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First-drug treatment failures in children with typical absence epilepsy
Brain & Development 37 (2015) 311–314 www.elsevier.com/locate/braindev
Original article
First-drug treatment failures in children with typical absence epilepsy Faruk Incecik ⇑, Sakir Altunbasak, Ozlem M. Herguner Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Cukurova University, Adana, Turkey Received 9 December 2013; received in revised form 6 May 2014; accepted 7 May 2014
Abstract Background: Childhood absence epilepsy (CAE) is a well-known syndrome with onset in middle childhood and is characterized by multiple typical absences per day. Pharmacological treatment is specific and usually successful with a single medication. The goal of the study was to assess on risk factors associated with failure to respond to the initial antiepileptic drug (AED). Methods: Fifty-two children with CAE were enrolled. Predictive factors were analyzed by survival methods. Results: Among 52 patients, 32 patients (61.5%) were girls and the remaining 20 (38.5%) were boys and the mean age at the seizure onset was 6.5 ± 1.78 years old (3–11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED treatment (Group A), and 10 (19.2%) were not responsed (Group B). Age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response were significantly associated with failure risk according to univariate analysis. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing poor response to initial AED treatment. Conclusion: Factors predicting failure to respond to the AED were age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response in children with CAE. Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Childhood absence epilepsy; First antiepileptic drug; Failure risk factors or predicting factors; Photoconvulsive EEG response
1. Introduction Absence seizures are characterized by an abrupt cessation of activity, change in facial expression, impairment of consciousness, eye fluttering and sometimes associated by automatisms. As defined by the International League Against Epilepsy (ILAE) criteria, childhood absence epilepsy (CAE) is defined as typical absence seizures beginning under the age of ten, with an EEG discharge of symmetrical, synchronous spike wave complexes, recurring regularly at a rhythm of about 3 Hz [1]. Childhood absence epilepsy accounts
⇑ Corresponding author. Address: Toros mah., Barısß Manc ßo Bul. ¸ ukurova, Adana, 78178 Sok., Yesßilpark evleri, A blok, kat:7/13, C Turkey. E-mail address: fi[email protected] (F. Incecik).
for 10% to 17% of childhood epilepsy and usually presents between ages 4 and 8 [1,2]. Typical absence seizures may occur many times a day usually not surpassing 30 s induration. The end of the attack is as sudden as its onset, often with the child unaware of the seizure. The prevalence of typical absence seizures is highest during the first decade of life and then drops dramatically [3]. Treatment response to initial monotherapy is suboptimal, with slightly more than half of children achieving complete seizure control with acceptable treatment associated side effects. In literature, only a few studies are available on factors associated with initial poor response to antiepileptic drugs (AED) [4–6]. Therefore, we conducted a retrospective study designed to identify the risk factors associated with initial poor response to AEDs in children with CAE.
http://dx.doi.org/10.1016/j.braindev.2014.05.005 0387-7604/Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
312
F. Incecik et al. / Brain & Development 37 (2015) 311–314
2. Subjects and methods This study was conducted a retrospective study of 52 children diagnosed with CAE and started on an AED in the pediatric neurology department of our hospital. Patients were selected based on the following inclusion criteria: (a) age from 3 to 13 years; (b) diagnosed typical absence seizures (ILAE Commission, 1981) [1] associated with generalized, synchronous 3-Hz (2.5– 4 Hz) spike and wave activity, lasting >3 s, occurring spontaneously or during one of two trials of 3 min hyperventilation with a 1–2 min rest between trials; (c) clearly observable clinical signs of typical absence seizures (e.g., staring or impairment of consciousness); (d) treated with AEDs for the first time; (e) normal clinical, neurologic, and computed tomography (CT)/magnetic resonance imaging (MRI) examination. The data were retrospectively collected from the clinic files and included sex, age of seizure onset, consanguinity, history of neonatal and febrile seizure, family history of epilepsy, coexisting other types of seizures, time lag to first treatment, electroencephalogram (EEG) findings (spike wave type and photoconvulsive response). Photoconvulsive response was defined as generalized epileptic discharge that was elicited during photic stimulation. Success of initial AED was defined as obtaining complete seizure control with the first AED. Failure of initial AED treatment was defined as inability to attain complete seizure control with the first appropriate AED.
