Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention: A matched control study

Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention: A matched control study

Epilepsy & Behavior 19 (2010) 69–77 Contents lists available at ScienceDirect Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i ...

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Epilepsy & Behavior 19 (2010) 69–77

Contents lists available at ScienceDirect

Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention: A matched control study Caterina Cerminara a,⁎, Elisa D'Agati a, Klaus W. Lange b, Ivo Kaunzinger b, Oliver Tucha c, Pasquale Parisi d, Alberto Spalice e, Paolo Curatolo a a

Unit of Child Neurology and Psychiatry, Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy Department of Experimental Psychology, University of Regensburg, Regensburg, Germany Department of Psychology, University of Groningen, Groningen, The Netherlands d Pediatric Department, II Faculty of Medicine University of Rome La Sapienza, Rome, Italy e Pediatric Department, I Faculty of Medicine University of Rome La Sapienza, Rome, Italy b c

a r t i c l e

i n f o

Article history: Received 25 May 2010 Revised 7 July 2010 Accepted 7 July 2010 Available online 16 August 2010 Keywords: Benign childhood epilepsy with centrotemporal spikes Attention Spike index Electroencephalography

a b s t r a c t Although the high risk of cognitive impairments in benign childhood epilepsy with centrotemporal spikes (BCECTS) is now well established, there is no clear definition of a uniform neurocognitive profile. This study was based on a neuropsychological model of attention that assessed various components of attention in 21 children with BCECTS and 21 healthy children. All participants were tested with a computerized test battery using the multicomponent model of attention performance. In comparison with healthy participants, the children with BCECTS showed significant impairment in the measure of selectivity and in one measure of intensity of attention (arousal). Our results did not correlate with the electroclinical variables of age at onset of seizures and spike index on sleep EEGs. To the best of our knowledge, this is the first study in which the multicomponent model of attentional function has been used in children with BCECTS to provide a clearer neuropsychological profile of these patients. © 2010 Elsevier Inc. All rights reserved.

1. Introduction Benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy (BRE), is one of the most common childhood epilepsy syndromes and represents about 20% of epilepsy in children younger than 15 years of age [1–3]. Characteristically, the seizures begin between 3 and 10 years of age, with a peak at 7 to 8, and resolve by puberty. Although BCECTS is considered a benign form of childhood epilepsy that occurs in children who show normal mental development, the risk of cognitive impairment is higher when comparing the test performance of children with BCECTS with that of healthy sex- and age-matched children. In the last two decades, a wide spectrum of neuropsychological and learning disabilities, such as speech and sound disorders, reading disabilities, attention deficit, and visuomotor and behavior difficulties, have been reported in children with BCECTS [4]. The heterogeneity of neuropsychological deficits in children with this syndrome contributes to the confusion in this area, even though many studies have touched on this topic. The impact of epilepsy on cognitive function is complex, with many variables that can influence cognitive ability and interact, making it difficult to determine which factors contribute to ⁎ Corresponding author. Pediatric Neurology Unit, Department of Neuroscience, Tor Vergata University of Rome, Via Montpellier 1, 00133, Rome, Italy. Fax: 06-20900018. E-mail address: [email protected] (C. Cerminara). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.07.008

impairment. Cognition and attention are closely related, and the lack of a specific neuropsychological profile of children with BCECTS may be due to a confused definition of attention. Attentional functioning can be considered a building block for other more complex forms of cognitive activity. It might be better to consider attention as a construct of cognitive psychology rather than a cognitive function. Recent neuropsychological theories of attention include unitary concepts of attention within multidimensional models, with several distinct components of functions of attention [5]. In their multicomponent model of attention, Van Zomeren and Brouwer include the concept of alertness, subdivided into tonic and phasic alertness, vigilance/sustained attention, selective attention, divided attention, and strategy/flexibility [6]. Attention is impaired in many idiopathic and nonidiopathic types of epilepsy and is influenced by many different factors. A better definition of the epileptic syndromes could help in the choice of the best attentional model study, and this could contribute to define a neurocognitive related-syndrome profile. In our study, we used the multicomponent model of attention to demonstrate the existence of specific attentional dysfunctions in children with BCECTS. The high risk of cognitive impairment in BRE is now well established [7,8]. However, conflicting results and the heterogeneity of study parameters combine to form a inhomogeneous neuropsychological profile of children with BCECTS [9,10]. Children with BCECTS have sustained attention difficulties. Some authors have suggested that right-sided

