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1 Seizure 19 (2010) Contents lists available at ScienceDirect Seizure journal homepage: Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood Petra M.C. Callenbach a, *, Paul A.D. Bouma b, Ada T. Geerts c, Willem Frans M. Arts d, Hans Stroink e, Els A.J. Peeters f,g, Cees A. van Donselaar h, A.C. Boudewijn Peters i, Oebele F. Brouwer a a Department of Neurology, University Medical Centre Groningen, University of Groningen, P.O. Box , 9700 RB Groningen, The Netherlands b Department of Neurology, Tergooi Hospital, P.O. Box , 1201 DA Hilversum, The Netherlands c Department of Neurology, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands d Department of Paediatric Neurology, Erasmus University Medical Centre, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands e Department of Neurology, Canisius-Wilhelmina Hospital, P.O. Box 9015, 6500 GS Nijmegen, The Netherlands f Department of Neurology, Juliana Children s Hospital, P.O. Box , 2506 LP The Hague, The Netherlands g Department of Neurology, Westeinde Hospital, P.O. Box 432, 2501 CK The Hague, The Netherlands h Department of Neurology, Medical Centre Rijnmond-South, P.O. Box 9119, 3007 AC Rotterdam, The Netherlands i Cuycklaan 16, 2343 AJ Oegstgeest (formerly: Department of Paediatric Neurology, University Medical Centre Utrecht, Utrecht), The Netherlands ARTICLE INFO ABSTRACT Article history: Received 22 February 2010 Received in revised form 10 June 2010 Accepted 9 July 2010 Keywords: Benign childhood epilepsy with centrotemporal spikes BECTS Outcome Long-term follow-up Purpose: To determine long-term outcome in a cohort of children with newly diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS). Methods: 29 children with BECTS were included in the Dutch Study of Epilepsy in Childhood. Each child was followed for 5 years, and subsequently contacted years after enrolment to complete a structured questionnaire. Twenty children had typical BECTS, nine had atypical BECTS (age at onset <4 years, developmental delay or learning difficulties at inclusion, other seizure types, atypical EEG abnormalities). Results: Mean age at onset of epilepsy was 8.0 years with slight male preponderance. Most common seizure-types before enrolment were generalized tonic clonic seizures (GTCS) and simple partial seizures; in 86% of the children seizures occurred during sleep. After years, 96% had a terminal remission (TR F ) of more than 5 years and 89% of more than 10 years. Mean duration of epilepsy was 2.7 years; mean age at reaching TR F was 10.6 years. Many children (63%) had experienced one or more (secondary) GTCS. Antiepileptic drugs were used by 79% of the children with a mean duration of 3.0 years. None of the children seemed to have developed learning problems or an arrest of cognitive development during follow-up. No significant differences were observed in patient characteristics or outcome between children with typical BECTS and children with atypical BECTS. Conclusions: All children in our cohort, both those with typical and atypical BECTS, had a very good prognosis with high remission rates after years. None of the predictive factors for disease course and outcome observed in earlier studies (other seizure types, age at onset, multiple seizures at onset) were prognostic in our cohort. ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. 1. Introduction Benign childhood epilepsy with centrotemporal spikes (BECTS, benign rolandic epilepsy) is the most common partial epilepsy syndrome in childhood, with male predominance. It is characterized by brief, simple, orofacial partial seizures (paresthesias and tonic or clonic activity of the lower face, often spreading to the ipsilateral arm, associated with drooling and anarthria), often * Corresponding author. Tel.: ; fax: address: p.m.c.tijink@neuro.umcg.nl (Petra M.C. Callenbach). occurring during sleep or upon awakening. 1,2 Frequently, patients have additional motor and/or sensory symptoms with or without secondary generalization. The interictal EEG shows blunt highvoltage centrotemporal spikes, often followed by slow waves that are activated by sleep and tend to shift from side to side, but other brain regions may also be involved. The age at onset ranges from 1 to 14 years (peak at 7 10 years) and complete remission of seizures occurs before the age of 18 years in most patients. Patients with BECTS may, however, develop behavioural or cognitive problems, which are reversible in most of them. 3 9 Furthermore, atypical features such as status epilepticus, developmental delay, daytime-only seizures, screaming as a seizure component, and /$ see front matter ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi: /j.seizure

