Pediatric Neurology 156 (2024) 4e9

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Pediatric Neurology
journal homepage: www.elsevier.com/locate/pnu

Research Paper

Clinical Profile and Predictors of Recurrent Simple Febrile Seizure

Jon Soo Kim, MD, PhD a, Hyewon Woo, MD a, Won Seop Kim, MD, PhD a, b,
Won Young Sung, MD c, *
a
Department of Pediatrics, Chungbuk National University Hospital, Cheongju, Republic of Korea
b
Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
c
Department of Emergency Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, Republic of Korea

a r t i c l e i n f o a b s t r a c t

Article history: Background: Recurrent simple febrile seizure (SFS) refers to febrile seizure (FS) that recurs within
Received 18 September 2023 24 hours. Patients with recurrent SFS often undergo unnecessary neurodiagnostic tests. To address this,
Accepted 1 April 2024 we compared the clinical characteristics of recurrent SFS with those of SFS and investigated the risk
Available online 5 April 2024
factors associated with recurrent SFS.
Methods: We retrospectively reviewed electronic medical records of patients aged six to 60 months who
Keywords:
had been hospitalized for FS at two training hospitals between January 2016 and December 2019. The
Febrile seizure
primary outcome was a comparison of the clinical features of patients with SFS and recurrent SFS.
Recurrent simple febrile seizure
Recurrence
Additionally, the risk factors associated with seizure recurrence within 24 hours were evaluated.
Fever Results: Three quarters (n ¼ 191, 75.2%) of the 254 enrolled patients experienced a single seizure episode
Risk factor during the febrile illness period. The remaining 63 patients (24.8%) were diagnosed with recurrent SFS.
Body temperature Significant differences between SFS and recurrent SFS were observed in the history of recurrent SFS, time
from fever onset to seizure, and body temperature on hospital arrival. Multiple logistic regression
analysis revealed that a history of previous recurrent SFS (odds ratio [OR] 10.161) and a body temperature
below 39 C on arrival (OR 2.377) were significantly associated with early seizure recurrence.
Conclusions: This study highlights that early FS recurrence is common and has a self-limiting clinical
course similar to that of SFS. We recommend close monitoring of the patient for six to eight hours when a
history of early recurrence is present or if the seizure occurs at a low body temperature.
© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction caregivers in the emergency department (ED): (1) whether the

cause of fever is an acute symptomatic disease such as bacterial
Febrile seizure (FS) is the most common seizure disorder in meningitis or acute encephalitis/encephalopathy; (2) that the
children, typically occurring in children aged six months to five seizure may be the first triggered seizure of epilepsy, or that it may
years.1,2 FS has an incidence of 2% to 5% in the United States and later progress to epilepsy; and (3) the possibility of an immediate
Western Europe; however, this ranges from 6% to 11% in Korea and recurrent seizure during the current febrile illness.
Japan.3-7 Although seizures are usually self-limiting and do not In cases of complex febrile seizure (CFS), which is characterized
require special treatment, parents may be worried to witness a by focal seizure semiology, prolonged seizure duration (>10 to
seizure in their healthy child. Even parents who have witnessed FS 15 minutes), or multiple seizures within a 24-hour period, health
multiple times may develop “fever phobia.”8 The following three care providers often recommend a more comprehensive evalua-
concerns arise when dealing with children with FS and their tion.9 This evaluation may encompass neurodiagnostic testing and
hospitalization, which is advised for approximately 42% to 52% of
patients experiencing first-time CFS.9-11 However, recent studies
Funding: This research did not receive any specific grant from funding agencies have reported low diagnostic yields for routine lumbar puncture
in the public, commercial, or not-for-profit sectors. (LP), neuroimaging, and urgent electroencephalography (EEG).10-13
* Communications should be addressed to: Dr. Sung; Department of Emergency
After the 2011 American Academy of Pediatrics (AAP) guidelines for
Medicine; Daejeon Eulji Medical Center; Eulji University; 95 Dunsanseo-ro, Seo-gu;
Daejeon 35233, Republic of Korea. simple febrile seizure (SFS) were published, a significant reduction
E-mail address: [email protected] (W.Y. Sung). in unnecessary diagnostic tests, hospitalizations, and costs

