Dr. Ahmadi discusses how to differentiate epiletic spasms from other pediatric neurologic and non-neurologic conditions. He also reviews the treatment of epileptic spasms and advice on vaccination in patients with epileptic spasms.
Hi, good morning. A lot of you know me, um, Today, I'm gonna discuss approach to epileptic spasms from the perspective of uh pediatrics, general pediatrics, and uh um pediatricians. So, I don't have any, uh sorry. I don't have any relevant uh financial disclosures to this presentation. Oh, I see. So the objective of today's talk would be to kind of define and learn about the clinical course of infantile spasms or epileptic spasms, differentiate spasms from common pediatric and neurologic and non-neurologic conditions, which you guys probably encounter more than us. And uh briefly talk about treatment and the advice on vaccination for these children. Before we jump into spasms, I had a few slides on epilepsy versus seizures, since this is a wide, uh, big crowd of uh uh pediatricians. First seizure based on ILA criteria is a transient occurrence of signs or symptoms due to abnormal or excessive synchronous neural activity in the brain, and to be precise, it can be, it has to be around 6 to 10. Uh, cc of brain tissue which has to seize at the same time for you to generate a seizure. Seizure is pretty common. But epilepsy is not that common. Epilepsy means increased probability of having another seizure. So, if you have Two unprovoked seizures separated by 24 hours, then you have a higher risk of having a third one, and hence you have epilepsy. The other definition is you can have one unprovoked seizure for a child who walks into your ER and you do an EEG. EEG is abnormal. Now their risk is automatically high, and you will be diagnosing them with epilepsy. And a third one is someone who walks into an ER with a seizure, and clearly has other signs and symptoms of developmental delay, and you send genetic testing, it comes back positive, and you're diagnosed with a syndrome. Then they also have epilepsy, even though they might not have a second seizure yet. To emphasize the lifetime risk, uh, this is from the Epilepsy Foundation. Um, as I said, seizure is common, 1 in 10 people will have a seizure in their lifetime. Versus 1 in 26 people will develop epilepsy during their lifetime. And uh this distinction. Helps create the diagnostic framework that we need to kind of see. So, at the top, there are different seizure types. These are not all the seizure types that we see, but I listed some of the more common ones. And this is where you guys come in, because this is what you're gonna see in uh uh on the floors in the ER and elsewhere in the clinic. Where a patient presents with epileptic spasms or a first-time generalized tonic-clonic seizure, or a myoclonic seizure, which is just a jerk, atonic seizure where they'll fall down, absence, which is one of the most common kinds of epilepsies in childhood, where they stare, and, uh, tonic seizures where they just stiffen, but they don't have jerking. And our job is to differentiate that from whether it's a seizure or not. Once you have determined that's a seizure, the next step is to identify the type of epilepsy, whether it's essentially generalized, which means the whole body is affected, or focal, where a part of the body is affected. And then you go into epilepsy syndromes, where you define based on all the seizure types that they might have, whether they have infantile epileptic spasm syndrome, which means they will keep having spasms for a long, prolonged period of time, or childhood absence, again, the most common epilepsy in childhood, where they stare. Up to 100 times a day. And the cause of these can be structural, genetic, idiopathic, metabolic infection like meningitis encephalitis in the ICU and who can have seizures. And idiopathic where we don't have a single cause, but many different reasons might be leading to a syndrome. So, to start off with a very brief case, uh, if you have, this is something we commonly see, uh, a 14-year-old boy who say, walks in the ER because he suffered a concussion after playing football, and uh he had a first time right-sided tonic-clonic seizure 5 minutes later, which lasted for about 1 minute. In the ER you examine them, they are at neurologic baseline, um, and no focal deficits. You do a head CT because they had a seizure after they fell down, and no symptoms otherwise. So, clearly it's a seizure. But is it an epilepsy? So not yet, because you need two unprovoked seizures to have epilepsy. So, for the same patient, say they develop a 2nd seizure. Yeah. Correct. Good question. So the same patient now has another seizure a month later. Again, a seizure, but not really epilepsy, right? Because this is our first unprovoked seizure, astutely pointed out by this resident. And then, say, 2 months later, they develop a 3rd seizure, and this time, this is the 2nd unprovoked seizure. So hence, now they have epilepsy. But going back to the