a b s t r a c t

Introduction: The primary goals of emergency department (ED) clinicians when dealing with a pediatric patient experiencing a seizure are to control the seizure and prevent seizure-related complications. After stabilizing the patient, the clinician should determine whether the patient is likely to have recurrent seizures that may need treatment such as Antiepileptic drugs (AEDs). The early identification of pediatric seizure patients at high risk for recurrence can be of great help in consulting with their parents. This study aimed to identify predictors of sei- zure recurrence in pediatric patients who visited the ED for first-onset aFebrile seizure.

Methods: This retrospective study was conducted with pediatric patients aged 1 month to 18 years who visited our ED for afebrile seizure from January 2016 to March 2020. Children with a known seizure disorder, known un- derlying genetic or Metabolic disorder, or acute trauma history, and those lost to follow-up were excluded. Mul- tivariable logistic regression analysis was performed to identify factors associated with Seizure recurrence.

Results: A total of 253 pediatric patients were included in the study. Seizure recurrence was observed in 117 pa- tients (46.3%). From the multivariable logistic regression analysis, older age at onset (11-15 years, odds ratio [OR] 5.781, p = 0.001; 16-18 years, OR 6.223, p = 0.002), a longer seizure duration (1-5 min, OR 3.043, p = 0.002;

6-10 min, OR 5.629, p = 0.002; >10 min, OR 8.882, p = 0.002), blood pH under 7.2 (OR 8.308, p = 0.015),

and a glucose level over 144 mg/dL (OR 6.408, p = 0.030) were significantly associated with seizure recurrence. The area under the receiver operating characteristic curve for the multivariable logistic regression analysis was 0.774.

Conclusion: Age at onset >=11 years, a longer seizure duration, acidosis, and hyperglycemia were predictors of sei- zure recurrence in children who had experienced first-onset afebrile seizure.

(C) 2021

1. Introduction

Seizure is one of the most common neurological conditions in pedi- atrics [1]. The prevalence of pediatric seizures is approximately 1% of all children; it is highest in children <1 year old and in certain high-risk groups such as those with developmental delay or autism [2]. The most common type of pediatric seizure between 6 months and 5 years of age is febrile seizure [3]. On the other hand, afebrile seizure is rela- tively uncommon, but it is clinically significant because the recurrence rate of afebrile seizure is remarkable [4]. Overall, in untreated individ- uals, approximately 40-50% of patients with unprovoked seizure can

* Corresponding author at: Department of Emergency Medicine, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Bucheon 14584, Republic of Korea.

E-mail address: [email protected] (S. Han).

expect a recurrence within 2 years of the initial seizure [4-6]. Because afebrile seizure children are at higher risk of recurrence than the others, it is essential to evaluate the risk of recurrence in the first seizure [7].

Recently, many studies have focused on the quality of life and life ex-

pectancy of patients suffering from recurrent seizures. People with re- current seizures are at increased risk of suffering from chronic conditions such as psychosocial sequelae [9]. The Life expectancy was also reduced in people who had developed recurrent seizure [10]. To prevent seizure recurrence, early use of antiepileptic drugs (AEDs) has been suggested. According to a multi-center study conducted in Italy, treatment of a first seizure with AEDs led to a significant reduction in the risk of relapse [5]. However, clinicians, especially those in the emergency department (ED), must consider whether to treat pediatric patients with AEDs after the first unprovoked seizure because of side effects in children such as poor concentration and learning disabilities [11-13].

https://doi.org/10.1016/j.ajem.2021.08.031

0735-6757/(C) 2021

From this perspective, the early identification of pediatric afebrile seizure patients who are at high risk of seizure recurrence would be helpful for clinicians in terms of deciding whether to initiate treatment such as AEDs and in consulting with the patients’ parents. A current clin- ical practice guideline for evaluating a first non-febrile seizure in chil- dren recommends clinicians to perform electroencephalography (EEG) after all first non-febrile seizures [7]. However, it is difficult to routinely perform EEG in the ED due to lack of professional personnel and equipment [8]. Therefore, numerous studies have sought to identify early risk factors for seizure recurrence through relatively readily avail- able information; age at onset, seizure duration, blood pH, and glucose values [4-6,14-18]. However, each of these studies has reported differ- ent results.