https://doi.org/10.1016/j.pediatrneurol.2024.04.001
0887-8994/© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
J.S. Kim, H. Woo, W.S. Kim et al. Pediatric Neurology 156 (2024) 4e9

occurred, without any delayed diagnosis of bacterial meningitis.1 that occurred in infants and children aged six to 60 months without
Since the introduction of Haemophilus influenzae type b and central nervous system infection or an acute electrolyte imbal-
pneumococcal vaccines, bacterial meningitis is only identified in ance.20,21 SFS was classified as FS without any focal features
0.3% to 0.7% of FS cases.1,13,14 Therefore, invasive procedures such as (generalized) that resolved spontaneously within 15 minutes and
LP should be selectively recommended in patients with FS, did not recur within a 24-hour period.19 Recurrent SFS referred to
including those with CFS. Additionally, intracranial abnormalities patients with recurrent FS within 24 hours, with a return to the
are rare in patients with CFS; therefore, testing is not necessary baseline state after each event.16 CFS was defined as FS that had
unless abnormalities or focal findings are found on neurological evidence of focality, lasted longer than 15 minutes, or recurred
examination.9,11 The overall risk of subsequent epilepsy in patients within 24 hours.19
with CFS is approximately 6% to 8%. This risk is higher in cases with
focal features (6.3%) and longer seizure durations (29.4%).15 Clinical protocol
Conversely, FS recurrence within a 24-hour period carries the
lowest risk (3.6%) of subsequent epilepsy. The predictive value of According to our FS management guidelines, our recommen-
interictal EEG remains controversial and does not provide signifi- dations for SFS comprise controlling the fever, providing caregiver
cant assistance in the acute management of FS.9 education, and allowing patients to be discharged from the ED and
In 2013, Grill and Ng introduced the term “simple febrile seizure return home. For patients with CFS, we advise hospitalization for
plus” to describe patients who experience recurrent FS within further neurodiagnostic tests, such as brain magnetic resonance
24 hours.16 This subgroup accounts for approximately 14% to 24% of imaging, EEG, and LP, and close monitoring of clinical progression.
patients with FS.1,2,17-19 The authors reported a slightly increased However, for cases in which caregivers display excessive anxiety
risk of subsequent afebrile seizures, although these were diagnos- known as fever phobia, hospitalization for SFS may be considered
tically similar to SFS.16 Despite many studies having reported that to actively manage fever or address potential seizure recurrence,
most patients with SFS plus rarely have an acute symptomatic depending on a patient's circumstances.
disease, these individuals still undergo unnecessary neuro-
diagnostic tests, leading to repeated hospitalizations and increased Data collection
family anxiety.1,2 We agree that SFS plus should be considered a
distinct disease entity from traditional CFS. However, we opt to use Patient data regarding the ED or hospital course were extracted
the term “recurrent SFS” instead of “SFS plus” in our study to avoid from the medical records. These included: age; sex; family history
potential confusion with “genetic epilepsy with febrile seizure of epilepsy and FS; history of FS and recurrent SFS; comorbid
plus” or “febrile seizure plus.” Therefore, the purpose of our study conditions such as developmental delay, intellectual disability, and
was (1) to compare the clinical characteristics of recurrent SFS with autism spectrum disorder; age at first FS; time interval from last FS;
