Keywords
adolescent - seizures - epilepsy
Introduction
Epilepsy in adolescence represents a considerable neurological burden, with a prevalence
ranging from approximately 1.5 to 2%.[1] The World Health Organization defines adolescence as the period of life between
10 and 19 years of age.[2] Adolescence is a period of substantial change involving growth into adulthood across
physiological, psychological, and behavioral aspects.[3]
[4]
[5] During this period, the population faces challenges associated with their pursuit
of independence, perception of invulnerability, tendency toward risk-taking behavior,
and emphasis on peer relationships.[3]
[4]
[5]
[6]
[7] Special attention is particularly crucial for teenagers with epilepsy, as epilepsy
and its long-term treatment can pose additional difficulties.[6]
[7] Furthermore, these individuals gradually become more actively involved in treatment
of their epilepsy, no longer relying solely on parents or caregivers. Therefore, having
accurate information and a proper understanding of epilepsy becomes crucial for maintaining
a successful treatment journey.
Adolescent epilepsy encompasses not only epilepsy that emerges during adolescence
but also various epilepsy syndromes that manifest in infancy or childhood and persist
through adolescence such as photosensitive occipital lobe epilepsy, Lennox–Gastaut
syndrome, generalized epilepsy with febrile seizure plus, childhood absence epilepsy,
and epilepsy with myoclonic astatic seizures.[1]
[8]
[9] Although it is challenging to precisely categorize epilepsy with onset during adolescence,
several epilepsy syndromes have been recognized including juvenile myoclonic epilepsy
(JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clonic
seizures alone (GTCA), which are commonly grouped under the term idiopathic generalized
epilepsy (IGE). Additionally, later-onset self-limited epilepsy with centrotemporal
spikes (SeLECTS), mesial temporal lobe epilepsy, and focal epilepsy syndromes have
been defined.[1]
[8]
[9]
[10] Adolescent-onset epilepsy (AOE), which warrants particular attention, is recognized
for its positive clinical trajectory, being quite responsive to medication, and often
resolving on its own.[4] This disease is highly associated with a nonlesional etiology and infrequent neurological
and psychiatric comorbidities.[11]
A limited number of studies have described the profile of AOE and identified potential
risk factors for unfavorable outcomes such as seizure recurrence.[11]
[12]
[13]
[14]
[15] Regrettably, many of these analyses focused on specific epilepsy syndromes in adolescence
or investigated all types of epilepsy during this period, not just AOE. Furthermore,
cultural differences, societal perceptions such as social stigma, and treatment environments
within the society to which the adolescents belong must also be considered. Consequently,
it has been challenging to provide a comprehensive understanding of the characteristics
unique to AOE. The initial treatment response, which can provide insight into the
final prognosis, is crucial not only for patients and their families facing AOE but
also for clinicians. The objective of this study was to outline the clinical attributes
of AOE and explore predictive factors influencing first-year seizure freedom.
Methods
Patients
This retrospective study included patients with AOE, who were prescribed antiseizure
medication (ASM) treatment at the pediatric epilepsy center of the Chungbuk National
University Hospital (CBNUH) in South Korea, spanning from March 2018 to February 2023.
We classified epilepsy syndromes according to the recently published International
League Against Epilepsy classification of epilepsy syndromes.[8]
[16] All patients who met the following inclusion criteria and did not meet any of the
exclusion criteria were enrolled in the study. The inclusion criteria encompassed
(a) first unprovoked seizure (UPS) occurring between the ages of 10 and 19 years,
(b) a presumptive diagnosis of epilepsy (comprising at least two UPSs) or a specific
epilepsy syndrome, (c) prompt treatment following the first UPS, and (d) a minimum
follow-up duration of 12 months after ASM treatment initiation. Patients with a history
of prior epilepsy treatment, insufficient data due to reasons like transfer to another
hospital, or those who had not received ASM treatment were excluded.