2 502 P.M.C. Callenbach et al. / Seizure 19 (2010) postictal Todd s paresis may occur In some children, BECTS may evolve into epilepsy with continuous spike-waves during slow-wave sleep (CSWS)/electrical status epilepticus during slow sleep (ESES) syndrome, atypical benign focal epilepsy of childhood (ABFEC) or Landau Kleffner syndrome, all with severe neuropsychological impairments. 2,14,15 A meta-analysis we performed some years ago on the clinical course of typical BECTS confirmed its favourable outcome. 16 The syndrome is strongly age-dependent: at the age of 18 years, 99.8% of the patients had entered remission, the last seizure occurring at age 13 in most patients. The mean duration of the active seizure disorder could not be calculated precisely in this meta-analysis, but was shown to be less than 3 years in most children. From the meta-analysis it seemed that a younger age at onset may be associated with a longer duration of the active disease period, and patients with multiple seizures in the first month after onset may have significantly longer active disease periods than patients who have isolated ones, but the studies analyzed did not present enough data to draw definite conclusions. Several studies have been performed afterwards observing high remission rates as well. 4,11,13,17 23 Most of them, however, had a retrospective design. We here present a prospective study, with a long follow-up durationof years, in29childrenwithnewlydiagnosedbects included in the Dutch Study of Epilepsy in Childhood (DSEC). We determined long-term outcome both in children with typical BECTS based on the criteria of the International League Against Epilepsy and in children with atypical BECTS on basis of seizure semiology or EEG characteristics. Aim ofour study was todetermine whether prognosis in children with BECTS, diagnosed shortly after onset, is indeed as good as described and whether outcome differs between children with typical BECTS and atypical BECTS. Furthermore, we compared the results from our cohort with the earlier findings from the metaanalysis and from studies performed afterwards. 2. Methods 2.1. Patients The paediatric neurology departments of two university hospitals, one children s hospital and one general hospital participated in the DSEC. Between August 1, 1988 and August 1, 1992, all children aged 1 month to and including 15 years presenting with two or more newly diagnosed unprovoked seizures or a status epilepticus were enrolled in the Prognosis study (n = 494 of whom 28 were excluded from analyses for several reasons). 24 Detailed inand exclusion criteria and study procedures have been presented elsewhere It has been estimated that the recruitment of this study was close to 75% of the expected number of children younger than 16 years with newly diagnosed epilepsy in this area and that the population was representative for the general population under the age of 16 years with epilepsy. 24 This study was approved by the medical ethical boards of all participating hospitals. All parents or caregivers gave informed consent Follow-up Each child was followed with regular intervals for 5 years. After 5 years, follow-up was continued in those who were still being treated with medication or who needed medical attention. Furthermore, all children were contacted between January 2004 and January 2006 (12 17 years after enrolment) by regular mail or phone to complete a structured questionnaire about the date of their last seizure, the use of AEDs, their education, and their general health at that time-point Syndrome classification At enrolment, a committee of three paediatric neurologists who were involved in the study classified all epilepsies according to the classification of the epilepsies of Gastaut and Zifkin. 28 Two years after enrolment or 2 years after starting medication, all epilepsies were classified according to the 1989 classification of epilepsies and epileptic syndromes of the International League against Epilepsy. 