and eight months with the peak at six months. And then they become rare after 18 months. We certainly see spasms occurring after two years of age as well, but for these older children and adults, we use the term epileptic spasms.
In comparison to epileptic spasm, infantile spasms are far more often responsive to standard therapy such as adrenocorticotropic hormone, which is ACTH, high-dose prednisolone which is a steroid, and the anti-seizure medication called vigabatrin. But infantile spasms nearly always occur in the setting of West syndrome or what is likely in the future to be called infantile spasms syndrome as our nomenclature evolves.
Typical features for this syndrome include infantile spasms, developmental problems, whether it be stagnation or regression, a very abnormal electroencephalogram which we call EEG, which is a test that detects electrical brain activity on the scalp. And the term that we use to describe this very abnormal EEG is epileptic encephalopathy.
And infantile spasms can arise from hundreds of possible causes or what we call etiology. For example, some children experience to prior brain injury around the time of birth due to a lack of oxygen or blood to the brain. Other children may have experienced a stroke or brain infection or have a genetic problem that negatively impacts brain development or function.
And in a minority of children with spasm, the etiology can't be determined even with advance diagnostic testing. Children with tuberous sclerosis complex in particular are highly prone to develop infantile spasms.
Dr. Mike Patrick: I want to back up just a second and sum up a little bit of what you said and just to make sure that I'm understanding this correctly. So, infantile spasms are a type of seizure but often, they are really a symptom rather than a disease of some other thing that is sort of happening in the background in the brain. One of those would be West syndrome which if you're not in the United States, this maybe a term that you have heard before.
I think in other parts of the world, infantile spasms, and West syndrome kind of go hand in hand named after William James West. I just love the history part of this. He was a physician in the 1800s and had a child that was affected by infantile spasms and was the first one to characterize this disorder.
And then you mentioned that tuberous sclerosis complex can also be related to infantile spasms. So, I wanted to have Dr. Bebin jump in here and just explain what tuberous sclerosis complex is and then how does that relate to this certain type of seizure called infantile spasms.
Dr. Martina Bebin: Sure. Tuberous sclerosis complex, also known as TCS, is a genetic condition and it's also autosomal dominant. And it either is inherited from one of the parents or occurs because of a spontaneous mutation. We know and we see children, it breaks down to about one-third of the cases are inherited from one of the parents, but two-thirds occur because of a spontaneous mutation.
It's a condition that affects multiple organs. Really in the first decade, we very much concentrate on the brain and the neurologic development. So that's why the epilepsy is so front and center really in the first 12 months of life.
In relation to infantile spasms, we know that it's about 1 in 2,000 children will develop infantile spasms. And when you look at the etiologies or the causes of the spasms, about 35% are consequence of having tuberous sclerosis. They present very much in the similar way.
Probably one of the unique things about TSC is that many times, the infantile spasms are preceded by very subtle focal or partial seizures. And you often have not only the spasms but another seizure type going occurring at the same time. So, really early recognition is absolutely critical.
Dr. Mike Patrick: I think that's an important point with infantile spasms, whether they are related to tuberous sclerosis complex or whether they're a part of West syndrome or there's some other thing going on in the brain that is causing infantile spasm.
One really hugely take-home message here for all of us today is that these, and we'll talk more about what they look like and how parents can identify them, but the infantile spasms are really neurologic emergency because you really want to figure out what's going on and intervene as soon as possible, because they can have a dramatic impact on the future development of a child, which can have lifelong consequences. And so, this is really something that we want to figure out what it is as soon as possible.
Now, when I went to medical school, I just remember it being called tuberous sclerosis. I don't remember the complex being added on to the end. And so, for folks who may not heard of this disease before, as we mentioned, it's a genetic disorder. A lot of times, it just happens spontaneously because of gene mutation, so it can be passed on genetically. But oftentimes, it just happens even though it is a genetic issue.
And what happens and please correct me if at any point if I'm wrong about this. I would like to try to simplify things in my own brain to help explain it to parents a little easier. But with tuberous sclerosis, there are some sort of non-cancerous or benign tumors that grow in many body systems.
And so, depending on where those are located will really determine what sort of symptoms you have. Which is then why we called it complex because it can look different in different kids, depending on where these benign growths are occurring. I know that's really simplifying it, but am I on the right track on that, Dr. Bebin?
Dr. Martina Bebin: That's exactly right. And that's why when we look at the different stages of life, what we typically see is the issues neurologically are really the most dominant concern in the first three years of life, and in particular, between birth in the age of a year or 12 months.
One of the unique things about TSC with the advent of some of the obstetrical prenatal care, probably about up to two-thirds maybe diagnosed prenatally because of the presence of the lesions we see in the hearts. As well as what we can detect either by the ultrasound or a fetal MRI, which puts tuberous sclerosis at a great advantage to be able to diagnose many of these babies prenatally or when they're in the nursery.