The aim of this study was to identify predictors of seizure recurrence in pediatric patients who visited the ED due to first-onset afebrile sei- zure using clinical and historical findings, physical and neurologic ex- aminations, and laboratory results.

1. Methods
   1. Study design and setting

This was a retrospective observational study of pediatric patients who visited the ED for seizures from January 2016 to March 2020. Our hospital’s ED serves approximately 65,000 patients per year. Previously healthy children aged 1 month to 18 years presenting with first-onset afebrile seizure were included [6]. Patients who had a recent history of minor infection but were asymptomatic and afebrile for at least 24 h prior to seizure were included in the study population. The following were excluded: children with a known seizure disorder, known under- lying genetic or metabolic disorder, or acute trauma history; and those lost to follow-up. This study was approved by our hospital institutional trial review board (IRB file no. 2021-03-030).

• 1. Definition of afebrile seizure and seizure recurrence

Our definition of seizure recurrence is based on the Guidelines for Epidemiologic Studies on Epilepsy published by the International League Against Epilepsy [19]. Recurrence of seizure is defined as the oc- currence of at least two unprovoked seizures occurring more than 24 h apart. We defined first-onset afebrile seizure as the first seizure without any acute provoking factors such as fever or other severe metabolic de- rangement.

• 1. Clinical and laboratory assessments/data collection

The electronic health records of 846 patients evaluated at our pediatric ED for seizures from January 2016 to March 2020 were retrospectively reviewed. Data were extracted from the ED providers’ notes by two expe- rienced reviewers. The following data were extracted from the medical records: age at onset [2]; gender; past history (i.e., birth history, Neonatal intensive care unit [NICU] admission history, and familial history); the oc- currence of single or Multiple seizures in the first 24 h after presentation; seizure duration [13]; focal manifestations such as Todd’s palsy; seizure type; pHysical examination findings; laboratory results (i.e., complete blood cell count , blood pH [14], lactate, glucose [20], blood urea ni- trogen [BUN], creatinine [Cr] [21], aspartate aminotransferase [AST], alka- line phosphatase [ALP], electrolytes, C-reactive protein [CRP]). The categorizations of extracted data are summarized in Table 1.

After the data were collected, the subjects were followed up through telephone interviews for a period of at least 1 year, and some children were followed up for a period of up to 5 years. Because seizures rarely occur in the physician’s office, information obtained from follow-up by telephone should be as reliable as that obtained via direct contact dur- ing the clinical follow-up [6]. Therefore, the ascertainment of seizure re- currence was primarily done based on history. In our ED, one unified

Table 1

Summarization of clinical and laboratory data categorization

Variables Data categorization

Age at onset, years < 2; 2-5; 6-10; 11-15; and 16-18 Gender Female; and male

Past history IUP; birth weight; C-sec history; NICU history; and Familial history

Duration of seizure, min < 1; 1-5; 6-10; and > 10 Seizure type GTC; focal; and secondary GTC

Physical examination Lethargy; neck stiffness; Kernig’s sign; Babinski sign; and lateralizing sign

Laboratory result

Glucose Hypoglycemia (< 50 mg/dL); normoglycemia (50 <= glucose <=144 mg/dL); and hyperglycemia (> 144 mg/dL; > 8.0 mmol/L)

Blood pH < 7.2; and >= 7.2

Cr <=1.2 mg/dL; and > 1.2 mg/dL

Abbreviations: IUP, Intrauterine pregnancy; C-sec, caesarean section; NICU, neonatal in- tensive care unit; GTC, generalized tonic-clonic; pH, potential of hydrogen; Cr, creatinine.

protocol is applied to all pediatric patients with an afebrile seizure. This way, it ensures that most of the pediatric patients with afebrile sei- zure undergo similar tests in the ED.