The SPSS version 19.5 was used for statistical analysis. Statistical significance was accepted at p < 0.05. The chi-square tests were used to determine the associations among categorical data. We carried out univariate and multivariable analyses of potential predictors of recurrence risk using by Cox regression analysis. The level of statistical significance was established at p- value of <0.05. Initially, we performed a univariate analysis, in order to determine which would used in multivariate analysis. 3. Results The general characteristics of children treated with initial AED and factors for success and failure to the first AED are shown in Table 1. Fifty-two children, mean age 7.50 ± 1.67 years (4–12.5 years), were included in this study. Among the 52 patients, 20 (38.5%) were boys and 32 (61.5%) were girls, and the mean age at the seizure onset was 6.50 ± 1.78 years (3–11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED (Group A), and 10 (19.2%) did not responsed to initial AED treatment (Group B). Two patients (3.8%) had past history of febrile convulsion, and thirteen patients (25.0%) had family history of convulsive disorders. Twelve patients had coexisting other types of seizures: 10 patients (83.3%) had
Table 1 Summary of demographics and factors associated with success or failure of the first AED. Parameters
Sex Neonatal seizure History of febrile seizure Consanguinity Family history of epilepsy Age of seizure onset
Coexisting other types of seizures Focal spike activity on EEG Photoconvulsive EEG response Time lag to first treatment
P1: p value of univariate analysis. P2: p value of multivariate analysis.
Responders
Boy Girl Yes No Yes No Yes No Yes No <5 years 5–10 years >10 years Yes No Yes No Yes No 1 month 1–6 months >6 months
Non-responders
n
%
n
%
17 25 0 52 1 41 11 31 8 34 10 31 1 7 35 6 36 2 40 14 19 9
85.0 78.1 100 100 50.0 82.0 78.6 81.5 61.5 87.1 62.5 91.1 50.0 58.3 87.5 85.7 80.0 40.0 85.1 87.5 82.6 69.2
3 7 0 0 1 9 3 7 5 5 6 3 1 5 5 1 9 3 7 2 4 4
15.0 21.9 0 0 50.0 18.0 21.4 18.5 38.5 12.9 37.5 8.9 50.0 41.7 22.5 14.3 20.0 60.0 14.9 22.5 27.4 30.8
P1
P2
0.408
0.351 0.545 0.057 0.035
0.139
0.039
0.743
0.519 0.043 0.228
0.027
F. Incecik et al. / Brain & Development 37 (2015) 311–314
generalized tonic-clonic seizures, and 2 patients (16.7%) had myoclonic seizures. All children had a full lead EEG at presentation. The background rhythms were normal of all the children. In 45 (86.5%) of patients, the spike and waves were generalized, and in 7 (13.5%), there were additional focal abnormalities. Among the 52 treated patients, most widely used AED was valproic acid (VPA). Fourty nine patients (94.2%) were treated with VPA, and 3 patients (5.8%) were treated with levetiracetam. In VPA-treated group, mean dose and serum level were 26.49 ± 4.63 mg/kg/day (26–41 mg/kg/day) and 73.05 ± 11.30 lg/ml (55–92 lg/ ml) respectively. In a levetiracetam-treated group, mean dose was 30.00 ± 5.00 mg/kg/day (25–35 mg/kg/day). Serum levetiracetam level could not been measured. There was no correlation between response to initial AED treatment and sex, consanguinity, history of neonatal and febrile seizure, history of family epilepsy, time lag to first treatment, localized and generalized findings on EEG. But, there was statistically significant correlation between response to initial AED treatment and age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing response to initial AED treatment. 4. Discussion In literature, there have been many studies for determining the risk factors affecting failure to respond to the initially prescribed AED in epileptic children. Reported failure rates have reported 20% by Camfield et al. and 40% by Carpay et al. in literature [7,8]. Also, in children with epilepsy, if the initial AED fails to control seizures, the prognosis for seizure control is often thought to be poor. There are only a few studies specifically in with CAE associated with the prognostic significance of initial AED failure [4–6]. We detected 19.2% of children were not responding successfully responding to the first AED treatment in our study. The failure rates have been reported 15–40% in the literature [4–6]. In first study, Wirerel et al. [4] found failure rate as 40%. In anothers studies, Covanis et al. and Nadler et al. reported failed rate as 15% and 17.3%, respectively [5,6]. Epidemiologically, typical CAE affects girls more commonly than boys in a 60 to 40% ratio [9]. In our study, there was a female predominance (61.5%). We did not find sex as a significant risk factor for respond to treatment with the first AED treatment. This finding is in agreement with other two studies [4,6]. But, Nadler et al. [5] reported male gender as a significant risk factor for failure to treatment with the first AED treatment.
