This case-based presentation from pediatric neurologist and epilepsy specialist Ernesto Gonzalez-Giraldo, MD, sheds light on the significance of a first seizure, providing the evidence on risk of recurrence and epilepsy, and offering workup guidelines. Here’s help with responding to parents’ common questions and prepping them to cope if there’s a subsequent seizure.
I'm talking to you guys today about a first seizure and considerations that might be helpful for primary care doctors and pediatricians. I have no disclosures and overall I have three in general learning objectives today. So I'm gonna discuss some basic terminology about epilepsy um to make sure that everybody is on the same page. I'm gonna uh discuss things to understand the risk of recurrence of seizures and the risk of developing epilepsy after a federal seizure of first unprovoked seizure and acute symptomatic seizure or chronic symptomatic seizures. And then finally, I'm going to discuss discuss some anticipatory guidance that for parents that might be helpful um after a first seizure and prior to seeing a neurologist, um obviously please feel free to ask any questions that might come up. So some basic terminology and epileptic seizure is uh paroxysmal clinical event that's presumed to be a result of an abnormal or excessive neuronal discharge. That leads to neurologic dysfunction. So it's many cells where many neurons firing together in synchrony at a time when they're not supposed to be firing um and causing a transient alteration of normal neurological function. What um the clinical sociology for for a seizure can look like depends on whether the seizures focal or generalized focal seizures tend to involve a single or a few joints. They tend to have a rhythmic twitching. Um They can have eye deviation, head deviation. Um They tend to uh can be associated with staring, but the staring tends to be prolonged. Um And then finally you can you can have stereotyped automate ISMs or paroxysmal vital sign changes. Generalized seizures tend to be more generalized or bilateral rhythmic shaking. Um That is clinic um Either or generalized stiffening, like tonic seizures um drop attacks to falling to the floor, I either becoming all of a sudden a tonic and falling to the floor or becoming tonic and sort of uh like a board falling on the floor. And then finally uh staring episodes that are briefer, tend to be absences. And When Epilepsy, the definition of epilepsy changed in 2014. It used to be just .1 here. So to unprovoked seizures recurring greater than 24 hours apart. Um a couple of features were added. So um you can call epilepsy if somebody has one unprovoked seizure and then a probability of additional seizures that's greater than 60%. And as you can tell the That's 60 is a little bit more difficult to determine. And some of the data that we will go through today is going to be relevant to that. And then finally the diagnosis of an epilepsy syndromes. So for example, somebody, if somebody comes in with my climbing jerks in the morning and you do any G. And they have a, you know, six hertz, generalized polly spikes. Um that fits the criteria for juvenile my clinic epilepsy. So I don't have to wait for to generalized tonic clonic seizures before I call epilepsy. Just based on the fact that they fit in epilepsy epilepsy diagnosis, I can call them having epilepsy. Um Why uh does this user occur? So there's um in in the normal brain there's a nice balance between excitation and inhibition. Um and when that balance gets uh in the direction of excitation, it leads to an imbalance of excitation and inhibition and seizures. Um Why does it matter? Uh procedures are the most common neurological disorder in Children. Around 4-10 of Children suffer at least one seizure in their 1st 16 years of life. Um around 150,000 year, or 350,000 Children sustain the first times user each year in the United States, Um around 30,000 developed epilepsy each year in the United States, um seizures can cause significant anxiety to parent and have extensive social consequences as I'm sure you guys have seen. Um so that now that I sort of talked a little bit about some basic terminology, I wanted to um go to the meat of of the presentation, which is gonna be to understand the risk of seizure recurrence after a first seizure depending on what kind of seizure it is. Um So I'm going to do this in a case based uh style. So first case you have a three year old girl who has no past medical history Who presented with two episodes of generalized shaking of all of her extremities that lasted 2-3 minutes um in the last three hours, she's well appearing on exam now, She's totally back to her baseline. Um and nothing like this has ever happened before. So, um I think the key, the key sailing parts of this history is that she has no past medical history. She's a typically developing child Um and she has two episodes that are likely consistent with the seizure that happened in less than 24 hours and she is now well appearing and totally at her baseline. So you don't think you're not concerned about ongoing seizures? Um so this is a, what I would categorize as an idiopathic or a first unprovoked seizure. Uh it's probably the most common type of seizure that I see in, in the, in my clinic. Um so the key thing to uh calling something idiopathic