Dr. Mike Patrick: So that's another really important point that's going to be crucial for us to remember as we move on with our conversation, is that one of the places that often you see an issue with tuberous sclerosis is in the heart. And specifically, cardiac rhabdomyoma is the name of the type of sort of benign growth or tumor that can be there. But that can be picked up on an ultrasound, including a prenatal ultrasound.
And so, you may be able to identify someone who is at risk for infantile spasms even before the first infantile spasm actually occurs. And then if you can intervene in those kids, you may save some developmental problems down the road. We'll talk much more about that as we move on.
But then there are other things that also can be related to or can end up causing or being associated with infantile spasms, neonatal infections, structural problems with the brain. There's other genetic conditions such as down syndrome, even there are some rare metabolic condition. So, it really is that infantile spasms are a symptom, but it is a specific type of seizure. We'll talk about what exactly that looks like in a moment.
So, I also wanted to sum up how common these are because they are relatively rare. And in fact, that's why a lot of parents may not have heard about them. And yet it's important, I think, and I think that all of you would agree that it's important that all parents have some working knowledge of this because you might be the person that a family friend, colleagues, someone that you work with might mention, "Hey, my baby is doing this." And that may ring a bell for you, "Hey, infantile spasms could be an issue."
And because it's so important to get this diagnosed as quickly as possible, I think it's important that all parents have an awareness about this.
So, tell us again, Dr. Bebin, in terms of epidemiology, how common are infantile spasms and tuberous sclerosis complex?
Dr. Martina Bebin: So, in general infantile spasms is about 1 in 2,000 children and of that 35% of that group will have tuberous sclerosis. So, if you look at the incidence of tuberous sclerosis, it's 1 in 6,000 life bursts. Like Dr. Mytinger mentioned, they typically present itself between four and six months of life.
And I think with the advent of cellphones and everyone has them, we encourage all parents to video the event and show their pediatrician. And we get probably request two or three times a week to look at videos and we're glad to do it. And that accelerates the referral because before, when I started my practice several decades ago now, we wouldn't see the seizures until after they have been present and ongoing for several weeks.
Now, with the advent of the video and the use of cellphones, the idea is we see these babies ideally within 24 hours to 48 hours after the onset. And that's critical and that's totally changed how we approach the condition.
Dr. Mike Patrick: Yeah, absolutely. Dr. Mytinger, what do these look like? What on a video would you be watching for? What do parents need to know in terms of what an infantile spasm looks like?
Dr. John Mytinger: Sure, yeah. These seizures often involved sudden flexion or extension of a body part. For example, common presentation would include the sudden reaching out of the arms with a crunch of the abdomen and a flexion at the hips, almost like a crunch or sit-up.
But other children can have subtle spasm which are difficult to detect and that can actually delay diagnosis. In these cases, the spasm may be limited to a down turning of the lower lip, which in some people think just looks like a grimace. I think it appears similar to the facial expression during a wretch. And that facial movement can be associated with an upper growing of the eyes. In other times, the spasms may be limited to the subtle movement of the limps over an abdomen.
But the key to the diagnosis is the recognition of cluster of spasms because it's such a common phenomenon. And particularly on awakening, so a child that wakes up and from a nap or from a night sleep and has a cluster of movements, you really have to consider a possibility of infantile spasm. Single spasms can also occur, but the clustering again is very helpful for diagnosis.
And a couple other things may be helpful to children can become less responsive during a cluster and they often become very quiet during cluster of spasms. They may have cry immediately after a spasm.
And when you think about the interval, this is very helpful to me as a clinician, when you think about the interval between each spasm. It's very often between about 3 and 30 seconds. So, if you see these movements that are occurring at fairly, not perfectly, but fairly regular intervals that are about 3 to 30 seconds, then that very well could be infantile spasms. And that interval, as well as the other features that I mentioned, is something that we use as we analyze this home videos that Dr. Bebin mentioned.
Dr. Mike Patrick: So, these can really range from being pretty dramatic and of vigorous jerking movement to being subtle. And it may just be certain muscle groups or even facial movements. But the issue is that they cluster together. So, whatever that movement is, it's the same movement at regular intervals in a fairly short amount of time that would be more concerning. Is that correct?
Dr. John Mytinger: Yeah, that's correct. Yeah, these clustering movements, particularly again, on awakening occurring at fairly regular intervals and can last for several minutes at a time.
Dr. Mike Patrick: Now, babies also normally make lots of sort of funny movements. What other things could cause movements that aren't as concerning? What are those things look like?
Dr. John Mytinger: Sure. I guess we can look at this from two angles. One would be a situation in which a clinician would misdiagnose infantile spasms. So, for example, some children may be initially misdiagnosed as having just normal baby movements. That's something fairly common that we hear.