diagnostic framework briefly, uh, you found two unprovoked seizures. They are focal, so the highlighted part, uh, it's a focal seizure. And in terms of epilepsy syndrome, it would be the post-traumatic epilepsy, because they have unprovoked seizures after having trauma, and it may or may not be structural depending on their, uh, imaging findings. OK, so this was just to give you kind of a brief overview of the diagnostic framework, and now we can jump into spasms. So epileptic spasms are essentially 1 to 2 2nd brief seizures, and they have to be less than 2 to 3 seconds, because if they're longer than that, then they are referred to as tonic seizures, because now you are just in a state of tonic contraction. Epileptic spasms is a newer terminology. Infantile spasms is what we are used to talking about on a daily basis, and the reason is, um, the reason for the change is that spasms can occur after the first year of life when a child is not an infant. And hence, uh, the more accepted terminology is now epileptic spasms. The other reason is to emphasize the fact that it is epileptic and not a non-epileptic spasm, um, that is a change on EEG. The other terminologies that you might have heard of include West syndrome, which essentially is a child who has epileptic spasms, has the classic board testable EEG findings of hips arrhythmia, and developmental stagnation or regression. So if you have all these three things, then you have West syndrome, and feel free to interrupt, please. Um, And I have, I always like to discuss this brief history of West syndrome, because it's interesting that uh Doctor West, one of his own child, had events that he couldn't figure out if they are, uh, what's going on. And so, in the 1800s, what would you do? You would, how would you get a second opinion or a consult? Well, during that time, what you would do is you would write to The Lancet. And you ask people in your community what this could mean. So he elegantly described what he saw in his own child, where um He saw a little bit of bobbing, head bobbing and attacks of what he described as improstoonis, which is the kind of an opposite ofophotoonus, and I put a figure there to show you that they hunch and they have the arms and the legs come forward versus are not and not arch where back. And in blue what I highlighted is uh the other things which come along with spasms that he kind of described in this first description of, uh, which essentially means intellectual disability or developmental delay, and inability to move limbs because of loss of tone. And so, Epileptic spasms, if you go back to the diagnostic framework, is a seizure type. West syndrome goes down that pyramid, where you diagnose them with the syndrome, and for the syndrome, you need the EEG finding and developmental delay regression. And uh of course, uh, two centuries later, we uh epileptologists meet and they're like, well, we don't want to call it West syndrome anymore. We're going to call it infantile epileptic spasm syndrome, because we want to include patients who only have epileptic spasms and no EEG findings, or they have all of these, or they have one of these. No matter what the combination, if they have any of these things, we're going to call it. Infantile epileptic spasm syndrome. So you're never gonna be wrong if you say IESS because that is encapsulates all of it, or one of it. So, in this slide, what I wanted to really emphasize is, uh, in terms of the etiology of spasms, there are more than 200 causes of epileptic spasms, where you can have a structural brain lesion, or a genetic syndrome, or a um focal genetic lesion. And spasms can be focal. We are the more common are generalized spasms where the whole body is kind of coming together, but focal means only one side of the body is is spasming, and that can be from a Early onset hemi megalocephaly are one hemisphere being affected and not the other. And hips arrhythmia is essentially an EEG which is pretty chaotic, no matter what direction you look at it, it's gonna look chaotic. And developmental regression again. So IESS encapsulates one or all of this. So with all that terminology jargon, uh, the current terminology essentially is going to be epileptic spasm for the seizures, and infantile epileptic spasm syndrome for the syndrome in that hierarchy. So these are some of the common questions that you might see. Is my child having spasms when they come to your office or the ER? And uh the other questions are, is it safe to give vaccines because uh the neurologist said to start high-dose steroids yesterday. So we're going to discuss about that later in our slides. And now we have a whole bunch of videos, uh, I'm gonna briefly go through some. And this is what a spasm looks like. And this is from the Pediatric Epilepsy Surgery Alliance, uh, it's all the contributors here. Some more cute baby videos with spasms. This is just a head drop, as you saw, the arms and legs did not come together. So IESS or infantile epileptic spasm syndrome, occurs