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Neurology

Febrile Seizures

Febrile Seizures are among the most common neurological problema in young children, occurring in 1 out of 50 children between the ages of 6 months and 5 years of age. This episode of PEM Currents: The Pediatric Emergency Medicine Podcast is a Question and Answer style exploration of some of the most common learning points in this incredibly important topic.

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References

Xixis KL, Samanta D, Smith T, et al. Febrile Seizure. [Updated 2024 Jan 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448123/

Feenstra B, Pasternak B, Geller F, et al. Common variants associated with general and MMR vaccine-related febrile seizures. Nat Genet 2014; 46:1274.

Mullan PC, Levasseur KA, Bajaj L, Nypaver M, Chamberlain JM, Thull-Freedman J, Ostrow O, Jain S. Recommendations for Choosing Wisely in Pediatric Emergency Medicine: Five Opportunities to Improve Value. Ann Emerg Med. 2024 Feb 11:S0196-0644(24)00017-9. doi: 10.1016/j.annemergmed.2024.01.007. Epub ahead of print. PMID: 38349290.

Guedj R, Chappuy H, Titomanlio L, De Pontual L, Biscardi S, Nissack-Obiketeki G, Pellegrino B, Charara O, Angoulvant F, Denis J, Levy C, Cohen R, Loschi S, Leger PL, Carbajal R. Do All Children Who Present With a Complex Febrile Seizure Need a Lumbar Puncture? Ann Emerg Med. 2017 Jul;70(1):52-62.e6. doi: 10.1016/j.annemergmed.2016.11.024. Epub 2017 Mar 2. PMID: 28259480.

Shinnar S, Hesdorffer DC, Nordli DR Jr, Pellock JM, O’Dell C, Lewis DV, Frank LM, Mosh√© SL, Epstein LG, Marmarou A, Bagiella E; FEBSTAT Study Team. Phenomenology of prolonged febrile seizures: results of the FEBSTAT study. Neurology. 2008 Jul 15;71(3):170-6. doi: 10.1212/01.wnl.0000310774.01185.97. Epub 2008 Jun 4. PMID: 18525033.

Murata S, Okasora K, Tanabe T, Ogino M, Yamazaki S, Oba C, Syabana K, Nomura S, Shirasu A, Inoue K, Kashiwagi M, Tamai H. Acetaminophen and Febrile Seizure Recurrences During the Same Fever Episode. Pediatrics. 2018 Nov;142(5):e20181009. doi: 10.1542/peds.2018-1009. Epub 2018 Oct 8. PMID: 30297499.

Transcript

Note: This transcript was partially completed with the use of the Descript AI

Welcome to PEMCurrents, the Pediatric Emergency Medicine Podcast. As always, I’m your host, Brad Sobolewski. This episode is all about febrile seizures, one of the most common neurological problems that you will see in the emergency department in children. And you know what? I’m going to structure this episode like a bit of a question and answer session.

I’ll ask a question, and then I’ll answer it. So the first and perhaps most important question is, What are febrile seizures and how common are they? Well, they are the most common neurologic disorder of infants and young children, and they happen in about 2 to 4 percent of children between the ages of 6 months and 5 years of age.

I’ll tell parents that they happen in about 1 out of 50 kids. It’s associated with fever, but in a child without evidence of intracranial infection. They are not considered a form of epilepsy. They peak between 12 and 18 months of age, the male to female ratio is 1. 6 to 1, and there is a higher prevalence reported in certain regions like Japan’s Mariana Islands.

A febrile seizure, very simply, is a convulsion associated with a temperature greater than 38 degrees Celsius. The child does not have any acute systemic metabolic problems like hypoglycemia or hyponatremia, and you don’t have to test for those. We’ll talk about that later. And they have no history of previous afebrile seizures.

So why do they happen? Well, they’re likely related to a vulnerability of the developing nervous system to the effects of fever. The neurons that generate these seizures aren’t completely myelinated until age 6. And these neurons that are undermyelinated are more hyper excitable by cytokines during fever in these younger children who get sick more often.