Another thing that pops up is the misdiagnosis of reflex. So, these children are actually are having seizures but again, they can be subtle and difficult to detect. And clinicians need to be aware of infantile spasms. So, I would just caution all clinicians to be wary about reaching the conclusions of things like normal baby movements or reflex without thoroughly considering the possibility of infantile spasms.
And then the other way to look at this, what are some movements that are actually not infantile spasms but sometimes confused with that, like you are mentioning, Mike? For example, in some children who are normally developing, they have an enemy called benign myoclonus of early infancy. That is a similar appearing movement that can occur in clusters, but these are not seizures. And the EEG in that case is typically necessary to distinguish between the two.
Still other children particularly those with high muscle tone such as children with cerebral palsy. They may have an exaggerated startle reflex, so they may have repeating startles, particularly when they're trying to get off to sleep and sometimes that confused with infantile spasms.
But regardless of the movement, to again emphasize what you and Dr. Bebin were talking about before regarding the home video, that's really the critical piece because families can take this home video and show it to a clinician. If that clinician is unsure, then go to the next level and show this to a pediatric neurologist.
Dr. Mike Patrick: Yeah, absolutely. Is this something that if you do have a question of whether it's infantile spasms or just normal baby movement… And especially when you have kids that are affected by colic, for instance, I mean, they may be fuzzy and moving around a lot and maybe there are some movements that seem like they're repetitive movement but it's really colic.
So, when there's question in our mind, whether it could be infantile spasm or not, it seems like this is one of those things you want to make sure it's not infantile spasm. I mean, you don't want to miss that.
And you had mentioned an EEG, how does an EEG, what role does it play in diagnosing this? And then is that something that primary care pediatricians could just order, or do they need to actually see a pediatric neurologist?
Dr. John Mytinger: These are all good questions. And sometimes, it can vary from case to case. But there are really just two ways that I think of in terms of confirming the diagnosis of infantile spasm.
The first way is kind of an obvious method would be to capture the infantile spasms using a video EEG. And this, yes, the pediatrician can order the EEG, but it often does require some coordination from a pediatric neurologist.
So again, one way of making the diagnosis is to capture the infantile spasms on the video EEG. And we look for the EEG changes that are typical for a spasm on the EEG. So that help to confirm the diagnosis.
There is another way. So, if you have a child that is having typical clustering spasms, either by the home video or by caregiver description, plus you have this EEG, particularly during sleep, that suggest that there's an epileptic encephalopathy that bad, disorganized, very irritable EEG that I mentioned before. If you put those two together, then you can provide the diagnosis of infantile spasm in that setting.
And the reason that's important is that the use of the home video or history of clustering spasm, plus the bad EEG, allowing us to arrive at the diagnosis of infantile spasm, that situation allows for us to not rely so heavily on a long-term video EEG, which is expensive, resource-intensive, and not universally available in the United States.
To summarize, one way is to capture the spasm on video EEG. The other way is to use some history home video, plus the finding of the routine EEG of an epileptic encephalopathy and put that together and get the diagnosis of infantile spasm.
And again, these tests are typically coordinated between a primary care physician and the pediatric neurologist, epileptologist to make sure that we're getting all the information that we need.
Dr. Mike Patrick: So, sort of the take-home here for the pediatric providers in the crowd, and even though this is a parent podcast, we also have a lot of pediatricians and others who take care of kids who listen. The take-home for them is number one, take it seriously when a parent reports movements that kind of have their mom or dad radar going. That there's something different, there's something here that I'm not comfortable with, take that seriously so that we don't miss any of this.
And then, second, if you have the availability of a pediatric neurologist in your area, getting them in as long as they can see them in a fairly quick turnaround time, that would be ideal. And then they can order the video EEG so then they can actually see what the clustered movements look like and what the EEG is doing at that time.
Or if that's not available to you or it's going to take a long time to get in to see them, at least ordering EEG, that's going to check the brainwaves out while the baby is resting, not necessarily when they're doing the movement. But then when you order that EEG, make sure you specifically say, "I'm concerned about the possibility of infantile spasm," so whoever is reading that EEG kind of knows what you're worried about. Would you say that's a safe summary of that?
Dr. John Mytinger: Yeah, and I would just add to that, that there is an urgency in the diagnosis and treatment, as you mentioned already. And so, if a family doctor pediatrician, primary care clinician is ordering that EEG, what they really should be doing is making sure that test is going to get done that day. And if it's not going to get done that day, then they're communicating with the facility that can help get that EEG very quickly.