SFS and (2) to investigate the relevant risk factors associated with time interval from fever onset; body temperature on ED arrival;
this patient subgroup to guide clinical management and prevent diurnal patterns of seizure occurrence: night (00:00 to 05:59),
unnecessary testing. morning (06:00 to 11:59), afternoon (12:00 to 17:59), and evening
(18:00 to 23:59); sources of fever; serum sodium level at the ED
Methods visit; and neurodiagnostic results. In addition, information
regarding subsequent seizures was collected, including the time
Study design and patients interval from the former seizure and frequency of additional
seizures.
This retrospective observational cohort study was conducted at
two university-affiliated training hospitals in South Korea, Chungbuk Outcome measures
National University Hospital and Eulji University Hospital. We
reviewed the electronic medical records of pediatric ED between The primary outcomes of the study were the clinical features of
January 2016 and December 2019. The inclusion criteria were as recurrent SFS compared with those of SFS. Secondary outcomes
follows: (1) met the defined criteria for FS, (2) age six to 60 months, were risk factors for FS recurrence during the 24-hour period after
and (3) subsequent hospitalization for 24 hours. Patients with a onset of the initial FS. We considered multiple potential predictors
pre-existing diagnosis of epilepsy, chromosomal abnormalities, of recurrent SFS, including male sex, age <12 months at presenta-
inborn errors of metabolism, or intracranial lesions such as traumatic tion, family history of FS, history of previous FS and recurrent SFS,
brain injury, brain tumors, intracranial hemorrhage, or hydroceph- first detection of fever on ED arrival, body temperature <39.0 C and
alus were excluded from the study. Additionally, patients were serum sodium level <135 mEq/L at the ED visit, and diurnal
excluded if they exhibited focal ictal features, if the duration of any nighttime FS occurrence.
seizure exceeded 15 minutes, or if abnormalities were detected
during neurological examination. In cases of multiple ED visits by the Statistical analyses
same patient, only the clinical information from the second visit was
included in the study. This approach was used to acquire a more Statistical analyses were conducted using SPSS (version 22.0;
comprehensive dataset of patients’ medical histories. IBM Corp., Armonk, NY, USA). Clinical data were compared between
children in the SFS and recurrent SFS groups. The normality of
Definitions continuous variables was assessed using the Kolmogorov-Smirnov
test. Normally distributed continuous variables are presented as
Patients were diagnosed with FS by physicians in our EDs based mean ± S.D. and were compared using the Student t test. Non-
on interviews with parents or caregivers who described jerking normally distributed continuous variables are expressed as
movements and impaired consciousness that met the criteria for median and interquartile range and were compared using the
FS. In accordance with the guidelines set by the International Lea- Mann-Whitney U test. Furthermore, categorical variables are pre-
gue Against Epilepsy and the AAP, FS was defined as a seizure sented as numbers and percentages and were compared using the
accompanied by fever (body temperature 38.0 C or 100 F during chi-square or Fisher exact test. Posthoc adjustment for multiple
the seizure or within a 24-hour period before or after the seizure) comparisons was conducted using the Bonferroni correction.
5
J.S. Kim, H. Woo, W.S. Kim et al. Pediatric Neurology 156 (2024) 4e9

