Epilepsy & Behavior 37 (2014) 54–58
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Attention-deficit/hyperactivity disorder and attention impairment in children with benign childhood epilepsy with centrotemporal spikes Eun-Hee Kim a, Mi-Sun Yum a, Hyo-Won Kim b, Tae-Sung Ko a,⁎ a b
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Psychiatry, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 15 February 2014 Revised 25 May 2014 Accepted 27 May 2014 Available online 27 June 2014 Keywords: Benign childhood epilepsy with centrotemporal spikes Benign rolandic epilepsy Attention-deficit/hyperactivity disorder Attention impairment
a b s t r a c t Attention-deficit/hyperactivity disorder (ADHD) is a common comorbidity in children with epilepsy and has a negative impact on behavior and learning. The purposes of this study were to quantify the prevalence of ADHD in benign childhood epilepsy with centrotemporal spikes (BCECTS) and to identify clinical factors that affect ADHD or attention impairment in patients with BCECTS. The medical records of 74 children (44 males) with neuropsychological examination from a total of 198 children diagnosed with BCECTS at Asan Medical Center were retrospectively reviewed. Electroclinical factors were compared across patients with ADHD and those without ADHD. Mean T-scores of the continuous performance test were compared across patients grouped according to various epilepsy characteristics. Forty-eight (64.9%) patients had ADHD. A history of febrile convulsion was more common in patients with ADHD than in patients without ADHD (p = 0.049). Bilateral centrotemporal spikes on electroencephalogram were more common in patients receiving ADHD medication than in patients with untreated ADHD (p = 0.004). Male patients, patients with frequent seizures prior to diagnosis, and patients with a high spike index (≥40/min) on sleep EEG at diagnosis had significantly lower visual selective attention (p b 0.05). Children with BCECTS had a high prevalence of ADHD, and frequent seizures or interictal epileptiform abnormalities were closely related to impairment of visual selective attention in children with BCECTS, indicating the need for ADHD or attention impairment screening in children with BCECTS. © 2014 Elsevier Inc. All rights reserved.
1. Introduction The prevalence of behavioral and cognitive problems such as attention-deficit/hyperactivity disorder (ADHD) is higher in children with epilepsy than in children with other chronic illnesses and children in the general population [1,2]. Inattention and hyperactivity are the most common clinical complaints of children presenting with epileptic epilepsy syndromes [2,3]. Attention deficits in children with epilepsy are influenced by multiple factors, including the neurological and seizure status, medication, and various environmental factors. Impaired attention and concentration negatively impact learning and mental development [4,5]; therefore, early diagnosis and appropriate treatments of attention problems in children with epilepsy are very important. Benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy, is the most common childhood epilepsy syndrome and accounts for 15–25% of epilepsy diagnoses in children
⁎ Corresponding author at: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea. Tel.: +82 2 3010 3381; fax: +82 2 3010 3725. E-mail address: [email protected] (T.-S. Ko).
http://dx.doi.org/10.1016/j.yebeh.2014.05.030 1525-5050/© 2014 Elsevier Inc. All rights reserved.
younger than 15 years of age [6]. Benign childhood epilepsy with centrotemporal spikes classically occurs in neurologically and cognitively healthy children, and the presentation is usually a nocturnal partial seizure with a typical electroencephalogram (EEG) that shows centrotemporal spikes (CTSs) [6]. Although BCECTS is considered a benign form of childhood epilepsy, formal neuropsychological evaluations have revealed a higher prevalence of cognitive impairment in children with BCECTS than in healthy sex- and age-matched children [7]. In the last two decades, a wide spectrum of neuropsychological and learning disabilities such as speech and language disorders, reading disabilities, attention impairment, visuomotor and behavior impairments, and psychiatric problems including aggression and oppositional behavior have been reported in children with BCECTS [8–12]. Attention-deficit/hyperactivity disorder is also considered as a comorbidity associated with BCECTS by interference, based on some studies [13–15]. However, the incidence of ADHD in BCECTS and the causes of this comorbidity remain unclear. Besides, it is uncertain which epilepsy characteristics (seizure frequency, epileptic discharges, or age at seizure onset) cause the negative neuropsychological consequences that impact attention. The purposes of the present study were to quantify the prevalence of ADHD in children with BCECTS and to evaluate the associations
E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58
between epilepsy factors and ADHD/attention impairment in patients with BCECTS. 2. Materials and methods 2.1. Participants One hundred and ninety-eight children were diagnosed with BCECTS at Asan Medical Center Children's Hospital from 2007 to 2012 and followed for at least 1 year after diagnosis. The clinical diagnosis of BCECTS was confirmed by pediatric neurologists according to the International League Against Epilepsy classification. The following exclusion criteria were applied: (1) age younger than 2 years or older than 16 years at diagnosis; (2) diagnosis of any epilepsy other than BCECTS; (3) any brain magnetic resonance imaging abnormality that could affect the diagnosis of BCECTS; (4) any accompanying neurologic disorder such as cerebral palsy, neurometabolic disease, or mental retardation (intelligence quotient b 70); and (5) follow-up duration for less than 1 year after diagnosis. Among the 198 children, however, 124 children were not enrolled in this study as their parents refused a neuropsychological assessment for the reasons of negative attitude or unrecognized necessity. In the end, 74 children who received a neuropsychological examination by neuropsychologists were eligible for the study and formed the study sample. 2.2. EEG recordings Electroencephalogram recordings were obtained before the initiation of antiepileptic drug (AED) treatment. All subjects underwent EEG recording during wakefulness and/or sleep. At least 30 min of digital recording were obtained using the international 10–20 system for electrode placement. Routine activation procedures including hyperventilation, eye closure, and photic stimulation were performed if possible. Sleep EEGs were recorded until induction of stage II sleep was confirmed by the technician. Sleep EEGs were obtained from 71 patients among the 74 patients. All EEG records were evaluated by three board-licensed pediatric neurologists (TS Ko, MS Yum, and EH Kim). The number of CTSs was manually counted, and the amplitude of the most active individual epileptic spike on visual inspection was measured. The spike index (number of spikes per minute) during wakefulness and sleep was calculated, and spikes with amplitude ≥ 200 μV were defined as high-amplitude spikes. 