313
We found that age at onset of seizure was a significant risk factor for failure to respond to the initial AED treatment. In our study, patients were divided into three groups according to the age of seizure onset (Table 1). We identified seizure onset before 5 years old was a significant risk factor for failure to respond to the initial AED treatment. In our study, we found that age at onset of seizure significantly increased failure risk in both univariate and multivariate analysis. In another studies, they reported that age of seizure onset was not risk factor for failure to respond to the initial AED treatment [4–6]. We did not identify family history of epilepsy, febrile seizure, and consanguinity as a risk factors for failure to respond to the initial AED treatment, which is consistent with other studies. CAE are less often associated with other seizure types (generalized tonic-clonic and myoclonic seizure) than in patients with JAE. Some studies report perioral myoclonia and single or arrhythmic myoclonic jerking of limbs, head, or trunk during seizure in a small number of children with CAE [10]. We found coexisting other types of seizures as a risk factor for failure to respond to the initial AED treatment. We detected that patients who had generalized tonic-clonic seizures prior to treatment had less success with controlling their CAE. In other study, Wirrel et al. [4] found that poor initial response to treatment, myoclonic jerks or generalized tonic-clonic seizures before or during the active phase of absences are associated with unfavorable prognosis. These findings were similiar to our study. But, the other study was not agreed with these findings [5]. The biggest clue of a “typical absence seizure” is the presence of a bilateral, symmetrical and synchronous discharge of regular 3cyc/s spike-and-wave complexes with normal background activity on the EEG. In literature, a lot of reports have been written about the prognosis of patients with CAE [6,11,12]. However, few of these reports have focused on the EEG prognosis [4–6,13]. In our study, we evaluated background rhythm, focal interictal spikes, and photoconvulsive response findings on EEG. We detected photoconvulsive EEG response as a risk factor for failure to respond to the initial AED. Wirrell et al. also found similar findings, whereas Covanis et al. and Nadler et al. did not find them [4–6]. Valproic acid and ethosuximide (ESM) have been shown to be equally effective as monotherapy for typical absence seizures, and at present, they are generally considered first-choice drugs for this seizure type [4,14]. VPA controls absences in 75% of patients, in addition to being effective against generalized tonic-clonic seizures and myoclonic seizures. ESM produces complete control of absences in 70% of treated patients, it is suitable as monotherapy. But, this drug is not available in our country. Recently, lamotrigine and levetiracetam
314
F. Incecik et al. / Brain & Development 37 (2015) 311–314
were shown to be effective as both add on and monotherapy for typical absence seizures [15]. We cannot refer efficacy and relation of these two drugs, because we used VPA in nearly all patients. In conclusion, we found age at onset of seizure, coexisting other types of seizures, and photoconvulsive EEG response are risk factors for failure to respond to the initial AED treatment in this study. There is still no general agreement on the criteria to predict respond to treatment with the first AED. We think that additional new studies should be design to this topic. References [1] The Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501. [2] Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. How well can epilepsy syndromes be identified at diagnosis? A reassessment 2 years after initial diagnosis. Epilepsia 2000;41:1269–75. [3] Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975;16:1–66. [4] Wirrell E, Camfield C, Camfield P, Dooley J. Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy. Epilepsia 2001;42:760–3.