Dr. Mike Patrick: Maybe you're a new provider and this would be a good time to figure out who your resources are going to be. So, if this is something we want to happen quickly, it's a good idea before anyone even comes to you and says, "Hey, I'm worried about this movement that my baby is doing," for you to really have a good idea of what you're going to do, what's the plan, how am I going to get this child evaluated and get EEG as quickly as possible. Because, again, identifying and then making the diagnosis and then intervening is really important to save development down the road.
The other part of this is, okay, so we're diagnosing infantile spasm in the manner that we've described but we also have to think about that underlying associated disorders. So, this is another reason to have them see a pediatric neurologist because infantile spasms usually don't happen in isolation. And so, is this a child who had a newborn infection? Do they have tuberous sclerosis complex? Is there some other thing going on? So, there's going to be more of a workup than just identifying the infantile spasm, correct?
Dr. John Mytinger: That's true. That's right. Yeah, it's critical to pay attention to etiology. There is a reason for infantile spasms in every child. Most of the time or majority of the time, we can't provide an associated etiology as the likely cause. And I mentioned about a minority child, we can't provide that diagnosis.
But it starts with a physical examination, a physical neurological examination, and then certainly paying close attention to the skin. There are certainly signs on the skin that may lead you, for example, to the diagnosis of tuberous sclerosis complex which we talked about.
And beyond that, the highest yield diagnostic test is going to be a brain MRI. So that would be we would perform an epilepsy protocol for an MRI. And that is a standard of care test that the children should receive assessing for an etiology of infantile spasm.
And then beyond that, let's say the MRI's normal, we start to consider other possibilities like genetic causes. In today's diagnostic testing repertoire, we have epilepsy gene panels which have become very useful in our practice. And some children move on, for example, to have a more detailed study, a whole exome sequencing study.
And so, the diagnostic yields for these studies, a gene panel whole-exome sequencing after no diagnosis on the MRI, we're looking at maybe approximately a third of children or more being diagnosed using those newer techniques.
Dr. Mike Patrick: So, lots to think about and even more reason to see a pediatric neurologist if this is a concern for a particular family.
So, let's keep walking this down this the road. We have, let's say, a family that is rightly concerned about a repetitive clustered movement that their baby is making. And they bring that up to their pediatrician. The pediatrician takes them seriously and says, "We need to figure out what's going on here." They're either sent to a pediatric neurologist and or they get the EEG quickly.
And let's say that there is concern for infantile spasms based on the result of the workup. So, then what is next, Dr. Bebin? We mentioned that intervening quickly is important, what is that intervention look like? How do we treat infantile spasms?
Dr. Martina Bebin: Well, I always talk to the families about two paths. One is the day-to-day management and the initiation of treatment as soon as possible. In the case of tuberous sclerosis, if you've made that diagnosis, the treatment of choice is vigabatrin. We usually try to get that initiated within 24 hours of seeing a baby and confirming that diagnosis.
If it's another etiology, many clinicians opt to do the ACTH or the prednisolone. And again, there's a very quick titration schedule and outline is the treatment management.
The second pass is if you've diagnosed tuberous sclerosis, there's things that you need to do besides the MRI and genetic testing and a full physical examination, also an eye exam. They see the pediatric cardiologist to look for evidence of cardiac rhabdomyomas. And we do a renal ultrasound.
If we suspect a different diagnosis, we need to also be thorough and complete that workup, particularly the genetic testing, because for many of these epilepsies, we're finding alternative genetic etiology. And often understanding that, we can then give more information to the family in terms of prognosis and what to expect, not only the control of the spasms but are they likely to evolve into different type of seizures?
So, it's very intensive and it's something, I think as a neurologist, we want to be there at the beginning of the problem, which makes it much easier to manage than delay the care.
Dr. Mike Patrick: So once the diagnosis is made, regardless of how it's made, you really do want that child to see a pediatric neurologist at that point because they're going to be the quarterback. There's got probably be lots of specialty folks involved and you really need someone who understands the disease process and is making sure that all the i's get dotted, and t's get crossed in and all of that. So, it's going to be really important that that's the specialist that your child sees.
Dr. Martina Bebin: Correct.
Dr. Mike Patrick: And then, when folks look up, they Google treatment for infantile spasm, they're going to see medication but there also going to come across things like the ketogenic diet and brain surgeries. Are there roles for those things still in the treatment of infantile spasms?
Dr. Martina Bebin: Absolutely. And I think this is part of the continuum of being involved and initiate treatment as soon as possible. You go through the drug of choice for tuberous sclerosis complex, it's vigabatrin first and then it's often followed by ACTH or prednisolone.
And the thing is it's a constant work in progress because the ultimate goal is to have the baby be seizure-free. A significant proportion of these babies will have persistent seizures, but we don't accept that as clinicians. We continue to work to try to find the best combination. And that's where if the child is having persistent seizures, the ketogenic diet comes in as a consideration for treatment. And then also they need to look and to see if they're an epilepsy surgery candidate.