2.3. Evaluation of attention impairment Selective and sustained attention impairments were evaluated using a computerized continuous performance test (CPT) [16]. The Korean version of the CPT has been standardized, and its validity and reliability have been established [17]. The four variables quantified were omission errors (failure to respond to the target), commission errors (erroneously responding to a nontarget), response times (RTs) for a correct target, and the standard deviation (SD) of the RTs. Only 49 patients could perform the CPT before receiving the ADHD medication, and the attention score was presented with T-scores adjusted for age. A T-score of 65 (1.5 SD above the mean) or greater was taken as indicative of attention impairment. These results of the CPT were not directly used to diagnose ADHD or assess ADHD severity. 2.4. Procedures All data were retrospectively retrieved from electronic medical records. The clinical variables recorded were age at the onset of seizures, history of febrile convulsions, family history of epilepsy, seizure type, seizure frequency in the year prior to diagnosis, number of AEDs, response to first AED, duration of medical therapy, duration of followup, the control of seizures at follow-up (complete or incomplete),
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and the presence or absence of ADHD and comorbidities such as tic disorder, oppositional or conduct disorder, anxiety, depression, and learning disabilities. Attention-deficit/hyperactivity disorder was clinically diagnosed by a pediatric psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria of ADHD: the diagnosis of ADHD was made if more than six out of nine symptoms of inattention or hyperactivity–impulsivity had persisted for at least six months, using the questionnaire of ADHD symptoms for parents. 2.5. Data analysis All statistical analyses were performed using SPSS statistical software, version 18.0 (SPSS, Inc., Chicago, IL). Clinical and EEG variables were compared across patients with BCECTS with ADHD and patients with BCECTS without ADHD and across patients with BCECTS with treated ADHD and patients with BCECTS with untreated ADHD using independent t-tests for continuous variables and χ2 and Fisher's exact tests for categorical variables. The CPT outcomes (T-scores for omission errors, commission errors, RTs, and RT SD) were compared across sex, seizure onset age (b7 or ≥ 7 years), number of seizures in the year prior to diagnosis (b 4 or ≥ 4), seizure control at follow-up, responses to monotherapy, CTS amplitude (b200 or ≥200 μV), unilateral or bilateral CTSs, a spike index during wakefulness (b10 or ≥10/min), and a spike index during sleep (b40 or ≥40/min) using independent t-tests. A p b 0.05 was considered statistically significant. 3. Results 3.1. Characteristics of patients with BCECTS The clinical characteristics of the 74 children with BCECTS are shown in Table 1. The mean age was 10.9 (range = 6.5–16.5) years. The mean duration of follow-up was 3.0 (range = 1.0–6.2) years. At final followup, 69 (93.2%) patients were being treated with AEDs: 54 patients were being treated with monotherapy, and 15 patients were being treated with polytherapy. The mean duration of medication was 2.3 (range = 0.2–6.5) years. The most common AED was oxcarbazepine (n = 52, 75.4%), followed by lamotrigine (n = 13, 18.8%). Of the 74 patients with BCECTS, 48 (64.9%) were diagnosed with ADHD. Additional comorbid neuropsychiatric problems were present in 15 (20.3%) patients: tic disorder, n = 7; oppositional defiant disorder or conduct disorder, n = 4; anxiety disorder, n = 2; depressive disorder, n = 1; language disability, n = 1; and adjustment disorder, n = 1. Electroencephalogram background rhythm was normal for age in all patients. The EEG findings are shown in Table 2. 3.2. Association between ADHD and electroclinical characteristics in patients with BCECTS Clinical characteristics and EEG findings were compared between patients with ADHD and those without ADHD (Tables 1 and 2). The history of febrile convulsions was the only factor that was significantly different between groups (p = 0.049; Table 1). Of the 48 patients diagnosed with BCECTS and comorbid ADHD, 14 (29.2%) received pharmacotherapy for ADHD (methylphenidate, n = 8 and atomoxetine, n = 6). On the assumption that patients with severe ADHD received pharmacologic treatment, we compared the clinical characteristics and EEG findings across patients with BCECTS with treated comorbid ADHD and patients with BCECTS with untreated comorbid ADHD. Bilateral CTSs were more frequent in treated patients than in untreated patients (p = 0.004), but all other clinical variables were similar in the two groups (Table 3).
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E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58
Table 1 Clinical characteristics of 74 children with BCECTS and the comparison of clinical characteristics between patients with ADHD and those without ADHD.
Males, n (%) Age at seizure onset, years Mean ± SD (range) b7 years, n (%) ≥7 years, n (%) Frequency of seizure Mean ± SD, times/year (range) b4/year, n (%) ≥4/year, n (%) Secondarily generalized seizure, n (%) History of febrile convulsions, n (%) Family history of epilepsy, n (%) Number of AEDs Mean ± SD (range) Failure of monotherapy, n (%) Duration of AED use, years Mean ± SD (range) Control of seizure, n (%) Complete Not complete Coexisting neuropsychiatric problems, n (%)
All patients n = 74
With ADHD n = 48
Without ADHD n = 26
p-Value
44
31 (64.5)
13 (50)
0.223
7.4 ± 1.9 (3.3–11.6) 30 44
7.3 ± 1.9 (3.7–10.9) 22 (45.8) 26 (54.2)
7.7 ± 2.1 (3.3–11.6) 8 (30.8) 18 (69.2)
0.376 0.208
2.1 ± 1.5 (1–10) 66 8 60 11 4
2.2 ± 1.7 (1–10) 42 (87.5) 6 (12.5) 38 (79.2) 10 (20.8) 2 (4.2)
2.1 ± 0.9 (1–4) 24 (92.3) 2 (7.7) 22 (84.6) 1 (3.8) 2 (7.7)
0.642 0.525
1.1 ± 0.5 (0–3) 14
1.2 ± 0.5 (0–3) 10 (20.8)
1.1 ± 0.5 (0–3) 4 (15.4)
0.700 0.568
2.3 ± 1.6 (0.2–6.5)
2.2 ± 1.7 (0.2–6.5)
2.6 ± 1.6 (0.2–5.3)
0.138
42 32 15
24 (50.0) 24 (50.0) 9 (18.8)
18 (69.2) 8 (30.8) 6 (23.1)
0.111
0.049⁎ 0.522
0.960
Abbreviations: BCECTS: benign childhood epilepsy with centrotemporal spikes, ADHD: attention-deficit/hyperactivity disorder, AED: antiepileptic drug.