[5] Nadler B, Shevell MI. Childhood absence epilepsy requiring more than one medication for seizure control. Can J Neurol Sci 2008;35:297–300. [6] Covanis A, Skiadas K, Loli N, Lada C, Theodorou V. Absence epilepsy: early prognostic signs. Seizure 1992;1:281–9. [7] Camfield PR, Camfield CS, Gordon K, Dooley JM. If a first antiepileptic drug fails to control a child’s epilepsy, what are the chances of success with the next drug? J Pediatr 1997;131:821–4. [8] Carpay HA, Arts WF, Geerts AT, et al. Epilepsy in childhood: an audit of clinical practice. Arch Neurol 1998;55:668–73. [9] Holmes GL. Generalized seizures. In: Swaiman KF, Ashwal S, Ferriero DM, editors. Pediatric neurology; principles & practice. Philadelphia: Mosby-Elsevier; 2006. p. 1019–35. [10] Sadleir LG, Farrell K, Smith S, Connolly MB, Scheffer IE. Electroclinical features of absence seizures in childhood absence epilepsy. Neurology 2006;67:413–8. [11] Grosso S, Galimberti D, Vezzosi P, Farnetani M, Di Bartolo RM, Bazzotti S, et al. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia 2005;46:1796–801. [12] Sato S, Dreifuss FE, Penry JK. Prognostic factors in absence seizures. Neurology 1976;26:788–96. [13] Yoshinaga H, Ohtsuka Y, Tamai K, Tamura I, Ito M, Ohmori I, et al. EEG in childhood absence epilepsy. Seizure 2004;13:296–302. [14] Panayiotopoulos CP. Treatment of typical absence seizures and related epileptic syndromes. Paediatr Drugs 2001;3:379–403. [15] Penovich PE, Willmore LJ. Use of a new antiepileptic drug or an old one as first drug for treatment of absence epilepsy. Epilepsia 2009;50(Suppl. 8):37–41.
Original article
First-drug treatment failures in children with typical absence epilepsy Faruk Incecik ⇑, Sakir Altunbasak, Ozlem M. Herguner Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Cukurova University, Adana, Turkey Received 9 December 2013; received in revised form 6 May 2014; accepted 7 May 2014
Abstract Background: Childhood absence epilepsy (CAE) is a well-known syndrome with onset in middle childhood and is characterized by multiple typical absences per day. Pharmacological treatment is specific and usually successful with a single medication. The goal of the study was to assess on risk factors associated with failure to respond to the initial antiepileptic drug (AED). Methods: Fifty-two children with CAE were enrolled. Predictive factors were analyzed by survival methods. Results: Among 52 patients, 32 patients (61.5%) were girls and the remaining 20 (38.5%) were boys and the mean age at the seizure onset was 6.5 ± 1.78 years old (3–11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED treatment (Group A), and 10 (19.2%) were not responsed (Group B). Age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response were significantly associated with failure risk according to univariate analysis. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing poor response to initial AED treatment. Conclusion: Factors predicting failure to respond to the AED were age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response in children with CAE. Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Keywords: Childhood absence epilepsy; First antiepileptic drug; Failure risk factors or predicting factors; Photoconvulsive EEG response
1. Introduction Absence seizures are characterized by an abrupt cessation of activity, change in facial expression, impairment of consciousness, eye fluttering and sometimes associated by automatisms. As defined by the International League Against Epilepsy (ILAE) criteria, childhood absence epilepsy (CAE) is defined as typical absence seizures beginning under the age of ten, with an EEG discharge of symmetrical, synchronous spike wave complexes, recurring regularly at a rhythm of about 3 Hz [1]. Childhood absence epilepsy accounts
⇑ Corresponding author. Address: Toros mah., Barısß Manc ßo Bul. ¸ ukurova, Adana, 78178 Sok., Yesßilpark evleri, A blok, kat:7/13, C Turkey. E-mail address: fi[email protected] (F. Incecik).
