A male doctor in scrubs analyzing brain scans on his computer.

Webinar: Transforming Data into Seizure Control with Learning Healthcare Systems

“Learning healthcare systems” is a method of improving clinical outcomes in patients by collecting and analyzing privatized electronic health data, then rapidly disseminating findings to change medical practices.  This approach is highly collaborative, bringing together patients, families, doctors, and researchers from institutions around the country and even globally.

Two learning healthcare system initiatives are actively working towards this goal specifically for people with epilepsy, one focused on care for adults and one focused on care for children.

This webinar will discuss the progress and potential impact of the Pediatric Epilepsy Learning Healthcare System to epilepsy patients, their families, and to the entire epilepsy research community. At the end of the presentation, audience viewers asked Dr. Zach Grinspan questions on how data and collaboration is being used to improve patient care and outcomes.

You can download the full transcript below.

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Dr. Zach Grinspan

This webinar is presented by Dr. Zach Grinspan, Associate Professor of Population Health Sciences and Pediatrics, and Director of Pediatric Epilepsy at Weill Cornell Medicine.  He is primary investigator of the Pediatric Epilepsy Learning Healthcare System project and the Rare Epilepsies in New York City project, and currently serves as chair of the steering committee for the Pediatric Epilepsy Research Consortium.

Audience Q&A with Dr. Grinspan

From a digital perspective, what are your biggest data-gathering needs at this point?

Let me be a little wordy with my response. We’ve had many conversations with IT groups around the country about how do we standardize process of getting electronic health records. Other groups have done that and I think we need to get better at that.

Right now, it’s a lot of phone calls and a lot of specifications. It works. We’re getting there, but we could certainly be more efficient. We have a good system to transfer the data. Now that we have the data, we’re starting to run into some bottlenecks with the processing. We have one analyst working through it. As we scale up, we’ll need more people processing the data and getting it ready. A lot of the technology is free, so we have a good pipeline to get the reports out.

We have electronic health record system questionnaires deploying over the next few months. Epic is going to release our questions this month. Cerner is not far behind, and someone has already built the questionnaires in Athena. We’ll want to expand to other electronic health record vendors, because we really want to be vendor agnostic. Then, we’d like to bring more data in.

Data from EEGs, MRIs, devices, and patient-reported outcomes would be amazing. People who wear devices are walking around collecting data moment to moment with an RNS or a VNS, and so we want to explore partnering or working together to include that data. Some of it is humanware. I think technology is relatively straightforward. It’s just a matter of all of the conversations and figuring out how to get the data out, move it, and link it.

Have advancements in implants, watches, and other devices helped you understand more about medication efficacy for patients? Has this new data increased the whole picture of an epilepsy patient’s day and changed the way you view potential versus multi-drug prescription regimens?

It’s a great question, because what it gets at is that, in the digitized world, you have people who are creating oceans of data, begging the question, “Can we do anything with it?” For some patients, the answer is absolutely. Certain kinds of data, like VNS and RNS data, can help doctors make very targeted changes. The question is, how do we scale that process and how do we learn from it? And the question is very compelling. We are not there yet, because we don’t quite know how to do this yet at scale. It’s a long-term goal of ours.

Can the collected, aggregated data be individualized? Or can that data be available to doctors and patients for a fee? For example, if RNS data is collected, would somebody need to pay in order to see their own data?

I’ve never had anyone ask me for a copy of their VNS or RNS data. It’s certainly doable and the data is, after all, coming from the patient. I don’t see any obstacle to that.

Other learning health systems use identified data, so their databases know your name, date of birth, everything. These systems actually do provide as the questioner poses direct services. “Here is a patient-level report about how your patient is doing.”

We shied away from that for privacy reasons. Data breaches can be devastating for so many reasons, so we opted to use less personalized data. We don’t know anyone’s name, date of birth… we do know zip codes, but we don’t know where patients live or their medical record number. That was intentional.

Our thought process here is that we can send information to individual centers, which can identify the patient. The report might say, “Patient ABC had this happen.” Then the center has the ability to say, “ABC is actually John Smith.” They have to do that extra step. I don’t know it’s John Smith. I know it’s ABC.

This method helps make the data more secure, but we’re very much about data sharing, and so we have promised all of our collaborators that they can have their own data with no questions asked. We’ll just give it back to them. We’ve crunched it and processed it a little bit because we want to promote your new faculty, we want to promote residents, and fellows who do research projects. Then, for the network, if one investigator says, “I have an idea. It works on my own data. Can I do it on everyone else’s data?” Then, we have a very straightforward process to allow that to happen, too. We really all want to learn together.

You’ve talked about data sharing. Will data sets be made publicly available?

I don’t think we’ve thought about that really. The data sets we have qualify as limited protected health information (PHI), so we can’t share information like dates of birth and zip codes. But the full data sets… I mean, theoretically we could. I think we’d have to talk and think a bit more about that.

A lot of networks want to make sure that patient data is used for a purpose that’s aligned with the mission of the organization, so there’s often a process. We don’t have such a process in place right now, but if that became something of interest to the community, there’s no reason we couldn’t start planning.

How have you had to overcome the barriers of institutions not wanting to share their data with other institutions?

I thought that was going to be a huge problem, but it doesn’t seem to be an issue. Everyone’s so happy to share. It’s really nice. As much as I’d like to say I’m a pioneer, I’m not. People have been working on this in other fields for more than a decade, so the ground has really shifted and we’re in a new world.

The Pediatric Hospital Inpatient System has data from roughly 45 centers, including data from Cornell, Columbia, NYU… and you can walk from one to the next in an hour. I think that the culture, particularly in pediatric hospitals, is very mission-driven, so these potential issues of competition and “you can’t have my data” has just not been a problem.

What are you doing to monitor and measure the impact of diet on seizure control?