Treatment Approach
Our standard protocol for pediatric epilepsy treatment follows these steps: For patients
presenting with their first UPS, a comprehensive approach is taken. This includes
detailed medical history collection, neurological examination, blood tests, interictal
electroencephalogram (EEG), and brain magnetic resonance imaging (MRI). The decision
to initiate ASM treatment is made through discussions with the patient and their caregivers.
The factors under consideration encompass the diagnosis of epilepsy and the assessment
of the risk associated with future seizures. In other words, depending on the seizure
burden, ASM treatment may be initiated even if it was a single episode of UPS. In
patients with two or more epileptic seizures, a more proactive treatment approach
is recommended. The choice of ASM is based on the unique characteristics of the patient's
epilepsy syndrome and their treatment adherence. If persistent seizures occur after
initiating the first ASM, the clinical decision may involve switching to another ASM
or adding a second ASM. In cases where adverse events occurred, we either switched
ASM or adjusted the dosage, sometimes adding another medication based on tolerability.
Follow-up EEGs are scheduled initially between 6 and 12 months after treatment initiation
and subsequently on an annual basis. Patient compliance is assessed by direct questioning
during visits, along with periodic measurement of blood drug levels when feasible.
Generally, we advise gradually discontinuing ASMs if the patient remains seizure-free
for at least 2 years and maintains a normal EEG. However, considering patient and
caregiver preferences, treatment periods can be extended. This assessment involves
considering potential risks and the potential impact of seizure recurrence on a child's
school life and overall well-being.
Data Collection
The retrospective collection of data was conducted by reviewing electronic medical
charts. The gathered information included sex, family history of epilepsy, prior history
of epilepsy treatment, comorbid conditions such as developmental delay (DD), intellectual
disability (ID), and autism spectrum disorder (ASD), seizure type at presentation
(predominant seizure semiology by eyewitness), type of epilepsy syndrome, age at the
occurrence of the first epileptic seizure and the commencement of ASM, results from
EEG and brain MRI, frequency of seizures, time interval between the first UPS and
ASM initiation, details about the number, types, and adverse events associated with
ASM use, duration of ASM treatment, and any issues related to compliance. We evaluated
the effectiveness of treatment by assessing seizure frequency at the 6-, 12-, and
24-month marks following ASM initiation. Additionally, we evaluated clinical predictive
factors associated with first-year seizure freedom.
Statistical Analysis
The statistical analysis was performed using R software, version 4.3.1 (R Foundation
for Statistical Computing, Vienna, Austria). Numerical values are presented as number
(percentage) or median (interquartile range). The comparison of variables was conducted
using Student's t-test, Wilcoxon's signed-rank test, chi-square test, and Fisher's exact test. To determine
the relationship between various independent variables and first-year seizure freedom,
we employed logistic regression analysis. Variables demonstrating a statistically
significant difference (p < 0.2) in univariate analysis were incorporated into the multivariate logistic regression
model. The results are presented as adjusted odds ratios (ORs) with their corresponding
95% confidence intervals (95% CIs). For all statistical tests, p < 0.05 was considered statistically significant.
Results
Patient Characteristics
Out of 76 patients diagnosed with AOE, 9 patients were excluded from the study due
to ASM treatment duration of less than 12 months (8 patients) and insufficient data
(1 patient). Consequently, 67 patients (44 [65.7%] male) were included in this study,
and their summarized details are presented in [Table 1]. The median age at the onset of the first UPS and the initiation of ASM was 13.4
(11.2–15.6) years and 13.8 (12.2–16.5) years, respectively, demonstrating an average
interval of 2.7 (1.0–9.9) months from onset to treatment initiation. The mean duration
of follow-up and ASM treatment was 44.8 (33.4–57.0) and 35.5 (26.0–48.9) months, respectively.
Six patients (9.0%) had a first-degree family history of epilepsy (9.0%), and 23 patients
(34.3%) had comorbid conditions.