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interictal epileptiform activity in children with BCECTS could interfere with right hemisphere activity including sustained attention [11,12]. Other studies on the impact of laterality of discharges on the type of cognitive deficits observed have often led to inconsistent results [13–15]. These children also show selective and divided attention difficulties if they have epileptiform discharges during sleep [16]. Several studies suggest a link between age at onset [17] of epilepsy and frequency of spikes on the EEG recording [18], which also appear to be two possible causal factors for attention deficits. Attention outcomes in BCECTS are important because an intact attention system permits the child to efficiently select and access sensory stimuli, information in his or her memory, or motor responses [19]. Our study was designed to assess several components of attention, as suggested by the multicomponent model, in children with BCECTS and healthy children using a computerized test battery for attention performance (TAP), which consists of a selective attention task, an impulsivity task, a task measuring focused attention, a measure of divided attention, two tests measuring arousal (tonic and phasic alertness), and a vigilance task [20]. The second goal was to determine whether some electroclinical variables, including age at onset of seizures and spike index on sleep EEGs, lead to different attention dysfunctions. 2. Methods 2.1. Participants One hundred twenty children with BCECTS were recruited from the Department of Child and Adolescent Neuropsychiatry of Tor Vergata University and from the Pediatric Department of the I Faculty of Medicine and II Faculty of Medicine of La Sapienza University in Rome. The diagnosis of BCECTS according to the ILAE classification, and based on clinical history and a recent EEG recording, was confirmed by neuropediatricians in all the pediatric neurology departments. Patients were selected on the basis of their age, diagnosis, intellectual function (IQ), and willingness to participate in the study. Children with BCECTS who were younger than 7 or older than 14 years of age, had an IQ below 85, had uncorrected hearing or visual impairments, or had psychiatric comorbidity were excluded from the study. Intellectual ability (IQ) was measured using the Wechsler Intelligence Scale for Children, Third Edition [21]. The IQ cutoff of 85 is 1 SD below the mean (mean IQ = 100) and was chosen to ensure that participants were able to understand the instructions for the TAP. Twenty-one children with BCECTS (12 boys, 9 girls) with a mean age of 9.86 ± 1.59 years were asked to complete a neuropsychological test battery (see Table 1). In addition, 21 healthy children who were matched to the children with BCECTS on the basis of age, sex, and handedness participated in this study. The healthy children, recruited in schools, were selected from a pool of subjects who voluntarily participated in the neuropsychological assessment. None of them had any history of neurological or psychiatric disease or displayed signs of BCECTS or learning disability. The diagnosis of Attention Deficit Hyperactivity Disorder according to DSM-IV-TR criteria was excluded Table 1 Characteristics of patients with rolandic epilepsy and matched healthy participants.

N (each group) Sex (F/M) Age (years)

Ro/Coa

Ro-EO/ Co-EO

Ro-LO/ Co-LO

Ro-HSI/ Co-HSI

Ro-LSI/ Co-LSI

21

9

12

11

9

9/12 9.86 ± 1.59b

3/6 9.22 ± 1.64

6/6 10.33 ± 1.43

6/5 9.45 ± 1.44

3/6 10.33 ± 1.80

Note. One patient was not classifiable on the basis of the EEG pattern. a Ro, patients with rolandic epilepsy; Co, healthy control participants; EO, early onset of seizures; LO, late onset of seizures; HSI, high spike index on sleep EEG; LSI, low spike index on sleep EEG. b Mean ± SD.