in 1,300,000 live birds, and with a higher geographic incidence in Sweden, Finland, and Denmark, and accounts for 10% of all epilepsies before 36 months of age. And this is kind of what the trajectory of a patient will look like after they are diagnosed with spasms. So, the usual age of diagnosis is between 3 months to 1 year, hence the initial term infantile spasms, but it can start after 1 year of age. And 30% of these patients will go on to develop drug resistant epilepsy or Lennox-Gasto, which is multiple seizure types, along with uh some developmental delay or regression. And early treatment is important, because if you don't treat here in the initial phase, then they can have a significant regression. And you want to prevent that. So it's an emergency. If you see, if you're in doubt, uh, we'll talk about what to do in a moment. And this is where you guys Um OK. So, characteristics. So, basic characteristics of spasms are, as I mentioned, brief contractions of axial muscles, and hence you see that hunching in the arms and legs uh coming forward, lasts less than 3 seconds, and uh subtle spasms can just present with minor head nods, as I showed you, or eye and chin movements. Usually occurs waking up, and it can be naps, like they might say that, oh, it happens throughout the throughout the day, but when you ask them, is it after a naps since, uh, you know, after they wake up in the morning, and they'll usually say yes. And they usually occur in clusters when they wake up. So clusters and waking up are kind of red flags to look for. Other things for you guys to ask during the uh encounter include questions about development, specifically ask about regression and isolated regression and visual attention, altered social responsiveness prior to developing spasms. Examine the skin because tuberosclerosis and a lot of the neurocutaneous. Uh, disorders including hypomelanosis of Ito, uh, which, uh, is apparently not very uncommon. I think I've seen a few cases in the last year. And look for dysmorphic features because that will point you towards getting a genetics consult and genetic testing, and examine the eyes. A eyes are kind of the windows to the brain. If you see abnormalities there, it might indicate uh a genetic condition. So now the second part, which is the really difficult part, you have someone who walks in and says, my child is having spasms, and you need to get an EEG right now. So, I initially had some of these videos with bowling, but we, oh, you have a pole, look at you. Thank you. So, if you guys are interested, please feel free to poll, uh, if this is a spasm or not, if this. I'm not showing you the EEG. OK. Yes. I'm just gonna get a feel from the room. No. I might do with your computer. Same time. Oh, nice. So right now we have 50/50. OK. No one wants to confidently yell. They're gonna say yes. The chief says yes. OK. You say no. No. I'm sorry guys. I'm not gonna show it again. I'm not gonna show it again. We'll, uh, move on to the next one. I, I can keep holding for the next 5 minutes. It's fine. You wanna say yes or no? You wanna say. Yes or no? No. Good. That's a shuddering episode that you can see uh more commonly in patients with autism. Uh, the arms, legs, and the head. Oh, thank you. Hm I think this is more to emphasize how subtle it could be or how obvious it could be, where the arms, legs, and heads all come together, and this is essentially the same baby but a different, um, a more broad semiology. OK, this is, this is a fun one, actually. Look at all the previous goal. Yeah. No. Yes. No. Yes. A lot of them are saying no online. Yeah OK, he wants to see it one more time. So, before I go to the next slide, what I'm gonna ask you to think about is my first statement, how long it has to be. It has to be always less than 2 seconds. Correct. This is Sandier. Reflux, colic, uh. Older child, you're thinking this is infantile spasms. What are we doing with her? Teenage boy. I don't know if you saw that. 4 500% yes online. 6100%. So, this is a, the reason I put it here is, this is more pronounced on the right side. This is one of the examples of uh epileptic spasms, which is more on the hemispasm uh category, from a left-sided lesion. This is another good one. No, she says no. Everyone says, no, I feel like. Online it's 100% no. OK. This is not a seizure because you can provoke it, right? Um, this is a rare genetic condition called hypeeclampsia, which is a glycine receptor mutation which results in increased excitability in the spinal cord. Once Everything you see. OK, this is another good one. You need a bold for this one. This is the last one. Oh sorry, I was not uh I wanted to loop. What do we think? Yes, it's. Nose, I see thumbs up. It just sums up and I can see, so that will give me a bowl of some sort. Or thumbs down. We are fifty-fifty online. So this one is probably the most difficult one to diagnose. Because those are, these are the ones where you absolutely need an EEG because it's not possible to tell just based