• 1. Statistical analysis

Fisher’s exact test or the chi-squared test was used for categorical variables. The normality of the data was assessed using the Shapiro- Wilk test; the Mann-Whitney test was used for continuous variables in this study, as none of the variables had a normal distribution (p < 0.05). Data are presented as absolute numbers or relative frequen- cies for categorical variables and as medians with interquartile ranges for continuous variables. In the logistic regression model, the dependent variable was defined as the risk of seizure recurrence. Multivariable lo- gistic regression analysis was performed on factors found statistically significant in univariable logistic regression (p-value <0.05) and vari- ables reported to be significantly associated with seizure recurrence in previous studies [4-7,14-18,22,23]. Odds ratios (ORs) with 95% confi- dence intervals (CIs) were calculated as an approximation of relative risk to indicate the association between each factor and seizure recur- rence. Two-tailed p-values <0.05 were considered to indicate statistical significance. The area under the Receiver operating characteristic curve for the multivariable logistic regression analysis was calcu- lated. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) for Windows version 26 (IBM, Armonk, NY, USA).

Fig. 1. Flow chart of patient selection. Abbreviation: ED, emergency department.

Table 2

General characteristics of pediatric patients with afebrile seizure in this study

Table 3

Comparison of baseline characteristics between non-recurrence and recurrence groups

Age at onset, years (%)

Total (N = 253)

Non-recurrence (n = 136)

Recurrence (n = 117)

P-value

< 2 60 (23.72)

2-5 82 (32.41)

6-10 36 (14.23)

11-15 47 (18.58)

16-18 28 (11.07)

Gender, n (%)

Female	109 (43.31)
Male	144 (56.69)
Past history IUP, weeks	39 [37-40]
Birth weight, kg	3.2 [2.9-3.5]
C-sec history, n (%)	77 (44.51)
NICU history, n (%)	22 (8.66)
Familial history, n (%)	41 (16.14)
Seizure features Number of seizures, n	1 [1-1]
Todd’s palsy, n (%)	8 (3.15)
Duration, min (%) < 1	71 (28.06)
1-5	137 (54.15)
6-10	26 (10.28)
> 10 Type, n (%)	19 (7.51)

GTC type	239 (94.47)
Focal type	12 (4.74)
Secondary GTC type	2 (0.79)

Categorical variables are given as numbers (percentage). Continuous non- parametric variables are given as medians [interquartile range]. Abbrevia- tions: IUP, intrauterine pregnancy; C-sec, caesarean section; NICU, neonatal intensive care unit; GTC, generalized tonic-clonic.

1. Results

During the study period, a total of 221,554 patients visited our ED; of these, 1810 visited the ED for seizures. Among these patients, 846 were pediatric patients who met our age criteria. After application of the ex- clusion criteria, 253 patients were included in the study (Fig. 1).

• 1. General characteristics

The general characteristics of the patients are summarized in Table 2. The median age was 6 (2-12) years. Twenty-two patients (8.66%) had a history of NICU admission, and 41 (16.14%) had a familial history of seizure. With respect to seizure features, eight (3.15%) pa- tients had Todd’s palsy, and the median duration of seizure was 3 (1-5) minutes.

• 1. Comparison of the non-recurrence and recurrence groups

Recurrence of seizure was observed in 117 patients (46.3%). No sig- nificant differences in gender, past history, number of seizures and type of seizures, or physical examination findings were found between the re- currence and non-recurrence groups. On Median age, patients in the re- currence group were older at onset than those in the non-recurrence group (9 vs. 5 years, p < 0.001). Also, the recurrence group had a longer seizure duration than the non-recurrence group (5 vs. 2 min, p < 0.001). Todd’s palsy was more common in the recurrence group than in the non- recurrence group (5.98% vs. 0.74%, p = 0.026). With respect to laboratory findings, there were no significant differences in lactate, bilirubin, elec- trolytes, or CRP between the two groups (Table 3).