Table 1
Summarized details of the study population (n = 67)
|
Variable
|
Value
|
|
Sex
|
|
Male
|
44 (65.7)
|
|
Female
|
23 (34.3)
|
|
Age at first UPS, years
|
13.4 (11.2–15.6)
|
|
Age at ASM initiation, years
|
13.8 (12.2–16.5)
|
|
Time interval between first UPS and ASM initiation, months
|
2.7 (1.0–9.9)
|
|
Follow-up duration, months
|
44.8 (33.4–57.0)
|
|
Duration of ASM treatment, years
|
35.5 (26.0–48.9)
|
|
Family history of epilepsy
|
6 (9.0)
|
|
Comorbid conditions (DD, ID, ASD)
|
23 (34.3)
|
|
Epilepsy type
|
|
Generalized
|
56 (83.6)
|
|
Focal
|
11 (16.4)
|
|
Seizure type[a]
|
|
Generalized tonic/tonic-clonic
|
54 (80.6)
|
|
Absence
|
1 (1.5)
|
|
Myoclonic[b]
|
8 (11.9)
|
|
Focal impaired awareness
|
4 (6.0)
|
|
Single episode of seizure
|
7 (10.4)
|
|
Brain MRI
|
|
Normal
|
62 (92.5)
|
|
Abnormal
|
5 (7.5)
|
|
EEG
|
|
Normal
|
41 (61.2)
|
|
Abnormal
|
26 (38.8)
|
|
Photosensitivity[c]
|
2 (3.0)
|
|
ASM treatment
|
|
Monotherapy
|
31 (46.3)
|
|
Dual therapy
|
28 (41.8)
|
|
Polytherapy (≥3 ASMs)
|
8 (11.9)
|
|
Mean number of ASMs, mean ± SD
|
1.8 ± 0.8
|
|
ASM-related adverse events
|
12 (17.9)
|
|
Seizure occurrence after ASM initiation
|
|
None
|
26 (38.8)
|
|
Seizure-free within 6 months
|
11 (16.4)
|
|
Seizure-free within 12 months
|
5 (7.5)
|
|
Seizure-free within 24 months[d]
|
8 (14.3)
|
|
Persistent seizures at 24 months[d]
|
18 (32.1)
|
|
Documented compliance issue
|
5 (7.5)
|
ASD, autism spectrum disorder; ASM, antiseizure medication; DD, developmental delay;
EEG, electroencephalogram; ID, intellectual disability; MRI, magnetic resonance imaging;
SD, standard deviation; UPS, unprovoked seizure.
Data are n (%) or median (interquartile range).
a Predominant seizure semiology based on eyewitness reports.
b Including coexisting generalized tonic-clonic seizure.
c Abnormal EEG response to visual stimuli known as a photoparoxysmal response.
d Data available from 56 patients.
Considering the seizure semiology and EEG findings, 56 patients (83.6%) were categorized
as having generalized epilepsy, specifically IGE epilepsy syndrome. Focal epilepsy
included late-onset SeLECTS (4 patients), frontal lobe epilepsy (1 patient), occipital
lobe epilepsy (1 patient), and other focal epilepsy syndromes (5 patients). The most
common type of seizure based on eyewitness accounts was generalized tonic-clonic (GTC)
seizures, accounting for 80.6%, followed by myoclonic seizures at 11.9% (with 6 patients
experiencing both GTC and myoclonic seizures), focal impaired awareness seizures at
6.0%, and absence seizures at 1.5%. Seven patients (10.4%) exhibited only a single
episode of seizure during the follow-up period. Among them, five patients displayed
abundant interictal epileptiform discharges on EEG, whereas two patients had both
ID and ASD, leading to a higher perceived risk of subsequent seizures, prompting the
initiation of ASM treatment. At the initiation of ASM treatment, brain MRI and EEG
findings were considered normal in 92.5 and 61.2% of patients, respectively. The abnormal
findings on brain MRI included mild cerebral atrophy in two cases, incomplete rotation
of the left hippocampus in one case, colpocephaly in one case, and cerebellar atrophy
in one case. Two patients (3.0%) exhibited photoparoxysmal responses on EEG, indicating
the presence of photosensitivity.