It’s not easy to figure out who is on an epilepsy-related diet and who isn’t from the data we have. I showed you that one question about the seizure frequency, but we built in some questions also about diet. It’s pretty epilepsy-specific, so the options we list are the ketogenic diet and modified Atkins, low glycemic index, or other. That’ll give us some high-level information about who’s on what diet, if it’s working, and similar information. More detailed information about specific foods and specific exposures would mean a whole different level of data collection.

Are you familiar with the Observational Health Data Sciences and Informatics (OHDSI)?

Let me nerd out for a bit! One of the major questions we’ve had is, “What does a tables look like in the database?” A lot of people have spent whole careers thinking about that for health data. The Patient-Centered Outcomes Research Institute, has advocated use of PCORnet, the PCORnet Common Data Model.

Our data looks a little bit more like PCORnet mixed with the OMOP model. Currently, our data model is our own, which could be sort of seen as a simplified version of OMOP and PCORnet. What we told our sites is, “If you have the data in PCORnet or if you have the data in OMOP, just send that. Don’t reinvent the wheel.” No one’s taken us up on the offer, so it seems like operationally, a lot of the sites are finding it easier just to kind of make a custom extract for us and just sending us what we want, which we’ve been fine with.

Would it be beneficial for a healthcare provider to have the PELHS questions answered before the visit versus during the visit?

Yes and no. We really want curated data reviewed by a clinician. The workflow that this question proposes is a good one, in which the parents or the young adult enters the data in prior to the visit, and then the clinician and the family review it together. That would be totally okay!

We’ve spoken with Rob Moss, who runs SeizureTracker, and he’s very excited about this idea. He’s been working to link his application with Epic, which is one of the electronic health record vendors. What we’ve asked is, “If you get that workflow there, can the SeizureTracker data populate the learning healthcare system data?” We’re agnostic on how the data gets into the system. If the data gets in there and the clinician vouches for it, then we’re good.

Are patients and their families aware you are collecting these data? How do they feel about participating?

We’ve been very deliberate from the beginning in maintaining communication with advocacy groups and including parents and people with epilepsy at the highest levels involved in developing this system, so there are representatives. That being said, if a parent bring their child to one of the centers involved in this project, they wouldn’t know that the information from that visit is being brought into our Learning Healthcare System.

The reason we forgo getting patient and caregiver consent is that the labor required is too much work for the kind of data we’re gathering. The way electronic health record data is used for research in this country tends to support that. Institutional review boards granted us an exemption from the federal regulations from HIPAA, which allows us to look at the data without getting explicit permission from a hundred thousand people.

We’re comfortable with because we feel the good things we’re going to learn far outweighs the risk to loss of privacy. We’ve been quite intentional, as I said, about making sure that the data that we have doesn’t have a lot of personal information – no names, no addresses. We have dates of birth, but lots of people share same dates of birth. When we’ve spoken to advocacy groups, most people are in agreement that the labor required is too much work to get those consents. We’d spend all of our effort doing that and the groups would rather us do the learning . We got all of the approvals. We have data use agreements. We have all of the legal and ethical infrastructure, but it’s true that you wouldn’t know that your data is going to be in there necessarily.

How have you involved patients in designing this system, the process, and the governance? Are differences between the Pediatric Epilepsy Learning Healthcare System and the other system that you mentioned in your presentation?

Both systems are quite deliberate and have made a big effort. The ELHS, the Epilepsy Learning Healthcare System, is run out of the Epilepsy Foundation, which at its heart is an advocacy organization. I think the DNA there I think is much more about patients’ perspectives. We were aware of that. We wanted to make sure we were listening and including that voice, which is why we bring everyone on the calls.

As a example, when we put our forms together, we wanted to have a scale like, “How often are you having seizures?” In the original scale, the most you could say was multiple per day. A couple of parents were like, “My kid has more than that.”

“What do you mean?” we asked. “Multiple per day, that’s it.” Parents said, “Yeah. I can’t even count because there’s so many.”

We said, “Oh, okay. We missed something important.” Now the highest level is “too many to count.”

Is there the possibility for an international collaboration? Could it be even better with hundreds or thousands in the wider group?

I love that. Whoever wrote that question, we are like mind melded. We’ve had some conversations about collaborating internationally. Building the questionnaire into the healthcare records vendors’ system, then all of their customers internationally can then use the form. Then, if you get a collaborator, then the data’s already there. The collaborator just has to send it.

How do I encourage my neurologist to participate in The Pediatric Epilepsy Learning Healthcare System?

Tell them to email me. We have some funding and we were provided 20 participating centers some seed funding. That money has run out, but some sites are willing to join with internal resources. At present, if there are sites that are enthusiastic, they can just find me and I can have a conversation with them.

The other thing is that 54 of the US Pediatric Epilepsy Centers are part of PERC, and I am pitching and giving updates on this through all of our PERC calls. We just had our annual meetings last week and we have calls every other month. Find out if your center is part of PERC, find out who the PERC representative is, and then having that person reach out to me.

The CURE Leaders in Epilepsy Webinar Series has covered many topics related to epilepsy and innovations in research. Check out our full list of available webinars here.

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

Female psychologist working with boy who has autism and epilepsy.

The Epilepsy-Autism Connection: Research, Diagnosis, and Treatment

It is estimated that over 30% of people with epilepsy also meet the diagnostic criteria for autism.1 In this webinar, presented by Dr. Jamie Capal, hear leading theories on the interconnection between autism and epilepsy. Learn about the most common seizure types in people with autism and dive into the current research on why so many children with autism develop epilepsy.

