Abstract

Objective:

This study was conducted to predict the response to treatment in patients treated with anti-epilepsy drugs.

Material and Methods:

This analytical questionnaire-based study was conducted in 2014 among 128 patients with epilepsy admitted to Mofid Children's Hospital, Tehran, Iran. The inclusion criteria were children 2 months to 12 yr of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. Patients were followed up for 6 months and the response to their treatment was recorded. The good response to treatment was defined as the absence of seizure with two drugs during follow up.

Results:

Seventy-two patients (56.3%) were boys. The age of the first seizure was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment.

Conclusion:

Abnormal EEG is an effective factor in treatment response in the children studied.

Key Words:

Pediatric, Anti-seizure drug, Response to treatment, Children, Epileps

Babaei, M.

Beshrat, M.

Ghofrani, M.

Hasanvand Amouzadeh, M.

Jafari, N.

Javadzadeh, M.

Karimzadeh, P.

Mollamohammadi, M.

Nasehi, M.M.

Saket, S.

Taghdiri, M.M.

Tonekaboni, S.H.

Zavehzad, A.

kashan university of medical sciences

94 Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
Mohammad GHOFRANI MD1,
Mohammad Mehdi NASEHI; MD1
Sasan SAKET MD1,
Mohsen MOLLAMOHAMMADI 
MD2, 
Mohammad Mahdi TAGHDIRI MD1,
Parvaneh KARIMZADEH MD1, 
Seyed Hassan TONEKABONI MD1,
Mohsen JAVADZADEH MD1,
Narjes JAFARI MD1, 
Azadeh ZAVEHZAD MD3, 
Masoud HASANVAND 
AMOUZADEH MD2,
Mahsa BESHRAT MD1,
Meysam BABAEI MD1
Received: 31- July -2017
Last Revised: 12-Sep-2017
Accepted: 24- Feb -2018
Prediction of Response to Treatment in Children with Epilepsy
1- Child Neurology Research Center, 
Shahid Beheshti University of Medical 
Sciences, Tehran, Iran
2- Department of Pediatric Neurology, 
Qom University of Medical Sciences, 
Qom, Iran
3- Department of Pediatric, Faculty 
of Medicine, Kashan University of 
Medical Sciences, Kashan, Iran.
Corresponding author:
Nasehi MM.
Child Neurology Research Center, 
Shahid Beheshti University of Medical 
Sciences, Tehran, Iran
Email: mmnasehi@gmail.com
Abstract
Objective: This study was conducted to predict the response to treatment in 
patients treated with anti-epilepsy drugs.
Material and Methods: This analytical questionnaire-based study was 
conducted in 2014 among 128 patients with epilepsy admitted to Mofid 
Children’s Hospital, Tehran, Iran. The inclusion criteria were children 2 months 
to 12 yr of age with epilepsy and patients who experienced fever and seizure 
attacks at least once were excluded from the study. Patients were followed up for 
6 months and the response to their treatment was recorded. The good response to 
treatment was defined as the absence of seizure with two drugs during follow up. 
Results: Seventy-two patients (56.3%) were boys. The age of the first seizure 
was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family 
history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), 
and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 
patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). 
Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or 
MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 
40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) 
responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal 
jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in 
response to treatment. 
Conclusion: Abnormal EEG is an effective factor in treatment response in the 
children studied.
Keywords: Pediatric; Anti-seizure drug; Response to treatment; Children; 
Epilepsy 
Introduction
Seizure is a chronic neurological disease, defined as epilepsy when it occurs 
2 times or more (1). “The cumulative incidence of epilepsy is 3% in a 
lifetime, with more than half of the cases occurring in childhood. However, 
the annual incidence of epilepsy is 0.5%-0.8%” (2). A high prevalence 
of seizure was in Iranian society and among children under 12 yr old in 
Tehran, as 32 per 1000 people (3). 
How to Cite This Article: Ghofrani M, Nasehi MM, Saket S, Mollamohammadi M, Taghdiri MM, Karimzadeh P, Tonekaboni SH, Javadzadeh M, 
Jafari N, Zavehzad A, Hasanvand Amouzadeh M, Beshrat M, Babaei M. Prediction of Response to Treatment in Children with Epilepsy. Iran J Child 
Neurol. Summer 2018; 12(3):94-100
ORIGINAL ARTICLE
95Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
for 1-2 year (8, 9). Therefore, predicting the 
response to treatment in these patients is always a 
major challenge. 
In previous studies, the age of first seizure, 
intellectual power status and neonatal seizure were 
considered as predictive factors (10, 11). Therefore, 
this study was conducted to predict the response 