3.3. Association between attention and electroclinical characteristics in patients with BCECTS Among 49 patients who performed the CPT, thirty patients performed the CPT while taking AEDs (oxcarbazepine, n = 23; lamotrigine, n = 4; topiramate, n = 3; and levetiracetam, n = 2), and one patient performed the CPT before the diagnosis of BCECTS. The mean T-score for commission errors in visual selection was higher in males than in females (p = 0.04) and higher in patients with a higher spike index (≥ 40/min) on sleep EEG than in patients with a lower spike index (p = 0.04). The mean T-score for omission errors in visual selection was higher in children with ≥4 seizures in the year prior to diagnosis than in patients with b 4 seizures (p = 0.01). The mean T-score for all four outcome variables (omission errors, commission errors, RTs, and RT SD) for auditory selection was within the normal range (T-score b 65) and did not differ according to demographic or clinical factors. The proportion of patients demonstrating suspicious (T-score between 60 and 65) or significant (T-score over 65) impairment of attention in the CPT was highest in omission errors in visual selection (Table S1). Also, when comparing between patients with ADHD and
those without ADHD, the rate of patients with relevant T-score for attention impairment was significantly higher in the domain of omission errors in visual selection (p = 0.002). 4. Discussion It is generally thought that long-term seizure and developmental outcomes in BCECTS are good [18]. However, recent studies have raised the issue of subtle neurocognitive deficits, reading disability, speech sound disorder, and behavioral comorbidities in patients with BCECTS. Inattention and hyperactivity are common behavioral problems in children with BCECTS [19–23], and there is growing interest in the clinical diagnosis of ADHD in children with BCECTS. Nevertheless, few studies have described the comorbidity of BCECTS and ADHD/attention problems in children with BCECTS. In the present study, 64.9% of the 74 children with BCECTS had ADHD. This is much higher than the reported prevalence of ADHD in otherwise healthy school children (3–5%) and children with epilepsy (8–33%) [2]. The high prevalence of ADHD in the current study cohort may have been affected by selection bias, as all patients were recruited
Table 2 EEG findings of 74 children with BCECTS and the comparison of EEG findings between patients with ADHD and those without ADHD.
Number of spike discharges, n (%) During wakefulness (n = 68) ≥10/min b10/min During sleep, stages I–II (n = 71) ≥40/min b40/min Amplitude of spike discharge, n (%) ≥200 μV b200 μV Laterality of spike discharges, n (%) Unilateral [right:left] Bilateral Other epileptiform discharges, n (%) Focal Generalized
All patients n = 74
With ADHD n = 48
Without ADHD n = 26
20 48
12 (27.9) 31 (72.1)
8 (32.0) 17 (68.0)
29 42
19 (40.4) 28 (59.6)
10 (41.7) 14 (58.3)
29 45
22 (45.8) 26 (54.2)
7 (26.9) 19 (73.1)
47 [22:25] 27
29 [15:14] (60.4) 19 (39.6)
18 [7:11] (69.2) 8 (30.8)
2 10
2 (22.2) 7 (77.8)
0 (0.0) 3 (100.0)
p-Value
0.575
0.503
0.112
0.452
Abbreviations: BCECTS: benign childhood epilepsy with centrotemporal spikes, ADHD: attention-deficit/hyperactivity disorder.
0.573 0.715
E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58 Table 3 Comparison of clinical characteristics between patients with BCECTS with stimulanttreated ADHD and patients with BCECTS with untreated ADHD.
Male, n (%) Age at seizure onset, years Mean ± SD (range) b7 years, n (%) ≥7 years, n (%) Frequency of seizures b4/year, n (%) ≥4/year, n (%) Laterality of spike discharges, n (%) Unilateral [right:left] Bilateral Number of AEDs Mean ± SD (range) Duration of AEDs, years Mean ± SD, year (range) Failure of monotherapy, n (%) Coexisting neuropsychiatric problems, n (%)
Stimulant-treated ADHD n = 14
Untreated ADHD n = 34
p-Value
9 (64.3)
22 (34.7)
0.978
7.1 ± 2.2 (3.7–10.5) 7.3 ± 1.6 (4.1–10.9) 0.714 8 (57.1) 14 (41.2) 0.313 6 (42.9) 20 (58.8) 0.810 12 (85.7) 30 (88.2) 2 (14.3) 4 (11.8) 0.004⁎ 4 [1:3] (28.6) 10 (71.4)
25 [14:11] (73.5) 9 (26.5)
1.3 ± 0.6 (1–3)
1.1 ± 0.5 (0–2)
0.349
1.9 ± 1.2 (0.2–4.0) 3 (21.4) 4 (28.6)
2.0 ± 1.6 (0.2–5.4) 7 (20.6) 6 (17.6)
0.793 0.948 0.263
Abbreviations: ADHD: attention-deficit/hyperactivity disorder, BCECTS: benign childhood epilepsy with centrotemporal spikes, AED: antiepileptic drug.