1 For this particular study, 31 children with BECTS according to one or both classifications were selected from the original cohort of 466 children. Twenty children fulfilled the criteria of typical BECTS (clinical and EEG characteristics both typical for BECTS). Nine children were classified as having atypical BECTS. Three had atypical clinical features such as age at onset before 4 years (n =1) or associated developmental delay or learning difficulties at inclusion (n = 2). Five children had atypical EEG abnormalities, such as frontal and temporal epileptiform abnormalities and generalized waves (n = 1), multifocal epileptiform abnormalities (n = 1), midtemporal and generalized epileptiform abnormalities (n = 1), multifocal spikes and generalized spike-wave complexes (n = 1), and generalized spike-wave complexes in one EEG and no abnormalities in other EEGs (n = 1). Of one child seizures occurred during sleep and were not witnessed, but postictal signs and EEG characteristics were compatible with BECTS. One child was originally classified as having BECTS with typical EEG abnormalities, but with symptomatology (paleness, unresponsiveness and jerks in his arms, age at onset before 4 years) resembling clinical features of Panayiotopoulos syndrome. He was therefore excluded from the analysis. One other child had atonic seizures of 5 45 min with auditory symptoms, speech arrest and drooling, and on the EEG a subclinical status epilepticus with left centrotemporal spikes and bilateral synchronous spike-waves. Since both clinical characteristics and EEG abnormalities were atypical, this child was excluded from the analysis as well Statistical analyses All analyses were performed using SPSS Comparisons between the group with typical BECTS and the group with atypical BECTS were made with chi-square tests (sex, seizure type, moment of seizures, compliance, and occurrence of (secondary) generalized tonic clonic seizures (GTCS)); t-tests (age at onset, number of seizures before enrolment, terminal remission (time from the last seizure to the moment of evaluation) after 5 years follow-up (TR 5 ), total number of seizures at 5 years, number of used AEDs, age at start AED, duration of AED use, age at stop AED, follow-up duration, terminal remission at final follow-up (TR F ), age at reaching terminal remission, and total duration of epilepsy); and Mann Whitney nonparametric tests (number of failed withdrawals, number of relapses, and time between becoming seizure-free (SF) and first relapse). Nonparametric correlation analysis (Spearman) was performed between the total number of seizures and TR 5. The number of seizures before the start of AEDs was compared between seizure types with ANOVA and t-tests. 3. Results Mean age at onset of epilepsy was 8.0 years and there was slight male preponderance (Table 1). None of the children had a positive family history for epilepsy; one child had a history of febrile seizures before the onset of BECTS. The most common seizuretypes before enrolment were GTCS and simple partial seizures. Most children (93.1%) had had less than five seizures at that time, and in the majority of children seizures occurred during sleep (Table 1). In 26 children a CT scan was made, showing no abnormalities in any of them.

3 P.M.C. Callenbach et al. / Seizure 19 (2010) Table 1 Patient characteristics and use of AEDs during the first 5 years of follow-up. Typical BECTS (n = 20) Atypical BECTS (n = 9) p-value Total (n = 29) Male (%) 10 (50.0) 6 (66.7) (55.2) Age at onset (years) (range; SD) 8.4 ( ; 1.9) 7.1 ( ; 2.3) ( ; 2.1) Seizure-type before enrolment SP 6 (30.0) 3 (33.3) 9 (31.0) CP 1 (5.0) 1 (3.5) GTC 10 (50.0) 1 (11.1) 11 (37.9) P + (S)G 3 (15.0) 4 (44.4) 7 (24.1) Unclear 1 (11.1) 1 (3.5) Number of seizures before enrolment (range; SD) 2.4 (1 6; 1.4) 2.6 (1 6; 1.7) (1 6; 1.5) Timing of seizures During sleep or on awakening 13 (65.0) 6 (66.7) 19 (65.5) Awake 3 (15.0) 1 (11.1) 4 (13.8) Both during sleep and awake 4 (20.0) 2 (22.2) 6 (20.7) Age at start AED (years) (range; SD) 9.2 ( ; 1.6) 7.4 ( ; 2.5) ( ; 2.0) Duration of AED use (years) (range; SD) 2.4 ( ; 1.5) 3.6 ( ; 1.0) ( ; 1.5) Total number of seizures at 5 years (45.0) 4 (44.4) 13 (44.8) (45.0) 4 (44.4) 13 (44.8) >50 2 (10.0) 1 (11.1) 3 (10.4) TR 5 (years) (range; SD) 4.0 ( ; 1.0) 3.3 ( ; 1.1) ( ; 1.1) AED = antiepileptic drug, BECTS = benign epilepsy with centrotemporal spikes; for criteria for typical and atypical BECTS see text, CP = complex partial, GTC = generalized tonic clonic, P + (S)G = partial and (secondary) generalized, SD = standard deviation, SP = simple partial, TR 5 = terminal remission at 5 years (defined as the time from the last seizure to the moment of evaluation). After 5 years of follow-up, all children had been seizure-free for at least 1 year (Table 1). A significant negative correlation was observed between the total number of seizures and TR 5 (p < 0.001). No significant differences were observed in patient characteristics or the outcome after 5 years between the 20 children with typical BECTS and the nine children with atypical BECTS (Table 1; some data not shown) Antiepileptic drugs During follow-up, 23 children (79.3%) had used antiepileptic drugs (AEDs). All but one of these children initially used