Thereafter, logistic regression analysis was used to assess the risk TABLE 1.
factors for FS recurrence within 24 hours. Variables that were Characteristics of the Study Population (n ¼ 254)

significantly different (P < 0.1) in the univariate analysis were Variable Value
incorporated into the multivariate logistic regression model. The FS episode
backward elimination method using the likelihood ratio was Single seizure 191 (75.2)
employed for the multivariate logistic regression analysis. Addi- Multiple seizures 63 (24.8)
tionally, the suitability of the model was evaluated using the Sex
Male 139 (54.7)
Hosmer-Lemeshow test. The results are presented as adjusted odds
Female 115 (45.3)
ratios (ORs) with corresponding 95% confidence intervals (CIs). For Age at presentation, months 21.4 (15.9-33.8)
all statistical tests, P < 0.05 was considered statistically significant. Comorbid conditions* 5 (2.0)
Family history of epilepsy 5 (2.0)
Family history of FS 76 (29.9)
Ethics statement
First-time FS 176 (69.3)
Age at first FS, monthsy 18.1 (14.3-25.4)
This study adhered to the principles outlined in the Declaration Time from last FS, monthsz 6.9 (2.7-13.1)
of Helsinki and was approved by the Institutional Review Boards of Time from fever onset, hours
Chungbuk National University Hospital (IRB No. 2023-08-007) and First detection at ED 27 (10.6)
<12 hours 111 (43.7)
Eulji University Hospital (IRB No. 2017-01-015). Given the retro-
<24 hours 77 (30.3)
spective nature of the study, the requirement for written informed <48 hours 39 (15.4)
consent was waived. Diurnal pattern at presentation
Night 42 (16.5)
Results Morning 80 (31.5)
Afternoon 77 (30.3)
Evening 55 (21.7)
Patient characteristics Duration of hospitalization, days 3.0 (2.0-4.0)
Neurological complication at discharge 0 (0.0)
During the four-year study period, 266 patients with FS aged six Abbreviations:
to 60 months visited one of the two pediatric EDs and were sub- ED ¼ Emergency department
sequently admitted to the hospital. Among them, 12 were excluded FS ¼ Febrile seizure
Data are presented as n (%) or median (interquartile range).
for the following reasons: history of childhood epilepsy or focal *
Including developmental delay, intellectual disability, and autism spectrum
semiology (n ¼ 3), diagnosis of SCN1A mutation-related Dravet disorder.
syndrome (n ¼ 1), and prolonged seizure (n ¼ 8). A total of 254 y
Data available from 232 patients.
z
patients were enrolled in the study, and detailed patient informa- Data available from 53 patients.
tion is summarized in Table 1.
Of the 254 patients, three quarters (n ¼ 191, 75.2%) experienced
a single seizure episode during the entire febrile illness period, Seizure characteristics
which was classified as SFS. The remaining 63 patients (24.8%) were
categorized as having recurrent SFS. The median age of all patients Among the 63 patients with recurrent SFS, the median fre-
was 21.4 months (interquartile range 14.5 to 33.4 months), and 139 quency of additional seizures was 1, ranging from 1 to 4 (Fig).
patients (54.7%) were male. Five patients (2.0%) had comorbidities, Among these individuals, 88.9% experienced only one additional
five (2.0%) had a family history of epilepsy, and 76 patients (29.9%) seizure, all of which were categorized as SFS. All second seizures
had a family history of first-degree FS. Among all the patients, 30.7% occurred within 24 hours, with 65.1% taking place within six hours
had previous episodes of FS, 12.8% of whom had experienced of the initial seizure.
recurrent SFS. Consequently, 176 (69.3%) patients experienced their Table 2 compares the clinical features of patients with recurrent
first FS during the study period. SFS and those with SFS. Significant differences were observed in the
In patients for whom a medical history was available (n ¼ 232), history of recurrent SFS, time from fever onset to seizure, and body
the median age at the first FS was 18.1 (14.2 to 25.6) months. temperature on ED arrival. Among patients who had previously
Furthermore, the median time interval between the previous FS experienced multiple seizures during a 24-hour period, 70% (seven
and the current episode was 6.9 (2.5 to 13.1) months. Fever sources, of 10) exhibited the same pattern again (P ¼ 0.003). In a posthoc
determined through clinical diagnosis via physical examination, analysis, a difference in the prevalence of recurrent SFS was
imaging studies, rapid antigen tests, and specific antibody tests, revealed in children with <12-hour vs 24- to 48-hour intervals
were categorized as follows: upper respiratory tract infection between seizures (P ¼ 0.03). Furthermore, upon arrival at the ED,
(64.6%), pneumonia (11.4%), seasonal influenza (7.5%), hand-foot- the body temperature of patients with recurrent SFS was signifi-
and-mouth disease (5.1%), exanthem subitum (2.8%), acute cantly lower than that of patients with SFS (38.9 C vs 39.3 C,
gastroenteritis (2.4%), enteroviral meningitis (2.0%), acute otitis P ¼ 0.007). Approximately one third of patients with recurrent SFS
media (1.6%), fever without a focus (1.6%), and urinary tract infec- underwent neurodiagnostic tests. Ten patients exhibited diffuse
tion (1.2%). slowing of background activity without epileptiform discharges on
Including the 27 patients (10.6%) who confirmed fever onset at EEG, which we believe was influenced by postictal confusion or
the time of the seizure, a total of 138 patients (44.3%) experienced a deep sedation. No other abnormalities were observed on brain
seizure within 12 hours of the first fever. The diurnal pattern of FS magnetic resonance imaging or in cerebrospinal fluid analysis.
predominantly occurred during the daytime (61.5%), specifically in
the morning and afternoon, whereas it was least common at night Risk factors for recurrent SFS
(16.5%). Additionally, most patients (86.2%) had a seizure duration
less than five minutes. Throughout the median hospital stay of 3 (2 Multiple logistic regression analysis was conducted to assess the
to 4) days and even upon discharge, none of the patients displayed association between seizure recurrence and various potential pre-
any neurological complications such as progression to status epi- dictive factors (Table 3). A history of recurrent SFS (OR 10.161, 95%
lepticus (SE). CI 2.460 to 41.965, P ¼ 0.001) and a body temperature <39 C on ED
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J.S. Kim, H. Woo, W.S. Kim et al. Pediatric Neurology 156 (2024) 4e9