in all participants [22]. This exclusion was relevant to 36 children with BCECTS who had a diagnosis of ADHD at their evaluation for recruitment in the study. At the time of the study, no healthy participant was taking medication known to affect the central nervous system. Prior to the start of this study, all parents were informed of the aims and nature of the study and gave written consent. 2.2. Electroclinical aspects of children with BCECTS In 9 patients seizures first occurred between 3 and 7 years of age (early onset), and in 12, between 8 and 12 years of age (late onset). None of the children had frequent seizures, and no patients were taking antiepileptic drugs. The EEG background rhythm was always normal for age. EEG paroxysmal abnormalities (typically slow diphasic, high-voltage centrotemporal spikes) were unilateral in 11 children and bilateral in 10. One patient was not classifiable on the basis of the EEG pattern (see Table 1). Sleep EEGs typically showed activation of interictal epileptic discharges (IEDs). The index of IEDs was evaluated by counting visually and manually each single epileptic spike on the most active lead; the spike count was stored for consecutive 1-minute epochs in computer memory. The spike index (number of spikes in a stage/time spent in that stage) in total sleep time and individual sleep stage was calculated [23]. A marked activation of IEDs during a sleep recording was considered a high spike index (HSI) in patients with a spike index N10/minute and a low spike index (LSI) in patients with a spike index b5/minute. 2.3. Procedure All participants were tested with a computerized test battery that consisted of a selective attention task, an impulsivity task, a task measuring focused attention, a measure of divided attention, two tests measuring arousal, and a vigilance task. Although selective attention, impulsivity, focused attention, and divided attention are regarded as aspects of selectivity of attention, arousal and vigilance represent expressions of intensity of attention [20,24]. Test procedures were presented on a computer screen and instructions were given orally. Participants were instructed to perform the computerized tasks as quickly as possible but to maintain a high level of accuracy. In each test, reaction times for correct responses, variability in reaction time, number of omission errors (lack of response to target stimuli), and/or number of commission errors (responses to nontarget stimuli) were calculated. To familiarize the participants with the tasks, a brief sequence of practice trials preceded each test. Tests were performed only after participants had completed practice trials without errors. Participants were assessed individually in a quiet room, and the examiner was present during the entire assessment. In the alertness tasks, participants were asked to respond by pressing a button when a visual stimulus (a cross about 1.2 × 1.8 cm) appeared on a computer screen. A total of 40 trials were undertaken. In the first 20 trials, the stimulus appeared on the screen without prior warning (tonic alertness task), whereas during the second 20 trials, a warning tone preceded the appearance of the stimulus (phasic alertness task). The time span between the warning tone and the appearance of the stimulus was random (between 300 and 700 ms). Measures of tonic and phasic alertness were calculated on the basis of the reaction time of the participant [20,24]. In addition, variability in reaction time and number of omission errors were measured. In the vigilance task, a structure consisting of two rectangles (each about 1 × 2 cm) was presented in the center of the screen. One rectangle was situated on top of the other. These rectangles were alternately filled with a pattern (stimulus) for 500 ms with an interstimulus interval of 1000 ms. The duration of the test was 15 minutes. A total of 600 stimuli (changes in pattern location) were presented. The participants were requested to press the response button when there was no change in pattern location. The target rate (i.e., no change in pattern location) was

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about one target stimulus per minute for a total of about 18 targets. The intervals between target stimuli were irregular. Reaction time for correct responses, variability in reaction time, number of omission errors, and number of commission errors were calculated [20,24]. The task measured vigilance by requiring the participant to remain alert and ready to react to infrequently occurring target stimuli over a relatively long and unbroken period. The divided attention task requires participants to concentrate simultaneously on a visual task and an acoustic task presented on a computer. In the visual task, a series of matrices (about 9.5 × 11 cm) appeared in the center of the screen. Each matrix, consisting of a regular array of 16 dots and crosses (4 × 4), was displayed for 2000 ms. The subjects were asked to press the response button when the crosses formed the corners of a square (visual target). In the acoustic task, the participants were requested to listen to a continuous sequence of alternating high (2000 Hz) and low (1000 Hz) sounds and to press the response button when irregularities occurred in the sequence (acoustic target). A total of 100 visual and 200 acoustic stimuli were presented including 17 visual and 16 acoustic targets. Reaction time for correct responses, variability in reaction time, number of omission errors (lack of response to target stimuli), and number of commission errors (responses to nontarget stimuli) were calculated as a measure of divided attention [20,24]. The go/no go task consisted of five different patterns that were briefly presented on the computer screen one at a time. Two of these five patterns were defined as target stimuli. When one of these patterns appeared on the screen, the participant had to press a button. The task required participants to produce a simple motor response to specific cues while inhibiting the response in the presence of other cues. Reaction time, as well as numbers of right and wrong reactions, was measured. This task measured inhibition and impulsivity [24]. In the incompatibility task, arrows (about 1.4 cm wide and 3.8 cm long) pointing to the left or the right were presented briefly on the left or the right side of a fixation point in the center of the screen. The participants were requested to press a response button on the side indicated by the direction of the arrow, independently of the position of the arrow. If the arrow's position and its orientation matched, the trial was classified as compatible; if presentation and orientation did not coincide, the trial was classified as incompatible. There were a total of 57 trials. The sequence of trials was random, with about half of the trials compatible and half incompatible. Reaction time, variability in reaction time, and the number of commission errors were calculated, thereby providing a measure of selective attention as the capacity to reject irrelevant information [20,24]. In the visual scanning task, a series of 5×5 matrices (about 8.8× 8.8 cm) were presented in the center of the computer screen. Each matrix consisted of a regular pattern of 25 squares (each about 1.2×1.2 cm), each of which had an opening on one side (top, bottom, left or right side). A square with an opening at the top was defined as the critical stimulus. This occurred only once in a matrix and was randomly distributed across the matrix. The subject was asked to press the left response button when a matrix contained the critical stimulus or the right response button when the critical stimulus was not present. There were a total of 50 trials (25 critical and 25 noncritical trials). Reaction time for correct responses, variability in reaction time, number of omission errors, and number of commission errors were calculated. This task assessed inhibition or impulsivity as a measure of selective attention [20,24].