Dr. Jamie Capal is Associate Professor of Pediatrics and Neurology at Cincinnati Children’s Hospital Medical Center. Dr. Capal has been an integral member of the multidisciplinary Tuberous Sclerosis Clinic Center of Excellence and maintains a busy clinical practice diagnosing and treating children with autism spectrum disorders and comorbid neurological disorders. Her current research is focused in the areas of autism spectrum disorder and Tuberous Sclerosis Complex.

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1 Spence, S., Schneider, M. The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders. Pediatr Res 65, 599–606 (2009). https://doi.org/10.1203/PDR.0b013e31819e7168.

To hear an author, journalist, and mother discuss how her family has navigated the dual diagnosis of autism and epilepsy to help her son live his best life, watch or listen to the Seizing Life episode Raising A Child with Both Autism and Epilepsy featuring Liane Kupferberg Carter.

Audience Q&A with Dr. Capal

Dr. Jamie Capal

Your presentation shared a lot of information about tuberous sclerosis complex. Can you speak to the information we’ve gathered there, and how that might translate to other neurodevelopmental disorders? 

That’s a great question. Currently what we’ve learned is that the earlier your brain gets disrupted (by seizures for example), you’re at a much higher risk for overall disorganization of the brain. And so, what we’re trying to figure out is, are there other things that can tell us what else is going on from a structural standpoint, from an EEG standpoint? Because the goal is prevention.

There are studies going on now, the PREVeNT trial for example, looking at early seizure treatment in babies with Tuberous Sclerosis Complex who have not had seizures yet, but do have abnormalities in their EEG. If you treat the abnormalities before the seizures come, will you get better results with development? And maybe better results as far as preventing autism? That study is closing right now, so we are very interested to learn the results, because really that’s the next step.

Many other neurodevelopmental disorders are also looking at similar things, and what we know is looking earlier is better. The earliest we can try to advocate for prevention, the better off we are to disrupt these mechanisms that result in developmental delays and autism.

EEG testing is not standard when screening for autism. What sort of information would need to be gathered in order to make that a more standardized approach?

I think what we really need is a protective studies – basically doing screening EEGs on all kids that are newly diagnosed with autism, and then follow them out longitudinally. But the problem is that this is a very expensive and long study, but I really think it’s something that needs to be done. That way, we have a true idea of what the percentage of kids with autism have abnormal EEGs, and what their risk of eventually developing epilepsy is. That will give us the evidence we need to say, “Everybody with autism needs to get an EEG as screening.” Right now we just don’t have anything.

In focal epilepsy, if seizures are emanating from a specific area of a brain, is a person more likely to develop autism?

A lot of people have looked at this. There is some evidence showing that maybe epilepsy in the frontal region of the brain, or the temporal region of the brain may predispose you to having autism, but it’s not universal. There’s some evidence showing that.

Has any research looked at if children with autism can improve cognitively with increase seizure control? 

The study I referred to in my presentation that is looking at the natural history of the development of autism is working to understand this. We collect all the seizure diaries form patients in this study, and we are going to see if anyone’s scores improve with treatment. There’s also a group looking at whether or not improving seizure control with epilepsy surgery increases cognitive development. Again, the goal though is to look at this early in life. That is where the field is going right now. Nothing has come out of it yet, but that’s we’re looking.

We know epilepsy can impact cognitive function, and then cause cognitive decline in a way that might make an adult look like they have some aspects of autism. Is this due to the seizure activity? Is there a way to protect the brain from that seizure activity?

That’s a difficult question to answer. Think about the epileptic encephalopathies, for example. Those are the patients who are having lots and lots of seizures, and even when they’re not having seizures, they’re background brain activity is abnormal. Their neuronal connections are not allowed to form correctly, so those patients are going to develop cognitive impairment. In those cases, by controlling the seizures, you would expect cognition to improve.

In other cases though, it’s less clear. I think you have to think about epilepsy as not causing necessarily causing the delays. There may be two things happening simultaneously, and epilepsy is just making it worse. So treating epilepsy may help, but it’s not going to reverse cognitive impairment.

Are there links between epilepsy, autism, and Alzheimer’s?

I can’t say that I know a lot about the literature for Alzheimer’s, but I can say there is a lot of interest in looking at the connection between Alzheimer’s and autism. I think there are a lot of shared genetic mechanisms between these conditions. That connection is definitely something I think needs to continue to be looked at as we do more genetic studies. We need to look at; what are the shared genetic links between individuals with Alzheimer’s and autism? That being said, research has found that there are many similarities in the connectivity of the brain in both of those disorders.

Many people with epilepsy, including those with autism, are not responsive to medications, and antiepileptic drugs can cause side effects, like mood changes, GI issues, anxiety, increased repetitive behaviors that worsen…. What are your thoughts about the VNS, and more specifically the noninvasive VNS that is not approved in the US as yet? Does it help with autistic behaviors at all?

I like VNS. I think there are some folks it works very well with. I had one patient, for example, who I was thinking about doing a VNS on, but because he is so active and his behaviors were so erratic, he wasn’t deemed a good candidate for it. Another patient I’m thinking of really did well with VNS,  because they were having so many negative side effects from antiseizure medications.

Should all children diagnosed with epilepsy, especially learning disabilities, be screened for autism?

Ideally, yes. The American Academy of Pediatrics has set up a guideline to screen young patients for autism with the M-CHAT, which is a questionnaire that parents get at 18 months, 24 months, and then again between ages two and three.

One problems is that when young individuals are diagnosed with epilepsy, other aspects of their development aren’t really paid attention to as much. So, clinicians are finding that individuals who are being diagnosed with autism much later, because maybe the doctors were spending more time really focused on the seizures. Those folks really should have good surveillance by their pediatrician. If there are any concerns for development, they should be referred on to developmental pediatrician for further work up.

So, this is really a place where parents could be advocating for that.

Very much so.

