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Epilepsy in Infants
S. Parrish Winesett, MD, explains afebrile seizures in the first year of life. He contrasts and compares the significance of febrile and afebrile seizures and if a child has a history of neonatal seizures and what providers can tell the parents to look for to signal a recurrence of seizures.
Featuring:
Dr. Winsett graduated from the University of Florida with a degree in microbiology and received his medical degree from the University of South Florida. He trained in pediatrics and internal medicine at the University of South Florida, child neurology at Vanderbilt University and epilepsy at the University of South Florida and the Cleveland Clinic.
Learn more about S. Parrish Winesett, MD
S. Parrish Winesett, MD
S. Parrish Winesett, MD, is a board-certified pediatric neurologist and pediatric epileptologist He has had extensive experience with complex epilepsy, including pre-surgical evaluations and advanced EED monitoring. He also has expertise in nonpharmagologic treatments for epilepsy, including vagal nerve stimulation and special diets, such as the ketogenic diet and the modified Atkins diet.Dr. Winsett graduated from the University of Florida with a degree in microbiology and received his medical degree from the University of South Florida. He trained in pediatrics and internal medicine at the University of South Florida, child neurology at Vanderbilt University and epilepsy at the University of South Florida and the Cleveland Clinic.
Learn more about S. Parrish Winesett, MD
Transcription:
The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of .25 AMA PRA category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I’m Melanie Cole and today, we’re discussing epilepsy in infants. Joining me is Dr. S. Parrish Winesett. He’s an Associate Professor of Pediatrics in the Division of Pediatric Neurology specializing in epilepsy at the University of Florida College of Medicine and he practices at UF Health Shands Children’s Hospital in Gainesville, Florida. He will explain afebrile seizures in the fist year of life. He’ll contrast and compare the significance of febrile and afebrile seizures and if a child has a history of neonatal seizures, what providers can tell the parents to look for to signal a recurrence. Dr. Winesett, it’s a pleasure to have you join us today. Tell us a little bit about the prevalence of seizures in infancy and why it’s important that we know about this.
S. Parrish Winesett, MD (Guest): Well the first thing is, is that during the first year of life, is one of the highest years for the incidence of epilepsy. Individually, each year is a little bit, but the first year is 70 out of a 100,000 patients will have epilepsy. And this is when a lot of our intractable epilepsies present.
Host: Well then let’s start with neonatal seizures Doctor. When should we worry? Please explain the significance of seizures in the first 28 days of life for a term infant.
Dr. Winesett: So, neonatal seizures are seizures that occur around the neonatal period. And one of the most important things to determine, if you’re a pediatrician seeing these patients in follow up, is was the neonatal seizure symptomatic with some sort of insult that is now resolved or was this not symptomatic? The difference is that if you look at studies in most neonates, the most common cause of seizures in a term neonate is hypoxic ischemic encephalopathy. So, this is an insult either right before, during or after birth and often they will seize at about 24 hours of life and seize for two to three days and then they stop seizing. For those patients, many of them will never seize again.
We look at data and what we find is there’s a group that has severe hypoxic ischemic encephalopathy who account probably for 86% of the future seizures in the group of patients who have neonatal seizures with hypoxic ischemic encephalopathy. For the children that have mild HIE, they almost never have seizures either around birth or later on. Moderate HIE, they will have a risk that is small, probably much less than 17%. And these kids continuing medicines after the neonatal period is probably not helpful.
The patients with severe hypoxic ischemic encephalopathy unfortunately are a group in which they often have cerebral palsy, intellectual disability and seizures. This group, there probably is not that much help from continuing the seizure medicines but unfortunately, they will often present with seizures later on in life. The medicines that we start at birth may delay the onset but don’t prevent epilepsy. The problem is most of these patients are – about half of these patients actually will present with infantile spasms which is not treated by routine seizure meds.
Host: And before we decide or discuss when a NICU graduate can be weaned off meds; what investigations do you do Dr. Winesett? What other conditions might have caused the seizure? Are there some red flags to help you in your diagnosis? What are some key considerations in your acute assessment?
Dr. Winesett: So, one of the main things is I look to see when the seizures occurred, when they began and when they stopped. If you get that history that this is a baby, particularly if they are term, and they had seizures from one to four days and there is evidence that it was hypoxia; then most of those patients can be safely weaned. In fact, we wean them before they leave the hospital but certainly can be weaned by six weeks to two months. If on the other hand, they started seizing after that period; then you start to think of other etiologies. There are certain etiologies in which they probably are not going to do well long term as far as seizures such as meningitis is one of the big ones. These kids unfortunately, have a lot of diffuse inflammation on the cortex and because of that will have seizures that are intractable and continue to occur.