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computed [25]. Following Cohen's guidelines for interpreting effect sizes, negligible effects (d b 0.20), small effects (d N 0.20), medium effects (d N 0.50), and large effects (d N 0.8) were distinguished [26,27]. 3. Results 3.1. Comparisons between patient group and control group 3.1.1. Alertness The comparison between the patient and control groups using Wilcoxon tests revealed a significant difference with respect to reaction time (Z = –2.09, P = 0.037), but not in the number of omission errors (Z = –1.63, P = 0.102) in the tonic alertness task. The patient group differed from the control group in reaction time (Z = –2.56, P = 0.011), but not in the number of omission errors (Z = –1.00, P = 0.317) in the phasic alertness task. Analysis of effect sizes revealed small to negligible differences in reaction time and number of omission errors in the tonic alertness task, and small to medium effect size differences in reaction time and number of omission errors in the phasic alertness task (see Table 2).

3.1.2. Vigilance No significant differences between patients and healthy participants were observed in reaction time (Z = –0.07, P = 0.940), number of commission errors (Z = –1.05, P = 0.295), and number of omission errors (Z = –0.59, P = 0.554). Analysis of effect sizes revealed negligible to large effect sizes in reaction time, number of commission errors, and number of omission errors. 3.1.3. Divided attention In the divided attention task, the patient group made significantly more omission errors (Z = –2.06, P = 0.039) than healthy participants, whereas no significant differences were observed in reaction time (Z = –0.029, P = 0.768) and the number of commission errors (Z = –1.86, P = 0.063) between the patient and control groups. Analysis of the effect sizes revealed a medium effect size for the number of omission errors, and negligible to small effects in reaction time and number of commission errors.

3.1.4. Impulsivity In the go/no go task, the comparison between the patient and control groups revealed significant differences in reaction time (Z = –2.02, P = 0.044) and number of commission errors (Z = –2.24, P = 0.025). Furthermore, no significant differences were observed in number of omission errors (Z = –1.49, P = 0.137). Analysis of effect sizes revealed small to medium effect sizes for reaction time, number of commission errors, and number of omission errors.

3.1.5. Focused attention On the incompatibility task, the patient group made significantly more commission errors (Z = -2.68, P = 0.007) than healthy participants, whereas no significant differences were observed in reaction time (Z = –0.85, P = 0.394). The differences between the patient and control groups represented negligible or medium effects.

2.4. Data analysis Wilcoxon signed-rank tests for matched-pair samples were used for statistical analysis. Participants were matched with respect to sex and age. Independent samples were compared with Mann–WhitneyU tests. For statistical analysis, the α level was 0.05. All statistical analyses were carried out using SPSS Version 15. Furthermore, effect sizes for the differences between paired observations were

3.1.6. Selective attention In the visual scanning task, the patient group made significantly more commission errors (Z = –2.55, P = 0.011) and omission errors (Z = –2.77, P = 0.006) than the healthy participants. No significant differences were observed in reaction time (Z = –1.62, P = 0.106). The differences between the patient and control groups represented small or medium effect sizes.