from a tertiary referral center, and parent participation in psychiatric evaluation may have been biased by a negative attitude to psychiatric care. In neuropsychological examination, the lack of structural interview or rating scales may also cause the overestimation of ADHD. However, the large difference in the current study reflects a significant difference in the incidence of ADHD in patients with BCECTS as compared with the general population. Many studies have suggested various pathogenetic mechanisms of ADHD including a common genetic predisposition or biochemical factors in children with epilepsy [14,15]. The higher striatal glutamate concentration in children with ADHD [24] and synaptic abnormality in excitatory glutamatergic transmission in animal models of ADHD may also explain the vulnerability of children with ADHD to epilepsy [25–27]. Several recent studies have proposed possible common pathophysiology between ADHD and epilepsy in the context of brain development [28,29]. A volume-based or functional imaging study also supports the common neurofunctional pathophysiology in abnormal brain development of ADHD and BCECTS [3,30–32]. To better understand the relation between ADHD and BCECTS, we analyzed three aspects of the association between comorbid ADHD and attention impairment in children with BCECTS: 1) the association between epilepsy characteristics and the presence of ADHD, 2) the association between epilepsy characteristics and ADHD severity, and 3) the association between epilepsy characteristics and attention impairment. We found that the presence of ADHD was not associated with other epilepsy characteristics but was associated with a history of febrile convulsion, suggesting that febrile convulsions may influence the incidence of ADHD in BCECTS. This is in line with a previous study that reported relatively high rates of mental retardation, behavioral disturbance, and academic difficulties in children with febrile convulsion [33]. However, the cognitive and behavioral outcomes of febrile convulsion have long been a subject of controversy, and recent population-based studies have demonstrated comparable intelligence and academic performance in children with febrile convulsion and in healthy controls [34–36]. Further study is needed to examine the effect of febrile convulsion on cognition. To determine the association between epilepsy characteristics and ADHD severity, we compared variables across patients with BCECTS with ADHD who were receiving stimulant treatment and patients with BCECTS with ADHD who were not receiving stimulant treatment. We found that bilateral CTSs on initial EEG were significantly more
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frequent in patients with treated ADHD. Neurocognitive deficit in epilepsy has been considered to be a chronic consequence of repetitive spikes inhibiting the same cortical area over a period of many years, leading to delayed or incomplete maturation of the brain [37–39]. Perhaps, left-lateralized language and auditory processing and typically right-lateralized sustained attention are both disrupted by bilateral CTSs, and these combined deficits produce more severe ADHD symptoms. The impact of epilepsy on attention is complex and various epilepsyrelated factors and psychosocial factors have been postulated to be responsible for the high prevalence of attention impairment in children with BCECTS [2]. Several studies suggest a link between attention function and age at the onset of epilepsy [40], the frequency of spikes on the EEG recording [41], or laterality of interictal epileptiform abnormalities [42,43]. In this study, we found that male patients, patients with more frequent seizures before diagnosis, and patients with high CTS frequency on sleep EEG had poor visual selection attention. These findings suggest that frequent ictal or interictal electrical activity in BCECTS interferes with visual attention rather than auditory attention and support a study showing that children with BCECTS had greater susceptibility to distracters in their visual field compared with healthy children or children affected by idiopathic generalized epilepsies [44]. Although the pathophysiology of attention impairment in children with BCECTS is still unknown, the overlap between neural circuitry for attention and the networks involved in the generation of rolandic seizures [31,32,45,46] may be the basis for this association. There are several limitations to this study: the selection bias involved in recruiting patients from a single tertiary center, the intersubject variability in the time interval between the diagnosis of BCECTS and the attention test, and the underestimation of influence of AEDs on neurocognitive results. The limited measure of attention is another weakness. The CPT used in this study is an effective measure of selective attention, sustained attention, or vigilance but cannot evaluate other executive function. Children with BCECTS had a high prevalence of ADHD. A history of febrile convulsions was associated with the presence of ADHD. Male gender, frequent seizures, and interictal abnormalities were related to attention impairments, indicating the need for accurate neuropsychological assessment and proper management of ADHD or attention impairment in children with BCECTS to offset possible learning difficulties and improve the long-term prognosis and quality of life of children with BCECTS. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.yebeh.2014.05.030. Conflict of interest All authors disclose that they have no conflicts of interest. References [1] Dunn DW, Austin JK. Behavioral issues in pediatric epilepsy. Neurology 1999;53: S96–S100. [2] Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50–4. [3] Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J, et al. The frequency, complications and aetiology of ADHD in new onset paediatric epilepsy. Brain 2007;130: 3135–48. [4] Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study. Epilepsia 2000;41:426–31. [5] Bulteau C, Jambaque I, Viguier D, Kieffer V, Dellatolas G, Dulac O. Epileptic syndromes, cognitive assessment and school placement: a study of 251 children. Dev Med Child Neurol 2000;42:319–27. [6] Engel J, Pedley TA. Epilepsy: a comprehensive textbook. 2nd ed. Philadelphia, Pa; London: Wolters Kluwer/Lippincott Williams & Wilkins; 2008. [7] Cerminara C, D'Agati E, Lange KW, Kaunzinger I, Tucha O, Parisi P, et al. Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention: a matched control study. Epilepsy Behav 2010;19:69–77. [8] Deonna T, Zesiger P, Davidoff V, Maeder M, Mayor C, Roulet E. Benign partial epilepsy of childhood: a longitudinal neuropsychological and EEG study of cognitive function. Dev Med Child Neurol 2000;42:595–603.