for 10% to 17% of childhood epilepsy and usually presents between ages 4 and 8 [1,2]. Typical absence seizures may occur many times a day usually not surpassing 30 s induration. The end of the attack is as sudden as its onset, often with the child unaware of the seizure. The prevalence of typical absence seizures is highest during the first decade of life and then drops dramatically [3]. Treatment response to initial monotherapy is suboptimal, with slightly more than half of children achieving complete seizure control with acceptable treatment associated side effects. In literature, only a few studies are available on factors associated with initial poor response to antiepileptic drugs (AED) [4–6]. Therefore, we conducted a retrospective study designed to identify the risk factors associated with initial poor response to AEDs in children with CAE.
http://dx.doi.org/10.1016/j.braindev.2014.05.005 0387-7604/Ó 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
312
F. Incecik et al. / Brain & Development 37 (2015) 311–314
2. Subjects and methods This study was conducted a retrospective study of 52 children diagnosed with CAE and started on an AED in the pediatric neurology department of our hospital. Patients were selected based on the following inclusion criteria: (a) age from 3 to 13 years; (b) diagnosed typical absence seizures (ILAE Commission, 1981) [1] associated with generalized, synchronous 3-Hz (2.5– 4 Hz) spike and wave activity, lasting >3 s, occurring spontaneously or during one of two trials of 3 min hyperventilation with a 1–2 min rest between trials; (c) clearly observable clinical signs of typical absence seizures (e.g., staring or impairment of consciousness); (d) treated with AEDs for the first time; (e) normal clinical, neurologic, and computed tomography (CT)/magnetic resonance imaging (MRI) examination. The data were retrospectively collected from the clinic files and included sex, age of seizure onset, consanguinity, history of neonatal and febrile seizure, family history of epilepsy, coexisting other types of seizures, time lag to first treatment, electroencephalogram (EEG) findings (spike wave type and photoconvulsive response). Photoconvulsive response was defined as generalized epileptic discharge that was elicited during photic stimulation. Success of initial AED was defined as obtaining complete seizure control with the first AED. Failure of initial AED treatment was defined as inability to attain complete seizure control with the first appropriate AED.
The SPSS version 19.5 was used for statistical analysis. Statistical significance was accepted at p < 0.05. The chi-square tests were used to determine the associations among categorical data. We carried out univariate and multivariable analyses of potential predictors of recurrence risk using by Cox regression analysis. The level of statistical significance was established at p- value of <0.05. Initially, we performed a univariate analysis, in order to determine which would used in multivariate analysis. 3. Results The general characteristics of children treated with initial AED and factors for success and failure to the first AED are shown in Table 1. Fifty-two children, mean age 7.50 ± 1.67 years (4–12.5 years), were included in this study. Among the 52 patients, 20 (38.5%) were boys and 32 (61.5%) were girls, and the mean age at the seizure onset was 6.50 ± 1.78 years (3–11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED (Group A), and 10 (19.2%) did not responsed to initial AED treatment (Group B). Two patients (3.8%) had past history of febrile convulsion, and thirteen patients (25.0%) had family history of convulsive disorders. Twelve patients had coexisting other types of seizures: 10 patients (83.3%) had
Table 1 Summary of demographics and factors associated with success or failure of the first AED. Parameters
Sex Neonatal seizure History of febrile seizure Consanguinity Family history of epilepsy Age of seizure onset
Coexisting other types of seizures Focal spike activity on EEG Photoconvulsive EEG response Time lag to first treatment
P1: p value of univariate analysis. P2: p value of multivariate analysis.