What evaluations are being done outside the brain and EEG? Are people looking at the gut, the autonomic nervous system, or sleep disruption that are implicated in both epilepsy and autism?

Yes. There are definitely folks looking at the gut-brain connection. I think there’s a lot of interest there. It’s almost like these subtypes of autism. Abnormal EEG is one subtype, then there are patients with GI disturbances in another group. Sleep can be disrupted for many reasons and you see this problem in various subtypes of autism. There’s an autoimmune interest in individuals that potentially have an autoimmune component to their autism, which I again think is another subtype worth studying. So, I think the more we learn about the underlying causes, the better able to study the clinical features we are.

We historically have been looking at autism as a set of symptoms. But if we study autism as the symptoms only, even though there could be hundreds of causes behind it, we’re not really going to learn anything.

There was a question about what type of preventative treatments would be given to a person with autism and abnormal EEGs, but it sounds like we really need to understand the biology.

Correct. We don’t know. There have been some small studies that have put kids with abnormal EEGs on depakote, for example, and really haven’t found a lot of benefit. The interest is: do we put these patients on medicine to prevent epilepsy? Do we put them on medicine to improve their EEG? We don’t know.

If we look at benign rolandic epilepsy, for example, those individuals may have a few seizures, but they have a lot of underlying EEG abnormalities when they’re sleeping. Some groups found if you treat the EEG abnormalities, cognition may improve. So, the same thought present here, but nobody has ever done a big enough study to tell us that treating EEG abnormalities is worth it. This area definitely needs to be studied.

It could be very difficult to get a non-sedated EEG on children with autism due to sensory and other issues, especially an overnight. Are there other ways to perform EEGs with a headband or other nontraditional approach? 

Some researchers are using the EEG cap. One group is actually desensitize the children in their study by having them wear a hat, so they can get used to the feeling. Those EEGs are pretty accurate versus the traditional leads.

Now, a lot of times we don’t do that clinically. I’m sure there are a lot of reasons financially and training-wise. But I know in research, to get all of these children to have EEGs, the scientists become really creative at desensitizing the kids. For all of our studies we do EEGs on all of our kids, and the tests are actually pretty successful.

What’s involved with genetic testing, and where can we direct people for more information?

Genetic testing can be done several ways. Typically and historically, it’s been a blood test. Your neurologist or developmental pediatrician can order it. What we tend to do is a “chromosomal microarray,” which looks at any deletions or duplication in genes. This test is a good place to start. There are many companies which have developed genetic panels that can be done by blood or saliva. Each panel is different and geared toward a certain set of genes – there’s a autism and developmental disability panel, there’s an epilepsy panel…. So, those are targeted tests.

Then you have the bigger whole exome sequencing. Currently, the Simons Foundation has a big study going on throughout the country called the SPARK study. The study team is collecting saliva from the patient and both parents to look at their exomes and really understand the genetic underpinnings of autism. You can even go to the Simons Foundation’s SPARK study, and can get a kit sent to your house. That’s a great, free way for families to get genetic information, since often genetic tests are not covered by insurance.

The CURE Leaders in Epilepsy Webinar Series has covered many topics related to epilepsy and innovations in research. Check out our full list of available webinars here.

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

Infantile Spasms


Plus, learn more about this severe form of pediatric epilepsy from Child Neurology Foundation Executive Director Amy Brin in this episode of our Seizing Life podcast.

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Audience Q&A with Dr. Jeff Noebels

Do all IS cases have a genetic cause? And if they don’t, what are some of the other presumed causes?

Right. So, IS, it’s not incredibly rare, but it’s uncommon. And among those who have it, we have now discovered that there are certain genes that are now well known that can underlie the syndrome. I mentioned tuberous sclerosis and Arx. There are some others. I won’t give you their names. But there are probably five to ten genes that we know about and we can look for in the case. And that can likely explain features of the syndrome that the infant has. As far as acquired causes, I mentioned perinatal insults and maternal CNS infections have been associated with it. Beyond that, that seems like a general category. We don’t know specifically which viruses, what kind of insults, because they often created a lot of damage in the developing brain, and so we can’t always predict what kind of epilepsy will emerge from that. So there are both genetic and acquired causes of this syndrome.

I understand that IS results secondary to a brain injury. Does the research differentiate between genetic causes of IS and those secondary to a brain injury?

What we know from these and the research is usually the firmest information we can get is from animal models at a very basic level. So we don’t have too many of those models in the animal. There are various drugs that can be injected into a developing brain that seem to produce spasms and even the EEG counterpart, the abnormality, the hypsarrhythmia to study. But we’re not confident always that those are the same as what happens in human. It’s just a model. They allow us to study basic parameters of this disorder without really telling us this is what any child might have. So there are ways of approaching this scientifically. The genes are probably the clearest and most reproducible way of learning more about each child with infantile spasms.

Do infantile spasms have an autoimmune etiology? And have auto antibody prevalence been studied in this population?

So in the group that CURE  Epilepsy brought together, we’re a group of scientists and clinicians, and we sat down and quickly realized that there are many questions we don’t understand. The autoimmune concept, just to explain to people, is that the nervous system in the body will start to generate antibodies against itself. Obviously a very dangerous chain of events, because you begin to attack normal structures in your brain. And there are several forms of childhood epilepsies in particular that have this autoimmune cause, where if you look at the cerebrospinal fluid, you can find antibodies directed against the very molecules that you need to properly signal the brain. These receptors can become degraded by your immune system and seizures can result. I’m not certain that we have a clear knowledge base on whether this is one form, whether infantile spasms can arise from it, but it’s a very tempting hypothesis that deserves to be explored. The forms that I’m aware of don’t cause infantile spasms, but they do cause seizures.