to treatment in patients with epilepsy based on the 
factors that affect the disease and based on other 
factors that are prevalent in Iran and can influence 
the prognosis.
Materials and Methods
This analytical questionnaire-based study was 
conducted in 2014 among patients with epilepsy 
admitted to Mofid Children’s Hospital, Tehran, 
Iran as a level three referral hospital. The inclusion 
criteria were children 2 months to 12 yr of age 
with epilepsy and patients who experienced febrile 
seizure at least once were excluded from the study. 
Samples were selected using improbable sampling 
and convenience sampling techniques. 
The obtained sample size was 128 people 
considering the main outcome of the study, which 
was proper response to therapy at the end of the sixth 
month and based on 66% response, significance 
level of 0.05, 8% accuracy and the corresponding 
formula. Epilepsy was diagnosed by a pediatric 
neurologist. After the initial recording of patient 
information, patients were followed up for 6 
months and the response to their treatment was 
recorded. The studied variables were as follows: 
Response to treatment, age of first seizure, gender, 
family history of seizure, history of birth asphyxia, 
history of neonatal seizure, IQ, the frequency of 
seizure before treatment, etiology, seizure type, 
sign of lesion in CT scan or MRI and EEG status. 
Less than half of seizures in childhood are 
epileptic seizures and in which recurrent seizures 
are stimulated in the brain. Epilepsy improves 
in many children. A seizure can be the sign of a 
serious underlying disorder in the central nervous 
system or a systemic disease that requires full-
fledged examination and treatment. The prognosis 
of children with epilepsy is usually good (2), but 
in 10% to 20% of children with seizure, the attacks 
still continue despite appropriate treatment (4). 
“After the first provoked seizure in children, the 
risk of relapse is about 50% and after the second 
seizure, the risk is about 80%” (5). 
The biological basis of seizure relapse is probably 
multifactorial and may include severe syndromes or 
underlying neuropathological diseases, abnormal 
reorganization of neurons, replacement in receptors 
and neurotransmitters, ion channel abnormalities, 
reactive autoimmunity and inappropriate use of 
antiepileptic drugs (6). After the first seizure, if the 
patient is normal in terms of neuronal development 
according to EEG and MRI tests, the risk of relapse 
is low and usually, the patient does not need to start 
treatment. However, if the patient’s EEG and MRI, 
neurodevelopment and neurological examination 
show abnormalities and they have positive family 
history of epilepsy, the risk of relapse is high and 
treatment should be started immediately (7). The 
determining factors of response to treatment in 
patients with epilepsy include etiology of epilepsy, 
epilepsy type, underlying syndrome and the 
frequency seizure. Environmental factors such 
as trauma and the simultaneous use of drugs and 
genetic factors in the metabolism of drugs may 
play a role in the therapeutic response (2). About 
60%-70% of children with epilepsy who become 
seizure-free can successfully stop their treatment 
Prediction of Response to Treatment in Children with Epilepsy
96 Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
Prediction of Response to Treatment in Children with Epilepsy
The good response to treatment was defined as 
the absence of maximum seizure with two drugs 
during follow up. 
Data were analyzed using SPSS (ver.20, Chicago, 
IL, USA) and logistic regression model was used 
to determine the predictive power of each of the 
variables studied in the prognosis of the disease. 
P<0.05 was considered as significance level.
Results
The present study was conducted among 128 
children with seizure treated with antiepileptic 
drugs. Overall, 72 patients (56.3%) were boys. The 
age of the first seizure was under 2 yr old in 90 
patients (70.3%). Overall, 108 patients (84.4%) 
lived in the city, and the type of delivery was vaginal 
for 63 patients (49.2%). History of febrile seizure 
was found in 16 patients (12.5%), family history of 
seizure was found in 41 patients (32%), history of 
asphyxia in 27 (21.1%), history of neonatal seizure 
in 24 patients (18.8%) and neonatal jaundice in 
38 patients (29.7%). IQ was was decreased in 79 
patients (61.7%). Seizure etiology was idiopathic 
in 90 patients (70.3%), and the number of seizures 
was 3-20 in 51 patients (39.8%). Fifty-seven 
patients (44.5%) had cerebral lesion according to 
CT scan or MRI, and EEG was abnormal in 101 
patients (78.9%). 
The type of seizure was generalized tonic-clonic in 
35 patients (27.3%) , simple partial in 13 patients 