Responders
Boy Girl Yes No Yes No Yes No Yes No <5 years 5–10 years >10 years Yes No Yes No Yes No 1 month 1–6 months >6 months
Non-responders
n
%
n
%
17 25 0 52 1 41 11 31 8 34 10 31 1 7 35 6 36 2 40 14 19 9
85.0 78.1 100 100 50.0 82.0 78.6 81.5 61.5 87.1 62.5 91.1 50.0 58.3 87.5 85.7 80.0 40.0 85.1 87.5 82.6 69.2
3 7 0 0 1 9 3 7 5 5 6 3 1 5 5 1 9 3 7 2 4 4
15.0 21.9 0 0 50.0 18.0 21.4 18.5 38.5 12.9 37.5 8.9 50.0 41.7 22.5 14.3 20.0 60.0 14.9 22.5 27.4 30.8
P1
P2
0.408
0.351 0.545 0.057 0.035
0.139
0.039
0.743
0.519 0.043 0.228
0.027
F. Incecik et al. / Brain & Development 37 (2015) 311–314
generalized tonic-clonic seizures, and 2 patients (16.7%) had myoclonic seizures. All children had a full lead EEG at presentation. The background rhythms were normal of all the children. In 45 (86.5%) of patients, the spike and waves were generalized, and in 7 (13.5%), there were additional focal abnormalities. Among the 52 treated patients, most widely used AED was valproic acid (VPA). Fourty nine patients (94.2%) were treated with VPA, and 3 patients (5.8%) were treated with levetiracetam. In VPA-treated group, mean dose and serum level were 26.49 ± 4.63 mg/kg/day (26–41 mg/kg/day) and 73.05 ± 11.30 lg/ml (55–92 lg/ ml) respectively. In a levetiracetam-treated group, mean dose was 30.00 ± 5.00 mg/kg/day (25–35 mg/kg/day). Serum levetiracetam level could not been measured. There was no correlation between response to initial AED treatment and sex, consanguinity, history of neonatal and febrile seizure, history of family epilepsy, time lag to first treatment, localized and generalized findings on EEG. But, there was statistically significant correlation between response to initial AED treatment and age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing response to initial AED treatment. 4. Discussion In literature, there have been many studies for determining the risk factors affecting failure to respond to the initially prescribed AED in epileptic children. Reported failure rates have reported 20% by Camfield et al. and 40% by Carpay et al. in literature [7,8]. Also, in children with epilepsy, if the initial AED fails to control seizures, the prognosis for seizure control is often thought to be poor. There are only a few studies specifically in with CAE associated with the prognostic significance of initial AED failure [4–6]. We detected 19.2% of children were not responding successfully responding to the first AED treatment in our study. The failure rates have been reported 15–40% in the literature [4–6]. In first study, Wirerel et al. [4] found failure rate as 40%. In anothers studies, Covanis et al. and Nadler et al. reported failed rate as 15% and 17.3%, respectively [5,6]. Epidemiologically, typical CAE affects girls more commonly than boys in a 60 to 40% ratio [9]. In our study, there was a female predominance (61.5%). We did not find sex as a significant risk factor for respond to treatment with the first AED treatment. This finding is in agreement with other two studies [4,6]. But, Nadler et al. [5] reported male gender as a significant risk factor for failure to treatment with the first AED treatment.