If you have someone who continues to have seizures, even though they started in those first few days of life and continue to have seizures at one month, two months; a lot of those have different etiologies which are going to be tougher to treat and probably shouldn’t have meds weaned at that time.
Host: So, when can you suspect that a NICU graduate can be weaned off those meds?
Dr. Winesett: Mainly going by the criteria of is this a symptomatic etiology such as hypoxic ischemic encephalopathy that resolved. Sometimes bleeds can act this way. If you have a bleed in the neonatal period that stabilizes and it is a insult, particularly the intraparenchymal bleeds. A lot of those patients if they go a few months without any seizures and don’t seize after four to five days; then they will do well. The other group is strokes. Strokes certainly are a cause of seizures later on in life but most of the time, if you have seizures at the neonatal period, it will be that same one to four day period and then after that, they will do fairly well. They may present again at three to four years of age with seizures but continuing them on medicines is probably harmful to the development and they’ll do better if you wean them off the seizures after the acute event.
Host: If a child has a history of neonatal seizures, what should providers tell the parents to look for to signal a recurrence of those and do you have any predictors of future events?
Dr. Winesett: So, one of the things you need to think about is that most seizures in babies, particularly neonates under sic months of age, are not going to be generalized tonic clonic seizures. The brain is not connected in ways that allow for generalized tonic clonic seizures in most instances. There are a few notable exceptions such as pyridoxine deficiency but for the most part, you’re going to get partial seizures in the first few months of life. So, if you’re telling a mom that you want her to look for seizures, things that I would say is look for periods of unresponsiveness, particularly if the eyes are fixed to the hard left or hard right. They can have unresponsiveness with jiggling eyes at times. They may have this very subtle rhythmic clonic jerking of one extremity and these are the ones the get missed a lot of times. The clonic jerking of one extremity will often occur for a fixed period of time and stop. So, if I hear a history of rhythmic jerking of one extremity for say one minute, five minutes, maybe even ten minutes; but then it starts and then has a beginning and then a definite end; then you want to think this may be a seizure. In older kids, a lot of times those seizures will generalize and become a generalized tonic clonic seizure but because the neurons are not connected as much in the first six months of life; then you don’t get that generalization.
Host: So, as we’re talking about afebrile seizures, are there times we should worry about febrile seizures? Please contrast and compare the significance of these two types of seizures and at what age do they typically present?
Dr. Winesett: So, this is really the after six months. So, almost all seizures under six months are worrisome. If they are febrile, you are worried about meningitis and infectious etiologies. But after six months, you get into the febrile seizure group and febrile seizures are once again a provoked seizure. Meaning that there is a reason the child seized and that’s a fever. And the fever should be a real fever, it can’t be 99.5. It needs to be a significant fever and these kids will often have generalized relatively brief meaning less than 15 minutes seizures that occur once during a febrile episode and those kids have a very good prognosis. In fact, their prognosis with simple febrile seizures is probably almost as good as the prognosis if you never had a seizure. There is a slight increase but it’s still much less than 2%.
If you start to have complicating features, then you have to start worrying more and more and what we most worry about is this group of kids that have seizures which are very prolonged, lasting up to an hour, often are one sided and they can switch sides even during the same seizure and clustering groups of four to five in 24 hours. In this group, we have to worry about certain gene mutations and this group has been called Dravet syndrome among other things. There’s also a milder variant called general febrile seizures plus but what we worry most about is the Dravet syndrome which will often be very normal infants who start to have febrile seizures at nine months. But it’s not simple febrile seizures. These children rapidly declare themselves as having clusters of seizures, having very prolonged seizures and it’s pretty obvious early on that this patient is something different than a regular febrile seizure patient.
These are kids that we want to become involved with quickly. There is now genetic testing that we can do to identify them, and we can often get them on medications that will be more effective than routine antiseizure medications.
Host: Along those lines, do you have an active management algorithm? What initial treatments do you use?
Dr. Winesett: For the Dravet syndrome, we often will start these kids on medicines that we typically try to avoid in infancy, valproic acid, clobazam, and them we proceed on to some of the newer medicines such as the cannabinoid that was recently approved and there’s a few others that are now being approved. But these are not medicines you would typically use for epilepsy in the first year of life, but they are much more effective in this Dravet syndrome category.
Host: So, Dr. Winesett, please describe what patients would benefit from early surgical intervention and what we have recently learned about that.