carbamazepine; the other child used valproic acid. In six of the children with carbamazepine this was changed to valproic acid (n = 4) or oxcarbazepine (n = 2) because of side-effects (n = 4) or inefficacy (n = 2). Two children had had polytherapy at a certain time point. AEDs were started after a median of three seizures (range 2 12; SD 2.9). Patients who presented with generalized seizures (with or without partial seizures) were treated with AEDs after significantly less seizures (mean 3.1; range 2 6; SD 1.2) than patients who only had partial seizures (mean 6.9; range 3 12; SD 3.6) (p = 0.02). Compliance was good in 82.6%. Six children (26% of the treated patients) had one or more failures to AED withdrawal. Three children used AEDs at the end of the 5-year follow-up period; in all of them AEDs were successfully withdrawn within the next 6 months afterwards. Children with atypical BECTS started AEDs at a significantly lower age than children with typical BECTS (Table 1). No other significant differences were observed between the group with typical BECTS and the group with atypical BECTS in AED use, failed withdrawals or compliance (data not shown) Final follow-up Twenty-seven children (90%) completed the structured questionnaire after a mean follow-up duration of 14.9 years. Most patients (96.3%) had a TR F of at least 5 years and 88.9% of even more Table 2 Final follow-up. Typical BECTS (n = 18) Atypical BECTS (n = 9) p-value Total (n = 27) Mean follow-up duration (years) (range; SD) 14.9 ( ; 1.2) 14.9 ( ; 1.2) ( ; 1.2) TR F (years) (range; SD) 13.2 ( ; 2.7) 11.8 ( ; 4.4) ( ; 3.3) Mean age at reaching TR F (years) (range; SD) 10.6 ( ; 2.8) 10.6 ( ; 4.3) ( ; 3.3) Total duration of epilepsy (years) (range; SD) 2.3 ( ; 3.1) 3.5 ( ; 4.8) ( ; 3.7) (Secondary) GTCS (%) 12 (66.7) 5 (55.6) (63.0) Relapse after being SF >6 months (%) 9 (50.0) 6 (66.7) (55.6) Seizure-type of relapse (% of group with relapse) SP 4 (44.4) 3 (50.0) 7 (46.7) CP 1 (11.1) 1 (6.7) GTC 2 (22.2) 1 (16.7) 3 (20.0) SP with SG 2 (22.2) 1 (16.7) 3 (20.0) Unclear 1 (16.7) 1 (6.7) Duration of AED use (years) (range; SD) 2.7 ( ; 2.0) 3.6 ( ; 1.1) ( ; 1.8) Age at stop AED (years) (range; SD) 12.0 ( ; 2.7) 11.0 ( ; 2.7) ( ; 2.7) AED = antiepileptic drug, BECTS=benign epilepsy with centrotemporal spikes; for criteria for typical and atypical BECTS see text, CP=complex partial, GTC=generalized tonic clonic, GTCS =the occurrence of one or more generalized tonic-clonic seizures before enrolment or during the follow-up period, SD=standard deviation, SF=seizure-free, SP = simple partial, SP with SG = simple partial with secondary generalization, TR F = final terminal remission (defined as the time from the last seizure to the end of follow-up).

4 504 P.M.C. Callenbach et al. / Seizure 19 (2010) Fig. 1. Period between first (") and last (b) seizure and between begin (&) and end () of AED use of the patients who were followed during the complete follow-up period of years (n = 27). T = children with typical BECTS (n = 18), A = children with atypical BECTS (n = 9, for criteria see text). than 10 years; one patient had a TR F of half a year (Table 2). Mean interval from first to last seizure was 2.7 years. Fig. 1 displays the age at onset, age at last seizure, and age at start and withdrawal of AEDs of the patients who were followed during the complete follow-up period. Most common age at onset was between 6 and 10 years; final remission was most frequently reached between 8 and 11 years. Two patients had a last seizure after the age of 13 years. One person had been seizure-free for 13 years when he experienced an isolated seizure at the age of 20 years (details are missing). This is the person with a TR F of half a year. One other person had three short seizures (about 8 s) in 1 day at the age of 18 years with aura during which he was unable to do anything (details are missing), after being seizurefree for 7 years. Since details of the last seizure of these patients are missing, we do not know whether they were typical for BECTS. The seizures these two children experienced during the 5-year follow-up period were typical for BECTS. Fifteen children had one or more relapses after having been seizure-free for at least 6 months (Table 2). Again, the most common seizure types were simple partial seizures and GTCS. None of the children was using AEDs at the end of the extended follow-up. The mean duration of AED use was 3.0 years and the mean age at the time of AED withdrawal was 11.7 years. Based on answers to questions about their education and career, it appeared that none of the children had any arrest of cognitive development during follow-up. Twelve children (44%) (had) followed (pre-)university or higher vocational education, ten (37%) intermediate vocational education. Overall, general health was good at the end of follow-up. No significant differences in final outcome were observed between the group with typical BECTS and the group with atypical BECTS (Table 2 and data not shown). 