DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY ORIGINAL ARTICLE

First-ever convulsive seizures in children presenting to the

emergency department: risk factors for seizure recurrence and
diagnosis of epilepsy
STEFANO SARTORI 1 | MARGHERITA NOSADINI 1 * | GIULIO TESSARIN 1 * | CLEMENTINA BONIVER 1 |
ANNA CHIARA FRIGO 2 | IRENE TOLDO 1 | SILVIA BRESSAN 3 | LIVIANA DA DALT3
1 Paediatric Neurology and Neurophysiology Unit, Department of Women’s and Children’s Health, University of Padua, Padua; 2 Biostatistics, Epidemiology and Public
Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua; 3 Emergency Department, Department of Women’s and Children’s
Health, University of Padua, Padua, Italy.
Correspondence to Margherita Nosadini at Neurologia Pediatrica, Pediatria, Via Giustiniani 3, 35128 Padova, Italy. E-mail: margherita.nosadini@gmail.com

*These authors contributed equally to this work.

This article is commented on by Gill on pages 9–10 of this issue.

PUBLICATION DATA AIM Aetiologies of first-ever convulsive seizures may be diverse, not all leading to recurrence
Accepted for publication 20th July 2018. or epilepsy diagnosis. We aimed to describe the epidemiology of first-ever convulsive
Published online 7th September 2018. seizures in children, investigating risk factors for recurrence and epilepsy diagnosis.
METHOD This was a retrospective study of children presenting with a first-ever convulsive
ABBREVIATIONS seizure to a tertiary-care paediatric emergency department (PED) in Italy, in a 12-month
CSE Convulsive status epilepticus period (2011–2012).
PED Paediatric emergency RESULTS One hundred and eight children (57 males, 51 females) presented to the PED for a
department first-ever convulsive seizure; 90.7% were 6 months to 6 years old (median age 1y 10mo,
mean 2y 7mo, range 0mo–14y 4mo). Seizure duration was less than 5 minutes in 76.8%.
Seizures were ‘unprovoked’ in 19.4% and ‘provoked’ in 80.6%. At 4-year follow-up, 37.9% of
patients experienced recurrence and 13.6% received a diagnosis of epilepsy. Factors
significantly associated with recurrence were the ‘unprovoked’ nature of the first seizure,
multiple seizures in the first 24 hours, positive family history of febrile seizures or epilepsy,
and pre-existing neurological conditions/problems. Factors significantly associated with a
diagnosis of epilepsy were the ‘unprovoked’ nature of the first seizure, age older than
6 years, pre-existing neurological conditions/problems, and focal onset of first seizure.
INTERPRETATION Children presenting to the PED with first-ever convulsive seizures represent
a heterogeneous group. The identification of prognostic factors for recurrence and epilepsy
diagnosis may help provide tailored counselling and follow-up.

Convulsive seizures affect 4% to 10% of children, account-
ing for 1% of all paediatric emergency department (PED)
visits,1 and may represent a major source of concern for
parents and a diagnostic challenge for the PED physi-
cian.2,3 The highest incidence of convulsive seizures has
been reported in children younger than 3 years, with
declining rates in older children.4 About half of the PED
admissions for epileptic seizures are because of first-ever
seizures,3,5 most commonly febrile seizures.1,5,6 An ade-
quate understanding of seizure aetiology may have relevant
implications for management and prognosis;7 in particular,
different aetiologies of a first-ever convulsive seizure may
carry different risks of seizure recurrence and of receiving
a diagnosis of epilepsy.6 In this regard, the distinction
between ‘unprovoked seizures’ (occurring in the absence of
a potentially responsible clinical condition or beyond the
interval estimated for the occurrence of acute symptomatic
seizures)6 and ‘provoked seizures’ is crucial because the
former have a remarkable risk of recurrence whereas the
latter are characterized by an increased risk of short-term
mortality.8
Despite the relatively high frequency of convulsive sei-
zures in the paediatric population, there are few and rela-
tively old epidemiological studies describing this
phenomenon in its complexity, often focusing solely on
specific subgroups of seizures (e.g. ‘unprovoked seizures’ or
febrile seizures) or using mixed populations of adults and
children. This study aimed to comprehensively describe
the epidemiology of first-ever convulsive seizures in chil-
dren presenting to the PED, and to assess risk factors for
seizure recurrence and development of epilepsy after a first
episode. These findings may provide relevant information
to guide the management of these patients, along with cor-
rect counselling and tailored neurological follow-up.