• 1. Main outcomes

The results of the multivariable logistic regression analysis are shown in Table 4. Age at onset was significantly associated with seizure recurrence. Furthermore, a longer seizure duration was significantly

Age at onset, years (%) <0.001*

< 2	44 (32.35)	16 (13.68)
2-5	47 (34.56)	35 (29.91)
6-10	19 (13.97)	17 (14.53)
11-15	17 (12.5)	30 (25.64)
16-18	9 (6.62)	19 (16.24)
Gender, n (%) Female	59 (43.38)	>0.999* 51 (43.59)
Male	77 (56.62)	66 (56.41)
Past history
IUP, weeks	39 [37-40]	39[37-40]	0.451
Birth weight, kg	3.25 [2.92-3.44]	3.2 [2.9-3.5]	0.358
C-sec history, n (%)	43 (44.79)	33 (43.42)	0.980*
Familial history, n (%)	22 (16.18)	19 (16.24)	>0.999*
NICU history, n (%)	9 (6.62)	13 (11.11)	0.298*
Seizure features
Number of seizures, n	1 [1-1]	1 [1-1]	0.146
Todd’s palsy, n (%)	1 (0.74)	7 (5.98)	0.026**
Duration, min (%)			<0.001*

< 1	53 (38.97)	18 (15.38)
1-5	68 (50)	69 (58.97)
6-10	11 (8.09)	15 (12.82)
> 10	4 (2.94)	15 (12.82)

Type, n (%) 0.221**

GTC type	128 (94.12)	111 (94.87)
Focal type	8 (5.88)	4 (3.42)
Secondary GTC type	0 (0)	2 (1.71)
Physical, n (%) Lethargy	25 (18.38)	32 (27.35)	0.121*
Neck stiffness	1 (0.74)	2 (1.71)	0.597**
Kernig’s sign	1 (0.74)	0 (0)	>0.999**
Babinski sign	0 (0)	1 (0.85)	0.463*
Lateralizing sign	1 (0.74)	4 (3.42)	0.185**
Laboratory WBC, 103/uL	8.64 [6.76-11.22]	8.44 [6.76-11.79]	0.977
Hb, g/dL	12.7 [11.8-13.15]	13 [12.3-13.8]	0.006
pH	7.36 [7.32-7.39]	7.33 [7.27-7.38]	0.004
Lactic acid, mg/dL	2 [1.42-2.98]	2.5 [1.49-3.8]	0.051
Glucose, mg/dL	100 [86.5-109.5]	107 [95.5-124]	<0.001
BUN, mg/dL	11.6 [9.9-13.8]	11.2 [8.95-13.25]	0.044
Cr, mg/dL	0.5 [0.4-0.6]	0.6 [0.5-0.8]	0.003
Bilirubin, mg/dL	0.38 [0.29-0.54]	0.41 [0.33-0.53]	0.539
AST, U/L	30 [23-36]	27 [20-34.5]	0.035
ALP, U/L	450 [284-729]	352 [235-630]	0.025
Sodium, mmol/L	138 [137-140]	138 [137-139.5]	0.758
Chloride, mmol/L	103 [102-105]	104 [102-105]	0.282
Calcium, mg/dL	9.1 [8.9-9.4]	9.1[8.8-9.3]	0.136
Phosphorus, mg/dL	4.6 [4.05-5.15]	4.5 [3.6-5.15]	0.184
Magnesium, mg/dL	2.1 [2-2.3]	2.1 [2-2.25]	0.456
CRP, mg/dL	0.05 [0.02-0.18]	0.05 [0.02-0.15]	0.791

Categorical variables are given as numbers (percentage) using *Pearson Chi-squared test or **Fisher exact test. Continuous variables are given as medians [interquartile range] by Mann-Whitney test (all continuous variables did not have a normal distribution.).