Now on the other side of the question, is that well why does prednisone and ACTH these steroids, why are they so effective as treatments? Because we know that they do impair, they tune down the inflammatory response in your body. That’s why they’re usually prescribed. So therefore, does that mean that the infantile spasms was an inflammatory disorder? Not necessarily, because these steroids have many other effects, including actually acting on GABA receptors which is the target for many of our best antiepileptic drugs. So there is some evidence that perhaps there could be an inflammatory response. I don’t believe it’s ever been well studied or firmly demonstrated. But just because a prednisone works so well when it does in blocking infantile spasms, doesn’t mean that that’s the mechanism for generating.

How often are anti inflammatory drugs used in this population?

Well in the sense of that prednisone is the front line treatment for these infants, so I would suspect that whenever it’s properly diagnosed and the prednisone is available, that is the first medicine that the child will see. It doesn’t always work. Also as I mentioned, infantile spasms sometimes can go away anyway without treatment. Another interesting aspect of the infantile spasms part of this syndrome, it’s what brings the child to the doctor’s attention. It is not necessarily itself a epileptic seizure in the sense that it may not actually be damaging the brain. So as I mentioned, one of the fascinating features of this is that it looks like a normal reflex. It’s just present in the nervous system at an age when that normal reflex would have disappeared. There’s no sign in the EEG, in the rest of the brain, of a seizure when this happens.

And so to my mind, we don’t have to worry as much as we do with convulsive seizures about whether the event itself is actually damaging to the brain. We would like it to go away, wish it wasn’t there in the first place, but it’s really just a tell tale that something developmentally is wrong in the wiring of the brain that these reflexes persist in some way or return. And as nice as it is to get rid of them, the infantile spasms themselves to me aren’t as much of a danger as just an important warning sign that there’s something else the matter, and if we know how to treat seizures that are to come, maybe we can prevent them.

Do you know whether combination treatment with estradiol and ACTH or vigabatrin will provide a greater level of effect?

Some of those studies are ongoing. So one of the things we decided among the CURE Epilepsy group would be to find out if in our model does our mouse model respond to prednisone, and we found out that it does. But what we haven’t done yet is to combine the two, prednisone plus estradiol, and see if that would really allow us to either use smaller doses or treat for a shorter period of time. Those are studies that we would really like to complete and get an answer for.

Do you think that there would be a difference in the actions in males compared with females in your study?

Well that’s interesting, because this was an excellent gene. And for everyone, that means that males will only have a single X chromosome. If they have the mutation on that chromosome that they inherited, they will have the disease. Whereas a female has only 50% chance and possibly no chance because she has a second normal X chromosome that could protect her from the disorder. Whereas the male has only one X chromosome to rely on, and if it has the mutation, you’re affected. So all of our studies are actually, and for this particular gene, are done in males, because they’re the only ones that are affected. Now other genes may not show that sex difference and they’ll be very interesting to see if estrogen levels, which might be different in females, are actually protective in that sense. So we don’t know the answer to that question, but it’s interesting.

Do we know what proportion of patients with IS have a TSC mutation? And on these lines, could you share your thoughts on the potential of mTOR inhibitors for the treatment of IS?

I’m sorry, I don’t know the answer. This is still really rare, and I’m sure there’s some studies that could answer that, your first question. But I don’t have that fact at my fingertips. But we’re talking about an uncommon … both disorders are somewhat uncommon. You hear about them a lot because we have the genes and we’re working on them intensively. But I don’t have the epidemiology of that question yet. But the mTOR inhibition issue is certainly an interesting one, and just like the estradiol, mTOR inhibition seems to be remarkably effective in certain kinds of epilepsy, including TS. But I don’t know whether it’ll be effective in all forms, or even same forms as the ones where estradiol will work. So again, these are open questions, and see how well we can prevent damage using these different sort of targeted therapies for very specific molecular pathways and cells.

What is your opinion on the existence of truly idiopathic infantile spasms where they were normal prior to diagnosis, rapid response to treatment, and normal tests, and normal developmental outcome?

Well my opinion, that word idiopathic helps a lot of people out because it’s a Greek term. That means we have no idea of what’s going on. So idiopathic infantile spasms up until recently was all of them were idiopathic. Now we have a few genes for some of them. But I can’t really comment as a group on what the natural history of idiopathic infantile spasms are. If you go into the old literature of infantile spasms before we knew these subtypes, then everything you read would be true, because they couldn’t distinguish between different types. Now you wonder whether something is idiopathic because you haven’t looked for all the things that we do know about yet. So you begin to question the use of the term idiopathic because we know there are certain answers. And in fact, the field of epilepsy as a whole has seemed to move away from the term idiopathic epilepsy, and now they call it genetic epilepsy under what I guess is the optimistic assumption that everything that doesn’t have an observable cause during the lifetime must be genetic, and therefore has a discoverable genetic problem.

We won’t probably ever be able to discover every single gene that contributes to epilepsy in every single person. But there is a sense that the entire field is now assuming that most cases, the more we study them, if we can get a pure culture of a specific type of epilepsy and study it intensely, we will find the cause of that particular type. But I think all of our listeners know that epilepsy comes in so many varieties. Different ages of onset, different seizure types, different responses to antiepileptic therapy, that we know we’re dealing with a very complicated disorder. Certainly it’s as complicated as all the cancers you’ve heard about, and that we just need to learn a lot more about these disorders and we need to split them apart and look at them, and then see if we can lump them back together.

Do you know of chloride regulation deficits in interneurons that impair migration or development of interneurons to cause infantile spasms?

Most ion channel mutations, chloride channel is one of them, are not known to interfere terribly with migration. At the moment, there’s a migration disorder in one of a number of forms is probably the best explanation for infantile spasms as far as I know. So of the chloride channels, I can’t think of one. There’s one in mice that obliterates the hippocampus, and that’s not anything like what you see in infantile spasms. But the other ones that are either triggered by electricity or opened by GABA inhibitory transmitter, I don’t know that there are … there should be defects in migration. I don’t know of a specific model where that’s been shown, and it shows to have the infantile spasms phenotype, but I would not be surprised if there’s one about to be reported.