82 DOI: 10.1111/dmcn.14015 © 2018 Mac Keith Press

METHOD
Study design, setting, and population
This was a 4-year follow-up retrospective study of paediatric
patients (age <16y) who presented to the PED of the
Department of Women’s and Children’s Health, University
of Padua, Italy, for a first-ever convulsive seizure between
March 1st, 2011 and February 29th, 2012. Patients trans-
ferred from other hospitals, patients presenting with
non-convulsive seizures (i.e. absence seizures), non-epileptic
convulsions (e.g. convulsive syncope), and children with
paroxysmal non-epileptic events (i.e. tics, migraine, psy-
chogenic disorders) were excluded. Our centre is an
academic hospital providing primary and secondary care for
a metropolitan area of 350 000 people (75 000 of whom are
younger than 15y) and tertiary care for a regional and extra-
regional population, with approximately 24 000 PED visits
per year. Our PED is equipped with a four-bed short-stay
observation unit, allowing for management of patients
whose expected length of stay is 4 to 24 hours.
Data collection
Data relative to the first PED visit were collected by
review of clinical charts, with a focus on seizure semiology
(as reported by parents or other witnesses, or observed by
the clinician if still ongoing at the time of presentation to
the PED) and duration, acute treatment of the seizure in
the PED, diagnostic investigations, and focal neurological
signs at interictal neurological examination. All subsequent
visits to the PED and to the specialist clinic in the 4 years
after the index visit were reviewed to assess for seizure
recurrence and a diagnosis of epilepsy. Data derived from
the clinical charts were integrated with a follow-up tele-
phone call 4 years after the index visit in order not to miss
relevant information; patients were classified as lost to fol-
low-up if there was no answer to six telephone calls per-
formed in six different working days.
Definitions and classifications
Seizures were classified on the basis of type, duration, and
aetiology.
Seizure type was defined as focal, generalized, or
unknown on the basis of the latest operational definition of
seizure type by the International League Against Epilepsy.9
On the basis of the criteria previously proposed,10–13 sei-
zure duration was classified as follows: (1) seizures lasting
no more than 5 minutes; (2) seizures lasting 5 to 30 min-
utes (‘early’ convulsive status epilepticus [CSE]); (3) sei-
zures lasting 30 to 60 minutes (‘established’ CSE); (4)
seizures lasting longer than 60 minutes or which required
more than three antiepileptic drugs (‘refractory’ CSE).
As regards the aetiological categorization of first-ever
epileptic seizures, seizures were categorized as follows on
the basis of the classification of CSE proposed by Chin
et al.14 (adapted): (1) febrile seizure: convulsive seizure in a
previously healthy child aged between 1 month and 6 years
during a febrile illness (body temperature >38°C), in the
absence of a defined central nervous system (CNS)
Epidemiology of First-Ever Convulsive Seizures in Children Stefano Sartori et al. 83
What this paper adds
• Seizures were ‘unprovoked’ in 19.4% and ‘provoked’ in 80.6% of children
presenting to the emergency department.
• At 4-year follow-up, 37.9% relapsed, and 13.6% received a diagnosis of
epilepsy.
• ‘Unprovoked’ first seizure, family history of febrile seizures, and pre-existing
neurological conditions were associated with recurrence.
• ‘Unprovoked’ first seizure, age younger than 6 years, and pre-existing neuro-
logical conditions were associated with epilepsy diagnosis.
infection.15 (2) Benign convulsion associated with gastroen-
teritis: convulsive seizure occurring in a previously neuro-
logically healthy child aged between 2 months and 6 years
during a non-febrile episode of gastroenteritis (body tem-
perature <38°C) without clinical signs of dehydration and/
or electrolyte imbalance. (3) Acute symptomatic seizure:
convulsive seizure in a previously neurologically healthy
child, within 1 week of an identified acute neurological or
systemic insult. (4) Acute on remote symptomatic seizure:
convulsive seizure in a child with previously known CNS
abnormality, within 1 week of a new identified acute neu-
rological or systemic insult (including febrile illness). (5)
Remote symptomatic seizure: convulsive seizure in a child
with previously known CNS abnormality, occurring more
than 1 week after an identified acute neurological or sys-
temic insult (including febrile illness). (6) First-ever seizure
in a presumed idiopathic age-related epileptic syndrome:
convulsive seizure that is not symptomatic, which can be
recognized as a first manifestation of a presumed idiopathic
age-related epileptic syndrome. (7) Unclassified seizure:
convulsive seizure that cannot be classified in any of the
above-mentioned categories.
We operatively grouped remote symptomatic seizure,
presumed idiopathic age-related epileptic syndrome, and
unclassified seizure under the term ‘unprovoked seizures’
as described by Beghi et al.6 (seizures occurring in the
absence of a potentially responsible clinical condition or
beyond the interval estimated for the occurrence of acute
symptomatic seizures), and febrile seizure, benign convul-
sion associated with gastroenteritis, acute symptomatic sei-
zure, and acute on remote symptomatic seizure under the
term ‘provoked seizures’.
According to the recently published International Lea-
gue Against Epilepsy practical clinical definition of epi-
lepsy,16 a diagnosis of epilepsy was made when any of the
following conditions were met: (1) at least two unprovoked
(or reflex) seizures occurring more than 24 hours apart; (2)
one unprovoked (or reflex) seizure and a probability of fur-
ther seizures similar to the general recurrence risk (at least
60%) after two unprovoked seizures, occurring over the
next 10 years; (3) diagnosis of an epilepsy syndrome.
Statistical analysis
Patients’ data were entered into a REDCap (Research
Electronic Data Capture) clinical report form.17 Survival
freedom from seizure recurrence and from epilepsy diagno-
sis was estimated with the Kaplan–Meier method consider-
ing the time between the index date (PED presentation)
and the date of seizure recurrence or epilepsy diagnosis for
patients with the event or the date of the last contact for
censored patients. The potential predictors of recurrence
and diagnosis were identified with univariate Cox regres-
sion analysis, and those that were statistically significant at
the two-tailed 5% level were entered into a multivariable
Cox regression model with stepwise backward selection.
Results of Cox regressions are expressed as the hazard ratio
(HR) with 95% confidence interval (95% CI). Because the
choice of the 5% significance level was arbitrary, the
predictor selection was validated with the leave-one-out
cross-validation, generating n (the number of patients with
available data) data set with n 1 observations left after
randomly selecting one observation to leave out. We
selected the predictors occurring at least 70% of the time.
Proportionality was checked graphically and with the
Kolmogorov-type supremum test. If the proportionality
assumption was rejected, the model included the interac-
tion term with the logarithm of time. The level of statisti-
cal significance was set at p<0.05. Electroencephalography
(EEG) data were analysed only in the subgroup of ‘unpro-
voked seizures’, to minimize the selection bias.
Ethical approval
The study complied with the general ethical requirements
for retrospective observational studies (in particular, no
experimental interventions were performed and patient
identity cannot be retrieved from the manuscript), and was
approved by the ethics committee (2843P) of the Depart-
ment of Women’s and Children’s Health, University of
Padua, Padua, Italy.
RESULTS
Data at PED admission for first-ever convulsive seizure
Epidemiology and demographics
In the study period, a total of 24 864 children visited our
PED; of these, 214 visits were for convulsive seizures.
Among these children, 108 out of 214 (50.5%) were expe-
riencing their first-ever episode, and represented the study
population (0.43% of the total visits to the PED in the
study period). Since our PED serves a population of
75 000 children, the estimated incidence of PED visits for
first-ever convulsive seizure was 144 out of 100 000 chil-
dren in that year. Most patients in the study population
were between 6 months and 6 years of age (98 out of 108,
90.7%), and 52.8% (57 out of 108) were male. A positive
family history of febrile seizure or epilepsy was reported in
23.1% (25 out of 108), and 13% (14 out of 108) of chil-
dren had pre-existing neurological conditions or problems.
Details of demographics and clinical characteristics of the
study population are given in Table I.
Seizure characteristics and management
Seizure onset was generalized (or apparently generalized)
in 83.3% (90 out of 108) and focal in 16.7% (18 out of
108). Seizure duration was shorter than 5 minutes in
76.8% of individuals (83 out of 108). A total of 15.7% of
84 Developmental Medicine & Child Neurology 2019, 61: 82–90
patients had multiple episodes in the first 24 hours (17 out
of 108). None of the patients presented with refractory
CSE. According to the definition of CSE (seizure lasting
>5min),12,13 the estimated incidence of PED admissions for
a first-ever episode of CSE was 33.3 out of 100 000 chil-
dren in the year. Only 6.5% (seven out of 108) of the
patients had ongoing seizures at arrival. Acute out-of-hos-
pital treatment was administered in 2.8% of patients only
(three out of 108; diazepam in three out of three cases),
leading to seizure cessation in all. In-hospital benzodi-
azepines were used in 6.5% of patients (seven out of 108)
(one out of seven had received out-of-hospital diazepam);
in three of these, additional phenytoin or phenobarbital
was administered to stop the seizure. Six out of 108 (5.6%)
patients required respiratory assistance. A total of 15.7% of
patients (17 out of 108) were hospitalized; of these, only
one (one out of 108, 0.9%) was admitted to the paediatric
intensive care unit. Hospitalization rate rose to 41.9%
when febrile seizures were excluded (13 out of 31).
Seizure aetiology
At discharge from the PED, a diagnosis of ‘provoked sei-
zures’ prevailed over ‘unprovoked seizures’ (87 out of 108,
80.6%, vs 21 out of 108, 19.4%) (Table I). Febrile seizures
were by far the most frequent aetiology among ‘provoked
seizures’ (77 out of 108, 71.3%) (simple febrile seizures in
68 out of 77, 68.3%; complex febrile seizure in nine out of
77, 11.7%),15 whereas unclassified seizures (13 out of 108,
12%) were the most common aetiology among ‘unpro-
voked seizures’ (13 out of 108, 12%).
Investigations
Details of investigations performed in the study population
are given in Table II. EEG was performed in 31.5% (34
out of 108) of patients, disclosing abnormalities in 52.9%
(18 out of 34) (pathological background activity in five out
of 18, epileptic discharges in 16 out of 18, diffuse slowing
in eight out of 18). During the PED stay or subsequent
hospitalization, EEG was performed in 21 of the 90
patients who presented with a seizure with generalized
onset; focal abnormalities were identified in 33.3% (seven
out of 21) of these. EEG was performed in 9.1% (seven
out of 77) of patients with febrile seizure (three out of
seven complex febrile seizure), and in 87.1% (27 out of 31)
of all other seizures. Neuroimaging (brain computed
tomography or magnetic resonance imaging) during disease
course was done more frequently in patients with focal
rather than generalized onset of first seizure (10 out of 18,
55.6%, vs 13 out of 85, 15.3%; p=0.001), in children with
epileptiform abnormalities at EEG rather than without (14
out of 16, 87.5%, vs 6 out of 16, 37.5%; p=0.009), and in
cases of seizure duration lasting longer than 5 minutes
rather than less than 5 minutes (11 out of 25, 44%, vs 12
out of 83, 14.5%; p=0.005). Neuroimaging was performed
in similar proportions in patients with seizure onset at age
younger than 2 years and older than 2 years (5 out of 10,
50%, vs 13 out of 19, 68.4%).
Table I: Demographics and clinical data according to aetiological category of first-ever convulsive seizure (as per diagnosis at discharge from PED)