Dr. Winesett: So, one of the things that’s come out recently is a very good paper, position paper from the International League Against Epilepsy. And it’s really targeted these children that have afebrile seizures in the first year of life. The reason they do that is because at least a third of them will end up being medically intractable and those that are medically intractable often have severe developmental delay. So, if we can identify those kids early, we can do a much better job of treating them. And one of the treatments that is very effective is surgical intervention. We know from the tubular sclerosis literature that if you can stop seizures between six months and 12 months of age; that this seems to be a critical time period for preventing autism. So, kids with tubular sclerosis often end up with autism and if you look at that group, most of them have had seizures between six months and 12 months of age.
So, if we can intervene and we certainly do this in the tubular sclerosis population and stop seizures by six months so that they go through the six month to 12 month range without seizures; we think we markedly improve their quality of life, their chance for normal development and future function. Unfortunately, we do not get a chance to evaluate many of these children before six months of age. So, one of the things we like to emphasize is that if you have an infant with afebrile seizures, this person probably needs to be evaluated by a specialist in epilepsy for infants and that person can then try to rapidly try medications because we would certainly like to use medications but if they are intractable to medications; to proceed on to a surgical evaluation. We think this is the ideal time to intervene on these children and have them have a better life and the chance for more normal development.
Host: What a fascinating topic. Dr. Winesett as we conclude, please let other providers know what you’d like to tell them about epilepsy in infancy and when you feel it’s important that they refer to the experts at UF Health Shands Hospital?
Dr. Winesett: I think the most important thing is to try to decide whether the child has febrile seizures. These are very benign and probably will do very well whether they see us or not. Or is this a child with afebrile seizures? So, one of the key things is you have to determine if they have seizures and we would prefer that you refer them early so that we can do appropriate studies and one of the best studies amazingly, is to get the parents to do a video of the spells. If they bring us a video from their cell phone of this spells, often we can say these are not seizures, these are not epilepsy. Your child is going to do fine. We can reassure them and avoid a lengthy and expensive workup. If, on the other hand, they bring us a spell which is clearly epilepsy; then we want to rapidly intervene on these children and try to optimize their treatment before that six to 12 month window. That’s not to say if they start having seizures at seven months that we don’t try to do our best and intervene so that we can save them from future seizures. But we certainly like them sooner rather than later.
I think that it’s really important to realize that even in children who look to be having normal development; if they have a seizure that is afebrile and clearly an epileptic seizure; probably a third of these will end up developmentally delayed. So, this is a group that we want to be very aggressive with. On the other hand, if they have seizures that are symptomatic or provoked either febrile seizures or seizures in the neonatal period from HIE; those children probably do better if we don’t treat them with antiseizure medicines and they are allowed to develop without having antiseizure medicines on board.
Host: Thank you so much Dr. Winesett for coming on with us today and sharing your incredible expertise on this topic. That concludes this episode of UF Health MedEd Cast with UF Health Shands Hospital. Please visit www.ufhealth.org/pediatrics for more information and to get connected with one of our providers. Please also remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I’m Melanie Cole.
The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of .25 AMA PRA category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.
Melanie Cole (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I’m Melanie Cole and today, we’re discussing epilepsy in infants. Joining me is Dr. S. Parrish Winesett. He’s an Associate Professor of Pediatrics in the Division of Pediatric Neurology specializing in epilepsy at the University of Florida College of Medicine and he practices at UF Health Shands Children’s Hospital in Gainesville, Florida. He will explain afebrile seizures in the fist year of life. He’ll contrast and compare the significance of febrile and afebrile seizures and if a child has a history of neonatal seizures, what providers can tell the parents to look for to signal a recurrence. Dr. Winesett, it’s a pleasure to have you join us today. Tell us a little bit about the prevalence of seizures in infancy and why it’s important that we know about this.
S. Parrish Winesett, MD (Guest): Well the first thing is, is that during the first year of life, is one of the highest years for the incidence of epilepsy. Individually, each year is a little bit, but the first year is 70 out of a 100,000 patients will have epilepsy. And this is when a lot of our intractable epilepsies present.
Host: Well then let’s start with neonatal seizures Doctor. When should we worry? Please explain the significance of seizures in the first 28 days of life for a term infant.
Dr. Winesett: So, neonatal seizures are seizures that occur around the neonatal period. And one of the most important things to determine, if you’re a pediatrician seeing these patients in follow up, is was the neonatal seizure symptomatic with some sort of insult that is now resolved or was this not symptomatic? The difference is that if you look at studies in most neonates, the most common cause of seizures in a term neonate is hypoxic ischemic encephalopathy. So, this is an insult either right before, during or after birth and often they will seize at about 24 hours of life and seize for two to three days and then they stop seizing. For those patients, many of them will never seize again.