So, we're finding that many of these babies, a decade ago, they weren't having surgery until they were five years or older. Now, there's many patients that we see that we've realized that they're refractory and they're being evaluated for surgery well under the age of two. So, it's something that it's intensive, it's ongoing and what the ultimate goal is to have control the epilepsy.
Dr. Mike Patrick: Because those constant seizures interfere with development.
Dr. Martina Bebin: Exactly.
Dr. Mike Patrick: Which then, you may not be able to get back.
Dr. Martina Bebin: Exactly. And we've seen this, is that the optimal outcome are those children that have good seizure control that was easily attained early on. And those that are refractory are at the highest risk and you can follow their development. And unfortunately, we get really concerned when we watch those developmental milestones drop off and they stop meeting their milestones. And then we know this baby is really at risk to have intellectual disabilities down the road.
Dr. Mike Patrick: Now, is it that and you may not be able to answer this but is it that the seizures themselves interrupt development? Or is it that more difficult it is to control the seizures, the more likely it is that there's some underlying thing that then also makes developmental problems? Does that make sense?
Dr. Martina Bebin: Sure. I mean, actually it's almost one and the same because if you think the foundation of this, whether it's tuberous sclerosis or some other conditions or even of a genetic condition, is genetics of the condition. And in tuberous sclerosis, it's a network problem.
It's not just the lesions we see on the MRI and we know whatever that network issue is, that's what we're up against. And the more we can control the seizure, it's going to come the network and allow normal development to progress.
It's very complicated and I think it really requires persistence and commitment and work with the family, so you have a plan. And it's not just the immediate, it's what plan B and C will be and have the family work very closely with them. So, we're monitoring this over really the first three years of life is the most intensive.
Dr. Mike Patrick: And we're still learning, as you mentioned whatever that network problem is, we don't necessarily understand it. And maybe as time progresses and there's more research on this, we hopefully will better understand and then that will help us develop better therapies in the future too, right?
Dr. Martina Bebin: Exactly.
Dr. John Mytinger: And, Mike, if I could just echo something that Martina had mentioned, it may be said in just a slightly different way just for emphasis, is we know the best possible developmental and epilepsy outcomes can only be achieved with early effective treatment and complete elimination of both the infantile spasm and the epileptic encephalopathy.
And I mentioned that because we do use the EEG as a means to monitor that epileptic encephalopathy. So, for example, some children have resolution of their infantile spasms but have persistence of the epileptic encephalopathy. So those children may require additional treatment beyond just controlling the seizure.
So, we're really looking for that all or none electroclinical remission we call it, resolution of seizures and resolution of the epileptic encephalopathy using that EEG to help us along the way, because we know that the longer the spasm and the epileptic encephalopathy go on, the worse the outcome.
And as we have already said, the diagnosis and treatment of infantile spasms is a neurological urgency, ideally with treatment starting very soon after spasms onset.
Dr. Mike Patrick: Really, really important. And again, driving that point home that early diagnosis and early treatment is so important.
Dr. Bebin, you're involved in a research project that's really being done on the national level called the Prevent Study. Tell us a little bit about that.
Dr. Martina Bebin: Well, we're very fortunate to have the study funded by the NIH and we will be being able to report out the primary objective of the study early next year. And what it is is because of tuberous sclerosis and our technologies and our ability to diagnose it prenatally, and we know that the seizures are such a risk in that first year. And it's something we call epileptogenesis, so it's the evolution of the seizures.
Could we intervene before the first seizure, clinical seizure manifest itself? And how does that impact the developmental outcome, the risk for refractory epilepsy, the risk to develop spasms? So that's kind of the background of the PREVeNT Trial.
And so, we are following 84 babies. They were blinded in randomized way to either start vigabatrin at the onset of the first abnormality that's evident on the EEG. We call it a biomarker. When you have epileptiform activity on the EEG, we knew there's a window of time of about three-and-a-half months in most cases before the first seizures emerges.
So, the idea is we start that treatment, and we follow these babies very closely until they're three years of age. And what we're trying tracking and trying to figure out is what impact does that preventative treatment have on the development of epilepsy and, most significantly, on their outcome.
So, it's something that's very exciting. We've never been able to be on the preventative side of epilepsy. So, I think we're excited to almost be able to really resolve this out of what it's going to do and how is it going to change clinical care. And I think this is kind of the Holy Grail. We want to be able to cure epilepsy and ideally prevent it before it ever starts.
Dr. Mike Patrick: Absolutely. So, a kid who has a cardiac rhabdomyoma on prenatal ultrasound even, this is a child that would be candidate for the study, correct?