Seizure Outcome
Thirty-one patients (46.3%) received ASM monotherapy, whereas 28 patients (41.8%)
underwent dual therapy ([Table 1]). On average, a total of 1.8 ASMs were used across the entire group. Twelve patients
(17.9%) experienced ASM-related adverse events, including sleepiness, dizziness, aggressive
behavior, hair loss, tremor, and skin rash. After beginning ASM treatment, 26 patients
(38.8%) experienced no further seizures until the last visit. An additional 11 patients
(16.4%) achieved seizure freedom within 6 months, and 5 more patients (7.5%) attained
a seizure-free status within 12 months. Thus, 42 patients (62.7%) experienced seizure
freedom during the first year. Nonetheless, 18 out of 56 patients (32.1%) who were
followed up for 24 months continued to experience seizures. Compliance issues with
medication adherence were observed in five patients (7.5%).
Epilepsy Features
[Table 2] compares the clinical features of patients with AOE based on their epilepsy type.
The two groups were not significantly different in terms of age at first seizure,
age at ASM initiation, and the interval from onset to initiation. Abnormalities in
MRI (3.6 vs. 27.3%, p = 0.028) and EEG (32.1 vs. 72.7%, p = 0.018) were more frequently observed in the focal epilepsy group. The average number
of ASMs was similar in both groups. Although monotherapy was more common in the focal
epilepsy group (63.6 vs. 42.9%) and dual therapy was more frequent in the generalized
epilepsy group (46.4 vs. 18.2%), this difference was not statistically significant.
The proportion of patients with only a single episode of seizure was slightly higher
in the focal epilepsy group at 18.2%, compared with 8.9% in the generalized epilepsy
group; however, this difference did not reach statistical significance. The percentage
of patients who became seizure-free within the first 12 months of treatment was not
significantly different between the generalized epilepsy (60.7%) and focal epilepsy
(72.7%) groups. Similarly, after 24 months, the percentage of patients who continued
to experience persistent seizures was similar in both groups, with rates of 32.7%
(16/49) and 28.6% (2/7), respectively. Although the number of cases is limited, compliance
issues such as simple forgetfulness and feelings of stigma related to taking ASMs
were also comparable, with rates of 7.1 and 9.1%, respectively.
Table 2
Comparison of clinical features between epilepsy types
|
Generalized
(n = 56)
|
Focal
(n = 11)
|
p-Value
|
|
Age at first UPS, years
|
13.6 (11.3–15.7)
|
12.5 (10.7–13.5)
|
0.095
|
|
Age at ASM initiation, years
|
14.1 (12.3–16.6)
|
12.9 (10.8–14.0)
|
0.055
|
|
Abnormal MRI
|
2 (3.6)
|
3 (27.3)
|
0.028
|
|
Abnormal EEG
|
18 (32.1)
|
8 (72.7)
|
0.018
|
|
Interval between first UPS and ASM initiation, months
|
2.9 (1.1–13.6)
|
1.5 (0.3–6.6)
|
0.064
|
|
ASM treatment
|
|
Monotherapy
|
24 (42.9)
|
7 (63.6)
|
0.322
|
|
Dual therapy
|
26 (46.4)
|
2 (18.2)
|
0.104
|
|
Polytherapy (≥3 ASMs)
|
6 (10.7)
|
2 (18.2)
|
0.609
|
|
Mean number of ASMs, mean ± SD
|
1.8 ± 0.8
|
1.6 ± 0.8
|
0.935
|
|
Single episode of seizure
|
5 (8.9)
|
2 (18.2)
|
0.323
|
|
Seizure occurrence after ASM initiation
|
|
Seizure-free within 12 months
|
34 (60.7)
|
8 (72.7)
|
0.518
|
|
Persistent seizures at 24 months
|
16 (32.7)[a]
|
2 (28.6)[b]
|
>0.999
|
Data are n (%) or median (interquartile range).
ASM, antiseizure medication; EEG, electroencephalogram; MRI, magnetic resonance imaging;
SD, standard deviation; UPS, unprovoked seizure.
a Data available from 49 patients.
b Data available from seven patients.