We look at data and what we find is there’s a group that has severe hypoxic ischemic encephalopathy who account probably for 86% of the future seizures in the group of patients who have neonatal seizures with hypoxic ischemic encephalopathy. For the children that have mild HIE, they almost never have seizures either around birth or later on. Moderate HIE, they will have a risk that is small, probably much less than 17%. And these kids continuing medicines after the neonatal period is probably not helpful.
The patients with severe hypoxic ischemic encephalopathy unfortunately are a group in which they often have cerebral palsy, intellectual disability and seizures. This group, there probably is not that much help from continuing the seizure medicines but unfortunately, they will often present with seizures later on in life. The medicines that we start at birth may delay the onset but don’t prevent epilepsy. The problem is most of these patients are – about half of these patients actually will present with infantile spasms which is not treated by routine seizure meds.
Host: And before we decide or discuss when a NICU graduate can be weaned off meds; what investigations do you do Dr. Winesett? What other conditions might have caused the seizure? Are there some red flags to help you in your diagnosis? What are some key considerations in your acute assessment?
Dr. Winesett: So, one of the main things is I look to see when the seizures occurred, when they began and when they stopped. If you get that history that this is a baby, particularly if they are term, and they had seizures from one to four days and there is evidence that it was hypoxia; then most of those patients can be safely weaned. In fact, we wean them before they leave the hospital but certainly can be weaned by six weeks to two months. If on the other hand, they started seizing after that period; then you start to think of other etiologies. There are certain etiologies in which they probably are not going to do well long term as far as seizures such as meningitis is one of the big ones. These kids unfortunately, have a lot of diffuse inflammation on the cortex and because of that will have seizures that are intractable and continue to occur.
If you have someone who continues to have seizures, even though they started in those first few days of life and continue to have seizures at one month, two months; a lot of those have different etiologies which are going to be tougher to treat and probably shouldn’t have meds weaned at that time.
Host: So, when can you suspect that a NICU graduate can be weaned off those meds?
Dr. Winesett: Mainly going by the criteria of is this a symptomatic etiology such as hypoxic ischemic encephalopathy that resolved. Sometimes bleeds can act this way. If you have a bleed in the neonatal period that stabilizes and it is a insult, particularly the intraparenchymal bleeds. A lot of those patients if they go a few months without any seizures and don’t seize after four to five days; then they will do well. The other group is strokes. Strokes certainly are a cause of seizures later on in life but most of the time, if you have seizures at the neonatal period, it will be that same one to four day period and then after that, they will do fairly well. They may present again at three to four years of age with seizures but continuing them on medicines is probably harmful to the development and they’ll do better if you wean them off the seizures after the acute event.
Host: If a child has a history of neonatal seizures, what should providers tell the parents to look for to signal a recurrence of those and do you have any predictors of future events?
Dr. Winesett: So, one of the things you need to think about is that most seizures in babies, particularly neonates under sic months of age, are not going to be generalized tonic clonic seizures. The brain is not connected in ways that allow for generalized tonic clonic seizures in most instances. There are a few notable exceptions such as pyridoxine deficiency but for the most part, you’re going to get partial seizures in the first few months of life. So, if you’re telling a mom that you want her to look for seizures, things that I would say is look for periods of unresponsiveness, particularly if the eyes are fixed to the hard left or hard right. They can have unresponsiveness with jiggling eyes at times. They may have this very subtle rhythmic clonic jerking of one extremity and these are the ones the get missed a lot of times. The clonic jerking of one extremity will often occur for a fixed period of time and stop. So, if I hear a history of rhythmic jerking of one extremity for say one minute, five minutes, maybe even ten minutes; but then it starts and then has a beginning and then a definite end; then you want to think this may be a seizure. In older kids, a lot of times those seizures will generalize and become a generalized tonic clonic seizure but because the neurons are not connected as much in the first six months of life; then you don’t get that generalization.
Host: So, as we’re talking about afebrile seizures, are there times we should worry about febrile seizures? Please contrast and compare the significance of these two types of seizures and at what age do they typically present?
Dr. Winesett: So, this is really the after six months. So, almost all seizures under six months are worrisome. If they are febrile, you are worried about meningitis and infectious etiologies. But after six months, you get into the febrile seizure group and febrile seizures are once again a provoked seizure. Meaning that there is a reason the child seized and that’s a fever. And the fever should be a real fever, it can’t be 99.5. It needs to be a significant fever and these kids will often have generalized relatively brief meaning less than 15 minutes seizures that occur once during a febrile episode and those kids have a very good prognosis. In fact, their prognosis with simple febrile seizures is probably almost as good as the prognosis if you never had a seizure. There is a slight increase but it’s still much less than 2%.