Abbreviations: IUP, intrauterine pregnancy; C-sec, caesarean section; NICU, neonatal in- tensive care unit; GTC, generalized tonic-clonic; WBC, white blood cell; Hb, hemoglobin; pH, potential of hydrogen; BUN, blood urea nitrogen; Cr, creatinine; AST, aspartate amino- transferase; ALP, alkaline phosphatase; CRP, C-reactive protein.

associated with seizure recurrence compared with a duration of shorter than 1 min. In terms of laboratory findings, pH values under 7.2 were significantly associated with seizure recurrence compared to pH over

7.2. Moreover, hyperglycemia was significantly associated with seizure recurrence compared with normoglycemia. The AUROC for the multi- variable logistic regression analysis was 0.774 (95% CI, 0.715-0.832)

(Fig. 2).

1. Discussion

In this study, we investigated predictors of seizure recurrence in children who visited the ED due to first-onset afebrile seizure. An older age at onset, especially an age of 11 years or older, and longer

Table 4

Factors associated with seizure recurrence in multivariable logistic regression analysis

Multivariable

	OR (95% CI)	p-value
Age at onset, years
< 2	1
2-5	1.183 (0.506-2.765)	0.699
6-10	2.068 (0.780-5.484)	0.144
11-15	5.781 (2.249-14.858)	0.001
16-18	6.223 (1.965-19.711)	0.002
Seizure features
Todd’s Palsy	5.876 (0.675-51.158)	0.109
Duration, min
<1	1
1-5	3.043 (1.483-6.245)	0.002
6-10	5.629 (1.844-17.186)	0.002
> 10	8.882 (2.187-36.083)	0.002
Laboratory
Cr > 1.2, mg/dL	0.106 (0.005-2.401)	0.159
pH < 7.2	8.308 (1.519-45.447)	0.015
Glucose, mg/dL
< 50	2.374 (0.122-46.231)	0.568
50-144	1
> 144	6.408 (1.195-34.370)	0.030

Multivariable logistic regression analysis was performed on factors including found statis- tically significant in univariable logistic regression (p-value <0.05) and variables reported to be significantly associated with seizure recurrence in previous studies.

Abbreviations: OR, odds ratio; CI, confidence interval; Cr, creatinine; pH, potential of hy- drogen.

seizure duration were significantly associated with seizure recurrence. Furthermore, in terms of laboratory findings, a blood pH under 7.2 and a glucose level over 144 mg/dL were significantly associated with seizure recurrence. To the best of our knowledge, this study is the first to investigate the predictors of first-onset afebrile seizure recurrence in- cluding laboratory results and physical examination findings.

A prospective cohort study with 407 children who experienced an unprovoked first seizure found that 171 children (42%) experienced re- currences [6]. In another cohort study, the seizure recurrence rate was 51% [5]. In our study, 117 (46.25%) of 253 pediatric patients experienced seizure recurrence after their first-onset afebrile seizure. Furthermore, numerous studies have shown that most seizure recurrences (over 90%) occurred within 1 year, with similar results obtained at the year 2 or 7 follow-up [5,22]. In our study, patients were followed for at least 1 year and up to a maximum of 5 years. Considering the results of previous studies, the majority of recurrences would have been in- cluded, even in the patients followed only for 1 year.