4. Discussion Our cohort of children with BECTS is representative for all children with BECTS suffering at least two seizures. Onset was between 2.5 and 11.4 years with a peak between 6 and 10 years. Most seizures occurred during sleep or on awakening. This is identical to what has been described earlier. 1,2,16,29 The prognosis in our children was very good, both in children with typical BECTS and with atypical BECTS, with almost 90% being seizure-free for more than 10 years after a mean follow-up of 15 years, and a mean duration of epilepsy of 2.7 years. Many children (63%) experienced one or more GTCS. Epilepsy in none of the children evolved to Landau Kleffner syndrome, epilepsy with CSWS or ESES syndrome, and none of the children seems to have developed learning problems. Since our meta-analysis in 1997, several other studies on outcome of BECTS have been published (Table 3). 4,11,13,17 23 Most studies had a retrospective design and described outcome at a certain time-point instead of after a certain follow-up period. This may have caused a selection bias with e.g. exclusion of children who had BECTS at onset but had an evolution into a BECTS-related disorder with a worse prognosis. The two studies with prospective design had no fixed follow-up duration: one followed patients until 6 months after full normalization of the EEG, 4 the other had a follow-up of at least eight years (actual duration of follow-up was not mentioned). 11 Some of the studies only included patients with typical BECTS, whereas other studies also included patients with atypical BECTS. Differentiating typical BECTS from variants remains problematic and as a consequence the definition of atypical BECTS varies considerably between studies. Massa et al. identified patients who developed social-familial problems as having atypical BECTS 4 ; Verrotti et al. placed patients with other seizure types, as described by Wirrell et al., in the atypical group 10,11 ; Tavares et al. included patients with other seizure types, seizures occurring exclusively during wakefulness, atypical EEG abnormalities or continuous spike-waves during sleep in the atypical group 22 ; and Datta and Sinclair categorized patients with onset of epilepsy before the age of 4 years, learning problems, abnormal neurological exam, other seizure types, and/or atypical EEG abnormalities as having atypical BECTS. 13 We used the same definition for atypical epilepsy as Datta and Sinclair. The different definitions between studies make comparisons for the atypical cases, however, difficult. Characteristics of the patients were quite similar in all studies, including ours: mean age at onset ranged from 5.5 to 8.8 years, there was slight male predominance in most studies, most seizures occurred during sleep or on awakening, total duration of active epilepsy was <1 3 years, and outcome was good with high remission rates (Table 3). Mean age at terminal remission was around 10 years in most studies. Cognitive or learning problems developed in % of the children studied. The proportion of patients with (secondary) GTCS differed considerably between studies (38 94%) as well as the number of patients treated with AEDs (36 89%). The occurrence of GTCS seems not to be correlated with the prescription of AEDs (Table 3). A possible explanation for the difference in number of treated patients may be that treatment regimens are different between countries. Some studies tried to identify predictive factors for outcome (Table 3). 4,11,13,19,21 None of these predictive factors (other seizure types, age at onset, multiple seizures at onset) seem to predict disease course and outcome in our cohort. There is a certain restriction to the analysis of factors indicative of a worse prognosis in a disorder that is characterized by an overall very good prognosis. Negative factors can only be explored on basis of individual variations in a cohort often without any bearing on overall statistics. Furthermore, the problem of evolution from typical BECTS to atypical BECTS or BECTS-related disorders with a worse prognosis is usually not analyzed. In contrast to findings from our meta-analysis on typical BECTS, 16 a younger age at onset was not associated with a longer duration of the active disease