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[28] Bechtel N, Kobel M, Penner IK, Klarhofer M, Scheffler K, Opwis K, et al. Decreased fractional anisotropy in the middle cerebellar peduncle in children with epilepsy and/or attention deficit/hyperactivity disorder: a preliminary study. Epilepsy Behav 2009;15:294–8. [29] McDonald BC, Hummer TA, Dunn DW. Functional MRI and structural MRI as tools for understanding comorbid conditions in children with epilepsy. Epilepsy Behav 2013;26:295–302. [30] Bechtel N, Kobel M, Penner IK, Specht K, Klarhofer M, Scheffler K, et al. Attentiondeficit/hyperactivity disorder in childhood epilepsy: a neuropsychological and functional imaging study. Epilepsia 2012;53:325–33. [31] Pardoe HR, Berg AT, Archer JS, Fulbright RK, Jackson GD. A neurodevelopmental basis for BECTS: evidence from structural MRI. Epilepsy Res 2013;105:133–9. [32] Besseling RM, Jansen JF, Overvliet GM, van der Kruijs SJ, Ebus SC, de Louw A, et al. Reduced structural connectivity between sensorimotor and language areas in rolandic epilepsy. PLoS One 2013;8:e83568. [33] Wallace SJ, Cull AM. Long-term psychological outlook for children whose first fit occurs with fever. Dev Med Child Neurol 1979;21:28–40. [34] Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med 1998;338:1723–8. [35] Ellenberg JH, Nelson KB. Febrile seizures and later intellectual performance. Arch Neurol 1978;35:17–21. [36] Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from birth. I — Prevalence and recurrence in the first five years of life. Br Med J 1985;290:1307–10. [37] Fonseca LC, Tedrus GM, Pacheco EM. Epileptiform EEG discharges in benign childhood epilepsy with centrotemporal spikes: reactivity and transitory cognitive impairment. Epilepsy Behav 2007;11:65–70. [38] Hommet C, Billard C, Motte J, Passage GD, Perrier D, Gillet P, et al. Cognitive function in adolescents and young adults in complete remission from benign childhood epilepsy with centro-temporal spikes. Epileptic Disord 2001;3:207–16. [39] Monjauze C, Broadbent H, Boyd SG, Neville BG, Baldeweg T. Language deficits and altered hemispheric lateralization in young people in remission from BECTS. Epilepsia 2011;52:e79–83. [40] Klenberg L, Korkman M, Lahti-Nuuttila P. Differential development of attention and executive functions in 3-to 12-year-old Finnish children. Dev Neuropsychol 2001;20:407–28. [41] Baglietto MG, Battaglia FM, Nobili L, Tortorelli S, De Negri E, Calevo MG, et al. Neuropsychological disorders related to interictal epileptic discharges during sleep in benign epilepsy of childhood with centrotemporal or rolandic spikes. Dev Med Child Neurol 2001;43:407–12. [42] Dalessandro P, Piccirilli M, Tiacci C, Ibba A, Maiotti M, Sciarma T, et al. Neuropsychological features of benign partial epilepsy in children. Ital J Neurol Sci 1990;11:265–9. [43] Bedoin N, Ciumas C, Lopez C, Redsand G, Herbillon V, Laurent A, et al. Disengagement and inhibition of visual-spatial attention are differently impaired in children with rolandic epilepsy and Panayiotopoulos syndrome. Epilepsy Behav 2012;25: 81–91. [44] Massa R, de Saint-Martin A, Carcangiu R, Rudolf G, Seegmuller C, Kleitz C, et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology 2001;57:1071–9. [45] Nicolai J, Aldenkamp AP, Huizenga JR, Teune LK, Brouwer OF. Cognitive side effects of valproic acid-induced hyperammonemia in children with epilepsy. J Clin Psychopharmacol 2007;27:221–4. [46] Sanchez-Carpintero R, Neville BG. Attentional ability in children with epilepsy. Epilepsia 2003;44:1340–9.
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Attention-deficit/hyperactivity disorder and attention impairment in children with benign childhood epilepsy with centrotemporal spikes Eun-Hee Kim a, Mi-Sun Yum a, Hyo-Won Kim b, Tae-Sung Ko a,⁎ a b
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Psychiatry, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 15 February 2014 Revised 25 May 2014 Accepted 27 May 2014 Available online 27 June 2014 Keywords: Benign childhood epilepsy with centrotemporal spikes Benign rolandic epilepsy Attention-deficit/hyperactivity disorder Attention impairment
a b s t r a c t Attention-deficit/hyperactivity disorder (ADHD) is a common comorbidity in children with epilepsy and has a negative impact on behavior and learning. The purposes of this study were to quantify the prevalence of ADHD in benign childhood epilepsy with centrotemporal spikes (BCECTS) and to identify clinical factors that affect ADHD or attention impairment in patients with BCECTS. The medical records of 74 children (44 males) with neuropsychological examination from a total of 198 children diagnosed with BCECTS at Asan Medical Center were retrospectively reviewed. Electroclinical factors were compared across patients with ADHD and those without ADHD. Mean T-scores of the continuous performance test were compared across patients grouped according to various epilepsy characteristics. Forty-eight (64.9%) patients had ADHD. A history of febrile convulsion was more common in patients with ADHD than in patients without ADHD (p = 0.049). Bilateral centrotemporal spikes on electroencephalogram were more common in patients receiving ADHD medication than in patients with untreated ADHD (p = 0.004). Male patients, patients with frequent seizures prior to diagnosis, and patients with a high spike index (≥40/min) on sleep EEG at diagnosis had significantly lower visual selective attention (p b 0.05). Children with BCECTS had a high prevalence of ADHD, and frequent seizures or interictal epileptiform abnormalities were closely related to impairment of visual selective attention in children with BCECTS, indicating the need for ADHD or attention impairment screening in children with BCECTS. © 2014 Elsevier Inc. All rights reserved.
1. Introduction The prevalence of behavioral and cognitive problems such as attention-deficit/hyperactivity disorder (ADHD) is higher in children with epilepsy than in children with other chronic illnesses and children in the general population [1,2]. Inattention and hyperactivity are the most common clinical complaints of children presenting with epileptic epilepsy syndromes [2,3]. Attention deficits in children with epilepsy are influenced by multiple factors, including the neurological and seizure status, medication, and various environmental factors. Impaired attention and concentration negatively impact learning and mental development [4,5]; therefore, early diagnosis and appropriate treatments of attention problems in children with epilepsy are very important. Benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy, is the most common childhood epilepsy syndrome and accounts for 15–25% of epilepsy diagnoses in children
⁎ Corresponding author at: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea. Tel.: +82 2 3010 3381; fax: +82 2 3010 3725. E-mail address: [email protected] (T.-S. Ko).
http://dx.doi.org/10.1016/j.yebeh.2014.05.030 1525-5050/© 2014 Elsevier Inc. All rights reserved.