313
We found that age at onset of seizure was a significant risk factor for failure to respond to the initial AED treatment. In our study, patients were divided into three groups according to the age of seizure onset (Table 1). We identified seizure onset before 5 years old was a significant risk factor for failure to respond to the initial AED treatment. In our study, we found that age at onset of seizure significantly increased failure risk in both univariate and multivariate analysis. In another studies, they reported that age of seizure onset was not risk factor for failure to respond to the initial AED treatment [4–6]. We did not identify family history of epilepsy, febrile seizure, and consanguinity as a risk factors for failure to respond to the initial AED treatment, which is consistent with other studies. CAE are less often associated with other seizure types (generalized tonic-clonic and myoclonic seizure) than in patients with JAE. Some studies report perioral myoclonia and single or arrhythmic myoclonic jerking of limbs, head, or trunk during seizure in a small number of children with CAE [10]. We found coexisting other types of seizures as a risk factor for failure to respond to the initial AED treatment. We detected that patients who had generalized tonic-clonic seizures prior to treatment had less success with controlling their CAE. In other study, Wirrel et al. [4] found that poor initial response to treatment, myoclonic jerks or generalized tonic-clonic seizures before or during the active phase of absences are associated with unfavorable prognosis. These findings were similiar to our study. But, the other study was not agreed with these findings [5]. The biggest clue of a “typical absence seizure” is the presence of a bilateral, symmetrical and synchronous discharge of regular 3cyc/s spike-and-wave complexes with normal background activity on the EEG. In literature, a lot of reports have been written about the prognosis of patients with CAE [6,11,12]. However, few of these reports have focused on the EEG prognosis [4–6,13]. In our study, we evaluated background rhythm, focal interictal spikes, and photoconvulsive response findings on EEG. We detected photoconvulsive EEG response as a risk factor for failure to respond to the initial AED. Wirrell et al. also found similar findings, whereas Covanis et al. and Nadler et al. did not find them [4–6]. Valproic acid and ethosuximide (ESM) have been shown to be equally effective as monotherapy for typical absence seizures, and at present, they are generally considered first-choice drugs for this seizure type [4,14]. VPA controls absences in 75% of patients, in addition to being effective against generalized tonic-clonic seizures and myoclonic seizures. ESM produces complete control of absences in 70% of treated patients, it is suitable as monotherapy. But, this drug is not available in our country. Recently, lamotrigine and levetiracetam
314
F. Incecik et al. / Brain & Development 37 (2015) 311–314
were shown to be effective as both add on and monotherapy for typical absence seizures [15]. We cannot refer efficacy and relation of these two drugs, because we used VPA in nearly all patients. In conclusion, we found age at onset of seizure, coexisting other types of seizures, and photoconvulsive EEG response are risk factors for failure to respond to the initial AED treatment in this study. There is still no general agreement on the criteria to predict respond to treatment with the first AED. We think that additional new studies should be design to this topic. References [1] The Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501. [2] Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. How well can epilepsy syndromes be identified at diagnosis? A reassessment 2 years after initial diagnosis. Epilepsia 2000;41:1269–75. [3] Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975;16:1–66. [4] Wirrell E, Camfield C, Camfield P, Dooley J. Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy. Epilepsia 2001;42:760–3.
[5] Nadler B, Shevell MI. Childhood absence epilepsy requiring more than one medication for seizure control. Can J Neurol Sci 2008;35:297–300. [6] Covanis A, Skiadas K, Loli N, Lada C, Theodorou V. Absence epilepsy: early prognostic signs. Seizure 1992;1:281–9. [7] Camfield PR, Camfield CS, Gordon K, Dooley JM. If a first antiepileptic drug fails to control a child’s epilepsy, what are the chances of success with the next drug? J Pediatr 1997;131:821–4. [8] Carpay HA, Arts WF, Geerts AT, et al. Epilepsy in childhood: an audit of clinical practice. Arch Neurol 1998;55:668–73. [9] Holmes GL. Generalized seizures. In: Swaiman KF, Ashwal S, Ferriero DM, editors. Pediatric neurology; principles & practice. Philadelphia: Mosby-Elsevier; 2006. p. 1019–35. [10] Sadleir LG, Farrell K, Smith S, Connolly MB, Scheffer IE. Electroclinical features of absence seizures in childhood absence epilepsy. Neurology 2006;67:413–8. [11] Grosso S, Galimberti D, Vezzosi P, Farnetani M, Di Bartolo RM, Bazzotti S, et al. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia 2005;46:1796–801. [12] Sato S, Dreifuss FE, Penry JK. Prognostic factors in absence seizures. Neurology 1976;26:788–96. [13] Yoshinaga H, Ohtsuka Y, Tamai K, Tamura I, Ito M, Ohmori I, et al. EEG in childhood absence epilepsy. Seizure 2004;13:296–302. [14] Panayiotopoulos CP. Treatment of typical absence seizures and related epileptic syndromes. Paediatr Drugs 2001;3:379–403. [15] Penovich PE, Willmore LJ. Use of a new antiepileptic drug or an old one as first drug for treatment of absence epilepsy. Epilepsia 2009;50(Suppl. 8):37–41.