on looking at the video. And uh this is not a seizure when you did an EEG. Because, uh, the, these are the most difficult ones. This is benign spasms of infancy, which looks like spasms, but they don't have an EEG change, which means they're not spasms. OK, so I hope that helps. Correct. Uh, so the previous, some of them, the semiology. Thank you. So the question is, if we need EEG for even the previous ones for which we thought they were clearly spasms or not spasms. And the question for the spasms part is, yes, if your confidence is like, I'm like 100% sure this is a spasm, you still need an EEG to confirm. The other reason to get an EEG is you confirm that it's a spasm, but second, you can look at the EEG in between the spasms, and if it shows hips arrhythmia, which I was showing with the chaotic EEG, then it kind of pushes you towards West syndrome or IESS, and you now have a syndromic diagnosis. So, the gold standard is to capture that on EEG. However, if you have, if you're not, don't have enough EEG machines, then what you can do is, uh, you can get an interrectal EEG, which means a short EEG, and if you see that, you see that chaotic pattern, then you can assume that you might have, uh, uh, they have spasms, because it's clearly very abnormal EEG, um, but the gold standard is to capture it on EEG. And it is for this exact reason that a lot of them will look like spasms, but they're not, or the other way around. So, this is just a list, a laundry list of, please, yeah. All of them are from publications and papers, so all of them have EG. Um, so those are the laundry list of the differentials. The biggest one is Sandifer, easy to, very easy to confuse. Again, they usually last longer. So the idea is less than 3 seconds, Individual spasms less than 3 seconds, usually occurs in clusters, and usually occurs on waking up. Um, benign sleep myoclonus is another thing you will see. They usually occur only exclusively during sleep, not with waking up. And shuddering attacks which I showed you, which are again very common to see, yeah. And hypeeclampsia is not a common disease. It's not, but it's a differential to keep in mind. Workup that we usually do is an EEG try to capture the event, and MRI to see if there are any structural lesions which we can follow up, since 30% of these patients will develop drug resistant epilepsy. So you want an MRI to see if you can take a surgical route later on. And genetic testing to look at uh any um syndromic diagnosis, and consideration for somatic testing if you have a brain lesion. The mechanisms of epileptic spasms, so this I'm gonna be very brief, since uh uh there is a lot of debate, a lot of questions, and a lot of unanswered questions, how it uh how so many different etiologies result in a single kind of uh epileptic semiology. So some of the uh hot questions are, why does, how can a single entity like epileptic spasms have more than 200 etiologies? In a way, you can imagine that's kind of a converging pathway, so you can. Oh I'm sorry. Can I use your um Because, uh And Nothing in the chat. It may have been by accident. OK. Thank you. Um, and the other questions are, why do epileptic spasms arise only between that time frame of 3 to 12 months? And the third one is, why, um, why are spasms associated with lasting cognitive dysfunction, and, uh, unlike most others respond to steroids and ACTH, which are the, um, Mainstream or the uh first line of treatment. So these are, this is, uh, this one slide probably has over 1000 different publications summarized. And uh the idea is that you can have all these causes on the left, which can be genetic, metabolic, structural, and it, in some form affects the HPA axis, or the brain stem hypothesis where the brain stem is dysfunctional and you have this whole body um change. There's also immune hypothesis where you have a lesion, and now around that lesion you have immune dysregulation, which then results into results in spasms, or global immune changes. And developmental desynchronization, which I'm not going to get into too much. Uh, Essentially with all that, the idea is you have a common excitatory pathways which are activated, and you develop these spasms in the time when your body is most susceptible to um inversing the ratio of uh excitation to inhibition. Treatment. So you might have seen this treatment of how spasms are treated. If not, you will see it, um, when you, uh, no matter what path you take, because, uh, most of these patients go on steroids or ACTH and they do need follow-up by the pediatrician, as well as by the neurologist. So why is early treatment important? Prompt diagnosis and treatment may prevent subsequent developmental delay, at least in the critical time of development, which is the 1st, 2nd, and the 3rd years of life. Up to 5 years, kind of the critical period. Increasing lead time to treatment is significantly associated with decreasing development scores at 4 years in all infants with spasms, hence, you have to treat them as soon as you