or first unprovoked seizure is that your have normal development, normal neurological examination and no obvious toxic or metabolic arrangements that could explain the seizure. Um Obviously, if if you had obvious toxic or metabolic arrangements like hypoglycemia hypoglycemia hyperglycemia, you would call that seizure provoked, not unprovoked. Um and then the fact that the child that there's no um uh abnormalities in your exam that makes you think that child is either currently or has in the past had some sort of cns injury, puts you in that idiopathic uh place. Um So these are questions that I often get from parents. So doctor, will this happen again? So, in in a prospective study of 283 Children that was done in New York by slow motion are um we um that looked at 2, 283 Children who presented with the first unprovoked seizure. Um the cumulative risk of a seizure recurrence for the entire group was in that first year around 29%. In the second year, Around 37%, and then in that third year around 42%. And after that 42%. Really that risk where after that 30 or excuse excuse me. Um that risk really sort of tapered off. So, um I like the number that I like to quote to my parents who are coming in and asking me after a first unprovoked seizures. What is the risk of my child developing epilepsy or having a second seizure? Is, I usually quote some somewhere along the lines of 40 to 45%. Um this was another meta analysis that looked at six papers that included 100 815 Children looking at um neurologically and developmentally normal Children between one month of age in 21 years of age um who were on no anti seizure medications and had their first uh the first time seizure. And as you see, the The overall analysis showed that the risk of recurrence or the risk of developing epilepsy was close to 45%. And again, that's including all comers. Um So, so that's a nice sort of easy to remember number to be able to quote your parents of your patients who are coming in after our first unprovoked seizure in terms of what the risk of recurrence is. Another question that I often get from parents of Children who had several seizures in in the same day is, you know, but they had two seizures today, um or two seizures already. Doesn't this mean that um that things are worse? Or doesn't this mean that she already has epilepsy? Um This is a really lovely paper by Ko and colleagues. Um and this is actually coming from adult data. The Children pediatric data that we've had isn't quite as good quality as the adult data, which is why I'm presenting you this. Um But but it's overall fairly similar. So um this study looked at 772 adult patients with multiple seizures in 24 hours um as their first seizure presentation and then compare them with 425 adult patients who are presenting with just a single seizure and then followed those uh those patients over uh several years to see how many of them ended up developing epilepsy are having a recurrence of seizures. And as you can see, um here, the in this graph, the the Y axis is the cumulative probability of additional seizures. The X axis is the time since the first seizure presentation in days. The uh red dash line um represents those people who had multiple seizures in that first day of having seizures. And then the blue line, um That is solid, represents the people who had just a single seizure and as you can see, the risk of developing, um or the risk of having another seizure really is independent, independent of whether that First seizure presentation included a single seizure or multiple seizures. So with pretty good data behind you with pretty high numbers behind you, you can fairly confidently say to a parent that, you know, even though the child had more than one seizure in that 1st 24 hours, even though that before you started mentor before they saw a neurologist, they had multiple seizures. Um The, the risk of recurrence is pretty much the same. Um and so I would still quote that parent around 45 50 of, of uh chance of seizure occurrence over the next few years. Another question that I often get from parents is how long do I have to wait to know if she doesn't or does have epilepsy? So what is the period of time when I when after which I can relax and sort of not think about the fact that she had a seizure. Um So this was a really lovely um uh Data published in 2015 by the American Academy of Neurology um that published in evidence-based guideline on the management of an unprovoked first teaser in adults. Again, this is adult data um and reviewed 281 publications which included more than 1500 patients and found that the period of greatest Recurrence Risk was that 1st 2 years. So you see that um after this is less than in this graph, you have the y axis is the percent of patients with seizure recurrence in the X axis is the years after the first seizure. So, in that first, and, and this is done in Bins rather than sort of as a truly continuous variable. Um and as you can see, the around 10 of patients had a recurrence of their seizure in the first um and less than one year afterward. Um That number went up pretty significantly after a year, So up to 30 in that first year, um by uh two years, around 40 of the people who did go up, go on to develop seizures had had their seizures. But you can see that there's this flattening of