Das et al. reported that among patients with a history of a single sei- zure episode, a longer seizure duration at presentation was associated with a higher risk or recurrence [14]. Another study of children with ep- ilepsy found that an individual who experienced status epilepticus last- ing more than 30 min as a first seizure was also at much greater risk of recurrent seizure episodes [24]. The results of our study are similar to those two studies in showing that a longer seizure duration at presenta- tion was significantly associated with seizure recurrence. The mecha- nism by which longer seizure duration affects seizure recurrence can

Fig. 2. Receiver operating characteristic curve for the multivariable logistic regression analysis for predicting afebrile seizure recurrence.

be explained as follows. First, the brain may be able to recover better from short seizures and may be more intrinsically compromised by lon- ger seizures [25]. Second, prolonged seizures may also suggest that the patient has a lower threshold to epileptic activity and is therefore at risk for seizure recurrence [26].

Age, as a surrogate for brain maturation, is a determinant of the spe- cific characteristics of seizure disorders [17]. The results of studies on whether age is associated with seizure recurrence are controversial. Several studies have concluded that age had little influence on the risk of seizure recurrence [4,6]. However, Sartori et al. reported that age at onset above 6 years was a factor associated with the diagnosis of epi- lepsy in children with first-onset unprovoked seizure [18]. In our study, we concluded that an age at onset of 11 years or older was asso- ciated with seizure recurrence compared with an age at onset of 2 years or younger.

Metabolic acidosis often develops in patients who have Generalized seizures [27,28]. The likely cause of acidosis during a seizure is increased anaerobic metabolism resulting from elevated oxygen utilization during Seizure activity [28]. Kilic et al. reported that pH values under 7.245 on blood gas analysis (BGA) can be predictive of whether patients will ex- perience seizure recurrence [15]. This is similar to our finding that blood pH values under 7.2 are significantly associated with seizure recurrence in pediatric afebrile seizure patients. These results could be of great help to ED clinicians in deciding whether pediatric seizure patients require Close monitoring based on the patients’ BGA results.

Research on the relationship between hyperglycemia and brain function disorders such as seizure is being actively conducted [16,23]. In our study, hyperglycemia (glucose level > 144 mg/dL) was associated with seizure recurrence in children with first-onset afebrile seizure compared with normoglycemia (50 <= glucose level <= 144 mg/dL). Pinchefsky et al. concluded that epochs of hyperglycemia were associ- ated with seizures and worse global brain function on amplitude- integrated electroencephalography [23]. Furthermore, Costea et al. re- ported that stress hyperglycemia was predictive of recurrence in chil- dren with febrile seizure [16]. The association between hyperglycemia and seizure recurrence can be explained as follows. First, seizure activity has common stress-related mechanisms with high metabolic states and relative hypoxic states due to higher oxygen demands [29]. Second, cy- tokines and hormones secreted via these mechanisms interact in a com- plex manner to support gluconeogenesis, glycogenolysis, and insulin resistance, which result in stress hyperglycemia [29].

According to a clinical practice guideline for evaluating a first non- febrile seizure in children, clinicians should consider to perform labora- tory tests and EEG on pediatric patients with non-febrile seizures, how- ever, there are limitations in implementation of EEG in the ED for the same reason as lack of professional personnel and equipment [7,8]. Since it was also hard to perform EEG in our ED, we conducted research on additional laboratory findings such as BGA and glucose level based on the previous studies as well as laboratory results recommended in the guideline [15,16,23]. As a result, acidosis and hyperglycemia were significantly associated with seizure recurrence.

In this study, we presented a prediction model for the recurrence of

non-febrile seizures in children based on Laboratory test results and in- formation such as age and seizure duration. Considering that these data can be obtained relatively easily in the ED, our model may provide ben- efit for emergency physicians in establishing an early diagnosis and treatment plan.

This study has several limitations. First, because it was a retrospec- tive study, selection bias might have occurred. However, the bias might have been minimized by the “critical pathway for pediatric afe- brile seizure” protocol employed in our ED, which is applied to children with afebrile seizures and ensures that most of the children undergo similar tests. Second, the number of patients who experienced focal sei- zures or Todd’s palsy was too low in our study to determine whether those factors were relevant. Other studies comparing Focal seizures with generalized seizures found that the former were associated with

a higher risk of recurrence [4,12]. Third, this was a single-center study; thus, the results may not be generalizable to other cities or coun- tries. Therefore, large-scale prospective studies on afebrile seizure re- currence in children that include physical examination findings and laboratory results are needed.