[Table 3] describes the clinical characteristics and treatment outcomes of 65 adolescents
with IGE. Among these, the majority (47 patients, 83.9%) had GTCA, 8 patients (14.3%)
had JME, and 1 patient (1.8%) had JAE. Approximately one-third of patients with GTCA
were female (29.8%), whereas in JME, this applied to half of the patients (50.0%).
The median age of the first seizure was higher in JME at 15.3 years, but the time
to treatment initiation was longer compared with GTCA, with a median interval of 4.7
months. Two-thirds of patients with GTCA (68.1%) and JME (75.0%) showed a normal EEG.
For patients with GTCA, levetiracetam was the first-choice ASM for about half (57.4%),
followed by lamotrigine (27.7%) and valproate (14.9%). Among patients with JME, levetiracetam
was also chosen in 75% of cases, with valproate (25.0%) being used in the remaining
cases. Only 38.3% of patients with GTCA received monotherapy, whereas for JME, it
was as high as 75.0%. The percentage of patients with a favorable treatment outcome
was 57.4% in the GTCA group and 75.0% in the JME group. While only one patient with
JAE was included in this study, making comparative analyses difficult, the results
were consistent with the characteristic clinical features of JAE. Seizure onset occurred
at the age of 11.2 years during early adolescence, with a considerable gap of 22.9
months until treatment initiation. Ethosuximide was the first medication used, and
seizure freedom was achieved within 12 months.
Table 3
Profiles of idiopathic generalized epilepsies (n = 56)
|
GTCA
|
JAE
|
JME
|
|
Patients
Female sex
Age at first UPS, years
Age at ASM initiation, years
Interval[a], months
Family history of epilepsy
Normal MRI
Normal EEG
First choice of ASM
Levetiracetam
Lamotrigine
Valproate
Ethosuximide
ASM monotherapy
Seizure-free within 12 months
|
47 (83.9)
14 (29.8)
13.5 (11.2-15.6)
14.1 (12.2-16.5)
2.7 (1.1-14.3)
4 (8.5)
45 (95.7)
32 (68.1)
27 (57.4)
13 (27.7)
7 (14.9)
0 (0.0)
18 (38.3)
27 (57.4)
|
1 (1.8)
1 (100.0)
11.2
13.1
22.9
0 (0.0)
1 (100.0)
1 (100.0)
0 (0.0)
0 (0.0)
0 (0.0)
1 (100.0)
0 (0.0)
1 (100.0)
|
8 (14.3)
4 (50.0)
15.3 (12.5-17.2)
15.4 (13.5-18.0)
4.7 (0.8-10.6)
1 (12.5)
8 (100.0)
6 (75.0)
6 (75.0)
0 (0.0)
2 (25.0)
0 (0.0)
6 (75.0)
6 (75.0)
|
Data are n (%) or median (interquartile range).
ASM, antiseizure medication; EEG, electroencephalogram; GTCA, epilepsy with generalized
tonic-clonic seizures alone; JAE, juvenile absence epilepsy; JME, juvenile myoclonic
epilepsy; MRI, magnetic resonance imaging; UPS, unprovoked seizure.
a Inteval between first unprovoked seizure and antiseizure medication initiation.
Predictive Factors for First-Year Seizure Freedom
[Table 4] demonstrates a comparison of the first-year seizure freedom rates among predictors.
In univariate analysis, only comorbid conditions (OR 3.47, 95% CI 0.20–2.33, p = 0.037) and ASM monotherapy (OR 4.66, 95% CI 0.48–2.71, p = 0.010) were significantly associated with an achievement of first-year seizure
freedom. In the multivariate analysis, which encompassed all independent variables
with p-values below 0.2, a negative family history of epilepsy (OR 12.1, 95% CI 1.27–115.44,
p = 0.030) was identified as a strong predictive factor, along with ASM monotherapy
(OR 3.99, 95% CI 1.05–15.21, p = 0.043).