the curve after two years. So in general, I tell my parents that um that after two years, they can sort of, if they, if the child hasn't had a seizure by then they can, you can relax and think that this was just a single time or a single um uh seizure and that they can relax and not, not worry so much about them having other seizures and and and relax the precautions that we'll talk about it in a little bit. Um So that that's, that's over all the data. I wanted to talk about sort of the threat first, unprovoked or idiopathic seizure. Um So again, just to recap the risk of developing epilepsy, your risk of having a second seizure after a first unprovoked seizure and typically developing normal child with a normal neurological examination is around 45 page 45%. Um The risk of developing epilepsy if you have more than one seizure or or less than one seizure in that 1st 24 hours is um is the same. Um And then finally, after a first seizure, the period of highest risk of having a second seizure is the first two years. So now we have the second case that I wanted to discuss. So this is an 18 month old boy. He has no past medical history. He presented with 20 million, a 20 minute long episode of right sided shaking. Um The child is federal temperature of 38.5, has evidence of an acute otitis media um with pure real infusion on his right to panic membrane and then um has decreased mobility and nomadic tosca. P. So this is a nice example of a febrile seizure. Um Child who's typically developing has known has a normal neurological exam, has a fever and then presents with their first with the seizure. Um as you guys, um so this is, this is a nice febrile seizure. So how common is this? Um, is a question that often parents ask, and I'll I'm sure that you guys see this a lot more often than we do. I think you guys do a really good job of managing this on on your own without necessarily getting neurology involved. But I wanted to discuss a little bit more about the data behind um why we manage several seizures the way we do. So federal seizures are our overall um more common than than one might expect, so, um or up 2-5 of patients in the white population, it's a little bit higher in the Asian population, 8-10%, for reasons that I'm not sure that I understand or have been well explained. Um as many as 25-40 with federal seizures have a family history of federal seizures and that that is pretty well understood. There's there's several genes that put that, um uh, effect. So either sodium or other electrolytic conduction in neurons that put somebody at risk for having seizures. Um, but but in general there's a pretty good um, genetic component for, for federal seizure frequency. Um, as you guys know, there's two, we sort of classify febrile seizures into two different groups. We have simple febrile seizures or complex, or oftentimes, I use the word complicated febrile seizures, Um and the way that one fits some, a child into a simple or a complex febrile seizure is, um if you have just a single seizure in 24 hours, that simple, if you have multiple seizures in 24 hours is complex. If you have a generalist onset seizure, it we classify that is simple. If you have a vocal um, onset seizure, um, it is uh categorized as complex and then if the seizure is less than 15 minutes, is, is simple and greater than 15 minutes is complex just to put it into into context. Around 20 to 30% of febrile seizures fit into that complex category. Um so another question that parents often asked is, you know, do I need to worry about this with every fever that the child has and and is my child going to have another febrile seizure? Obviously, this is a different question than is my child going to have another, a federal question. Um So it turns out that the chances of having another febrile seizure um aren't different between the complex and the simple febrile seizure. The risk overall of having other federal seizures is similar. This is um, a busy slide. Um but overall, in a prospective study looking at 347 Children who presented Um with a febrile seizure, um they found that around 30 of them went on to have another federal seizure within two years of, of uh after that first seizure, that first febrile seizure in another study. So that, that was, that was over here. So you can see that over time that grab in this graph that shows you a y axis, the probability of the occurrence and an X axis of months since the first febrile seizure. Um You can see that the, There's a nice uh increase in frequency or or increasing recurrence of federal seizures over the first year and after the first year, it's sort of um, levels off and around 30%. You can tell somebody that they have a 30 chance of having another federal seizure. Another study that looked at 700 and 1706 Children with febrile seizures. They found that around uh two thirds of patients with the federal seizure only have one federal seizure, so that's consistent with the data that had been reported before. Um But they looked at the rest at the Children who did have those um that recurrence to see how many of them had 23 or more than three seizures. So you can see that in that third of patients who have recurrence of febrile seizures, around half of them have a second federal seizure. A little less than half of them go on to have a third febrile