1. Conclusion

We found that an older age at onset (11 years or older); longer sei- zure duration; acidosis, especially blood pH under 7.2; and hyperglyce- mia with a glucose level over 144 mg/dL were predictors of seizure recurrence in children who visited the ED for first-onset afebrile seizure. The results of our study can help clinicians in the ED to make decisions about initiating treatment for pediatric patients who have undergone first-onset afebrile seizure. Also, pediatric seizure patients with such findings should be closely monitored.

Funding

This work was supported by Soonchunhyang University research fund.

Declaration of Competing Interest

The authors declare no conflicts of interest.

References

1. Tharp BR. An overview of pediatric seizure disorders and epileptic syndromes. Epilepsia. 1987;28:S36-44. https://doi.org/10.1111/j.1528-1157.1987.tb05755.x.
2. Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure dis- order. Pediatrics. 2012;129(2):256-64. https://doi.org/10.1542/peds.2010-1371.
3. Pediatrics AAO. Neurodiagnostic evaluation of the child with a simple febrile seizure.

Pediatrics. 2011;127(2):389-94. https://doi.org/10.1542/peds.2010-3318.

1. Berg AT. Risk of recurrence after a first unprovoked seizure. Epilepsia. 2008;49:13-8. https://doi.org/10.1111/j.1528-1167.2008.01444.x.
2. Musicco M, Beghi E, Bordo B, Viani F. Randomized clinical trial on the efficacy of an- tiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology. 1993;43(3):478-83.
3. Shinnar S, Berg AT, Moshe SL, O’Dell C, Alemany M, Newstein D, et al. The risk of sei- zure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up. Pediatrics. 1996;98(2):216-25.
4. Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Camfield P, et al. Practice parameter: evaluating a first Nonfebrile seizure in children: report of the quality standards sub- committee of the American Academy of Neurology, the child neurology society, and the American Epilepsy Society. Neurology. 2000;55(5):616-23. https://doi.org/10. 1212/WNL.55.5.616.
5. Yigit O, Eray O, Mihci E, Yilmaz D, Arslan S, Eray B. The utility of EEG in the emer- gency department. Emerg Med J. 2012;29(4):301-5. https://doi.org/10.1136/emj. 2011.112888.
6. Strine TW, Kobau R, Chapman DP, Thurman DJ, Price P, Balluz LS. Psychological dis- tress, comorbidities, and health behaviors among US adults with seizures: results from the 2002 National Health Interview Survey. Epilepsia. 2005;46(7):1133-9. https://doi.org/10.1111/j.1528-1167.2005.01605.x.
7. Cockerell OC, Hart Y, Sander JW, Goodridge D, Shorvon S, Johnson A. Mortality from epilepsy: results from a prospective population-based study. Lancet. 1994;344 (8927):918-21.
8. Hauser WA. Should people be treated after a first seizure? Arch Neurol. 1986;43 (12):1287-8. https://doi.org/10.1001/archneur.1986.00520120063017.
9. Rizvi S, Ladino LD, Hernandez-Ronquillo L, Tellez-Zenteno JF. Epidemiology of early stages of epilepsy: risk of seizure recurrence after a first seizure. Seizure. 2017;49: 46-53. https://doi.org/10.1016/j.seizure.2017.02.006.
10. Berg AT, Levy SR, Novotny EJ, Shinnar S. Predictors of intractable epilepsy in child- hood: a case-control study. Epilepsia. 1996;37(1):24-30. https://doi.org/10.1111/j. 1528-1157.1996.tb00507.x.
11. Das C, Sawhney I, Lal V, Prabhakar S. Risk of recurrence of seizures following single unprovoked idiopathic seizure. Neurol India. 2000;48(4):357.
12. Kilic TY, Yesilaras M, Atilla OD, Sever M, Aksay E. Can venous blood gas analysis be used for predicting seizure recurrence in emergency department? World J Emerg Med. 2014;5(3):187. https://doi.org/10.5847/wjem.j.issn.1920-8642.2014.03.005.
13. Costea RM, Maniu I, Dobrota L, Neamtu B. Stress hyperglycemia as predictive factor of recurrence in children with febrile seizures. Brain Sci. 2020;10(3):131. https://doi. org/10.3390/brainsci10030131.
14. Hauser WA. Seizure disorders: the changes with age. Epilepsia. 1992;33:6-14. https://doi.org/10.1111/j.1528-1157.1992.tb06222.x.
15. Sartori S, Nosadini M, Tessarin G, Boniver C, Frigo AC, Toldo I, et al. First-ever convul- sive seizures in children presenting to the emergency department: risk factors for