younger than 15 years of age [6]. Benign childhood epilepsy with centrotemporal spikes classically occurs in neurologically and cognitively healthy children, and the presentation is usually a nocturnal partial seizure with a typical electroencephalogram (EEG) that shows centrotemporal spikes (CTSs) [6]. Although BCECTS is considered a benign form of childhood epilepsy, formal neuropsychological evaluations have revealed a higher prevalence of cognitive impairment in children with BCECTS than in healthy sex- and age-matched children [7]. In the last two decades, a wide spectrum of neuropsychological and learning disabilities such as speech and language disorders, reading disabilities, attention impairment, visuomotor and behavior impairments, and psychiatric problems including aggression and oppositional behavior have been reported in children with BCECTS [8–12]. Attention-deficit/hyperactivity disorder is also considered as a comorbidity associated with BCECTS by interference, based on some studies [13–15]. However, the incidence of ADHD in BCECTS and the causes of this comorbidity remain unclear. Besides, it is uncertain which epilepsy characteristics (seizure frequency, epileptic discharges, or age at seizure onset) cause the negative neuropsychological consequences that impact attention. The purposes of the present study were to quantify the prevalence of ADHD in children with BCECTS and to evaluate the associations
E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58
between epilepsy factors and ADHD/attention impairment in patients with BCECTS. 2. Materials and methods 2.1. Participants One hundred and ninety-eight children were diagnosed with BCECTS at Asan Medical Center Children's Hospital from 2007 to 2012 and followed for at least 1 year after diagnosis. The clinical diagnosis of BCECTS was confirmed by pediatric neurologists according to the International League Against Epilepsy classification. The following exclusion criteria were applied: (1) age younger than 2 years or older than 16 years at diagnosis; (2) diagnosis of any epilepsy other than BCECTS; (3) any brain magnetic resonance imaging abnormality that could affect the diagnosis of BCECTS; (4) any accompanying neurologic disorder such as cerebral palsy, neurometabolic disease, or mental retardation (intelligence quotient b 70); and (5) follow-up duration for less than 1 year after diagnosis. Among the 198 children, however, 124 children were not enrolled in this study as their parents refused a neuropsychological assessment for the reasons of negative attitude or unrecognized necessity. In the end, 74 children who received a neuropsychological examination by neuropsychologists were eligible for the study and formed the study sample. 2.2. EEG recordings Electroencephalogram recordings were obtained before the initiation of antiepileptic drug (AED) treatment. All subjects underwent EEG recording during wakefulness and/or sleep. At least 30 min of digital recording were obtained using the international 10–20 system for electrode placement. Routine activation procedures including hyperventilation, eye closure, and photic stimulation were performed if possible. Sleep EEGs were recorded until induction of stage II sleep was confirmed by the technician. Sleep EEGs were obtained from 71 patients among the 74 patients. All EEG records were evaluated by three board-licensed pediatric neurologists (TS Ko, MS Yum, and EH Kim). The number of CTSs was manually counted, and the amplitude of the most active individual epileptic spike on visual inspection was measured. The spike index (number of spikes per minute) during wakefulness and sleep was calculated, and spikes with amplitude ≥ 200 μV were defined as high-amplitude spikes. 2.3. Evaluation of attention impairment Selective and sustained attention impairments were evaluated using a computerized continuous performance test (CPT) [16]. The Korean version of the CPT has been standardized, and its validity and reliability have been established [17]. The four variables quantified were omission errors (failure to respond to the target), commission errors (erroneously responding to a nontarget), response times (RTs) for a correct target, and the standard deviation (SD) of the RTs. Only 49 patients could perform the CPT before receiving the ADHD medication, and the attention score was presented with T-scores adjusted for age. A T-score of 65 (1.5 SD above the mean) or greater was taken as indicative of attention impairment. These results of the CPT were not directly used to diagnose ADHD or assess ADHD severity. 2.4. Procedures All data were retrospectively retrieved from electronic medical records. The clinical variables recorded were age at the onset of seizures, history of febrile convulsions, family history of epilepsy, seizure type, seizure frequency in the year prior to diagnosis, number of AEDs, response to first AED, duration of medical therapy, duration of followup, the control of seizures at follow-up (complete or incomplete),
55
and the presence or absence of ADHD and comorbidities such as tic disorder, oppositional or conduct disorder, anxiety, depression, and learning disabilities. Attention-deficit/hyperactivity disorder was clinically diagnosed by a pediatric psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria of ADHD: the diagnosis of ADHD was made if more than six out of nine symptoms of inattention or hyperactivity–impulsivity had persisted for at least six months, using the questionnaire of ADHD symptoms for parents. 2.5. Data analysis All statistical analyses were performed using SPSS statistical software, version 18.0 (SPSS, Inc., Chicago, IL). Clinical and EEG variables were compared across patients with BCECTS with ADHD and patients with BCECTS without ADHD and across patients with BCECTS with treated ADHD and patients with BCECTS with untreated ADHD using independent t-tests for continuous variables and χ2 and Fisher's exact tests for categorical variables. The CPT outcomes (T-scores for omission errors, commission errors, RTs, and RT SD) were compared across sex, seizure onset age (b7 or ≥ 7 years), number of seizures in the year prior to diagnosis (b 4 or ≥ 4), seizure control at follow-up, responses to monotherapy, CTS amplitude (b200 or ≥200 μV), unilateral or bilateral CTSs, a spike index during wakefulness (b10 or ≥10/min), and a spike index during sleep (b40 or ≥40/min) using independent t-tests. A p b 0.05 was considered statistically significant. 3. Results 3.1. Characteristics of patients with BCECTS The clinical characteristics of the 74 children with BCECTS are shown in Table 1. The mean age was 10.9 (range = 6.5–16.5) years. The mean duration of follow-up was 3.0 (range = 1.0–6.2) years. At final followup, 69 (93.2%) patients were being treated with AEDs: 54 patients were being treated with monotherapy, and 15 patients were being treated with polytherapy. The mean duration of medication was 2.3 (range = 0.2–6.5) years. The most common AED was oxcarbazepine (n = 52, 75.4%), followed by lamotrigine (n = 13, 18.8%). Of the 74 patients with BCECTS, 48 (64.9%) were diagnosed with ADHD. Additional comorbid neuropsychiatric problems were present in 15 (20.3%) patients: tic disorder, n = 7; oppositional defiant disorder or conduct disorder, n = 4; anxiety disorder, n = 2; depressive disorder, n = 1; language disability, n = 1; and adjustment disorder, n = 1. Electroencephalogram background rhythm was normal for age in all patients. The EEG findings are shown in Table 2. 3.2. Association between ADHD and electroclinical characteristics in patients with BCECTS Clinical characteristics and EEG findings were compared between patients with ADHD and those without ADHD (Tables 1 and 2). The history of febrile convulsions was the only factor that was significantly different between groups (p = 0.049; Table 1). Of the 48 patients diagnosed with BCECTS and comorbid ADHD, 14 (29.2%) received pharmacotherapy for ADHD (methylphenidate, n = 8 and atomoxetine, n = 6). On the assumption that patients with severe ADHD received pharmacologic treatment, we compared the clinical characteristics and EEG findings across patients with BCECTS with treated comorbid ADHD and patients with BCECTS with untreated comorbid ADHD. Bilateral CTSs were more frequent in treated patients than in untreated patients (p = 0.004), but all other clinical variables were similar in the two groups (Table 3).
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E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58
Table 1 Clinical characteristics of 74 children with BCECTS and the comparison of clinical characteristics between patients with ADHD and those without ADHD.