Table 4
Predictive factors for first-year seizure freedom
|
Factor
|
First-year seizure freedom (%)
|
Univariate analysis
|
Multivariate analysis
|
|
OR (95% CI)
|
p-Value
|
OR (95% CI)
|
p-Value
|
|
Sex
|
|
0.67 (−1.44–0.65)
|
0.625
|
–
|
–
|
|
Female
|
13/23 (56.5)
|
–
|
–
|
–
|
–
|
|
Male
|
29/44 (65.9)
|
–
|
–
|
–
|
–
|
|
Age at first UPS
|
|
1.95 (−0.41–1.84)
|
0.358
|
–
|
–
|
|
< 13 YO
|
16/22 (72.7)
|
–
|
–
|
–
|
–
|
|
≥13 YO
|
26/45 (57.8)
|
–
|
–
|
–
|
–
|
|
Family history of epilepsy
|
|
3.81 (−0.38–3.37)
|
0.186
|
12.1 (1.27–115.44)
|
0.030
|
|
Negative
|
40/61 (65.6)
|
–
|
–
|
–
|
–
|
|
Positive
|
2/6 (33.3)
|
–
|
–
|
–
|
–
|
|
Comorbid conditions
|
|
3.47 (0.20–2.33)
|
0.037
|
2.09 (0.56–7.73)
|
0.270
|
|
No
|
32/44 (72.7)
|
–
|
–
|
–
|
–
|
|
Yes
|
10/23 (43.5)
|
–
|
–
|
–
|
–
|
|
Epilepsy syndrome
|
|
1.92 (−0.91–2.63)
|
0.700
|
–
|
–
|
|
JME
|
6/8 (75.0)
|
–
|
–
|
–
|
–
|
|
Other than JME
|
36/59 (61.0)
|
–
|
–
|
–
|
–
|
|
EEG
|
|
0.35 (−2.22–0.003)
|
0.097
|
0.22 (0.05–1.04)
|
0.056
|
|
Normal
|
22/41 (53.7)
|
–
|
–
|
–
|
–
|
|
Abnormal
|
20/26 (76.9)
|
–
|
–
|
–
|
–
|
|
Epilepsy type
|
|
0.58 (−2.14–0.81)
|
0.518
|
|
|
|
Generalized
|
34/56 (60.7)
|
–
|
–
|
–
|
–
|
|
Focal
|
8/11 (72.7)
|
–
|
–
|
–
|
–
|
|
Time until ASM initiation[a]
|
|
1.31 (−0.76–1.35)
|
0.811
|
–
|
–
|
|
≥6 months
|
16/24 (66.7)
|
–
|
–
|
–
|
–
|
|
< 6 months
|
26/43 (60.5)
|
–
|
0.010
|
–
|
0.043
|
|
ASM treatment
|
|
4.66 (0.48–2.71)
|
–
|
3.99 (1.05–15.21)
|
–
|
|
Monotherapy
|
25/31 (80.6)
|
–
|
–
|
–
|
–
|
|
≥2 ASMs
|
17/36 (47.2)
|
–
|
–
|
–
|
–
|
|
ASM-related adverse events
|
|
2.88 (−0.21–2.39)
|
0.183
|
3.05 (0.56–16.47)
|
0.195
|
|
No
|
37/55 (67.7)
|
–
|
–
|
–
|
–
|
|
Yes
|
5/12 (41.7)
|
–
|
–
|
–
|
–
|
ASM, antiseizure medication; CI, confidence interval; EEG, electroencephalogram; JME,
juvenile myoclonic epilepsy; OR, odds ratio; UPS, unprovoked seizure; YO, years old.
a Time interval between the first UPS and ASM initiation.
Discussion
In the present study, 62.7% of all patients with AOE attained seizure freedom within
the first year. Among these patients, 88.1% (37/42) achieved being seizure-free within
6 months after initiating ASM treatment. Moreover, 38.8% (26/67) never had additional
seizures until their last visit, with a mean follow-up duration of 40.5 months. In
the 24-month evaluation, an even higher seizure-free rate of 74.6% was observed.