seizure, and then on less than than um five of the overall number. Um and I guess that would be around 20% of of uh of the people who do have recurrence and seizures, um going to have more than three febrile seizures. So overall, you can tell parents that the risk of recurrence is, is reasonably high a third, um, but most likely you're only going to have one or two more febrile seizure, so it's not something you're going to need to worry necessarily for the rest of their life. Um, And as you know, the in general, federal seizures tend to, to resolve by six years of age. Another really needs study that looked at the risk of recurrence of federal seizures based on the age of the first federal seizures found that, um, if the first federal seizure happened, um, by one year of age, you had a 50 recurring, so a little higher than the average. And then if the first febrile seizure was around three years of age or older, they had less of a chance of having a recurrence of federal seizures. Um, and then the, the other side of that coin. So the slightly different question is, you know, is he going to need to take seizure medications or will he have an a febrile seizure is really the bottom of that question. Um And this is this was is one of the best papers looking at that. It's a prospect of study looking at um Around uh 262 Children who were all in the state of New York, I believe. Um looking at the risk of epilepsy overall in in in patients presenting with febrile seizures and did a sub analysis comparing simple and complex febrile seizures. So in that um in the graph on the left, the Um why access is just showing you um the overall percentage. So this is um not giving you absolute numbers, but it's just giving you percentages. Um the patient, the percentage of simple febrile seizures to go on to develop epilepsy is in red here, and you can see that it's around 2%. So, um, you know, the general population has a risk of developing epilepsy of 1%. This is maybe twice as much, but it's still 98 chances of not having epilepsy or not developing a febrile seizures. On the other hand, for those patients with complex or complicated febrile seizures, the risk of developing developing epilepsy or having any federal seizure is a little higher, with um it's closer to two overall 56%. Um But it turns out that when you do a little sub analysis for the different categories of around seizures or the different things that make a federal seizure complex, you find that the risk is a little bit different. So, When I, when you look at that, um, the, you know, the differentiation meaning um, simple febrile seizures have just one single seizure in 24 hours, whereas um uh complex febrile seizures have multiple seizures in federal seizures in 24 hours. Um You see that the risk of developing epilepsy is not that actually that high among that group. So if somebody has more than one has complicated federal seizures, complex several seizures Just because they had more than one febrile seizure in 24 hours, the risk is actually pretty similar to the, to the risk of simple febrile seizures, so it may be something that's a little outdated and something you don't need to worry so much about. Um if you look at the risk of developing epilepsy after a prolonged febrile seizure, it's closer to six or 7%, so that's um definitely higher than than those people with simple Federal seizures or multiple federal seizures in 24 hours. And as you can see, the risk of developing um uh epilepsy after a folk, a federal seizure that had focal features is actually quite high. It's greater than 20%. Um, so that is a big, you know, that is the biggest um reason why I would ever consider working up a child who had a complicated federal seizure and where I might consider doing both imaging um any G and perhaps some, um, perhaps some genetic studies, um that is definitely a child that I would want to see in my own clinic rather than them staying with their pediatrician if they had a focal feature for their, with their, with their seizures with their febrile seizures. Um, so again, just to recap around uh, patients who have federal seizures have 2 to 5% risk of developing unprovoked seizures, 2% is closer to the simple febrile seizures. 5% is the overall risk of, of developing epilepsy in the complex febrile seizures. But as I mentioned, um uh those patients who have focal febrile seizures have a much, much, much higher risk of developing epilepsy, so probably should be seen by neurology. Um and then other predictive predictive risk factors that um that can help you sort of stratify those patients who had febrile seizures into whether or not they're going to develop epilepsy include the history of developmental delay and abnormal neurological exam. Um A history of complex federal as usual, which we already talked about in the first degree relative with epilepsy. Um So now that we talked about the data behind um febrile seizures, I wanted to to discuss um on my third case. So a five year old boy who was previously healthy presents with general is rhythmic shaking for three minutes on exam. Their federal lethargic and have nuclear rigidity. The um there's concern for meningitis and uh lumbar puncture is done. That shows a clear, please, I dosed it that is uh neutral, predominant um some uh low glucose and high protein. So this