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Table 2 Comparison of test performance between patients with rolandic epilepsy and control children. Children with rolandic epilepsy (N = 21) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorse Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focused attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e f

Healthy children (N = 21)

Za

P

db

377.57 ± 165.04c 0.19 ± 0.51

294.50 ± 37.80 0.00 ± 0.00

–2.09 –1.63

0.037d 0.102

0.49

360.71 ± 160.15 0.10 ± 0.30

274.67 ± 37.51 0.24 ± 0.54

–2.56 –1.00

0.011d 0.317

0.52 0.21

814.07 ± 165.03 10.19 ± 16.74 7.29 ± 4.65

833.88 ± 129.13 6.29 ± 6.24 6.48 ± 3.96

–0.07 –1.05 –0.59

0.940 0.295 0.554

0.09 0.23 0.12

824.95 ± 96.06 5.62 ± 6.61 7.43 ± 4.17

811.26 ± 57.59 3.10 ± 3.90 5.00 ± 3.54

–0.29 –1.86 –2.06

0.768 0.063 0.039

0.12 0.41 0.56

748.10 ± 244.99 2.90 ± 3.56 1.95 ± 4.40

657.24 ± 67.14 0.81 ± 1.17 0.14 ± 0.36

–2.02 –2.24 –1.49

0.044 0.025 0.137

581.26 ± 302.48 15.90 ± 10.59

562.29 ± 100.73 6.14 ± 6.15

–0.85 –2.68

0.394 0.007

3582.38 ± 2251.70 1.52 ± 2.36 8.48 ± 4.52

4356.57 ± 1639.45 0.14 ± 0.36 4.67 ± 2.97

–1.62 –2.55 –2.77

0.106 0.011 0.006

d

d d

d

d d

f

0.41 0.54 0.40 0.06 0.77 0.31 0.57 0.69

Z value, Wilcoxon test. Effect size index according to Cohen [25]. Mean ± SD. P b 0.05. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated because of missing correlation coefficient.

3.2. Comparisons between patients with early-onset and late-onset seizures

3.6. Comparison between patients with high spike index and healthy children

The comparison, using Mann–Whitney U tests, between patient groups, based on the onset of seizures, revealed no significant differences in any of the test measures of attention used in this study (see Table 3).

The comparison between patients with HSI and controls revealed significant differences in the number of omission errors (Z = –2.14, P = 0.032) in the visual scanning task and in the number of commission errors in the incompatibility task (Z = –2.50, P = 0.013), with a medium effect size (see Table 7).

3.3. Comparison between patients with early onset of seizures and healthy children The comparison between patients with early onset of seizures and the control group revealed a significant difference only in the number of omission errors (Z = –2.02, P = 0.044) in the visual scanning task, with a medium effect size (see Table 4). 3.4. Comparison between patients with late onset of seizures and healthy participants

3.7. Comparison between patients with low spike index and healthy participants The patient group made significantly more omission errors on the divided attention task (Z = –2.26, P = 0.024) and the visual scanning task (Z = –2.08, P = 0.037) than healthy participants. The differences between the patient and control groups represented medium effect sizes (see Table 8). 4. Discussion

The patient group made significantly more commission errors in the divided attention task (Z = –2.99, P = 0.003), go/no go task (Z = –2.77, P = 0.006), and visual scanning task (Z = –2.05, P = 0.041) than healthy participants. There was also a significant difference in reaction time in the go/no go task (Z = –2.67, P = 0.008). The differences between the patient and control groups represented medium effect sizes (see Table 5). 3.5. Comparisons between patients with low and high spike indexes Comparison between the patient groups on the basis of spike index, using Mann–Whitney U tests, revealed no significant differences in any of the test measures of attention used in this study (see Table 6).

Recent developments in research on cognitive abilities in BCECTS support the view that children with BCECTS show deficient performance in various neuropsychological areas, without a definition of a uniform profile [28]. Cognitive impairment in BRE is now well established. However, evidence regarding impairment of the attentional system in BCECTS appears to be less conclusive. Danielsson and Petermann could not find a single pattern of dysfunction or a typical profile or any significant differences in attention tests in patients with BCECTS [29]. Chaix et al. did not find attention impairments in patients with BCECTS [30]. Furthermore, they evaluated sustained and selective attention without a complete test battery or a specific model of attentional functions.