And of course, underlying genetic susceptibility plays a role. And so other risk factors include a high fever, A viral infection, certainly particular viruses. A recent immunization. Hmm. Family history of febrile seizures. Prenatal exposure to nicotine. Atopic diseases. And maybe iron deficiency anemia. And so check this out.

Febrile seizures are due to the degree of fever, not the rate of temperature rise, even though we see them as the temperature is increasing rapidly in the early parts of the illness. And this has been known since the 1950s. The majority of children have febrile seizures on the first day of illness. In some cases, it’s actually their first manifestation of illness.

Like, they’re just a little bit congested, and then they’re convulsing. And then they find out that they’re febrile. The degree of fever associated with febrile seizures is variable, and it depends on the kid’s threshold convulsive temperature. So everybody has a little bit of a different set point. But most often, the fever is greater than 39 degrees Celsius, but 25 percent of febrile seizures do occur between the temperatures of 38 and 39.

In a study of just over 100 children, the temperature of febrile seizures was significantly higher than the mean temperature of fevers in children that did not have seizures, so 104 versus 103. 3. The seizure threshold is lower in infants. who have more febrile illnesses. So viral infections are often associated with high fever in kids, you know that.

One of the most classic viruses associated with febrile seizures is HHV 6. So human herpes virus 6. Another common one is influenza, specifically influenza A. So HHV 6 is the cause in one third of all first time febrile seizures in U. S. children under 2 years of age. The mean maximum fever in infants with a primary HHV 6 infection is generally 39. 5 Celsius, so 103 Fahrenheit or higher. So the incidence of febrile seizures associated with primary HHV 6 infection is estimated as high as 36 percent in 12 to 15 month olds. Other common causes include adenovirus RSV, HSV, CMV, HHV 7, and in Asia, influenza A is number one. The type of viral infection is not important in predicting the future recurrence of febrile seizures or whether or not the child will have a complex febrile seizure.

In kids up to two and a half years of age, breastfeeding may be a preventative factor for febrile seizures. Vaccines don’t cause autism, but they might cause febrile seizures. So the risk of febrile seizures is increased after administration of diphtheria, tetanus, toxoid, and whole cell pertussis, along with measles, mumps, rubella, and MMR with varicella vaccines.

The absolute risk is small, and genetic susceptibility likely plays a role in seizures after vaccines. The risk of a future febrile seizure with a subsequent vaccine is generally lower than the risk of the disease that you are vaccinating against. In drug company sponsored studies, the absolute risk of a febrile seizure after an MMRV vaccine is about 3 to 4 febrile seizures for every 100, 000 children receiving the vaccine.

So again, pretty darn low. So how do we categorize febrile seizures? We all know that there’s simple, That may not be the best terms, but that’s what we’ve got. So the focality, in a simple febrile seizure, they are generalized. A complex febrile seizure is focal, so the shaking is limited to one limb or one side of the body.

The duration, the duration for simple febrile seizures is less than 15 minutes, though 10 minutes has been proposed. Complex febrile seizures, on the other hand, are longer than 15 minutes. A simple febrile seizure is limited to a single episode in a 24 hour period, whereas complex febrile seizures, there is a recurrence of more than once in that 24 hour period.

Overall, 80 percent or more febrile seizures are simple, and 20 percent are complex. Ultimately, though, the history that you get may not be reliable. Both the motor movements and characteristics of the seizure, as well as the duration, are really hard to assess in a patient’s home. Obviously, you should ask about immunization status and whether or not the child has any underlying medical or neurologic problems or developmental delay.

And let’s be honest, the term simple sort of undersells how scary this is for families. There’s nothing simple about watching their child have convulsions and looking like they were gonna die. And why does the complex heterogeneity? Think about it this way. Two one minute seizures occurring an hour apart in a well appearing febrile child seem different than focal one sided convulsions or febrile status epilepticus.

More research is needed. So what’s the recurrence risk after febrile seizures? This is an important thing that we talk to families about. So the overall recurrence rate is approximately 30 to 35%. I will tell parents it’s a one in three chance. If you have two or more febrile seizures, you have a 50% chance of subsequent events.