‘Provoked’ seizures (87/108, 81%) ‘Unprovoked’ seizures (21/108, 19%)

Aetiology of first-ever Total
convulsive seizure FS (n=77) CwG (n=5) AS (n=3) ARS (n=2) RS (n=6) ID (n=2) UN (n=13) (n=108)

Age at presentation
<1mo 0/77 (0) 0/5 (0) 2/3 (67) 0/2 (0) 0/6 (0) 0/2 (0) 0/13 (0) 2/108 (2)
1–6mo 2/ 77 (3) 0/5 (0) 0/3 (0) 0/2 (0) 1/6 (17) 0/2 (0) 0/13 (0) 3/108 (3)
6mo–3y 61/ 77 (79) 1/5 (20) 1/3 (33) 1/2 (50) 0/6 (0) 1/2 (50) 5/13 (38) 70/108 (65)
3–6y 14/ 77 (18) 4/5 (80) 0/3 (0) 1/2 (50) 4/6 (67) 0/2 (0) 5/13 (38) 28/108 (26)
>6y 0/ 77 (0) 0/5 (0) 0/3 (0) 0/2 (0) 1/6 (17) 1/2 (50) 3/13 (23) 5/108 (5)
Male 46/ 77 (60) 1/5 (20) 1/3 (33) 0/2 (0) 2/6 (33) 1/2 (50) 6/13 (46) 57/108 (53)
Female 31/ 77 (40) 4/5 (80) 2/3 (67) 2/2 (100) 4/6 (67) 1/2 (50) 7/13 (54) 51/108 (47)
Brought in by ambulance 52/ 77 (67) 3/5 (60) 0/3 (0) 1/2 (50) 2/6 (33) 2/2 (100) 1/13 (92) 72/108 (67)
Ongoing seizure at 1/77 (1) 0/5 (0) 1/3 (33) 1/2 (50) 1/6 (17) 0/2 (0) 3/13 (23) 7/108 (6)
arrival at the PED
Seizure duration
<5min 61/77 (79) 5/5 (100) 2/3 (67) 1/2 (50) 5/6 (83) 1/2 (50) 8/13 (61) 83/108 (77)
5–30min 15/77 (19) 0/5 (0) 1/3 (33) 1/2 (50) 1/6 (17) 1/2 (50) 4/13 (31) 23/108 (21)
30–60min 1/77 (1) 0/5 (0) 0/3 (0) 0/2 (0) 0/6 (0) 0/2 (0) 1/13 (8) 2/108 (2)
Seizures with focal onset 6/77 (8) 2/5 (40) 1/3 (33) 0/2 (0) 2/6 (33) 2/2 (100) 5/13 (38) 18/108 (17)
Out-of-hospital treatment 1/77 (1) 1/5 (20) 0/3 (0) 0/2 (0) 0/6 (0) 0/2 (0) 1/13 (8) 3/108 (3)a
In-hospital treatment 1/77 (1) 2/5 (40) 1/3 (33) 1/2 (50) 0/6 (0) 0/2 (0) 2/13 (15) 7/108 (6)
One AED 0/77 (0) 2/5 (40) 0/3 (0) 0/2 (0) — — 2/13 (15) 4/108 (4)
Two AEDs 1/77 (1) 0/5 (0) 1/3 (33) 0/2 (0) — — 0/13 (0) 2/108 (2)
Three AEDs 0/77 (0) 0/5 (0) 0/3 (0) 1/2 (50) — — 0/13 (0) 1/108 (1)
Hospitalization rate 4/77 (5) 3/5 (60) 3/3 (100) 2/2 (100) 1/6 (17) 1/2 (50) 3/13 (23) 17/108 (16)
Paediatric intensive care unit 0/77 (0) 0/5 (0) 0/3 (0) 1/2 (50) 0/6 (0) 0/2 (0) 0/13 (0) 1/108 (1)