FIGURE. Characteristics of additional seizures in patients with recurrent simple febrile seizure. The color version of this figure is available in the online edition.

arrival (OR 2.377, 95% CI 1.304 to 4.334, P ¼ 0.005) were signifi- Grill and Ng analyzed 32 patients with recurrent SFS who had no
cantly associated with immediate seizure recurrence. other complex features or abnormalities.16 This study reported that
46.9% of these patients experienced three to seven additional sei-
Discussion zures within 24 hours, and routine neuroimaging and EEG, which
are typically performed in patients with CFS, did not provide
In the present study, 24.8% of all patients with FS had recurrent meaningful diagnostic or prognostic information. Moreover, the
SFS, 88.9% of whom experienced only one additional seizure. Sei- authors suggested that these additional tests posed unnecessary
zures recurred within six hours in approximately two thirds of sedation risks and patients incurred high costs. In previous large
cases, and all were SFS. Additionally, the risk of early FS recurrence prospective cohort studies, seizure recurrence within 24 hours was
was significantly higher in patients who had previously experi- 16.2% in patients with CFS, which is more common than the pres-
enced recurrent SFS or had a body temperature <39 C upon arrival. ence of focal features (4%) or prolonged duration (7.6%) in these
Although approximately one third of patients with recurrent SFS patients.17,19 Similarly, single-center studies in Japan have reported
underwent neurodiagnostic tests, the results did not impact their recurrence rates of approximately 15% to 16% for recurrent SFS.1,18
treatment outcomes. Like those with SFS, these patients were dis- However, our finding of 24.8% is considerably higher than those
charged after fever control with no neurological abnormalities. of previous studies.1,17-19 In 2015, Japan's revised guidelines for
managing FS restricted the use of early prophylaxis with rectal
TABLE 2. diazepam to patients with a history of prolonged FS (15 minutes)
Comparison of Clinical Features Between Children With SFS and Recurrent SFS or of multiple FS with risk factors for FS recurrence.22 Consequently,
Variable Recurrent SFS (n ¼ 191) P the rate of early FS recurrence increased from 12% to 20% in the
SFS (n ¼ 63) Value years around 2015.18 Moreover, seeking medical attention and
Male sex 39 (61.9) 100 (52.4) 0.24 hospitalization for FS with active fever control is a common social
Age at presentation, 20.2 (14.5-33.0) 21.5 (16.3-34.0) 0.35 practice in South Korea; therefore, our results may better reflect
months real-world scenarios. However, when confined to hospitalization,
Family history of FS 24 (38.1) 52 (27.2) 0.14
the seizure recurrence rate in patients with CFS is low, ranging from
History of previous FS 25 (39.7) 53 (27.7) 0.12
History of previous 7 (11.1) 3 (1.6) 0.003 3.8% to 5.1%.13,23 In our study, additional seizures predominantly
recurrent SFS occurred within six hours of the first seizure at a frequency of one
Age at first FS, months* 17.1 (12.9-21.8) 18.4 (15.0-26.3) 0.09 episode. Japanese studies have also reported a high rate of seizure
Time from fever onset 0.04 recurrence within eight hours (82% to 86%).1,18 Eight hours after the
<12 hours 30 (47.6) 108 (56.5)
<24 hours 17 (27.0) 60 (31.4)
first seizure, the recurrence rate sharply dropped to 4.2%, sug-
<48 hours 16 (25.4) 23 (12.0) gesting that observing patients in the hospital for at least