The next question actually is regarding CURE Epilepsy’s team science approach to the IS initiative. And the question is can you explain what this means and do you think that this approach may lead to discoveries that could lead to breakthroughs sooner?

Yes, absolutely. And this is something that I think is happening all over science, but really needs to happen fast in disease or oriented sciences because we’re all counting on these breakthroughs to come. And what’s happening in science right now is the enormous growth of very powerful tools, both ways of manipulating brain cells at the molecular level and of tracking their functions with amazing tools of micro imaging and electrophysiology of single cells and of large groups and networks of cells. We’re really starting to be able to powerfully examine the nervous system, when it works and when it doesn’t work properly. So all of those techniques require time and skill, and no one laboratory really can do it. The ones that really have a tool that they can perform correctly don’t know as much about disease, and the people with a lot of disease background don’t necessarily have all the tools. So the idea of getting together with a focus group and attacking a problem, such as was done with the CURE Epilepsy initiative, was really a smart thing to do, and I think we need to see a lot more of it in the future.

Has the ketogenic diet been used as a first line approach to treatment for these babies?

I’m not a pediatric neurologist, I’m an adult neurologist studying the developing brain. So I don’t have firsthand information. The ketogenic diet keeps coming up in every form of epilepsy where the conventional drugs don’t work well is not the front line treatment for infantile spasms, but it is certainly something to try if the front line treatments haven’t given the desired effects. It’s a difficult treatment. I think it’s been tried in most different forms of epilepsy. I don’t know that anyone is claiming that it is the second line, but it’s certainly available and could work in some cases.


Young students in a classroom raising their hands to answer a question.

Epilepsy’s Impact on Learning and School Performance

This webinar highlights the latest research on how epilepsy impacts cognition, learning, and school performance.

The webinar is presented by Dr. Madison Berl, a neuropsychologist at Children’s National Hospital in Washington, DC. Dr. Berl’s presentation is followed by an interactive Q&A session. Some of the questions you might hear addressed include:

  • How do schools build an IEP for a child with epilepsy?
  • Are there services available to help my child transition into adulthood?
  • What laws are in place to support my child?

Resources Listed in this Presentation and compiled by Dr. Berl

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Attention/Processing Speed Resources:

Executive Functioning Challenges Resources:


Audience Q&A with Dr. Madison Berl

Do you have any sense on how successful the percentage of cases are aided by programs like CogMed and how great the impact is?

Yeah. So for our study and I think there’s one other published study in Epilepsia, it’s about 20% of the kids that were in the study showed a significant improvement. So it’s not nobody, but it’s not a majority either. And so that’s a concern. And I think we don’t have enough information of why those kids responded and the other kids didn’t. So that may be something else about it to learn about too.

And then the second factor is, okay, they improved. Usually they’re improving on the measures that are very specific to that task. So they can repeat more numbers backwards or something like that. But how that actually translates to real life school skills or other skills is really lacking. The other thing that we’ve seen with longitudinal studies, because these programs have been tested a lot more thoroughly in ADHD populations, is that even if they show significant gains on something like math fluency, which we actually found too, it goes away after six months.

So it’s very short lived. And so does that mean that you have to keep doing this training? Does it really change things long term or not? And so those are some questions that are still concerning that it really doesn’t generalize or last in the way that we hope it does.

Advocating for 504 and IEP combinations seems to be a daily challenge. How can we get better resources for the teachers in schools?

Yeah. So that can go in a lot of different levels, right? So, yes, we need more funding for our education system, hands down. I am an advocate of that. In terms of getting the resources for your child, I think you also come to a point where you just have to fight for your own. And use of advocates is wonderful. They can be expensive. It’s like hiring a lawyer. But there are often, at least around here, organizations that have access to advocates that are free or at least at a reduced costs because their nonprofit mission is to help children access the curriculum. And so if you can get an advocate, if your school is not being responsive, really the parents that are the loudest, the squeaky wheel gets the oil, be like a pit bull and just be after them. And nobody likes that when it gets contentious, but sometimes that’s what you need to do for your child.

Are there any thoughts on what it indicates if a child makes huge cognitive gains on seizure meds and with every increase in their seizure medication?

I think that’s a great reminder to know that if there’s great gain, that probably means that was interfering with your child’s ability to learn. And so the medicine’s quieted down that brain activity. I would be very cautious about saying that then more medicines mean better cognitive skills because that can go the other way too. Like making them blotto by giving them too much drugs. And you really have to work with your neurologists about that.

They usually are working with you by doing routine EEGs to see what the EEG looks like. And if some of the problems are like attention, that’s where, again, maybe going to the stimulant medication and it’s not necessarily more anti-epileptic medication but it may be a different medication that could be helpful.

Are there any other options when stimulants don’t seem to work for ADHD?

There are non-stimulants ADHD drugs. So those could be helpful. Again, depending on what is going on, sometimes I’ve seen really the inattention is around sleep. And so I’ve had some parents feel like melatonin at night actually does wonders for the attention during the day because now they’re sleeping better. So I really think you need to dig in to know maybe why that stimulant wasn’t effective and that might open up some other options for other drugs or maybe other interventions. And really then just the behavioral interventions in school are definitely something that needs to be carried out. Whether that’s smaller class size, working in small groups, those kinds of things.

Does failure to medicate for the purpose of mitigating inattention have any impact on longterm development IQs?