All data in parentheses are percentages. aAll three patients (one had FS, one had CwG, one had UN) received only one AED (diazepam).
PED, paediatric emergency department; FS, febrile seizure; CwG, benign convulsion associated with gastroenteritis; AS, acute symptomatic
seizure; ARS, acute on remote symptomatic seizure; RS, remote symptomatic seizure; ID, presumed idiopathic age-related epileptic syn-
drome; UN, unclassified seizure; AED, antiepileptic drug.

Follow-up data seizure recurrence (adjusted for the interaction of the

Seizure recurrence
Follow-up data were available for 95.4% of patients (103
out of 108) (Table III). Over the 4-year follow-up, 37.9%
of patients experienced seizure recurrence (39 out of 103)
(27 out of 83 [32.5%] of ‘provoked’ seizures; 12 out of 20
[60%] of ‘unprovoked’ seizures): 64% of these (25 out of
39) had only one further seizure, 23.1% (9 out of 39) had
two to four further seizures, and the remaining 12.8% (five
out of 39) had at least five further seizures. In 79.5% (31
out of 39) of the patients with seizure recurrence, the
relapse occurred within 1 year after the first seizure
(Fig. 1a). The ‘unprovoked’ nature of the first seizure (HR
2.40; CI 1.21–4.75; p=0.01), the occurrence of multiple sei-
zures in the first 24 hours (HR 3.03; CI 1.47–6.24;
p=0.003), the presence of a positive family history of febrile
seizure or epilepsy (HR 2.46; CI 1.29–4.72; p=0.006), and
of pre-existing neurological conditions or problems (HR
2.67; CI 1.26–5.66; p=0.01) were statistically significant
predictors of seizure recurrence (Table III). In the multi-
variable analysis of the factors with p<0.05 (Table III),
considering a stepwise backward method of selection, the
occurrence of multiple seizures in the first 24 hours (HR
11.93; CI 3.35–41.42; p<0.001), the presence of a positive
family history of febrile seizure or epilepsy (HR 2.56; CI
1.32–5.00; p=0.005), and pre-existing neurological condi-
tions (HR 2.96; CI 1.38–6.36; p=0.005) emerged as the
only statistically significant predictors associated with
occurrence of multiple seizures with the logarithm of time:
HR 0.73; CI 0.53–0.99; p=0.04).
Among patients with ‘unprovoked’ seizures, the propor-
tion who experienced seizure recurrence was higher in the
subgroup with EEG epileptiform discharges than in those
without (10 out of 13, 76.9%, vs two out of five, 40%;
p=0.29), although this was not statistically significant.
Epilepsy diagnosis
At 4-year follow-up after the first seizure, 13.6% (14 out
of 103) of patients received a diagnosis of epilepsy
(Fig. 1b). Factors significantly associated with an increased
risk of receiving a diagnosis of epilepsy at 4-year follow-up
were the ‘unprovoked’ nature of the first seizure (HR
37.02; CI 8.22–166.61; p<0.001), age older than 6 years at
first seizure (HR 12.04; CI 3.70–39.15; p<0.001), the pres-
ence of pre-existing neurological conditions or problems
(HR 7.63; CI 2.664–21.835; p=0.001), and focal onset of
the first seizure (HR 5.68; CI 1.99–16.23; p=0.001). In the
multivariable analysis of the factors with p<0.05
(Table III), considering a stepwise backward method of
selection, the ‘unprovoked’ nature of first seizure emerged
as the only statistically significant predictor associated with
a diagnosis of epilepsy at 4-year follow-up.
Among patients with ‘unprovoked’ seizures, the propor-
tion who received a diagnosis of epilepsy was higher in the
subgroup with EEG epileptiform discharges than in those

Epidemiology of First-Ever Convulsive Seizures in Children Stefano Sartori et al. 85

Table II: Investigations performed according to aetiological category of the first-ever convulsive seizure (as per diagnosis at discharge from PED)

‘Provoked’ seizures (87/108, 81%) ‘Unprovoked’ seizures (21/108, 19%)

Aetiology of first-ever
convulsive seizure FS (n=77) CwG (n=5) AS (n=3) ARS (n=2) RS (n=6) ID (n=2) UN (n=13) Total (n=108)