patient clearly has a an acute um uh neurological insult with this meningitis. Um This would be a patient that I would uh categorizes have been symptomatic seizure. So what is the symptomatic seizure is symptomatic seizure is a seizure that's grown by that's caused by a known or suspected disorder in the CNS. So something like meningitis, encephalitis, stroke, trauma or brain tumor. Um And it turns out that the risk of developing um epilepsy after a symptomatic seizure depends on when that symptomatic seizure occurs relative to the onset of the cns insult. Um And we just we divide those into acute symptomatic seizures and remote symptomatic seizures, ACUTE symptomatic seizures occur less than seven days after the onset of the cns insult. And remote symptomatic seizures occur um greater than or more than seven days after the onset of the cns insult. So in this child who had a seizure in the sort of first day after they developed a fever, lethargy and local rigidity, this child would be categorized as having a an acute symptomatic seizure. Um So if my parents, if a parent of that child asks me, will this happen again? Um I have good data to be able to help them. So this is uh Prospective study looking at 262 individuals who experienced the first Acute symptomatic seizure and 100, you know what, actually, I'm sorry, and this is what I got Little distracted here. So this is a six month seizure outcome of 105 Children who have acute symptomatic seizures from from a cns infection. This is a study out of India. Um and it turns out that the large majority of patients who have acute symptomatic seizures do not go on to develop epilepsy. So to three quarters of them don't develop epilepsy. Only about five of the patients in this study went on to develop epilepsy. So it's overall pretty pretty uh small number. Um six of them had been lost to follow up. And again this was a study out of India. And so the rates of death with um with meningitis were a little higher than we would see here. We don't have great studies out of the US. so that this is the data that I want that I had to show. Um And then finally um say for example my fourth case. So you have a four year old boy who has a history of right frontal interest, cerebral hemorrhage from a ruptured arteriovenous malformation presents with generalized rhythmic shaking for three minutes, um and has a left hemiplegic cerebral palsy, but is now back to baseline. Um So this would be a kid who has a known history way longer than seven days ago of of a cns insult they presented with their first seizure to, this would be a remote symptomatic seizure. Um and the question will this happen again is a little bit different. So this is this is the, I'm sorry, this is the day that I had mentioned before. So it's it's a prospective study looking at uh, at 347 um uh individuals who had an acute symptomatic seizure compared to um around 148 individuals who had a remote symptomatic seizure. Um so again that the difference there is the cns insult happened before or after uh seven days after the onset of the cns insults. And you can see that in this uh in this graph that has and as in the Y axis, the cumulative probability of subsequent unprovoked seizures in the by access the year since the cns insult. Um you can see that those people who had acute symptomatic seizures have a risk of developing epilepsy over 10 years, that's close to 20%, compared to a risk of nearly 70 in those people who have remote symptomatic seizure seizures. So um uh this is a nice data that can really help you guide the family who whose child just had a a cns insult in terms of reassuring them that if they, you know, those seizures that happened in that first week after a cns insult, don't necessarily um in part really high risk of developing epilepsy, whereas if it happens if it happens more than seven days, you have a much higher risk. Um And then finally, my third objective for the, for this talk was to um under sort of discuss and understand um anticipatory guidance for parents that um that you could discuss with a parent after their child has a first seizure and prior to them seeing a neurologist. Um So if if um they this is, this is uh anticipatory against that, I give literally every single one of my patients. Um So if this happens again, if the child goes on to have a second seizure, um these are the things that I tend to to tell my parents and my patients. I encourage them to stay calm. Um I encourage them to make sure that they are, that the patient is in a safe space or in safe surroundings. So this usually includes making sure that they're not underwater, make sure that they're not in the tub, make sure that they're not on top of the stairs. So if they start shaking, they would follow, make sure that they're not, you know, next to a bunch of knives or something like that. Um I encourage them to lay their patient on their side if it's possible. Um and this is, this is key, but take note of the time. As you guys know, seizures can be incredibly scary um and a seizure that lasts 20 seconds, Especially after if it's the first or second seizure will feel like it lasted for 20 minutes or 30 minutes for a parent. So make encouraging parents to literally take a look at their watch and making a note of the time. We're taking a look at their phone and making