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Table 3 Comparison of test performance between patients with rolandic epilepsy with early onset of seizures and those with late onset of seizures. Children with rolandic epilepsy with early onset (N = 9) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focussed attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e

Children with rolandic epilepsy with late onset (N = 12)

Za

P

db

348.39 ± 57.60c 0.22 ± 0.67

399.46 ± 214.21 0.17 ± 0.39

–0.57 –0.23

0.602 0.917

0.33 0.09

325.22 ± 51.80 0.00 ± 0.00

387.33 ± 207.07 0.17 ± 0.39

–0.25 –1.26

0.808 0.554

0.41

887.50 ± 155.48 8.89 ± 5.01 7.44 ± 4.00

754.00 ± 153.57 11.17 ± 22.11 7.17 ± 5.25

–1.71 –1.28 –0.36

0.095 0.219 0.754

0.86 0.14 0.06

811.56 ± 72.34 5.22 ± 6.04 7.67 ± 3.12

835.00 ± 112.75 5.92 ± 7.27 7.25 ± 4.94

–0.43 –0.39 –0.39

0.702 0.702 0.702

0.25 0.10 0.10

676.72 ± 76.85 1.11 ± 0.93 0.00 ± 0.00

801.62 ± 312.31 4.25 ± 4.22 3.42 ± 5.45

–0.96 –1.68 –2.14

0.345 0.111 0.111

0.55 1.03

524.17 ± 131.38 15.33 ± 12.52

624.08 ± 386.18 16.33 ± 9.45

–0.28 –0.07

0.808 0.972

0.35 0.09

3927.00 ± 2075.59 1.44 ± 2.45 8.78 ± 4.55

3323.92 ± 2432.14 1.58 ± 2.39 8.25 ± 4.69

–0.99 –0.23 –0.39

0.345 0.862 0.702

0.27 0.06 0.11

e

e

Z value, Mann–Whitney U test for independent samples. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated because of missing correlation coefficient.

Table 4 Comparison of test performance between patients with rolandic epilepsy with early onset of seizures and age- and sex-matched control children. Children with rolandic epilepsy with early onset (N = 9) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focused attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e f

Healthy children (N = 9)

Za

P

Db

348.39 ± 57.60c 0.22 ± 0.67

287.89 ± 43.60 0.00 ± 0.00

–1.96 –1.00

0.051 0.317

0.87

325.22 ± 51.80 0.00 ± 0.00

268.61 ± 47.00 0.33 ± 0.71

–1.84 –1.34

0.066 0.180

0.71

887.50 ± 155.48 8.89 ± 5.01 7.44 ± 4.00

766.67 ± 125.12 5.11 ± 4.70 9.00 ± 3.16

–1.84 –1.54 –0.89

0.066 0.123 0.374

0.75 0.47 0.27

811.56 ± 72.34 5.22 ± 6.04 7.67 ± 3.12

825.22 ± 63.57 4.44 ± 5.17 5.67 ± 4.27

–0.77 0.00 –1.20

0.441 1.00 0.231

0.19 0.09 0.42

676.72 ± 76.85 1.11 ± 0.93 0.00 ± 0.00

667.83 ± 66.22 1.44 ± 1.42 0.22 ± 0.44

–0.30 –0.53 –1.41

0.767 0.595 0.157

0.09 0.20

524.17 ± 131.38 15.33 ± 12.52

596.44 ± 132.62 5.22 ± 2.54

–1.01 –1.78

0.314 0.075

0.31 0.79

3927.00 ± 2075.59 1.44 ± 2.45 8.78 ± 4.55

4657.83 ± 2113.37 0.11 ± 0.33 4.56 ± 2.01

–0.41 –1.51 –2.02

0.678 0.131 0.044f

0.29 0.52 0.84

Z value, Wilcoxon test. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated due to missing correlation coefficient. P b 0.05.

e

e

e

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Table 5 Comparison of test performance between patients with rolandic epilepsy with late onset of seizures and age- and sex-matched control children. Children with rolandic epilepsy with late onset (N = 12) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focussed attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e f

Healthy children (N = 12)