Previous studies involving adolescents and adults reported 1-year seizure-free rates
ranging from 63.7 to 68.0%, which aligns with our findings.[17]
[18] These findings are also similar to the results recently reported by Kim et al, where
seizure freedom at 1 year was 58.4%.[14] This Korean study, which involved a 10-year follow-up observation of 137 AOE patients
aged 13 to 19 years, reported that terminal remission was achieved in 67.9% of cases.
Additionally, through bivariate logistic regression analysis, they confirmed a strong
association between seizure freedom at 1 year and terminal remission. By contrast,
in a large-scale Scottish study involving 332 adolescents aged 13 to 19 years who
received their first-time ASM, the overall 1-year seizure-free rate was reported to
be lower at 38.0% (126/332).[15] Considering that 29% in their study achieved seizure freedom beyond 12 months, the
higher rate of poor ASM tolerability at 21% could be a reason for the delayed seizure
control.
In the current study, 88.1% of all patients achieved seizure control with the use
of either one or two ASMs. However, the percentage of patients who achieved first-year
seizure freedom with monotherapy was lower at 59.5% (25 patients), compared with findings
in previous studies.[11]
[15] A Canadian study involving 65 adolescents stated that successful control of seizures
with monotherapy was achieved in approximately 85% of cases.[11] In the Scottish study, 83% of patients who achieved seizure freedom managed to do
so with monotherapy.[15] This difference can be attributed to a preference for dual therapy in our center.
When additional seizures or ASM-related adverse events occurred despite appropriate
dosages and treatment durations, our approach involved introducing combination therapy
with lower doses rather than switching to another medication and escalating the dosage.
Recent research targeting patients with IGE suggested that, when the first-line monotherapy
fails, switching to levetiracetam or lamotrigine monotherapy might be less effective
than employing combination therapy involving medications such as lamotrigine, levetiracetam,
or valproic acid.[19] This second-line combination therapy broadens the treatment spectrum mechanistically
and effectively reduces the occurrence of dose-dependent adverse events. A previous
Korean study had results similar to ours, with 65.0% utilizing monotherapy regimens.
The authors also mentioned that approximately 50% of patients with IGE required polytherapy
to achieve seizure freedom.[14]
The present study reported several interesting findings in patients with AOE. The
proportion of male patients was rather high at 65.7%, but this is not significant
because previous studies found no clear sex differences in patients with AOE.[11]
[12]
[13]
[15] Comorbid conditions such as DD/ID or ASD were relatively more frequent at 34.3%,
but the frequency of structural abnormalities in brain MRI was very low (7.5%). Hence,
it is likely that the inclusion of patients exhibiting complex phenotypes is due to
our institution being a referral center. Nevertheless, this factor is not considered
to have a direct contribution to the underlying causes of epilepsy. In the initial
EEG, 38.8% of our patients showed focal or generalized interictal epileptiform discharges.
This was similar to the 33.6% observed in the Scottish study.[15] On the other hand, it is worth noting that about two-thirds of patients with AOE
had a normal initial EEG. When diagnosing AOE, it is important not to overly rely
on EEG testing and to focus on thorough history taking. Additionally, repeat EEG testing
is necessary to verify any abnormal findings. In our study, two patients diagnosed
with JME were found to have generalized epileptiform discharges in subsequent EEG
testing although the initial EEG was normal. Furthermore, the high rate of GTC seizures
at 80.6% is noteworthy. This might be attributed to the fact that patients with IGE
accounted for 83.6% and that focal to secondary generalized seizures were included
without differentiation. Previous studies also showed rates ranging from 65.1 to 76.9%
when including focal to secondary GTC seizures.[11]
[12]
[15]
As evident from our study results, the majority of epilepsies in newly diagnosed teenagers
were categorized as IGE (83.6%). This proportion is quite substantial and comparable
to studies encompassing not only AOEs but also childhood-onset epilepsies, where the
percentage of patients diagnosed with IGE ranged from 43.9 to 60.0%.[11]
[13]
[20] Within this IGE spectrum, GTCA constituted an absolute majority at 83.9%. This may
be attributed to the fact that our patient population had a very low rate of focal
epilepsy due to scarce symptomatic etiologies, resulting in a relatively higher occurrence
of generalized epilepsy. Thus, these results provide a genuine representation of AOE.