EEG 7/77 (9) 5/5 (100) 2/3 (67) 1/2 (50) 5/6 (83) 2/2 (100) 12/13 (100) 34/108 (31)
<24h 1/7 (14) 3/5 (60) 1/2 (50) 0/1 (0) 3/5 (60) 1/2 (50) 8/12 (67) 17/34 (50)
During hospitalization 2/7 (29) 2/5 (40) 1/2 (50) 1/1 (100) 0/5 (0) 1/2 (50) 1/12 (8) 8/34 (23)
Within 30d from discharge 3/7 (43) 0/5 (0) 0/2 (0) 0/1 (0) 2/5 (40) 0/2 (0) 1/12 (8) 6/34 (18)
After 30d from discharge 1/7 (14) 0/5 (0) 0/2 (0) 0/1 (0) 0/5 (0) 0/2 (0) 2/12 (17) 3/34 (9)
EEG with pathological findings 1/7 (14) 1/5 (20) 1/2 (50) 0/1 (0) 4/5 (80) 2/2 (100) 9/12 (75) 18/34 (53)
Brain CT 0 (0) 2/5 (40) 0/3 (0) 1/2 (50) 0/6 (0) 0/2 (0) 3/13 (23) 6/108 (6)
<24h — 2/2 (100) — 0/1 (0) — — 3/3 (100) 5/6 (83)
During hospitalization — 0/2 (0) — 1/1 (100) — — 0/3 (0) 1/6 (17)
Within 30d from discharge — 0/2 (0) — 0/1 (0) — — 0/3 (0) 0/6 (0)
After 30d from discharge — 0/2 (0) — 0/1 (0) — — 0/3 (0) 0/6 (0)
CT with pathological findings — 0/2 (0) — 1/1 (100)a — — 0/3 (0) 1/6 (17)a
Brain MRI 1/77 (1) 0/5 (0) 1/3 (33) 0/2 (0) 1/6 (17) 2/2 (100) 8/13 (61) 13/108 (12)
<24h 0/1 (0) — 1/1 (100) — 0/1 (0) 0/2 (0) 1/8 (12) 2/13 (15)
During hospitalization 0/1 (0) — 0/1 (0) — 1/1 (100) 1/2 (50) 1/8 (12) 3/13 (23)
Within 30d from discharge 0/1 (0) — 0/1 (0) — 0/1 (0) 0/2 (0) 2/8 (25) 2/13 (15)
After 30d from discharge 1/1 (100) — 0/1 (0) — 0/1 (0) 1/2 (50) 4/8 (50) 6/13 (46)
MRI with pathological findings 0/1 (0) — 0/1 (0) — 1/1 (100)b 0/2 (0) 0/8 (0) 1/13 (8)b

All data in parentheses are percentages. aThe patient with positive brain CT had mild reduction of ventriculi, septo-optic dysplasia, and
herniation of cerebellar tonsils in the foramen magnum. The patient was febrile at the time of the first seizure and the aetiological classifi-
cation at discharge was acute on remote symptomatic seizure. No further seizures occurred during the follow-up. bThe patient with abnor-
mal brain MRI had a remote symptomatic seizure. The MRI showed slightly enlarged ventriculi, with mildly dysmorphic lateral ventriculi,
left atrial periventricular heterotopia, and delayed demyelination. PED, paediatric emergency department; FS, febrile seizure; CwG, benign
convulsion associated with gastroenteritis; AS, acute symptomatic seizure; ARS, acute on remote symptomatic seizure; RS, remote symp-
tomatic seizure; ID, presumed idiopathic age-related epileptic syndrome; UN, unclassified seizure; EEG, electroencephalography; CT, com-
puted tomography; MRI, magnetic resonance imaging.

without (10 out of 13, 76.9%, vs two out of five, 40%;
p=0.17), although this was not statistically significant.
Chronic antiepileptic drug treatment
Among the 14 patients who received a diagnosis of epilepsy,
nine were started on chronic antiepileptic drugs (one
antiepileptic drug in five out of nine; two antiepileptic drugs
in four out of nine; valproic acid in eight out of nine; carba-
mazepine in two out of nine; phenobarbital in one out of
nine; lamotrigine in one out of nine; clobazam in one out of
nine). Two patients discontinued antiepileptic drugs after
2 years with complete control of seizures; none of the
patients in this study developed drug-resistant epilepsy.
The main body of available published research to date
has focused on subgroups of patients, in particular on the
subset of ‘unprovoked seizures’ which, although represent-
ing an important diagnostic challenge, do not represent the
main cause of PED visits for seizures.19–25 Several other
works only included the category of febrile seizure. In other
cases, mixed populations of children and adults,26 or
cohorts of patients without distinction between first-ever
episodes and subsequent seizures, were studied together.3
In this context, our study provides unique comprehen-
sive data on the epidemiology, aetiology of first seizures,
the risk of recurrence, and of epilepsy diagnosis in a ter-
tiary-care European paediatric setting.

DISCUSSION Epidemiology and seizure characteristics

Although convulsive seizures represent a relatively com-
mon cause of admission to the PED, recent epidemiologi-
cal studies on first-ever epileptic seizures in children in this
setting are lacking, especially encompassing all the differ-
ent key aspects of the phenomenon, including frequency
and aetiology of the first seizure, risk of recurrence, and of
receiving a diagnosis of epilepsy. The two most compre-
hensive studies in this respect, most similar to our work,
and focusing on epidemiological data and the risk of recur-
rence in children after the first seizure, including both ‘un-
provoked’ and ‘provoked’ aetiologies, date back over
20 years.5,18 A third, similarly comprehensive study was
performed more recently in Taiwan, although, it should be
noted, in a socio-economic setting very different to ours.1
PED admissions for first-ever convulsive seizures repre-
sented 0.43% of total PED visits in the present study, and
50.5% of the total visits for convulsive seizures in the 12-
month study period, similarly to the figures reported by
Smith et al.5 in 1996 (0.6% and 59% respectively). Most
of the patients in our cohort were aged between 6 months
and 6 years, in agreement with other literature data;1
indeed, this is the age of greatest frequency of febrile sei-
zure, by far the most common cause of PED visit for
epileptic seizures.1,3,5,27
Seizures resolved within 5 minutes in 76.9% of cases in
our cohort, strengthening the validity of this threshold to
define CSE also in children.12,13 According to this temporal
definition, the estimated incidence of PED admissions for

86 Developmental Medicine & Child Neurology 2019, 61: 82–90

 Table III: Proportion of patients who experienced seizure recurrence and who received a diagnosis of epilepsy at the 4-y follow-up, according to aetiological category (top part)