Body temperature at ED, C 38.9 (38.3-39.5) 39.3 (38.7-39.7) 0.007 eight hours is a safe recommendation. Furthermore, similar to our
þ
Serum Na at ED, mEq/L 136.0 (134.0-137.0) 136.0 (135.0-137.0) 0.39 results, the authors also showed that the majority (76%) of patients
Neurodiagnostic
experienced only one additional seizure.18
evaluation
Brain MRI 19 (30.2) 6 (3.1) <0.001 Previous studies identified various predictors of early FS recur-
EEG 23 (36.5) 4 (2.1) <0.001 rence, including male sex, lower body temperature, family history
Lumbar puncture 18 (28.6) 7 (3.7) <0.001 of FS, hyponatremia, nongeneralized seizure types, and prolonged
Abbreviations: seizure duration.1,2,18,24-26 However, the findings are inconsistent,
ED ¼ Emergency department likely due to differences between the target populations as well as
EEG ¼ Electroencephalography differences in the risk factors assessed, which affected the multi-
FS ¼ Febrile seizure
variate analyses. We identified two significant risk factors in the
MRI ¼ Magnetic resonance imaging
SFS ¼ Simple febrile seizure multivariate analysis. First, patients with a history of recurrent SFS
Data are presented as n (%) or median (interquartile range). were likely to experience recurrence with the same pattern.
*
Data available from 232 patients. Although an increased risk of CFS has been reported in patients
who previously had multiple seizures, our study identified this as a
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J.S. Kim, H. Woo, W.S. Kim et al. Pediatric Neurology 156 (2024) 4e9

TABLE 3.
Logistic Regression Analyses of Risk Factors in Children With Recurrent SFS

Factor Recurrent SFS Univariate Analysis Multivariate Analysis

OR (95% CI) P Value OR (95% CI) P Value

Male sex 39/139 (28.1) 1.4979 (0.826-2.647) 0.19

Younger than 12 months (yes) 8/22 (36.4) 1.839 (0.733-4.614) 0.19
Family history of FS (yes) 24/76 (31.6) 1.645 (0.903-2.998) 0.10
History of previous FS (yes) 25/78 (32.1) 1.713 (0.944-3.108) 0.08
History of previous recurrent SFS (yes) 7/10 (70.0) 7.833 (1.961-31.294) 0.004 10.161 (2.460-41.965) 0.001
First detection of fever at ED (yes) 9/27 (33.3) 1.602 (0.680-3.772) 0.28
Night occurrence (yes) 13/42 (31.0) 1.452 (0.702-3.005) 0.31
Body temperature <39.0 C at ED (yes) 34/103 (33.0) 2.073 (1.164-3.690) 0.01 2.377 (1.304-4.334) 0.005
Serum Naþ <135 mEq/L at ED (yes) 11/61 (18.0) 0.597 (0.289-1.233) 0.16

Abbreviations:
CI ¼ Confidence interval
ED ¼ Emergency department
FS ¼ Febrile seizure
OR ¼ Odds ratio
SFS ¼ Simple febrile seizure
Data are presented as n (%).