I think what if your child is not available to learn, whether they’re sitting in the classroom and not listening or never attended school, it would be the other extreme, then, yes, that can impact their development. So, yes, if you are afraid of medication and decided not to, you may be hampering them because they are just not available to learn. But again, I’m not saying that it’s the only way. It’s just that it is a tool. And I feel most of the parents I work with are more hesitant to add a medication. And so that’s why it sounds like… I’m just telling you not to be hesitant and to consider it. It doesn’t mean that has to be the only way. But for sure, I would just think it should be considered more and I think many parents that I work with are a little bit more afraid than the typical parent because they already are on medications.

At what point do you think that homeschooling is a viable option for a particular child or student?

working with an advocate can be helpful. Fighting that process can be long and hard. And even what’s an acceptable amount of time that your child is not accessing the curriculum? Is one year too long? Is two years too long? And so I can sympathize and empathize with parents that say, “You know what? I can do this better and I can do this at home and we don’t have to waste all this time.” And I have had lots of families that have done a great job at that. I think you have to think about you and what you’re able to do and your willingness. I think there’s lots of tools and resources. We have lots of co-ops around here, so you don’t have to do it on your own. And then again, I would just make sure you at least worked with an advocate or a professional to make that decision just to have the discussion with somebody else so that an issue you hadn’t considered or options you hadn’t considered, that everything was turned over before you made that decision.

Again, some kids it’s just they need to because you know the school that you have access to. Or you know your child. We have some children that really, they’re so variable that they need to sleep till 10 o’clock in the morning and they can work and then they need to take a nap or they are going to be seizing every two hours. And so just because of them, they may do some of their best learning at seven o’clock at night and school’s not open. And a child that really needs that much more flexibility might be another reason to decide to do homeschooling. So there’s lots of factors that go into it. But I would mostly just recommend that having that discussion maybe with several people so that you’re considering all the options. But again, I’ve seen wonderful teachers, parents that are way better teachers than what’s in the school system. So it can definitely be a good decision.

A blond woman cradles her infant in her arms, trying to soothe them.

Diagnostic and Treatment Challenges of Infantile Spasms

This webinar focuses on the challenges of diagnosing and treating infantile spasms, and how advances in epilepsy medicine and technology have improved this process. This presentation also examines currently available treatment options.

The presenter is Dr. Shaun Hussain, Assistant Professor of Pediatrics at UCLA, Director of the UCLA Infantile Spasms Program, and inaugural recipient of the Elsie and Isaac Fogelman Endowed Chair in Pediatric Neurology. His clinical and research endeavors focus on Infantile Spasms and other forms of severe pediatric epilepsy, including Lennox-Gastaut syndrome and Dravet syndrome.

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Audience Q&A with Dr. Hussain

If an infant gains control over their infantile spasms and normalize the hypsarrhythmia, is there a greater likelihood of normal neurological development?

That’s a tough question. That is certainly the goal of therapy in the short term, and it seems to be pretty clear that if you don’t completely abolish spasms and the hypsarrhythmia, development will not turn out well. At UCLA, we follow almost 500 patients, and I can’t think of a single one who had a long-term burden of infantile spasms or long-term burden of hypsarrhythmia and did well.

In order to get a good developmental outcome, you have to abolish spasms. You have to abolish hypsarrhythmia. And you have to be a little bit lucky. You have to find that the cause of the infantile spasms is not itself something that can damage development. But in short, I would say you simply can’t tolerate any infantile spasms or hypsarrhythmia. If either of those are present, it means that you need to try different therapy.

If a gene panel doesn’t reveal a known cause genetic cause of infantile spasms, but a child has been seizure- and med-free for several years, do you recommend further genetic testing?

It’s tough. The answer to that question has to be pretty individualized, but usually the answer is no. The odds of us identifying a meaningful genetic abnormality that impacts our treatment – would tell us to begin or stop a therapy – is actually very, very low at that point.

On the other hand, if the parents are thinking about having another kid, it would be very nice to do that genetic testing and get a sense of whether there is any risk posed to the next child. There is unfortunately, very little data about the risk in general. In thinking about our cohort here at UCLA of nearly 500 patients, there have been only a couple cases in which a sibling also had infantile spasms after the first child.

Let’s say overall risk is pretty low. If it was me, I would want to do that genetic testing to figure that out. But there are also risks of genetic testing. Sometimes you might find out that a child, sibling, or parent are at risk for some other disorder associated with infantile spasms. It’s a big discussion, a difficult decision often, and you have to go into that decision-making process knowing all the risks and benefits of genetic testing.

If the first course treatment was not effective, does this equate to a delay in treatment and, therefore, a poor prognosis for future development?

We don’t actually know the answer. My sense is that the delay in finding an effective therapy probably poses some risk, but we don’t know how much. The first therapy not working probably means that the child has overall worse infantile spasms and may be at risk for bad outcomes on that basis.

The short answer is, I don’t know. But the second answer is that it doesn’t matter. If you’ve got ongoing spasms, you just got to change your treatment approach and be aggressive. Don’t be afraid of those side effects and focus on eradicating infantile spasms.

Is surgery only considered when seizures don’t respond to certain medications? Or can it also be an option when the MRI and PET scans indicate a specific portion of the brain causing abnormal EEG activity, indicating a risk of seizures, even after hypsarrhythmia has been resolved?

There is certainly no consensus in answering that, so I want point out a couple things. There are patients who have structural abnormalities – things like cortical dysplasia – who will respond to first line therapy and not need that surgery. We have multiple individuals in our cohort who responded to therapy and seemed to be doing just fine.

I will also tell you that there are patients with that exact story ; they had infantile spasms,  they had a lesion that could be removed, they responded to therapy, and we said, “Well, you don’t have hypsarrhythmia, you don’t have spasms, you seem to be doing well developmentally.” Then several years later or a decade later, we have either the return of infantile spasms, epileptic spasms, or other types of seizures. Then we have to think, “Whoa, it would have been nice to have removed that piece of brain back when that patient was an infant and when the risks and costs of surgery would have been less.”