find them, or if you suspect them. And neurodevelopmental outcomes and spasms are better in infants who have had a shorter duration of spasms in time from initial treatment. So why, how did, how did we come with ACTH? So if you go back in 1958 in France, uh, ACTH was a new drug which, which came out. So they were trying it on every possible uh um person that walked into their hospital, and they accidentally used it on a patient who had infantile spasms, and they saw excellent improvement. At that time, the mechanism was unclear. Even this time, the mechanism is unclear, and the rationale is also not very clear why ACTH would essentially work, except for now we have these 1,000+ publications showing us how there is some immune dysregulation and HPA access dysregulation which can potentially help with ACTH treatment. Now, ACTH is not easy to give. You have to give injections. So, UCLA, they did a trial where they were like, well, if ACTH works, would prednisone work? So what they did was they either gave ACTH to one arm or gave prednisone to the other, and if prednisone did not work, they would then give ACTH. And in this trial, they showed that very high dose steroids. Are as efficacious as ACTH and hence in Saint Louis Children's, we usually use steroids as our first line. The other reason is high dose steroids cost $89 for a two-week course, versus ACDH injections cost $100,000 for a two-week course. So, uh, being mindful of that and the fact that they are equally efficacious, we go with steroids and not ACTH. Vigabatrin is first line for any structural related uh infantile spasms or epileptic spasms, where um you have like tuberosclerosis or other structural changes that you may see on MRI. Then you would want to use something like Vigabarin because you're gonna be using it a little long term, and not just for two weeks. And finally, vaccination. Because these patients do uh are are on high dose steroids. So when do we vaccinate? Again, we want to go back in history a little bit because epileptic spasms and vaccinations have a pretty tenuous history. Um, Again, spasms occur around the time when you give a lot of the childhood vaccines, and the developmental regression starts about a year, a few months later. And so, a term was coined called vaccine encephalopathy, where people thought that vaccines cause spasms. And when the National Childhood Vaccine Injury Fund was established in 1986, more than $5 billion were were disimbursed to patients who had infantile spasms or epileptic spasms, and it was one of the leading reasons for filing a claim. And this is a summary where in 90 the human genome project started in 1992. And in 1997, it was established that tuberosclerosis is caused by a mutation in TSC gene and not vaccines. And so all those claims, which constitute a large number of claims were uh Next In 2012, SCN1A mutation, which was very well established for over a decade at that point, was shown to cause Dravet, and again, the idea was Dravet is caused by SCN1A and not vaccines. So the takeaway for the, for, in relationship to vaccines is you, your recommendation for vaccines should be the same for infantile spasms as for or epileptic spasms as any other um patient that walks into your uh clinic or on your floor or ER um, but one thing to keep in mind is steroids do suppress your immune response. And so the ILE recommendation or the International League Against Epilepsy's recommendation is to not give live vaccines for 4 weeks after discontinuation of steroids, and this is complete discontinuation of steroids. And so you wait for 4 weeks before you give a vaccines so you can develop a robust response. So the takeaways, uh, Uh, from today are, if suspicious, refer urgently because early treatment is equal to better outcome. Um, the second one is probably the one I utilize the most, use cell phone cameras. And um look at videos. The more videos you look at, the your, your brain, you're gonna train your brain to kind of figure out which patients are ultimately getting a diagnosis and who are not. And you'll get better at uh. Differentiating that Get a detailed developmental history? And because you want to know where they are and if they're regressing. Vaccines have no causal relationship to spasms, and so you would recommend that as you would for any other child. And live vaccines should not be given until 4 weeks after discontinuation of steroids. And assess for steroid side effects during your clinic visit. That is where you come in, uh, if you monitor blood pressures, blood sugars if needed, especially while they are on, uh, steroids. Because they might not be able to make many in-hospital visits or in clinic visits with neurologists during that time. And patients with spasms are at increased risk of future epilepsy. As I said, 30% will develop drug resistant epilepsy, which is going to be difficult to control and might need epilepsy surgery. And that is all I have. The 3rd division
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