The subsequent seizure is almost always similar to the first. So 95% of initial simple febrile seizures have recurrent, simple febrile seizures. And interestingly, they’re usually about the same length as well. The risk of recurrence is much higher in children under 12 months of age. So, though it’s one third overall, it’s about 50- 65 percent in children under 12 months of age when they have their first febrile suture.

In older children, like preschool and above, the risk is less than 20 percent. In a study published by Berg in Archives of Pediatrics and Adolescent Medicine in 1997, when I was a freshman in college, they looked prospectively at 428 children with a first febrile seizure. They noted that 17 percent had one recurrence, 9 percent had two recurrences, and 6 percent had three or more.

Three quarters of these recurrences were within one year of the initial seizure, and almost all were within two years. They found four factors for increased recurrence risk. Young age, history of febrile seizures in a first degree relative, lower degree of fever while in the emergency department, and brief duration between the onset of fever and the initial seizure.

Kids with all four of those had a 70 percent risk of recurrence, none of them only 20%. Complex features on the initial seizure were not associated with the risk of recurrence. Other factors that have been reported regarding recurrence in the literature include abnormal development before the first febrile seizure, recurrence of seizures within the same illness, children with one recurrence, and of course children who have had an unprovoked seizure after a febrile seizure are more likely to have future febrile seizures.

So what’s the risk of epilepsy following a febrile seizure? Well, 1% One out of a hundred human beings have epilepsy. If you have one simple febrile seizure, your risk of epilepsy is somewhere between 1 and 1. 5 percent. So it really doesn’t go up significantly. In a normal child with a simple febrile seizure, that risk is only slightly above that of the general population.

So they don’t really need a neurologic workup. Complex febrile seizures or a child with abnormal developmental history, or a child with a family history of epilepsy, have a risk of epilepsy development of about 5 to 10 percent after a febrile seizure. Some other factors related to the risk of epilepsy, if that first seizure is complex, the risk of epilepsy is about 18 times that of simple febrile seizures.

If the child has focal seizures, prolonged seizures, and repeated episodes within 24 hours during the same illness, the risk of epilepsy is 2%, 7%, 20 percent and 50 percent was 3, or all of those risk factors. One cohort study of almost 200 children with febrile seizures found the risk of epilepsy was highest in the first five years and appeared to decrease over time.

And other risk factors for epilepsy that have been identified in independent studies include Todd’s paralysis, short fever duration before the seizure, late onset of febrile seizures over three years of age, and multiple febrile seizure recurrences. There’s a tenfold increase. So what’s the evaluation and management for simple febrile seizures?

I joke that it’s discharge home, but really, Choosing Wisely recommends that we do not order laboratory studies or CT scans for a patient with a simple febrile seizure who has returned to baseline mental status. Labs just aren’t necessary. This postictal period is usually brief, so 20 to 30 minutes or up to 2 hours.

I think 2 hours is too long. And if the kid returns to a neurologic baseline, they’re unlikely to have a metabolic or structural abnormality that you’re going to need to identify. So in that child who has recovered with a normal neurological examination, You don’t need labs. They’re painful, they can give you erroneous or unexpected or irrelevant results, and they’re expensive.

So really focus on targeted testing. If you think they’re at risk for a UTI, well, yeah, get a urine. Go after COVID and flu if you think the swabs are beneficial or strep, but otherwise, you can avoid labs. In general, I think parents are most worried that their child’s gonna have a brain tumor or something wrong inside their head, and naturally, their minds will gravitate towards getting a CT scan.

These are expensive studies with a large amount of radiation, and in the absence of concerning signs on history in the exam, the rate of scarring abnormalities, mass, stroke, or other problems is really, really low, so like less than 1%. So in general, you don’t need a CT scan to show that the brain looks normal.

Children with recurrent febrile seizures or epilepsy following febrile seizures benefit more from MRI and EEG. What about complex febrile seizures? How do we evaluate and manage them? So again, focal onset greater than 15 minutes and or recurrent within 24 hours. The majority of children who develop complex febrile seizures will do so with their first seizure.