Dr. Martina Bebin: Exactly. And what's changed is we really, as pediatric neurologist, want to see those babies when they're in the nursery. They don't need to have their first seizure. They need to be with the pediatric neurologist from the time it is recognized. And we meet with several, often the mothers and the fathers, before the babies even born. So, we're with them and supporting them and going through what is required to closely monitor this baby. So, we make sure they have the best outcome.
Dr. Mike Patrick: So, this is something that even OB-GYN docs need to be aware of.
Dr. Martina Bebin: Absolutely.
Dr. Mike Patrick: They're doing a prenatal ultrasound and you see a heart lesion, that's someone that you need to talk to the pediatric, not only the cardiologist, they also need to talk to the pediatric neurologist as well, right?
Dr. Martina Bebin: Exactly. And I can tell you why my closest colleague is the pediatric cardiologist and he often sends me a text and says, "I got this baby," and we see him within a couple of days. Because he knows how critically important it is to really be partners in this because that's how we're going to make the greatest impact.
Dr. Mike Patrick: And then, do you automatically start the medicine or no, you do serial EEGs? And then when you first see an abnormality, is that when you start it?
Dr. Martina Bebin: Right. The study is designed that we did serial EEGs every six weeks. And the first appearance of the abnormality on the EEG, then the baby was randomized, either vigabatrin or placebo. And then we watch them and continue the serial EEGs.
If they had a clinical seizure, then they went what we call into open-label vigabatrin. So, we never delay treatment but, really, the emphasis is on the preventative side of this, to see what impact it makes.
Dr. Mike Patrick: And when are you expecting results again? When will we…?
Dr. Martina Bebin: By first quarter next year.
Dr. Mike Patrick: Okay, great. And so, we may then have indication to do this for all kids if we see that this is really making a difference.
Dr. Martina Bebin: Right. And I think that's where a lot of the infantile spasms groups have gotten excited. And a lot of other epileptic conditions is are there biomarkers for other epilepsies that could put you on the preventative side? Because that's a game changer for clinical care.
Dr. Mike Patrick: Absolutely. So, then what is the long-term outlook for those with tuberous sclerosis complex and infantile spasms, especially if we get the treatment going as soon as possible? Does it really make a big difference in terms of development ongoing?
Dr. Martina Bebin: That's one of the questions we had. And actually, that was the FDA's primary question is how does preventative treatment impact development? We know that those with the refractory are much more at risk for intellectual disability and autism. So, this is kind of a complicated question to sort through because it's not only the seizures but it's the genetics.
It's either TSC1 or TSC2. It has to do with what the MRI looks like, what's we call the tuber load, what's the network involvement. So, it’s like skin of an onion. It peels layers and layers and we're beginning to understand the complexity of this. But I think how we approach clinical management as one of the cornerstones of how we're going to change the outcome of these children.
Dr. Mike Patrick: Yeah, absolutely. So, time will tell but we're optimistic, right?
Dr. Martina Bebin: Yes.
Dr. Mike Patrick: We're optimistic that this is going to make a difference.
Dr. Martina Bebin: Yes.
Dr. Mike Patrick: Like all areas of medicine, the care of folks with both tuberous sclerosis and infantile spasms and their families has really been impacted by the pandemic. Dr. Mytinger, at Nationwide Children's Hospital, how has approach to identifying these kids, treating these kids, following them up, how have things changed with the COVID-19?
Dr. John Mytinger: We're initially concerned that some children with infantile spams would go undiagnosed or undertreated because of limited access to things like EEG and other resources. But fortunately, at Nationwide Children's Hospital, that's not been our experience.
In fact, I think that the pandemic has actually improved our care of children with infantile spasms. For example, the pandemic prompted us to improve our efficiency by creating formal triage protocol in which we can quickly look at our home video and just utilize the resources that are absolutely necessary.
Sometimes in-patient admission and long-term EEG isn't necessary. And we have really done a good job I think of avoiding sending children to the emergency department. That's been a major change.
And so, we also streamlined our treatment protocol to allow for the rapid initiation of standard therapy often as an outpatients. So, for example, hydroxyprednisolone is widely available, inexpensive and we can just quickly start this in the outpatient setting.
And I think helpful is a publication in 2020 from the Child Neurology Society, which worked in collaboration with the Pediatric Epilepsy Research Consortium or PERC to publish this important open-access resource regarding the care of children with infantile spasms. And the first author of that publication is Grinspan and it's published in the Journal of Child Neurology.
Dr. Mike Patrick: Great. And Dr. Bebin, has that been your experience as well in terms of changes that have occurred in Alabama with the pandemic and how you approached this?
Dr. Martina Bebin: Oh, absolutely. I think telemedicine has actually been a godsend because it provided much faster access for families. It allowed us them to maintain a link to their physician, so they weren't getting lost, and we were able to schedule a telehealth the same day. And then we look at videos. I think we've relied on technologies so much more.