Za

P

Db

399.46 ± 214.21c 0.17 ± 0.39

299.46 ± 33.95 0.00 ± 0.00

–1.02 –1.41

0.308 0.157

0.47

387.33 ± 207.07 0.17 ± 0.39

279.21 ± 30.00 0.17 ± 0.39

–1.73 0.00

0.084 1.00

0.52 0.00

754.00 ± 153.57 11.17 ± 22.11 7.17 ± 5.25

884.29 ± 111.64 7.17 ± 7.26 4.58 ± 3.48

–1.78 –0.18 –1.26

0.075 0.859 0.209

0.65 0.20 0.38

835.00 ± 112.75 5.92 ± 7.27 7.25 ± 4.94

800.79 ± 53.03 2.08 ± 2.35 4.50 ± 2.97

–0.86 –2.99 –1.70

0.388 0.003f 0.090

0.26 0.70 0.66

801.62 ± 312.31 4.25 ± 4.22 3.42 ± 5.45

649.29 ± 69.61 0.33 ± 0.65 0.08 ± 0.29

–2.67 –2.77 –1.89

0.008f 0.006f 0.058

0.57 0.94 0.60

624.08 ± 386.18 16.33 ± 9.45

536.67 ± 63.14 6.83 ± 7.93

–0.31 –1.89

0.754 0.059

0.22 0.71

3323.92 ± 2432.14 1.58 ± 2.39 8.25 ± 4.69

4130.62 ± 1228.29 0.17 ± 0.39 4.75 ± 3.62

–1.73 –2.05 –1.89

0.084 0.041f 0.059

0.32 0.59 0.57

e

Z value, Wilcoxon test. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated due to missing correlation coefficient. P b 0.05.

Table 6 Comparison of test performance between patients with rolandic epilepsy with a low spike index (LSI) and patients with rolandic epilepsy with a high spike index (HSI). Children with rolandic epilepsy with LSI (N = 9) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focussed attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d

Children with rolandic epilepsy with HSI (N = 11)

Za

P

Db

346.33 ± 83.88c 0.33 ± 0.71

408.32 ± 215.87 0.09 ± 0.30

–0.42 –0.86

0.710 0.603

0.38 0.44

325.56 ± 95.13 0.11 ± 0.33

389.00 ± 205.09 0.09 ± 0.30

–0.68 –0.15

0.503 0.941

0.40 0.06

769.28 ± 160.04 8.00 ± 6.96 6.89 ± 5.16

859.25 ± 173.76 12.18 ± 22.64 8.18 ± 4.12

–0.57 –0.34 –0.65

0.604 0.766 0.552

0.54 0.25 0.28

792.56 ± 112.31 4.11 ± 4.86 6.56 ± 4.56

852.82 ± 80.88 7.00 ± 8.01 8.18 ± 4.09

–0.95 –0.68 –0.95

0.370 0.503 0.370

0.62 0.44 0.37

686.72 ± 86.13 2.56 ± 2.92 1.44 ± 2.96

811.68 ± 322.65 3.45 ± 4.16 2.55 ± 5.54

–1.48 –0.43 –0.35

0.152 0.710 0.824

0.53 0.25 0.25

497.11 ± 76.40 13.67 ± 10.28

651.04 ± 408.15 18.73 ± 10.70

–0.34 –0.87

0.766 0.412

0.52 0.48

2798.94 ± 1962.55 1.11 ± 1.45 7.00 ± 3.16

4222.77 ± 2460.80 2.00 ± 2.97 10.09 ± 5.11

–1.78 –0.08 –1.49

0.080 0.941 0.152

0.64 0.38 0.73

Z value, Mann–Whitney U test for independent samples. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli.

C. Cerminara et al. / Epilepsy & Behavior 19 (2010) 69–77

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Table 7 Comparison of test performance between patients with rolandic epilepsy with a high spike index and age- and sex-matched control children. Children with rolandic epilepsy with HSI (N = 11) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focused attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e f

Healthy children (N = 11)

Za

P

Db

408.32 ± 215.87c 0.09 ± 0.30

301.41 ± 26.66 0.00 ± 0.00

–1.38 –1.00

0.168 0.317

0.49

389.00 ± 205.09 0.09 ± 0.30

283.00 ± 28.54 0.27 ± 0.65

–1.60 –0.82

0.110 0.414

0.50 0.24

859.25 ± 173.76 12.18 ± 22.64 8.18 ± 4.12

860.91 ± 103.16 7.82 ± 7.59 6.36 ± 3.85

–0.15 –0.26 –0.98

0.878 0.797 0.327

0.01 0.18 0.30

852.82 ± 80.88 7.00 ± 8.01 8.18 ± 4.09

812.86 ± 65.43 4.55 ± 4.76 6.09 ± 4.46

–0.98 –0.89 –1.11

0.328 0.373 0.265

0.44 0.30 0.40

811.68 ± 322.65 3.45 ± 4.16 2.55 ± 5.54

671.73 ± 72.06 1.00 ± 1.48 0.18 ± 0.40

–1.38 –1.49 –0.96

0.168 0.137 0.336

0.46 0.53 0.42

651.04 ± 408.15 18.73 ± 10.70

563.27 ± 90.66 4.91 ± 2.51

–0.27 –2.50

0.790 0.013f

0.20 1.23

–1.16 –1.90 –2.14

0.248 0.058 0.032f

0.23 0.62 0.80

Za

P

Db

4222.77 ± 2460.80 2.00 ± 2.97 10.09 ± 5.11

5113.68 ± 1754.53 0.09 ± 0.30 4.82 ± 3.09

e

Z value, Wilcoxon test. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated due to missing correlation coefficient. P b 0.05.