If you start to have complicating features, then you have to start worrying more and more and what we most worry about is this group of kids that have seizures which are very prolonged, lasting up to an hour, often are one sided and they can switch sides even during the same seizure and clustering groups of four to five in 24 hours. In this group, we have to worry about certain gene mutations and this group has been called Dravet syndrome among other things. There’s also a milder variant called general febrile seizures plus but what we worry most about is the Dravet syndrome which will often be very normal infants who start to have febrile seizures at nine months. But it’s not simple febrile seizures. These children rapidly declare themselves as having clusters of seizures, having very prolonged seizures and it’s pretty obvious early on that this patient is something different than a regular febrile seizure patient.
These are kids that we want to become involved with quickly. There is now genetic testing that we can do to identify them, and we can often get them on medications that will be more effective than routine antiseizure medications.
Host: Along those lines, do you have an active management algorithm? What initial treatments do you use?
Dr. Winesett: For the Dravet syndrome, we often will start these kids on medicines that we typically try to avoid in infancy, valproic acid, clobazam, and them we proceed on to some of the newer medicines such as the cannabinoid that was recently approved and there’s a few others that are now being approved. But these are not medicines you would typically use for epilepsy in the first year of life, but they are much more effective in this Dravet syndrome category.
Host: So, Dr. Winesett, please describe what patients would benefit from early surgical intervention and what we have recently learned about that.
Dr. Winesett: So, one of the things that’s come out recently is a very good paper, position paper from the International League Against Epilepsy. And it’s really targeted these children that have afebrile seizures in the first year of life. The reason they do that is because at least a third of them will end up being medically intractable and those that are medically intractable often have severe developmental delay. So, if we can identify those kids early, we can do a much better job of treating them. And one of the treatments that is very effective is surgical intervention. We know from the tubular sclerosis literature that if you can stop seizures between six months and 12 months of age; that this seems to be a critical time period for preventing autism. So, kids with tubular sclerosis often end up with autism and if you look at that group, most of them have had seizures between six months and 12 months of age.
So, if we can intervene and we certainly do this in the tubular sclerosis population and stop seizures by six months so that they go through the six month to 12 month range without seizures; we think we markedly improve their quality of life, their chance for normal development and future function. Unfortunately, we do not get a chance to evaluate many of these children before six months of age. So, one of the things we like to emphasize is that if you have an infant with afebrile seizures, this person probably needs to be evaluated by a specialist in epilepsy for infants and that person can then try to rapidly try medications because we would certainly like to use medications but if they are intractable to medications; to proceed on to a surgical evaluation. We think this is the ideal time to intervene on these children and have them have a better life and the chance for more normal development.
Host: What a fascinating topic. Dr. Winesett as we conclude, please let other providers know what you’d like to tell them about epilepsy in infancy and when you feel it’s important that they refer to the experts at UF Health Shands Hospital?
Dr. Winesett: I think the most important thing is to try to decide whether the child has febrile seizures. These are very benign and probably will do very well whether they see us or not. Or is this a child with afebrile seizures? So, one of the key things is you have to determine if they have seizures and we would prefer that you refer them early so that we can do appropriate studies and one of the best studies amazingly, is to get the parents to do a video of the spells. If they bring us a video from their cell phone of this spells, often we can say these are not seizures, these are not epilepsy. Your child is going to do fine. We can reassure them and avoid a lengthy and expensive workup. If, on the other hand, they bring us a spell which is clearly epilepsy; then we want to rapidly intervene on these children and try to optimize their treatment before that six to 12 month window. That’s not to say if they start having seizures at seven months that we don’t try to do our best and intervene so that we can save them from future seizures. But we certainly like them sooner rather than later.
I think that it’s really important to realize that even in children who look to be having normal development; if they have a seizure that is afebrile and clearly an epileptic seizure; probably a third of these will end up developmentally delayed. So, this is a group that we want to be very aggressive with. On the other hand, if they have seizures that are symptomatic or provoked either febrile seizures or seizures in the neonatal period from HIE; those children probably do better if we don’t treat them with antiseizure medicines and they are allowed to develop without having antiseizure medicines on board.
Host: Thank you so much Dr. Winesett for coming on with us today and sharing your incredible expertise on this topic. That concludes this episode of UF Health MedEd Cast with UF Health Shands Hospital. Please visit www.ufhealth.org/pediatrics for more information and to get connected with one of our providers. Please also remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I’m Melanie Cole.