5 P.M.C. Callenbach et al. / Seizure 19 (2010) Table 3 Studies on the course and prognosis of benign childhood epilepsy with centrotemporal spikes. Study Design FU (years) N Subjects Mean age at onset (years) (range; SD) Male (%) PFH (%) FS < BECTS (%) Single seizure (%) Sleep (%) Bouma et al. 16 M, R < ( ) Astradsson et al. 17 Po, R T 8.8 ( ) Peters et al. 18 Po, R 79 T 7.4 ( ) Massa et al. 4 H, P >6 months no EEG T T A a A62 Verrotti et al. 11 H, P >8 years T T A b A Kramer et al. 19 H, R 87 c T 8.1 (2 14;2.7) Al-Twaijri and Shevell 20 H, R 66 T 6.4 ( ) 48.5 Ma and Chan 21 H, R T 7 (3 13) Tavares et al. 22 H, R T T T 6.3 (2 11) A A d A 5.9 (2 10) Zhao et al. 23 H, R 276 T 5.5 (3 12) Datta and Sinclair 13 H, R T 6.5 (3 13) A e T 7.3 A 5.5 Current study H, P T 8.0 ( ;2.1) A e Study GTCS (%) AED (%) SF (%) SF% at age 18 years Mean age at TR (years) (range; SD) Duration of epilepsy (years) (range; SD) Cognitive problems f (%) Predictive factors for outcome Bouma et al ( ) (3 35) <3 None Astradsson et al (5 16) 1.9 ( ) Peters et al Massa et al T + A 10 2 T g EEG h A32 Verrotti et al < A: more learning and behavioural problems Kramer et al (6 17; 2.6) 2.0 (0 8; 2.2) Onset <3 years: more seizures Al-Twaijri and Shevell Ma and Chan < None Tavares et al T 7.7 (2 13) T 13.0 A 8.8 (4 16) A 11.1 Zhao et al (4 19) Datta and Sinclair T 62.1 T 9.3 T i A: seizures harder A 73.3 A 7.6 A 2.1 to control; identical outcome Current study (96.2 >1 year) ( ; 3.3) 2.7 (0 15.9; 3.7) 0.0 None >6 months no EEG =more than 6 months after full normalization of EEG, A = atypical BECTS, AED = antiepileptic drugs, BECTS = benign childhood epilepsy with centrotemporal spikes, EEG =electroencephalogram, FS = febrile seizures, FU = mean follow-up duration, GTCS = generalized tonic clonic seizures, H = hospital-based, M = meta-analysis, N = number, ND = not defined, P = prospective, PFH = positive family history for epilepsy, Po = population based, R = retrospective, SD = standard deviation, SF = seizure-free, sleep = percentage of children with seizures occurring only during sleep or on awakening, T = typical BECTS, TR = terminal remission. a Development of social-familial problems. b Other seizure types. c 30 patients in analysis of outcome parameters. d Other seizure types, seizures occurring exclusively during wakefulness, atypical EEG abnormalities or continuous spike-waves during sleep. e Age at onset <4 years, learning problems, abnormal neurological exam, other seizure types, atypical EEG abnormalities. f Developed during follow-up. g 17% of the other children already had cognitive problems at onset of epilepsy. h Intermittent slow-wave focus, multiple asynchronous spike-wave foci, long spike-wave clusters, generalized 3 Hz absence-like spike-wave discharges, conjunction of interictal paroxysms with negative or positive myoclonia, and abundance of interictal abnormalities during wakefulness and sleep were correlated with the development of problems with educational performance and familial maladjustment. i Not stated whether these were present at onset or developed afterwards. period, and patients with multiple seizures in the first month after onset did not have significantly longer active disease periods than patients who had isolated ones (data not shown). We realize that our cohort was quite small with 29 patients and that one or more of the described predictive factors for outcome could have been present without reaching significance levels. Furthermore, defining the occurrence of developmental or behavioural problems was not part of the original study design, making it impossible to state with certainty that these problems did indeed not occur in our cohort. Nicolai et al. described that cognitive problems were reversible in most children after becoming seizure-free. 6 Since most children in our cohort were seizurefree for more than 10 years at the end of follow-up, it is possible that if these problems had existed they had resolved at the time of last evaluation. In conclusion, long-term outcome was good in our cohort. Except for age at the start of AEDs, no significant differences were observed between children with typical BECTS and children with atypical BECTS. No predictive factors could be identified for the course of the epilepsy. Since our cohort is representative for the whole group of children with BECTS suffering at least two seizures and has a very long follow-up period, the results warrant the prediction of a favourable prognosis in children who are diagnosed of having BECTS. Acknowledgments The Dutch Study of Epilepsy in Childhood has financially been supported by grants from the Dutch National Epilepsy Fund (A72, A86 and 05-06).

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