And if I need to see a baby, we saw them in person. So, I think everyone has learned how to adapt. I think it will change medicine going forward. And some were tentative about telemedicine, but I think it's been just absolutely critical for the early diagnosis and access to care that these patients need.
Dr. Mike Patrick: Yeah, absolutely. We have another guest that is also with us that I mentioned at the beginning of the program, and that is Kari Rosbeck. And, again, she is president and CEO of the TSC Alliance. Tell us, Kari, what is the TSC Alliance and the Infantile Spasms Action Network. Tell us about your organizations.
Kari Rosbeck: Well, thanks, Dr. Mike, for having me. The TSC Alliance is an internationally recognized non-profit that does what it takes to improve the lives of people with tuberous sclerosis complex. So, in short, we drive research, we increase care quality and access, we inspire hope, and we advocate with and for all people impacted by the disease.
In 2015, the TSC Alliance partnered with the Child Neurology Foundation on a multiyear IS Infantile Spasms Awareness and Education Initiative. And this evolved into the Infantile Spasms Action Network, which today includes 32 different organizations.
And what's really unique about the Infantile Spasms Action Network is it includes patient advocacy groups like the TSC Alliance, but also professional societies like the Child Neurology Society or American Epilepsy Society. And it also includes industry, so those that are developing medication or have medications specifically to treat infantile spasms. And really, the goal of this Action Network is to raise awareness of infantile spasms.
Dr. Mike Patrick: Absolutely. And we'll put a link in the show notes that folks can find over at pediacast.org for this episode, 507, to the TSC Alliance and also the Infantile Spasms Action Network. We'll put links to both of those so folks can find you very easily and learn more about what you do.
I imagine that this is really, really difficult for families. I mean, it's hard enough for us as medical providers to kind of wrap our brains around what's going on with these. And also, as we've mentioned to providers, please take this seriously. Take parents' concerns seriously.
And the reason that we have to keep saying that is because, oftentimes, we don't, because we don't recognize the significance of these movements. So even for families that are going through this who aren't medically inclined, I mean, if it's difficult for us, it must be really challenging for them, right?
Kari Rosbeck: A hundred percent. I really like your comment about mom or dad radar because I think that's really important. Follow that gut instincts you have. If you notice that something is wrong, and we use a lot of words to describe infantile spasms. But I think a repeated startle reflex, or a simple head nod over and over are some simple things to think about when considering that your child might have infantile spasms.
I think what's challenging for families is getting to a diagnosis of infantile spasms whether you have TSC or not, it's really getting that diagnosis and then getting that proper treatment.
Dr. Mike Patrick: And then what kind of support do your organization provide for families that are travelling down this path?
Kari Rosbeck: So, first and foremost, the member agencies of Infantile Spasms Action Network try to get families to the proper care, whether it's epilepsy centers or with TSC, TSC Comprehensive Care Clinics like the one at UAB that Martina directs.
We also think it's really important to connect peer-to-peer support. So, this is kind of a scary diagnosis, right? We want to make sure that we are pairing them with somebody that's walked this journey before them.
And then we all try to provide comprehensive information, not only about infantile spasms but in our case, about TSC, being diagnosed with TSC, what to anticipate or expect and to make sure that they know we are here for them for the long haul.
Dr. Mike Patrick: We're going to have a lot of listeners today who have not been impacted by infantile spasms or tuberous sclerosis complex and who never will be. Tell us how important is it for communities to really rally together and support these families? How can we all make a difference for these kids?
Kari Rosbeck: Oh, my gosh. Well, first and foremost, help us raise awareness. You said early on, right, that it's just critical to be aware it's 1 in 2,000 births. But if you're that one, then it's critical that you are aware that infantile spasms exist. I think that's the most important thing that folks can do is share information on infantile spasms.
There are some great videos out there about infantile spasms that are produced by the Infantile Spasms Awareness Network. Share those so people understand these very very subtle movements that happen repetitively in clusters are something to take seriously and make sure you check out.
Dr. Mike Patrick: And that really leads us nicely into Infantile Spasms Awareness Week, which is sponsored by a coalition of organizations including The Epilepsy Foundation, the Infantile Spasms Action Network. Tell us about Infantile Spasms Awareness Week.
Kari Rosbeck: It happens every year. This is the seventh year of Infantile Spasms Awareness Week. It's December 1st through the 7th. And we did that because it coincides with the American Epilepsy Society Annual Meeting. The purpose, of course, is to raise awareness of infantile spasms, to hasten diagnosis and appropriate treatment.
And we have this mnemonic that I want to be sure to share. It's called STOP IS. S is see the sign, T is take a video like Dr. Bebin mentioned, O is obtain a diagnosis, P, prioritize treatment. And for more information to see some videos of actual infantile spasms, your audience can go to www.infantilespasms.org.