a note of the time so that they can time things is really helpful um obtained a video Now. Nowadays most people have smartphones and most people have phones that have cameras. Um and it is um uh incredibly helpful for a neurologist to have videos of of seizure. So I encourage you guys to uh you know, ask the patients to do that And then if the seizure reaches the five minute stage um either give emergency medication if they were prescribed it or call 911. Um And the reason for that is that the most seizures in the world end within five minutes of onset on their own. Um But if the seizure is reaches the five minute stage it is um there's enough um of a change in the in the way that the neurons are set up in. There is an acidosis of um inhibitory uh receptors and and and and um sort of more availability of calcium, more availability of excitatory um uh neurotransmitters. And so those after five minutes really the patient is in status epileptic asses and they need to get therapy um before they see neurology, I I often see um uh parents sort of discussed a great variability of of whether or not pediatricians are willing to give them emergency meds in general. I only encourage pediatricians to prescribe emergency meds before a child sees neurology if If they are if that first seizure that they had lasts longer than five minutes or if the convulsion involved a significant amount of either cyanosis or or vital sign changes. Um Otherwise, if the seizure was short and there wasn't a significant amount of of sort of really scary sounding vital sign changes, it oftentimes it's better not to give the rescue medication. Um Overall, I find that patients who don't need rescue medications who always have short seizures, um uh the presence of or the prescription for a rescue medication causes more anxiety in the parents. It's sort of creates this thing that needs to travel with the child and needs to always be present and needs to always be available, um which in the child who tends to have short seizures um is unnecessary and can create anxiety and, and guilt if the parents didn't bring the usual rescue with them. Um Water precautions is something else that I that I make sure that I discussed with my patients parents, so no unmonitored baths. It's better for patients to take showers than it is to take baths if possible. Um if they are going to be swimming or taking baths, it's important for there to be a 1-1 monitor. Um there, so an adult who is um strong enough to carry the child and who is looking at that child one on one. So this is, you know, they're going to be in a pool. This isn't the life saver or the lifeguard in the pool. This is literally somebody who is looking at the child the entire time that they are in the pool. In general, I don't let any of my patients scuba dive unless they've been seizure free for quite a long time. Um and that's because it's nearly impossible to rescue somebody who's having a seizure while scuba diving. And then um in general, I encourage people not to do swimming in what we call dark water, so in lakes or or somewhere where you can't see the bottom, that's because if somebody has a seizure um and and they sink and you're not able to see them, you know, you don't have sort of a nice contrast between the bottom of the pool and and their bodies. It's often hard to to rescue them too. So if there and if if they're going to go on on on on a lake or something like that, I I definitely encourage them to always make sure that they're wearing a life jacket. Um And obviously that's something that every every child should do, but it's especially important for patients who have epilepsy driving. So as you guys know, California's Amanda mandatory reporting um state for seizures to the G. M. B. And that's something that the the physician has to do. We, you know, if if the patient is seeing a neurologist um we do a really great job of doing that. So I don't, you know, once they're seeing a neurologist, I don't think the pediatricians need to do that reporting. But until that happens um it is it is important to both uh tell the parent the patient that they cannot drive until they've been seizure free for some time and make that uh that reporting to the to the D. M. V. And finally the D. M. V. Makes the decision about how long um you have to wait before you have another seizure. And so once that patient has been reported to the D. M. V. Usually they give the form that they then bring back to the neurologist to uh inquire more details about this the um epilepsy um and based on that they will determine whether or not they can drive. So um again the take home points that I wanted uh to um have you guys to take home today? It was that um really was that the recurrence risks based on each first seizure category? So, unprovoked seizures have a risk of 45 of seizure. Recurrence Febrile seizures have 2-5 risk of recurrence Um of of developing epilepsy rather, and 30 risk of having additional febrile seizures. acute symptomatic seizures have somewhere between 15 and 20 risk of Developing epilepsy and then remote symptomatic seizures can be as high as 70%. So I um that was all I was gonna chat with you guys about here on my references. Um This is our epilepsy team at um at UCSF um and then um we have a nice easy way to refer patients to us if you guys need us.