Todd’s paresis, so transient hemiparesis following a febrile seizure, usually of a complex or focal type, is rare and happens in about 1. 5 to 2 percent of cases. Prolonged or focal febrile seizures have a higher likelihood of meningitis or structural abnormalities, but still that risk is low. And so even in complex febrile seizures, if the child recovers, EEG or MRI may be the only test, if any, that they need.

You should develop a specific plan for each patient with each patient. A pediatric neurologist. So in terms of lumbar puncture, yes, you can get an LP and CSF studies to exclude meningitis or encephalitis in a child with a complex febrile seizure. The literature has long told us that in children older than 6 months of age who are completely vaccinated, you do not need to get an LP and CSF.

to rule out meningitis in a child with a simple febrile seizure. Admittedly, 25 percent of children with meningitis will have seizures at or before the initial presentation, but almost all of these kids will also have other signs and symptoms of meningitis, like altered consciousness, nuclear rigidity, a petechial rash.

So if you have a child with a complex febrile seizure, but they don’t have any other signs of meningitis, you don’t necessarily need to tap them. If febrile seizures occur after the second day of illness, if you have febrile status epilepticus, these should be other considerations as to whether or not an LP is needed.

But overall, the yield of LP is very low. Now note that pleocytosis can be seen in epileptic seizures, but it’s actually rare in febrile seizures without meningitis. So what does the AAP say? Well, they say that LP should be performed when there are meningeal signs or symptoms or other clinical features that suggest possible meningitis or intracranial infection.

Yeah, you should consider it in infants between 6 and 12 months of age if the immunization status for Hib or strep pneumonia is deficient or undetermined. So, 3, Strep pneumos, and two or three HIBs. And you should also consider an LP when the patient is on antibiotics, because antibiotic treatment could mask the signs and symptoms of meningitis.

This is perhaps the most nuanced scenario. If a child has a complex febrile seizure, and fortunately it’s a rare one that you’ll see, but you should consider, maybe they’re on otitis media, and then they have a febrile seizure, and it’s complex, probably tap that kid. In a study from Kim published in Pediatrics in 2010, they looked at 526 children with complex febrile seizures.

Almost two thirds of this population got lumbar punctures and only three had meningitis, all with a reason to suspect it. So one was clinically non responsive, one had a bulging fontanel and apnea, that’s a bad combo, and one was well appearing but had a positive blood culture for strep pneumonia and they didn’t do an LP, so they just presumed that they have meningitis?

I’m squinting. You can’t see that on the podcast, but that kid probably didn’t have meningitis. Another relatively large cohort of children with complex febrile seizures, published in 2017, showed that the incidence of bacterial meningitis in 839 patients with complex febrile seizures was 0. 7%, and none of them had HSV.

All five of those patients with meningitis had a concerning exam, and four out of five were less than 12 months of age. So, if somebody with a complex febrile seizure is going to have meningitis, there’s going to be other stuff going on. Simple febrile seizures do not require neurology consults or admissions.

They can be discharged home. Previously healthy and developmentally and neurologically normal children with two brief self resolved seizures within a 24 hour period, so technically a complex febrile seizure, can be discharged home with as needed neurology referral if the family and you are comfortable with that plan.

For Febrile status epilepticus, you should stop the seizure with medicines and admit to neurology in the PICU. And complex febrile seizures with focal features, strongly consider admission and always discuss with child neurology. And so briefly, let’s talk about that neurology referral and follow up.

Neurology will often see children in the near term with complex febrile seizures who you felt are safe for discharge but need evaluation. EEG itself is not useful in determining the risk of recurrent febrile seizures. If you’re looking for epilepsy, abnormalities are more likely to be seen on EEG when it’s performed shortly after the seizure, so less than 10 days, and when convulsions are of a longer duration and have focal features.

In children with focal complex febrile seizures, neurology is almost always going to get an MRI as well, and in children under 6, they’re probably going to need general anesthesia to do that. Alright, so what about the management of febrile status epilepticus? So originally this was defined as greater than 30 minutes.