risk factor for recurrent SFS.13,17 Second, the risk of early FS recur- our knowledge has grown, we have learned that FS exhibits a more
rence was significantly higher when the patient's body tempera- heterogeneous clinical phenotype.16,33-36 The FEBSTAT (Conse-
ture at the ED visit was <39 C; this corroborates the findings of a quences of Prolonged Febrile Seizures in Childhood) study group
previous study, suggesting that a lower temperature may indicate a defined the upper limit of SFS duration as 10 minutes and found
lower seizure threshold in individuals with genetically predisposed that a prolonged duration was associated with hippocampal injury
brains.9 We did not find associations with younger age, shorter and subsequent mesial temporal lobe epilepsy.33-35 Additionally,
fever duration, evening occurrence, or other factors known to be frequent recurrence of FS, especially of four or more episodes, is a
related to later recurrent FS.19,27-29 well-known risk factor for subsequent epilepsy development.36
The use of prophylactic rectal diazepam (0.3 to 0.5 mg/kg sup- Based on this evidence, we propose a more refined classification
pository on arrival) is known to be effective in preventing early FS system for FS. Broadly, we categorize FS into (1) typical FS, which is
recurrence.1,18,30 Inoue et al. reported that prophylactic diazepam an age-dependent phenomenon characterized by its benign nature,
administration was the sole factor preventing seizure recurrence, and (2) atypical FS, which requires evaluation of the underlying
reducing the FS recurrence rate from 21% to 6%.18 However, because FS brain pathology. Further subdivisions based on the characteristics
is generally benign and diazepam can decrease consciousness and of various phenotypes, immediate or later risk, and need for neu-
potentially obscure the symptoms of acute encephalopathy, the rodiagnostic evaluation are summarized in Table 4. The typical SFS
routine use of diazepam is no longer recommended.30 Therefore, the subgroup generally does not require neurodiagnostic evaluation,
Japanese Society of Child Neurology recommends that the use of according to the 2011 AAP guidelines.37 Furthermore, the recurrent
prophylactic diazepam should depend on the individual patient's SFS and frequent FS subgroups, although having a low likelihood of
situation and whether the benefits outweigh the risks.22 If a patient acute symptomatic disease as the etiology, may be candidates for
has the risk factors of a history of recurrent SFS or a body temperature later EEG testing because of the low risk of subsequent epilepsy. FS
<39 C on arrival, administration of a single diazepam suppository plus occurs in patients with a previous history of FS and is mostly
might be considered. This approach may help alleviate parental self-limited; however, performing brain neuroimaging, EEG, LP, or
anxiety, reduce subsequent hospitalizations, and ensure clinical genetic evaluation such as targeted gene panel sequencing can be
safety.1 considered in cases where acute symptomatic etiology or epilepsy
Health care professionals still use a classification from approx- is suspected. Finally, atypical FS can be classified into focal featured
imately 50 years ago that dichotomizes SFS and CFS based on his- FS, prolonged FS, and febrile SE. Most patients in this group require
torical and empirical origins rather than scientific evidence.31,32 As extensive neurodiagnostic evaluation, with febrile SE carrying the

TABLE 4.
Heterogeneous Clinical Phenotypes of Febrile Seizures

Phenotype Features Risk for Acute Risk for Subsequent Epilepsy Indication for
Symptomatic Diseases Neurodiagnostic Evaluation*

Typical FS
Simple FS Generalized, <10 min, single episode - - Not recommended
Recurrent SFS More than one episode within 24 hours - ± Arbitrary
Frequent FS Multiple recurrence (four or more) - ± Arbitrary
FS plus Continuation beyond 6 years ± ± Arbitrary
Atypical FS
Focal featured FS Focal semiology þ þ Mandatory
Prolonged FS Lasting 10 min þ þ Mandatory
Febrile SE Lasting 30 min þþ þþ Mandatory

Abbreviations:
FS ¼ Febrile seizure
SE ¼ Status epilepticus
SFS ¼ Simple febrile seizure
*
Including brain neuroimaging, electroencephalography, lumbar puncture, and/or targeted gene panel sequencing.

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J.S. Kim, H. Woo, W.S. Kim et al. Pediatric Neurology 156 (2024) 4e9

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19 infection. Ann Child Neurol. 2023;31:137e139.
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5. Byeon JH, Kim GH, Eun BL. Prevalence, incidence, and recurrence of febrile
reduce unnecessary and uncomfortable testing as well as subse- seizures in Korean children based on national registry data. J Clin Neurol.
quent hospitalizations. 2018;14:43e47.
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limited. This fact could be attributed to the focus on inpatients to febrile seizures. Pediatrics. 2008;121:1281e1286.
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Dev. 2010;32:64e70.
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focal featured FS or prolonged FS, likely due to the relatively low seizures: a Greek nationwide survey. Eur J Pediatr. 2023;182:3293e3300.
incidence of these seizure types. We believe that in the future, 9. Smith DK, Sadler KP, Benedum M. Febrile seizures: risks, evaluation, and
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illustrate the benign nature characteristics of recurrent SFS. Finally, 2010;126:62e69.
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