Males, n (%) Age at seizure onset, years Mean ± SD (range) b7 years, n (%) ≥7 years, n (%) Frequency of seizure Mean ± SD, times/year (range) b4/year, n (%) ≥4/year, n (%) Secondarily generalized seizure, n (%) History of febrile convulsions, n (%) Family history of epilepsy, n (%) Number of AEDs Mean ± SD (range) Failure of monotherapy, n (%) Duration of AED use, years Mean ± SD (range) Control of seizure, n (%) Complete Not complete Coexisting neuropsychiatric problems, n (%)
All patients n = 74
With ADHD n = 48
Without ADHD n = 26
p-Value
44
31 (64.5)
13 (50)
0.223
7.4 ± 1.9 (3.3–11.6) 30 44
7.3 ± 1.9 (3.7–10.9) 22 (45.8) 26 (54.2)
7.7 ± 2.1 (3.3–11.6) 8 (30.8) 18 (69.2)
0.376 0.208
2.1 ± 1.5 (1–10) 66 8 60 11 4
2.2 ± 1.7 (1–10) 42 (87.5) 6 (12.5) 38 (79.2) 10 (20.8) 2 (4.2)
2.1 ± 0.9 (1–4) 24 (92.3) 2 (7.7) 22 (84.6) 1 (3.8) 2 (7.7)
0.642 0.525
1.1 ± 0.5 (0–3) 14
1.2 ± 0.5 (0–3) 10 (20.8)
1.1 ± 0.5 (0–3) 4 (15.4)
0.700 0.568
2.3 ± 1.6 (0.2–6.5)
2.2 ± 1.7 (0.2–6.5)
2.6 ± 1.6 (0.2–5.3)
0.138
42 32 15
24 (50.0) 24 (50.0) 9 (18.8)
18 (69.2) 8 (30.8) 6 (23.1)
0.111
0.049⁎ 0.522
0.960
Abbreviations: BCECTS: benign childhood epilepsy with centrotemporal spikes, ADHD: attention-deficit/hyperactivity disorder, AED: antiepileptic drug.
3.3. Association between attention and electroclinical characteristics in patients with BCECTS Among 49 patients who performed the CPT, thirty patients performed the CPT while taking AEDs (oxcarbazepine, n = 23; lamotrigine, n = 4; topiramate, n = 3; and levetiracetam, n = 2), and one patient performed the CPT before the diagnosis of BCECTS. The mean T-score for commission errors in visual selection was higher in males than in females (p = 0.04) and higher in patients with a higher spike index (≥ 40/min) on sleep EEG than in patients with a lower spike index (p = 0.04). The mean T-score for omission errors in visual selection was higher in children with ≥4 seizures in the year prior to diagnosis than in patients with b 4 seizures (p = 0.01). The mean T-score for all four outcome variables (omission errors, commission errors, RTs, and RT SD) for auditory selection was within the normal range (T-score b 65) and did not differ according to demographic or clinical factors. The proportion of patients demonstrating suspicious (T-score between 60 and 65) or significant (T-score over 65) impairment of attention in the CPT was highest in omission errors in visual selection (Table S1). Also, when comparing between patients with ADHD and
those without ADHD, the rate of patients with relevant T-score for attention impairment was significantly higher in the domain of omission errors in visual selection (p = 0.002). 4. Discussion It is generally thought that long-term seizure and developmental outcomes in BCECTS are good [18]. However, recent studies have raised the issue of subtle neurocognitive deficits, reading disability, speech sound disorder, and behavioral comorbidities in patients with BCECTS. Inattention and hyperactivity are common behavioral problems in children with BCECTS [19–23], and there is growing interest in the clinical diagnosis of ADHD in children with BCECTS. Nevertheless, few studies have described the comorbidity of BCECTS and ADHD/attention problems in children with BCECTS. In the present study, 64.9% of the 74 children with BCECTS had ADHD. This is much higher than the reported prevalence of ADHD in otherwise healthy school children (3–5%) and children with epilepsy (8–33%) [2]. The high prevalence of ADHD in the current study cohort may have been affected by selection bias, as all patients were recruited
Table 2 EEG findings of 74 children with BCECTS and the comparison of EEG findings between patients with ADHD and those without ADHD.
Number of spike discharges, n (%) During wakefulness (n = 68) ≥10/min b10/min During sleep, stages I–II (n = 71) ≥40/min b40/min Amplitude of spike discharge, n (%) ≥200 μV b200 μV Laterality of spike discharges, n (%) Unilateral [right:left] Bilateral Other epileptiform discharges, n (%) Focal Generalized
All patients n = 74
With ADHD n = 48
Without ADHD n = 26
20 48
12 (27.9) 31 (72.1)
8 (32.0) 17 (68.0)
29 42
19 (40.4) 28 (59.6)
10 (41.7) 14 (58.3)
29 45
22 (45.8) 26 (54.2)
7 (26.9) 19 (73.1)
47 [22:25] 27
29 [15:14] (60.4) 19 (39.6)
18 [7:11] (69.2) 8 (30.8)
2 10
2 (22.2) 7 (77.8)
0 (0.0) 3 (100.0)
p-Value
0.575
0.503
0.112
0.452
Abbreviations: BCECTS: benign childhood epilepsy with centrotemporal spikes, ADHD: attention-deficit/hyperactivity disorder.
0.573 0.715
E.-H. Kim et al. / Epilepsy & Behavior 37 (2014) 54–58 Table 3 Comparison of clinical characteristics between patients with BCECTS with stimulanttreated ADHD and patients with BCECTS with untreated ADHD.