It’s back down to 15 minutes, but there’s a current movement to define status epilepticus as greater than 5 minutes. And 5 minutes is a really long time to watch a kid seize, so I get it. In 1 third of febrile status epilepticus, the actual seizure duration is underestimated in the emergency department.

And the clinical clues that a seizure has ended are often subtle. So a child that is no longer seizing will have closed eyes and deep breathing. If the eyes are persistently open and deviated, even if there’s no limb convulsions or stiffening, they may have ongoing focal seizures. It’s really hard to figure this out.

I’ve also seen kids that are febrile having rigers, or just from a sympathetic surge after a seizure. So, response to painful stimuli, closed eyes, regular breathing. These are all subtle findings along with your vitals like capnography that can help you figure out if that kid is still seizing. In a wonderfully named study called Febstat, which was initially published back in 2008 as a multi center perspective cohort of 119 children one month of five years with febrile status, they noted that the median duration of seizures was 68 minutes.

They were convulsive in all but one child. They were continuous in half and intermittent in the other half. Two thirds of these status. Patients were partial. It was the first febrile seizure for 3 out of 4 children in the study. And HHV 6 was the most common identified infectious etiology. There was also a higher than expected family history of epilepsy in this population.

So if the seizure is going on longer than 5 minutes, start with an IV benzodiazepine if you can. So diazepam or lorazepam. Buckle midazolam or rectal formulations like diastat are alternatives if you don’t have an IV. If that first benzodiazepine doesn’t work, give it again at five minutes. If that doesn’t work five minutes later, give a second line drug.

Generally, levotiracetam or Keppra is the first choice for second line, but you could use fosfenitoin or valproate if you’ve got them. So are febrile seizures associated with an increased risk of mortality? This is very pertinent to familial concerns. Early reports actually suggest that febrile seizures were associated with an increased risk of sudden death later on.

We found that that’s probably not true and that small excess in mortality is really restricted to complex febrile seizures. These patients have pre existing neurologic abnormalities. Those are the ones that are really most at risk. Alright, well what about prescribing preventative medicines or rescue drugs?

I don’t think that children that have a single simple febrile seizure need to be prescribed rectal diastats. But if they’ve had a prolonged febrile seizure, including febrile status epilepticus, or have had multiple febrile seizures, prescribing diazepam rectal gel or midazolam nasal spray in an older child who is an appropriate size could be a good idea.

One dose administered rectally or nasally will not lead to respiratory depression. And so in general, if you’ve got a child that’s at risk for a prolonged future febrile seizure, are good candidates for rescue meds. through a process of shared decision making. Now, you could prevent the risk of subsequent febrile seizures by putting a kid on prophylactic anti epileptic medications.

Most febrile seizures are benign and the side effects of the AEDs generally outweigh the benefits. So you don’t need to put somebody on phenobarbital to stop them from having another febrile seizure. So the use of antipyretics, so acetaminophen, ibuprofen, at the first sign of fever does not prevent a recurrence of febrile seizures in a child that’s had one before.

Morata and colleagues did a single center perspective randomized control trial back in 2018 that noted that regular antipyretics may reduce the recurrence of febrile seizures during the same fever episode, so during that illness. But other studies, including one from Rosenblum back in 2013, which was a meta analysis of three RCTs of acetaminophen, ibuprofen, and diclofenac, starting antipyretics, at the onset of illness could not reduce the rate of recurrent febrile seizures compared with placebo.

Why don’t antipyretics work? Well, they facilitate heat loss, but they don’t inhibit heat production, or lower the threshold convulsive temperature during the initial stage of fever that triggers a seizure. Now, interestingly, phenobarbital can actually treat fever and seizures, but, you know, there’s side effects, so it’s not recommended.

Okay. So is there anything else on the differential? If you’re sure it’s a febrile seizure and you know what you’re doing, generally, you’re right. But, kids can have shaking chills, which are involuntary movements in febrile children that are fine, rhythmic, and oscillatory movements about a joint. They rarely involve the facial or respiratory muscles.