Seizure recurrence and a diagnosis of epilepsy according to seizure aetiology in the total population with
available data at follow-up (n=103) Seizure recurrence at follow-up Diagnosis of epilepsy at follow-up

‘Provoked’ seizures (n=83) 27 (32) 23 (2)

Febrile seizures (n=74) 25 (34)a 2 (3)
CwG (n=4) 2 (50) 0 (0)
Acute symptomatic (n=3) 0 (0) 0 (0)
ARS (n=2) 0 (0) 0 (0)
‘Unprovoked’ seizures (n=20) 12 (60) 12 (60)
Remote symptomatic (n=6) 4 (67) 4 (67)
ID (n=2) 0 (0) 2 (100)
Unclassified seizure (n=12) 8 (67) 6 (50)
Total (n=103) 39 (38) 14 (14)b

Predictors of seizure recurrence and of receiving No seizure Seizure p HR (95% CI) No diagnosis Diagnosis p HR (95% CI)
a diagnosis of epilepsy in the total population recurrence recurrence of epilepsy of epilepsy
with available data at follow-up (n=103)

Female (n=49) 30 (61) 19 (39) 0.73 1.12 (0.60–2.09) 43 (88) 6 (12) 0.75 0.84 (0.29–2.43)
Male (n=54) 34 (63) 20 (37) 46 (85) 8 (15)
c
Age ≤6y at first convulsive seizure (n=97) 61 (63) 36 (37) 0.35 1.74 (0.54–5.67) 87 (90) 10 (10) <0.001 12.04 (3.70–39.15)
Age >6y at first convulsive seizure (n=6) 3 (50) 3 (50) 2 (33) 4 (67)
Generalized onset of first seizure (n=85) 56 (66) 29 (34) 0.12 1.77 (0.86–3.65) 78 (92) 7 (8) 0.001c 5.68 (1.99–16.23)
Focal onset of first seizure (n=18) 8 (44) 10 (56) 11 (61) 7 (39)
Seizure lasting ≤5min (n=78) 52 (67) 26 (33) 0.10 1.75 (0.90–3.40) 70 (90) 8 (10) 0.08 2.53 (0.88–7.30)
Seizure lasting >5min (n=25) 12 (48) 13 (52) 19 (76) 6 (24)
‘Provoked’ seizures (n=83) 56 (67) 27 (32) 0.01c 2.40 (1.21–4.75) 81 (98) 2 (2) <0.001c 37.02 (8.22–166.61)
‘Unprovoked’ seizures (n=20) 8 (40) 12 (60) 8 (40) 12 (60)
c
Single seizure in the first 24h (n=88) 59 (67) 29 (33) 0.003 3.03 (1.47–6.24) 76 (86) 12 (14) 0.99 0.99 (0.22–4.44)
Multiple seizures in the first 24h (n=15) 5 (33) 10 (67) 13 (87) 2 (13)
Negative family history of febrile seizures or epilepsy (n=78) 54 (69) 24 (31) 0.006c 2.46 (1.29–4.72) 68 (87) 10 (13) 0.66 1.30 (0.41–4.14)
Positive family history of febrile seizures or epilepsy (n=25) 10 (40) 15 (60) 21 (84) 4 (16)
c c
No pre-existing neurological conditions/problems (n=90) 60 (67) 30 (33) 0.01 2.67 (1.26–5.66) 83 (92) 7 (8) 0.001 7.623 (2.66–21.83)
Pre-existing neurological conditions/problems (n=13) 4 (31) 9 (69) 6 (46) 7 (54)

EEG predictors of seizure recurrence and of receiving a diagnosis of No seizure Seizure p HR (95% CI) No diagnosis Diagnosis p HR (95% CI)
epilepsy in the patients with ‘unprovoked’ seizures who underwent recurrence recurrence of epilepsy of epilepsy
EEG and who had available data at follow-up (n=18)

No diffuse slowing at EEG ≤30d from first seizure (n=11) 4 (36) 7 (64) 0.64 1.32 (0.42–4.17) 3 (27) 8 (73) 0.38 0.58 (0.17–1.95)
Diffuse slowing at EEG ≤30d from first seizure (n=7) 2 (29) 5 (71) 3 (43) 4 (57)
No epileptiform discharges at EEG ≤30d from the first seizure (n=5) 3 (60) 2 (40) 0.29 2.27 (0.49–10.41) 3 (60) 2 (40) 0.17 2.95 (0.63–13.75)
Epileptiform discharges at EEG ≤30d from the first seizure (n=13) 3 (23) 10 (77) 3 (23) 10 (77)
d
Normal background activity at EEG ≤30d from the first seizure (n=15) 4 (27) 11 (73) 0.40 0.41 (0.05–3.23) 3 (20) 12 (80) 0.14 0.11 (0.005–2.09)
Pathological background activity at EEG ≤30d from the 2 (67) 1 (33) 3 (100) 0 (0)
first seizure (n=3)

All data are n (%) unless otherwise indicated. Aetiological categories are presented in the top part of the table. Univariate Cox regression analysis results: predictors of seizure recurrence
and of receiving a diagnosis of epilepsy at 4-y follow-up (middle and bottom parts of table). Data at follow-up were available for 103 out of 108 patients (95.4%), while the remaining five
out of 108 patients were lost to follow-up (5.6%). aRecurrence rate was 28.8% in patients with simple febrile seizures (19 out of 66) and 75% in the subgroup with complex febrile seizures
(six out of eight). bEpilepsy diagnoses at follow-up were focal symptomatic epilepsy (five out of 14, 35.7%), benign centro-temporal spike epilepsy (four out of 14, 28.6%), epilepsy with
myoclonic-astatic seizures (three out of 14, 21.4%), focal criptogenic epilepsy (one out of 14, 7.1%), and epilepsy with continuous spike-waves during slow-wave sleep (one out of 14, 7.1%).
c
Statistically significant value. dFirth’s penalized maximum likelihood estimation. CwG, benign convulsion associated with gastroenteritis; ARS, acute on remote symptomatic; ID, presumed

Epidemiology of First-Ever Convulsive Seizures in Children Stefano Sartori et al. 87

idiopathic age-related epileptic syndrome; HR, hazard ratio; CI, confidence interval; EEG, electroencephalography.
 (a) 1.0
0.9
0.8