Moreover, considering that one-third (33.9%) were adolescent girls undergoing pubertal
hormonal changes, levetiracetam or lamotrigine were preferentially selected as initial
ASMs over valproic acid.[21] In addition, 11 patients (19.6%) exhibited adverse events like increased sleepiness,
dizziness, and mood instability with the initial ASM. These adverse events were effectively
managed through the aforementioned combination therapy approach.[19]
We also investigated which predictive factors are associated with first-year seizure
freedom in patients with AOE. Many studies reported associations between seizure outcomes,
including seizure recurrence, and factors such as female sex, age under 13 years at
the first UPS, generalized epilepsy, JME, family history of epilepsy, and EEG abnormalities.[11]
[12]
[14]
[15]
[22] Our univariate analysis showed significant differences between those who achieved
first-year seizure freedom and those who did not in terms of comorbid conditions and
ASM monotherapy. Multivariate analysis specifically highlighted the significant association
with a negative family history of epilepsy and ASM monotherapy. Including our study
results, a family history of epilepsy has been observed in 9 to 15% of patients with
AOE.[14]
[15] A study of adolescents and adults has also reported a family history of epilepsy
as a predictive factor for poor outcomes.[22] Furthermore, it is well known that the seizures of most adolescent patients are
effectively controlled with monotherapy.[11]
[15] However, one report indicates a poor tolerability rate of up to 21% for the first
ASM.[15] Ultimately, it is necessary to have a tailored ASM regimen for each adolescent patient.
Since comorbidity also greatly affects compliance, effectively managing compliance
is crucial for achieving positive outcomes for AOE. Numerous previous studies focusing
on teenagers with epilepsy consistently emphasize the need for special attention and
care for this population.[11]
[13]
[20] In many cases, the first seizures that teenagers encounter are of GTC semiology
and have a higher likelihood of occurring at school. This experience can be impactful
for both the patients and their families. The rates of medication nonadherence among
adolescents with epilepsy vary widely, spanning from 35 to 79%.[23] This behavior is strongly influenced by two significant prognostic factors: young
age and a lack of awareness regarding the importance of taking prescribed medications.[4] These challenges are exacerbated by self-esteem issues commonly faced by adolescents.
Targeting treatment directly toward adolescents, not just their parents, is essential.
Providing proper education and information about epilepsy, involving teenagers in
treatment plans, and addressing not only the parents but also the adolescents themselves
are crucial steps.[23]
This study has several limitations. The patients were recruited from a single center,
which resulted in a small sample size, and the study was conducted retrospectively.
Nevertheless, standardized treatment was administered as it is the sole referral center
in the region. Additionally, because the follow-up period was short, long-term outcomes
could not be analyzed, and information about treatment outcomes and seizure recurrence
could not be provided. Nonetheless, considering the findings of previous studies indicating
that first-year seizure freedom, as assessed in our study, is correlated with the
ultimate outcome, it can serve as a crucial indicator for promoting strong adherence
among patients at the treatment outset. Finally, apart from issues related to ASMs,
the various physical, psychological, and social changes experienced by teenagers were
not investigated in relation to epilepsy treatment. This will be addressed in the
future through long-term tracking observations and the operation of specialized clinics
for adolescents.
Summary
In summary, our findings suggest that epilepsy onset during adolescence generally
demonstrates good control of seizures. Additionally, we have identified that a negative
family history of epilepsy and ASM monotherapy serve as strong predictors of achieving
favorable outcomes within the early stage of treatment. Understanding not only the
seizures but also the characteristics of adolescence is crucial for successful epilepsy
treatment. We expect that our study findings will offer support not only to health
care professionals but also to individuals and caregivers who are navigating their
initial experience with epilepsy and the subsequent treatment process.