Male, n (%) Age at seizure onset, years Mean ± SD (range) b7 years, n (%) ≥7 years, n (%) Frequency of seizures b4/year, n (%) ≥4/year, n (%) Laterality of spike discharges, n (%) Unilateral [right:left] Bilateral Number of AEDs Mean ± SD (range) Duration of AEDs, years Mean ± SD, year (range) Failure of monotherapy, n (%) Coexisting neuropsychiatric problems, n (%)
Stimulant-treated ADHD n = 14
Untreated ADHD n = 34
p-Value
9 (64.3)
22 (34.7)
0.978
7.1 ± 2.2 (3.7–10.5) 7.3 ± 1.6 (4.1–10.9) 0.714 8 (57.1) 14 (41.2) 0.313 6 (42.9) 20 (58.8) 0.810 12 (85.7) 30 (88.2) 2 (14.3) 4 (11.8) 0.004⁎ 4 [1:3] (28.6) 10 (71.4)
25 [14:11] (73.5) 9 (26.5)
1.3 ± 0.6 (1–3)
1.1 ± 0.5 (0–2)
0.349
1.9 ± 1.2 (0.2–4.0) 3 (21.4) 4 (28.6)
2.0 ± 1.6 (0.2–5.4) 7 (20.6) 6 (17.6)
0.793 0.948 0.263
Abbreviations: ADHD: attention-deficit/hyperactivity disorder, BCECTS: benign childhood epilepsy with centrotemporal spikes, AED: antiepileptic drug.
from a tertiary referral center, and parent participation in psychiatric evaluation may have been biased by a negative attitude to psychiatric care. In neuropsychological examination, the lack of structural interview or rating scales may also cause the overestimation of ADHD. However, the large difference in the current study reflects a significant difference in the incidence of ADHD in patients with BCECTS as compared with the general population. Many studies have suggested various pathogenetic mechanisms of ADHD including a common genetic predisposition or biochemical factors in children with epilepsy [14,15]. The higher striatal glutamate concentration in children with ADHD [24] and synaptic abnormality in excitatory glutamatergic transmission in animal models of ADHD may also explain the vulnerability of children with ADHD to epilepsy [25–27]. Several recent studies have proposed possible common pathophysiology between ADHD and epilepsy in the context of brain development [28,29]. A volume-based or functional imaging study also supports the common neurofunctional pathophysiology in abnormal brain development of ADHD and BCECTS [3,30–32]. To better understand the relation between ADHD and BCECTS, we analyzed three aspects of the association between comorbid ADHD and attention impairment in children with BCECTS: 1) the association between epilepsy characteristics and the presence of ADHD, 2) the association between epilepsy characteristics and ADHD severity, and 3) the association between epilepsy characteristics and attention impairment. We found that the presence of ADHD was not associated with other epilepsy characteristics but was associated with a history of febrile convulsion, suggesting that febrile convulsions may influence the incidence of ADHD in BCECTS. This is in line with a previous study that reported relatively high rates of mental retardation, behavioral disturbance, and academic difficulties in children with febrile convulsion [33]. However, the cognitive and behavioral outcomes of febrile convulsion have long been a subject of controversy, and recent population-based studies have demonstrated comparable intelligence and academic performance in children with febrile convulsion and in healthy controls [34–36]. Further study is needed to examine the effect of febrile convulsion on cognition. To determine the association between epilepsy characteristics and ADHD severity, we compared variables across patients with BCECTS with ADHD who were receiving stimulant treatment and patients with BCECTS with ADHD who were not receiving stimulant treatment. We found that bilateral CTSs on initial EEG were significantly more
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frequent in patients with treated ADHD. Neurocognitive deficit in epilepsy has been considered to be a chronic consequence of repetitive spikes inhibiting the same cortical area over a period of many years, leading to delayed or incomplete maturation of the brain [37–39]. Perhaps, left-lateralized language and auditory processing and typically right-lateralized sustained attention are both disrupted by bilateral CTSs, and these combined deficits produce more severe ADHD symptoms. The impact of epilepsy on attention is complex and various epilepsyrelated factors and psychosocial factors have been postulated to be responsible for the high prevalence of attention impairment in children with BCECTS [2]. Several studies suggest a link between attention function and age at the onset of epilepsy [40], the frequency of spikes on the EEG recording [41], or laterality of interictal epileptiform abnormalities [42,43]. In this study, we found that male patients, patients with more frequent seizures before diagnosis, and patients with high CTS frequency on sleep EEG had poor visual selection attention. These findings suggest that frequent ictal or interictal electrical activity in BCECTS interferes with visual attention rather than auditory attention and support a study showing that children with BCECTS had greater susceptibility to distracters in their visual field compared with healthy children or children affected by idiopathic generalized epilepsies [44]. Although the pathophysiology of attention impairment in children with BCECTS is still unknown, the overlap between neural circuitry for attention and the networks involved in the generation of rolandic seizures [31,32,45,46] may be the basis for this association. There are several limitations to this study: the selection bias involved in recruiting patients from a single tertiary center, the intersubject variability in the time interval between the diagnosis of BCECTS and the attention test, and the underestimation of influence of AEDs on neurocognitive results. The limited measure of attention is another weakness. The CPT used in this study is an effective measure of selective attention, sustained attention, or vigilance but cannot evaluate other executive function. Children with BCECTS had a high prevalence of ADHD. A history of febrile convulsions was associated with the presence of ADHD. Male gender, frequent seizures, and interictal abnormalities were related to attention impairments, indicating the need for accurate neuropsychological assessment and proper management of ADHD or attention impairment in children with BCECTS to offset possible learning difficulties and improve the long-term prognosis and quality of life of children with BCECTS. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.yebeh.2014.05.030. Conflict of interest All authors disclose that they have no conflicts of interest. References [1] Dunn DW, Austin JK. Behavioral issues in pediatric epilepsy. Neurology 1999;53: S96–S100. [2] Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003;45:50–4. [3] Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J, et al. The frequency, complications and aetiology of ADHD in new onset paediatric epilepsy. Brain 2007;130: 3135–48. [4] Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and behavioral performance: a prospective longitudinal study. Epilepsia 2000;41:426–31. [5] Bulteau C, Jambaque I, Viguier D, Kieffer V, Dellatolas G, Dulac O. Epileptic syndromes, cognitive assessment and school placement: a study of 251 children. Dev Med Child Neurol 2000;42:319–27. [6] Engel J, Pedley TA. Epilepsy: a comprehensive textbook. 2nd ed. Philadelphia, Pa; London: Wolters Kluwer/Lippincott Williams & Wilkins; 2008. [7] Cerminara C, D'Agati E, Lange KW, Kaunzinger I, Tucha O, Parisi P, et al. Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention: a matched control study. Epilepsy Behav 2010;19:69–77. [8] Deonna T, Zesiger P, Davidoff V, Maeder M, Mayor C, Roulet E. Benign partial epilepsy of childhood: a longitudinal neuropsychological and EEG study of cognitive function. Dev Med Child Neurol 2000;42:595–603.
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