Seizure recurrence
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 180 360 540 720 900 1080 1260 1440
Days from first seizure
Number
at risk 103 82 72 68 68 66 65 64 64

(b) 1.0
0.9
0.8
Epilepsy diagnosis

0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 180 360 540 720 900 1080 1260 1440
Days from first seizure
Number
at risk 103 94 90 90 90 89 89 89 89

Figure 1: Survival curve for (a) seizure recurrence and (b) receiving a diagnosis of epilepsy during a 4-year follow-up after visit to paediatric emer-
gency department for a first-ever convulsive seizure.

first-ever episode of CSE, calculated from our data, was 33.3
out of 100 000 children per year. This figure, the only one
available in Italy, is significantly higher than those reported
in most previous studies,2,28 in view of the new definition of
CSE adopted in our work.12,13 The hospitalization rate in
our cohort (15.7%) was considerably lower than that
reported by Smith et al.5 (80%, only a paediatric population)
and that described by Jallon et al.29 (61%, mixed popula-
tion). This difference may partly reflect the implementation
of specific therapeutic and diagnostic pathways at our PED,
especially for the management of febrile seizure, resulting in
a dramatic decline in the hospitalization rate for this particu-
lar category,30 with a favourable repercussion on the overall
hospitalization rate for convulsive seizures.
Seizure aetiology
As regards the aetiology of first seizure, ‘provoked seizures’
(febrile seizure, benign convulsion associated with
gastroenteritis, acute symptomatic seizure, and acute on
remote symptomatic seizure) outnumbered ‘unprovoked sei-
zures’ (remote symptomatic seizure, presumed idiopathic
age-related epileptic syndrome, and unclassified seizure) by
far in our population (80.6% vs 19.4%) (Table I). In particu-
lar, febrile seizure represented 71.3% of the total visits for
first-ever convulsive seizures, similar to the rates reported by
Chen et al.1 (68%)1 and Smith et al.5 (63%), underpinning
further the importance of defining specific therapeutic and
diagnostic paths for febrile seizure management. It is worth
noting that all patients aged 6 years or older in our cohort
fell under the grouping of ‘unprovoked’ seizures, while the
acute symptomatic seizure and acute on remote symptomatic
seizure forms (apart from febrile seizure and benign convul-
sion associated with gastroenteritis by definition) affected
children under 6 years, confirming an age-specific vulnerabil-
ity to present occasional seizures closely related to acute
events (e.g. fever, hypoglycaemia, hypoxia, hypocalcaemia).

88 Developmental Medicine & Child Neurology 2019, 61: 82–90

Investigations
EEG was performed in most patients with afebrile seizures
in our cohort. EEG is generally indicated in the case of a
first afebrile seizure in children.31 Conversely, EEG is not
recommended for febrile seizure,32 although there is not
enough evidence to support or refute its use after complex
febrile seizure in children.33
Neuroimaging was done particularly frequently in our
cohort in patients with long, focal seizures, and in the
presence of EEG epileptiform abnormalities. According to
the International League Against Epilepsy guidelines for
imaging infants and children with recent-onset epilepsy,34
imaging (preferably magnetic resonance imaging) should
be done when one or more of the following conditions are
present: focal epilepsy (with the exception of typical benign
idiopathic partial epilepsy); abnormal neurological exami-
nation; age younger than 2 years (excluding those with
simple febrile seizures); characteristics of a symptomatic
generalized epilepsy syndrome (e.g. infantile spasms or
early Lennox–Gastaut syndrome); failure to control sei-
zures, worsening seizures, changes in seizure manifesta-
tions, or developmental regression; new-onset seizures/
epilepsy presenting with evidence of a medical emergency
such as increased intracranial pressure or status epilepticus.
Seizure recurrence
Overall seizure recurrence rate at 4 years was 37.9% in our
population (32.5% of ‘provoked’ seizures and 60% of ‘unpro-
voked’ seizures). A recently published meta-analysis of seizure
recurrence after a first ‘unprovoked seizure’ in 815 neurologi-
cally and developmentally healthy children disclosed a slightly
lower recurrence rate at 3 years (45%),35 possibly because of
the shorter follow-up and the restriction to neurologically
healthy patients. Indeed, global developmental delay and
intellectual disability have been reported as risk factors for
seizure recurrence after a first ‘unprovoked seizure’ in chil-
dren.21,36 Other studies on ‘unprovoked seizures’ disclosed
variable rates of recurrence between about 35% and 65%,
depending on the different lengths of follow-up (2–5y) and
the designs and case definitions used.21,22,25,37–39 Factors sig-
nificantly related to risk of seizure recurrence in our study
were the ‘unprovoked’ nature of the first seizure, multiple sei-
zures in the first 24 hours, a positive family history of febrile
seizure or epilepsy, and pre-existing neurological conditions
or problems (Table III). Abnormal EEG has been previously
reported as a risk factor for seizure recurrence after a first
unprovoked seizure in children and adults, although it did not
reach statistical significance in our study.19–25 Seizure
recurrence occurred within 1 year in 79.5% of the patients
who relapsed in our population (Fig. 1a), confirming previous
data in the literature.20,24,40
Epilepsy diagnosis
At 4-year follow-up, 13.6% of the patients in our cohort
received a diagnosis of epilepsy (Table III). The epilepsy
diagnosis rate rose to 60% when only the ‘unprovoked sei-
zures’ group was considered, similar to other data in the
literature,41 whereas it was only 2.4% in the ‘provoked sei-
zures’ group. The ‘unprovoked’ nature of the first seizure
was the main predictor of receiving a diagnosis of epilepsy,
followed by age older than 6 years, pre-existing neurologi-
cal conditions or problems, and focal onset of first seizure,
emphasizing the importance of accurate history taking and
neurophysiological studies.
Limitations and conclusion
The main limitations of the present study relate to the sin-
gle-centre, retrospective nature and the restricted number
of cases. Indeed, a too-small ratio of events per variable
can affect the accuracy and precision of regression coeffi-
cients and their tests of statistical significance.42 Unfortu-
nately, the sample size was intrinsically linked to the size
of the population served by our PED, and therefore was a
non-modifiable factor. It should also be acknowledged that
data relative to family history may be underemphasized in
patients with a single seizure episode, especially febrile sei-
zure, possibly suggesting a reporting bias. Moreover, all
patients underwent a thorough paediatric assessment,
although not all were assessed by a paediatric neurologist,
especially patients with simple febrile seizure.
However, our work provides unique data about the epi-
demiology of first convulsive seizures in children present-
ing to the PED and the factors associated with seizure
recurrence and epilepsy diagnosis. In particular, our find-
ings suggest that a closer neurological follow-up would be
desirable when one or more of the above-mentioned risk
factors for recurrence and for epilepsy diagnosis are pre-
sent. This information may be useful in guiding not only
acute diagnostic work-up but also more appropriate and
tailored counselling and follow-up.
A CK N O W L E D G E M E N T S
We thank Marilena Vecchi, Silvia Bergamo, and Francesca Parata
for the care offered to the patients included in the study. The other
authors have stated that they had no interests that could be perceived
as posing a conflict or bias. The study did not receive any funding.