Dr. Mike Patrick: Yup, and we'll put links to all the things that we've been talking about in the show notes over at pediacast.org, Episode 507, so folks can find that easily.
Before we go, Dr. Mytinger, tell us about infantile spasms treatment and family support at Nationwide Children's Hospital. We have a fantastic program for folks in Central Ohio and beyond, right?
Dr. John Mytinger: Sure, yes. We established our Infantile Spasms Program here at Nationwide Children's Hospital in 2012. And the main thing with any infantile spasms program, to start it, is to have a plan.
So, what happens when a child with infantile spasms shows up on your doorstep? There should be a plan in place and if there is a plan whether it's a guideline or protocol at your institution, everybody knows what to do and that's what we created in 2012.
For example, after a diagnosis, families are always offered standard therapy. And as we mentioned, that could include ACTH, hydroxyprednisolone or vigabatrin. And for non-TSC related spasms, my preference is to use one of the hormone therapy which is either hydroxyprednisolone or ACTH as the first treatment because in our experience and recent evidence supports that hormone therapy is more effective than vigabatrin.
Of course, if somebody is diagnosed with tuberous sclerosis complex, then we want to treat those like Dr. Bebin said with vigabatrin as the first treatment. That's well-established in field of pediatric neurology.
And beyond that, if not yet used, if a child is requiring a second and third treatment, we would recommend standard therapy for them as well.
So unfortunately, some clinicians in the US and beyond continue to use non-standard therapy such as Topiramate as the first treatment, even when standard therapy is available. So, caregivers, just advocate. They should advocate for standard therapy if they're offered non-standard therapy as the first treatment. So, part of that is just educating our consumers, our family.
So, when I meet with the family, when our team meet with the family, we review reasons for optimism when they're present. For example, if there's an early diagnosis, that's wonderful. We also educate families about the need for standard therapy and the diligence in regard to the adherence to treatment and the follow-up. So, they have to get back to us, get that EEG, make sure that they were in remission and they stay in remission.
So, we also warn about the risk of relapse after an initial remission. That unfortunately happens roughly maybe a third of the time or so depending on the population looked at.
And we also discuss the possibility of additional seizure types. So, some children with infantile spasms may have had previous seizure types or they may later develop different seizure types, such as focal seizures, convulsions.
So, in regard to the different treatments, there's a lot of counselling that occurs, for example, with the hormone therapies, ACTH, and hydroxyprednisolone. We review the possibility of common side effects such as irritability, sleep disturbance, increased appetite, and the associated weight gain.
And we always discuss the possibility of death due to immunosuppression when you use this hormone therapies. I will say that fortunately this has become rare. Death related to immunosuppression has become rare with our short courses of treatment, but we certainly emphasize the need to seek an emergent medical evaluation for lethargy or fever of 100.4 degrees Fahrenheit or greater.
And in regard to vigabatrin, we thoroughly discuss the issue of potentially permanent visual field loss, but also discuss that a typical treatment course of about six months has a lower risk of clinically significant vision loss associated with that.
And so, if families are interested in this topic, as it relates to Nationwide Children's Hospital, they can certainly Google and search Nationwide Children's Hospital Infantile Spasms Program.
Dr. Mike Patrick: Or go to pediacast.org and in the show notes, we'll have a link to the Infantile Spasms Program at Nationwide Children's Hospital, which as you mentioned is evidence-based but also individualized. And you're going to walk parents down risks and benefits of any decisions that need to be made as you progress through treatment.
And of course, that's for folks in Central Ohio, but beyond there too, you guys see folks from all around the country for infantile spasms. Unless they're in Alabama, and then they should go see Dr. Bebin, right?
All right, well, we really appreciate all of you taking time to talk to our audience about infantile spasms. It's really been an enlightening conversation.
So once again, Dr. John Mytinger from Nationwide Children's Hospital, Dr. Martina Bebin from Children's of Alabama, and Kari Rosbeck from the TSC Alliance. Thank you all so much for being here today.
Dr. Martina Bebin: Thank you.
Dr. John Mytinger: Thank you, Dr. Mike. This was great and I think it's critically important.
Kari Rosbeck: Thank you, Dr. Mike, and I will just emphasize from a family perspective, this is a medical emergency and family should seek treatment right away. Thank you so much for helping us raise awareness.
Dr. Mike Patrick: We are back with just enough time to say thanks once again to all of you for taking time out of your day, making PediaCast a part of it. Really do appreciate that. Also, thanks again to our guests Dr. John Mytinger, pediatric neurologist at Nationwide Children's Hospital, Dr. Martina Bebin, pediatric neurologist at Children's of Alabama, and Kari Rosbeck, President and CEO of TSC Alliance.
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