It’s a really tough decision. I think if you asked a neurosurgeon, they would be hard pressed to remove pieces of brain in a patient who did not have ongoing infantile spasms or hypsarrhythmia. But I’m not sure that’s the right decision.

I would put it this way though: if you have ongoing spasms or hypsarrhythmia and you have identified a lesion that can be removed to potentially cure the infantile spasms, that is almost always the right path. We’ve seen that all the relapse rates are pretty high across the board, they’re much lower and those patients who are good surgical candidates and undergo a successful surgery.

You mentioned the importance of immediate diagnosis. To clarify, does that mean from the first visible spasm or from the onset of hypsarrhythmia? Could there have been hypsarrhythmia for weeks or months prior to the first visible spasm?

It refers to the interval from the first identified spasm to effective treatment. And it’s very possible that hypsarrhythmia is brewing or emerging or growing before that first spasm.

A big focus of ongoing research is to identify patients who are at risk and then sequentially check their EEG every few weeks looking for the possibility that hypsarrhythmia or infantile spasms are on the way. That might be an opportunity to treat infantile spasms when they aren’t as bad, meaning there maybe a higher opportunity to prevent them from ever happening at all.

What are the chances of stopping spasms with the combination of ACTH and vigabatrin, if the spasms have been going on for one year or more?

The odds are not great, but they’re not zero. When we look at the patients who are relatively new to the treatment combination, the response rate is in the mid-70s, about 75% is our best estimate. The odds of response after months or years of ongoing spasms – especially with ongoing hypsarrhythmia – is considerably lower. We don’t have good estimates of what that risk looks like.

But there have been plenty of patients who have had spasms for a year and failed specific therapies, like the first line therapies, but when the medications were tried a year later, they did work.

I think it’s worth consideration. Just because a therapy didn’t work a year ago doesn’t mean that it won’t work now. Infantile spasms and hypsarrhythmia are dynamic process and they’re changing. And just because it didn’t work in the past doesn’t mean that it won’t work now.

Unfortunately, the reverse is also true. You can imagine a patient who was diagnosed quickly, who responded to say ACTH and that spasms returned six months later. Just because they responded the first time doesn’t mean that they’ll respond the second time.

If a child’s spasms are brought under control, is this child more likely than the general population to develop epilepsy down the road?

It’s absolutely true. We don’t quite know the magnitude of that risk. But I would say that it’s pretty substantial. It also depends on the cause of epilepsy. For example, if a patient has one of the most common structural abnormalities that cause the infantile spasm (something like a focal cortical dysplasia), then the risk of epilepsy down the road in the absence of surgery is pretty substantial. I would say it’s probably in the neighborhood of 50 or more percent.

But it really varies. It’s hard to predict. I would just say that, yes, you’re at elevated risk. You have to be on the lookout for the return of infantile spasms or the emergence of other types of epilepsy.

You mentioned that vision loss can accompany infantile spasms. Do you have any advice if delayed speech is concerned in a child who has suffered from IS?

That is actually one of the most common concerns. To the extent that infantile spasms and hypsarrhythmia can hurt development, it seems that they disproportionately affect language. But we actually don’t know why that is.

When we conceptualized infantile spasms, they are a form of seizure and epilepsy that hijacks the entire brain, but seem to have a disproportionate impact on the temporal lobes. And the temporal lobes are very important, especially the left temporal lobe, for processing and understanding language. That seems to be a pretty big barrier for graduates of infantile spasms, including those who have responded pretty quickly to therapy.

We have a very low threshold for referring patients for speech therapy. I would say many cases, especially those which have responded robustly and quickly to therapy, are actually very good responders to speech therapy. It is something actionable, but not something too alarming. I would say that there are many, many patients who have good outcomes after infantile spasms, and many of them had some degree of speech delay.

Can other seizure types early on mask the presence of infantile spasms?

Absolutely. Another factor is that infantile spasms are sometimes subtle and don’t really register as seizures with most people. When you think about the general public, if they saw a video of a child having infantile spasms, most people would not say, “Oh, that looks like a seizure.” They would say, “I’m not sure what that is. It’s probably nothing. Maybe it’s an infant heartburn or gastroesophageal reflux.”

Infantile spasms visually don’t register and don’t register on that fear meter. But when you think about most other types of seizures, they’re rather dramatic, especially if you think about something like a generalized tonic-clonic seizure seizure, those are much scarier, much more obvious.

If you imagine a patient who’s having both generalized tonic-clonic seizures and infantile spasms, it’s pretty easy to see how everyone’s attention – parents, pediatricians, neurologists – would likely be focused on those generalized tonic-clonic seizures because they’re so dramatic. That is also probably part of the challenge. We have to keep infantile spasms in mind as part of the possibilities of seizures and infancy.

When we teach our trainees, our residents and fellows, we’re telling them, “Look, this is an infant. You need to have infantile spasms in the back of your mind, no matter what kind of seizure they’re showing you right now.”

Is vigabatrin known to cause myoclonic jerks? If these jerks are not epileptic, can you stop once the child is weaned?

It’s not exactly clear. There’s a pretty widespread rumor that vigabatrin can cause myoclonic jerks or myoclonic seizures, and that they can be classified as epileptic or nonepileptic. I would say, don’t worry about any of that.

I think it’s probably true that a minority of patients who are treated with vigabatrin have either the emergence or worsening of myoclonic seizures. These seizures are reversible after stopping vigabatrin therapy.

The big question is; if vigabatrin is working to stop the spasms, should you stop the vigabatrin to make those myoclonic jerks and myoclonic seizures better? I think that has to be considered on a case by case basis.