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 DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY ORIGINAL ARTICLE

RESUMEN
~
PRIMER EVENTO DE CRISIS CONVULSIVA EN NINOS ATENDIDOS EN EL DEPARTAMENTO DE URGENCIAS: FACTORES DE RIESGO

PARA RECURRENCIA DE CONVULSIONES Y DIAGNOSTICO DE EPILEPSIA

OBJETIVO La etiologıa del primer evento convulsivo es diversa, no todas llegan a recurrir o a recibir el diagno stico de epilepsia.
Nuestro objetivo es describir la epidemiologıa de la primera crisis convulsiva en nin ~ os, investigando factores de riesgo para
recurrencia y diagno  stico de epilepsia.
METODO Estudio retrospectivo de nin~ os que fueron asistidos por una primera crisis convulsiva en la urgencia pediatrica (URG) de
un centro de tercer nivel de atencio  n en Italia, en un periodo de 12 meses (2011-2012).
RESULTADOS Ciento ocho nin~ os (57 varones, 51 mujeres) fueron asistidos en la URG por una primera crisis convulsiva; 90.7%
tuvieron entre 6 meses y 6 an ~ os de edad (mediana de edad 1 an ~ o y 10 meses, media 2 an ~ os y 7 meses, rango 0 meses a 14 an
~ os
y 4 meses). La duracio  n de la crisis fue menor a 5 minutos en el 76.8%. Las convulsiones fueron “no provocadas” en el 19.4% y
provocadas en el 80.6%. A los 4 an ~ os de seguimiento, el 37.9% de los pacientes experimentaron recurrencia y el 13.6% fueron
diagnosticados con epilepsia. Los factores que significativamente se asociaron con recurrencia fueron causa “no provocada” de
crisis, mu  ltiples crisis en menos de 24 horas, historia familiar de convulsiones febriles o epilepsia y condiciones/problemas
neurolo  gicos preexistentes. Los factores significantemente vinculados al diagno  stico de epilepsia fueron causas “no provocados”
de crisis, edad mayor a 6 an ~ os, condiciones/problemas neurolo  gicos preexistentes y origen focal de la primera crisis.
INTERPRETACION  Los nin~ os que se presentan a la URG con un primer evento de crisis convulsiva representan un grupo muy
heteroge neo. La identificacio  n de factores prono  sticos de recurrencia y diagno  stico de epilepsia puede ayudar proveyendo
asesoramiento y seguimiento adecuados.

RESUMO
ß AS QUE COMPARECEM AO DEPARTAMENTO DE EMERG^
PRIMEIRA CRISE CONVULSIVA EM CRIANC ENCIA: FATORES DE RISCO PARA
RECORR^ENCIA DA CONVULSAO 
~ E DIAGNOSTICO DE EPILEPSIA

OBJETIVO As etiologias das crises convulsivas que acontecem pela primeira vez pode ser diversa, nem todas levando a
recorre ^ ncia ou diagno  stico de epilepsia. Visamos descrever a epidemiologia das primeiras crises convulsivas em criancßas,
investigando fatores de risco para recorre ^ncia e diagno stico de epilepsia.
METODO Tratou-se de um estudo retrospectivo de criancßas apresentando uma convulsa~o pela primeira vez que comparaceram a
um departamento de emerge ^ncia pediatrica (DEP) de nıvel tercia
rio de cuidado na Ita lia, em um perıodo de 12 meses (2011-2012).
RESULTADOS Cento e oito criancßas (57 do sexo masculino, 51 do sexo feminino) compareceram ao DEP devido a uma convulsa~o
pela primeira vez; 90.7% tinham de 6 meses a 6 anos de vida (idade mediana 1a 10m, me  dia 2a 7m, variacßa ~ o 0m–14a4m). A
duracßa~ o da convulsa ~o foi menor do que 5 minutos em 76.8%. As convulso ~ es foram “na ~o provocadas” em 19.4% e “provocadas”
em 80.6%. No acompanhamento de 4 anos, 37.9% dos pacientes apresentou recorre ^ncia e 13.6% recebeu diagno  stico de epilepsia.
Fatores significativamente associados com recorre ^ncia foram as primeiras convulso ~ es de natureza “na ~ o provocada” convulso ~s
mu ltiplas nas primeiras 24 horas, histo  ria familiar positiva de convulso ~ es febris ou epilepsia, e condicßo ~ es/problemas neurolo  gicos
-existentes. Fatores significativamente associados com diagno
pre  stico de epilepsia foram a natureza “na ~o provocada” da primeira
convulsa ~o, idade maior do que 6 anos, condicßo ~ es/problemas neurolo  gicos pre-existentes, e inıcio focal da primeira convulsa ~o.
INTERPRETAC ~ Criancßas se apresentando no DEP com crises convulsivas que acontecem pela primeira vez representam um
ß AO
grupo heteroge ^ neo. A identificacßa
~o de fatores progno  sticos para recorre ^ ncia e epilepsia pode favorecer o aconselhamento e
acompanhamento individualizados.