(10.2%), infant spasm in 5 patients (3.9%), tonic 
in 16 patients (12.5%), atonic in 5 patients (3.9%), 
myoclonic in 16 patients (12.5%), mixed in 14 
patients (10.9%), complex partial in 4 patients 
(3.1%), 1 case of absence (0.8%) and 1 case clonic 
(0.8%). 
In 3-months follow-up, 43 patients (33.6%) 
responded well to the treatment, 75 patients 
(58.6%) responded poorly to the treatment and 10 
patients (7.8%) had no response to treatment. In 
6-month follow-up, 40 patients (31.3%) responded 
well to the treatment and 88 patients (68.8%) 
responded poorly to the treatment. Mortality was 
not observed in any of the patients. 
Table 1 presents the distribution of effective factors 
in response to treatment according to the status 
of response to treatment, 6 months after starting 
the treatment. History of asphyxia (OR = 6.82), 
neonatal jaundice (OR = 2.81) and abnormal EEG 
(OR = 0.19) were effective factors in response to 
treatment (Table 2). 
97Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
Prediction of Response to Treatment in Children with Epilepsy
Table 1. The distribution of effective factors in response to treatment after 6 months
Good (n=40)
(%) N
Poorly (n=88)
(%) N
P-value
Age at first seizure
<2 yr 25 (62.5) 65 (73.9)
0.072-5 yr 6 (15) 16 (18.2)
>6 yr 9 (22.5) 7 (8)
Sex
Female 16 (40) 40 (45.5)
0.701
Male 24 (60) 48 (54.5)
Delivery
NVD 19 (47.5) 44 (50)
0.85
Cesarian 21 (52.5) 44 (50)
History of febrile convulsions 4 (10) 12 (13.6) 0.774
Familial history of epilepsy 13 (32.5) 28 (31.8) 1
Asphyxia 14 (35) 13 (14.8) 0.018
Neonatal seizure 6 (15) 18 (20.5) 0.626
intelligence 18 (45) 61 (69.3) 0.011
 Number of
seizures
1-2 11 (27.5) 25 (28.4)
0.9943-20 16 (40) 35 (39.8)
>20 13 (32.5) 28 (31.8)
Neonatal Icter 18 (45) 20 (22.7) 0.013
Etiology
Idiopathic 32 (80) 58 (65.9)
0.144
Symptomatic 8 (20) 30 (34.1)
Abnormal EEG 27 (69.2) 74 (89.2) 0.01
Abnormal MRI 11 (25.7) 46 (52.3) 0.012
98 Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
Prediction of Response to Treatment in Children with Epilepsy
Discussion
The present study aimed to determine the treatment 
response of patients with epilepsy based on the 
factors effective in the disease. Abnormal EEG in 
both single-variable and multivariate analyses are 
an effective factor in treatment response, where 
abnormal EEG was significantly associated with 
poor treatment response. In a study on 161 children 
with epilepsy, 23 predictors for treatment response 
in children were examined. Age at the onset of the 
disease, type of seizure, abnormal spike-waves in 
EEG one year after treatment, and presence of 3-Hz 
spike-wave in patients’ EEG in the first 6 months 
of treatment were effective factors in treatment 
response and disease control (11). Children without 
adverse factors may have 80%-90% success rate 
because factors have additive effect, and those 
with all adverse factors may only have a success 
rate of 10%-20% (5).
In the present study, a relationship was found 
between IQ and treatment response in the single-
variable analysis. Such relationship was not 
observed in the multivariate analysis. Normal 
intelligence (or normal rational power), onset of 
epilepsy in the age less than 6 yr, lack of history 
of epilepticus status, and lack of seizure in the first 
week of treatment were among the predictors for 
controlling seizure (10). In Bangladeshi epileptic 
children at the age of 2 months to 15 yr, motor 
disorder, cognitive impairment, and multiple 
seizure types were reported to be effective clinical 
factors in predicting epilepsy control and treatment 
Table 2. The multivariate analysis of effective factors in response to treatment after 6 months
Variable OR CI95% P-value
 Age at first
seizure
<2 yr - - 0.197
2-5 yr 0.270 0.065-1.121 0.071
>6 yr 0.351 0.065-1.906 0.225
Sex (male) 1.750 0.640-4.788 0.276
Delivery (cesarean section) 0.706 0.262-1.905 0.492
History of febrile convulsions 0.442 0.085-2.286 0.330
Familial history of seizure 0.825 0.283-2.404 0.725
Asyphexia 6.825 1.960-23.767 0.003
Neonatal seizure 0.937 0.202-4.351 0.934
Low IQ 0.479 0.165-1.391 0.176
 Number of
seizures
1-2 - - 0.866
3-20 0.722 0.220-2.372 0.591
>20 0.860 0.272-2.717 0.798
Icter 2.810 1.019-7.749 0.046
Etiology (idiopathic) 2.268 0.578-8.901 0.241
Abnormal EEG 0.195 0.056-0.676 0.010
Abnormal MRI 0.537 0.171-1.690 0.288

100 Iran J Child Neurol. Summer 2018 Vol. 12 No. 3
Prediction of Response to Treatment in Children with Epilepsy
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Prediction of response to treatment in children with epilepsy

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Prediction of response to treatment in children with epilepsy

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