seizure recurrence and diagnosis of epilepsy. Dev Med Child Neurol. 2019;61(1): 82-90. https://doi.org/10.1111/dmcn.14015.

1. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82. https://doi.org/10.1111/epi.12550.
2. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and American Diabetes Associa- tion consensus statement on inpatient Glycemic control. Diabetes Care. 2009;32 (6):1119-31. https://doi.org/10.2337/dc09-9029.
3. Phabphal K, Geater A, Limapichat K, Sathirapanya P, Setthawatcharawanich S. Risk factors of recurrent seizure, co-morbidities, and mortality in new onset seizure in el- derly. Seizure. 2013;22(7):577-80. https://doi.org/10.1016/j.seizure.2013.04.009.
4. Hirtz DG, Ellenberg JH, Nelson KB. The risk of recurrence of nonfebrile seizures in children. Neurology. 1984;34(5):637. https://doi.org/10.1212/WNL.34.5.637.
5. Pinchefsky EF, Hahn CD, Kamino D, Chau V, Brant R, Moore AM, et al. Hyperglycemia and glucose variability are associated with worse brain function and seizures in neo- natal encephalopathy: a prospective cohort study. J Pediatr. 2019;209:23-32.
6. Berg AT, Shinnar S, Testa F, Levy S, Frobish D, Smith S, et al. Status epilepticus after the Initial diagnosis of epilepsy in children. Neurology. 2004;63(6):1027-34. https://doi.org/10.1212/01.WNL.0000138425.54223.DC.
7. McCusker CG, Kennedy PJ, Anderson J, Hicks EM, Hanrahan D. Adjustment in chil- dren with intractable epilepsy: importance of seizure duration and family factors. Dev Med Child Neurol. 2002;44(10):681-7. https://doi.org/10.1111/j.1469-8749. 2002.tb00270.x.
8. Sackeim HA, Decina P, Portnoy S, Neeley P, Malitz S. Studies of dosage, seizure threshold, and seizure duration in ECT. Biol Psychiatry. 1987;22(3):249-68. https://doi.org/10.1016/0006-3223(87)90144-2.
9. Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures: a model for the study of an anion-gap acidosis not associ- ated with hyperkalemia. N Engl J Med. 1977;297(15):796-9. https://doi.org/10. 1056/NEJM197710132971502.
10. Bale G, Mitra S, de Roever I, Sokolska M, Price D, Bainbridge A, et al. Oxygen depen- dency of mitochondrial metabolism indicates outcome of newborn brain injury. J Cereb Blood Flow Metab. 2019;39(10):2035-47. https://doi.org/10.1177/ 0271678X18777928.
11. Dungan KM, Braithwaite SS, Preiser J-C. Stress hyperglycaemia. Lancet. 2009;373 (9677):1798-807. https://doi.org/10.1016/S0140-6736(09)60553-5.