They usually involve both sides of the body simultaneously, and they are not associated with the loss of consciousness, and they are suppressible by touch. So shaking chills can easily be differentiated from fevers. Children with breath holding spells, the cyanotic or pallid types, will sometimes have stiffening or convulsing when they lose consciousness.

And yes, I’ve seen kids with colds and fever who have breath holding spells. And then there’s genetic epilepsy plus febrile seizures, which you are not going to diagnose in the ED. These are autosomal dominant seizures. mutations of sodium and calcium channels that lead to seizures with fever in early childhood that continue beyond six years of age.

And then there’s Dravet syndrome. So, Dravet syndrome is also known as severe myoclonic epilepsy of infancy. It will often resemble complex febrile seizures under one year of age. It’s a de novo mutation, so not inherited, of a voltage gated sodium channel in more than 80 percent of the patients with it.

So that’s why phosphenytoin doesn’t work in Dravet syndrome. And if you’ve heard of Dravet, probably the only thing you remember is that phosphenytoin doesn’t work. And I’ve been told by a wise pediatric neurologist where I work that Any female patient under 12 months of age with complex febrile seizures has Dravet syndrome until proven otherwise.

So that’s one special population with a complex febrile seizure, even two in a 24 hour period that deserves special workup. So let’s end with the last and perhaps most important question. How do we talk to families about febrile seizures? Well remember, they are scared, right? I would acknowledge that this was perhaps the most frightening thing they’ve ever seen their child do.

They are worried that it’s not going to stop and that their child would die. They may have felt helpless, but reinforce what they did right. Maybe they moved their child to the floor in the rescue position, or quickly called 911, or got help. All of these are active decisions that the family made to help their child, even if they could not have prevented the febrile seizure.

Define what a seizure is in ways they’ll understand, including how common febrile seizures are. Again, simple febrile seizures, 1 out of 50 children. Explain how the body protects itself during seizures. So there’s a sympathetic surge leading to increased heart rate. The skin will look pale due to peripheral vasoconstriction and shunting of blood to the core organs.

And when you’re seizing, you will close your glottis, your vocal cords, to prevent from aspiration, which leads to perioral cyanosis. So parents often will recall their child stiff, convulsing, and blue in the face. All of these are physiologic things that we expect during seizures, and I think it’s important to address how those were things that the body did You are certainly going to want to say whether or not the child had a simple or complex febrile seizure, because that will dictate what you do next.

Discuss the recurrence risk and what to do if it happens again, i. e., one third after you’ve had one, 50 50 chance after two or more, and you should always be evaluated by default. Talk about the use of antipyretics and their limited impact on recurrence. So they could reduce the risk during this illness, but they don’t necessarily reduce the risk in a future febrile illness.

And use lab tests, and especially CT scans of the brain judiciously. In a child who has recovered, is back to their baseline, has a normal neurologic exam, and no underlying neurologic problems, they’re unlikely to recover. to have any central nervous system abnormalities seen on imaging, nor any significant metabolic or infectious abnormalities seen on targeted lab testing.

So it’s A OK to not get any studies, but remember, you’re not doing nothing. You’re providing education and reassurance to a worried family. You can do this. If the child has recovered and you think it’s a simple febrile seizure, even if you’ve never seen one before, you’re gonna be right. You They’re that common.

I definitely recommend that you practice your speech or approach to febrile seizures before you go into the room if you haven’t done this before. So find an experienced senior resident, fellow, or attending and review it with them. You want to make sure that you can both give the family useful information.

but also not overwhelm them and anticipate what questions they might have. Well that’s it for this episode focused on febrile cedars. I hope you found it useful and will take the information back with you to your next shift in the emergency department. If you have suggestions for other topics that you’d like me to address in the future, send them my way.

I’ll take an email, a comment on the blog, a message on a social media platform of your choosing. My 12 year old told me that I should remind you to subscribe, and and review. Bottom line is I’m just happy if more people listen because that means more people learn and any feedback you can send in my direction, even if it’s in the form of a review, is very welcome.

For PEM Currents, the Pediatric Emergency Medicine Podcast, this has been Brad Sobolewski. See you next time.