Table 8 Comparison of test performance between patients with rolandic epilepsy with a low spike index (LSI) and age- and sex-matched control children. Children with rolandic epilepsy with LSI (N = 9) Intensity of attention Tonic arousal (tonic alertness task) Reaction time (ms) Number of omission errorsd Phasic arousal (phasic alertness task) Reaction time (ms) Number of omission errors Vigilance (vigilance task) Reaction time (ms) Number of commission errors Number of omission errors Selectivity of attention Divided attention (divided attention task) Reaction time (ms) Number of commission errors Number of omission errors Impulsivity (go/no go task) Reaction time (ms) Number of commission errors Number of omission errors Focused attention (incompatibility task) Reaction time (ms) Number of commission errors Selective attention (visual scanning task) Reaction time (ms) Number of commission errors Number of omission errors a b c d e f

Healthy children (N = 9)

346.33 ± 83.88c 0.33 ± 0.71

287.67 ± 50.39 0.00 ± 0.00

–1.24 –1.34

0.214 0.180

0.59

325.56 ± 95.13 0.11 ± 0.33

264.83 ± 47.90 0.22 ± 0.44

–1.72 –0.58

0.086 0.564

0.61 0.18

769.28 ± 160.04 8.00 ± 6.96 6.89 ± 5.16

820.17 ± 152.93 4.89 ± 4.20 6.44 ± 4.50

–0.30 –1.12 –0.30

0.767 0.261 0.767

0.18 0.42 0.07

792.56 ± 112.31 4.11 ± 4.86 6.56 ± 4.56

806.78 ± 53.39 1.56 ± 1.88 3.44 ± 1.24

–0.30 –1.77 –2.26

0.767 0.076 0.024f

0.18 0.57 0.82

686.72 ± 86.13 2.56 ± 2.92 1.44 ± 2.96

641.61 ± 64.59 0.67 ± 0.71 0.11 ± 0.33

–1.72 –1.71 –1.07

0.086 0.088 0.285

0.51 0.59 0.44

497.11 ± 76.40 13.67 ± 10.28

547.17 ± 113.47 8.00 ± 8.92

–0.89 –1.26

0.374 0.208

0.33 0.43

2798.94 ± 1962.55 1.11 ± 1.45 7.00 ± 3.16

3435.44 ± 1062.36 0.22 ± 0.44 4.22 ± 3.03

–1.01 –1.72 –2.08

0.314 0.084 0.037f

0.30 0.60 0.85

Z value, Wilcoxon test. Effect size index according to Cohen [25]. Mean ± SD. Commission errors are responses to nontarget stimuli; omission errors are failures to respond to target stimuli. Effect size could not be calculated due to missing correlation coefficient. P b 0.05.

e

76

C. Cerminara et al. / Epilepsy & Behavior 19 (2010) 69–77

Recent neuropsychological theories of attention include unitary concepts of attention within multidimensional models, with several distinct components or functions of attention. On the basis of the multicomponent model of Posner and colleagues [31,32], who included selective attention, arousal, and vigilance as components of attention in their model, Van Zomeren and Brouwer delineated a theoretical framework of attentional functions [6]. Our study is the first in which this model has been used in children with BCECTS. In accordance with the new multicomponent model of attention of Van Zomeren and Brouwer the participants were tested with a computerized test battery for attention performance, which consisted of a selective attention task, an impulsivity task, a task measuring focused attention, a measure of divided attention, two tests measuring arousal, and a vigilance task [6]. Although tonic alertness refers to a relatively stable level of attention that changes slowly with diurnal physiological variations of the organism, phasic alertness is the ability to enhance the activation level following a stimulus of high priority. The ability to sustain attention enables a subject to direct attention to one or more sources of information over a relatively long and unbroken period. Vigilance is the ability to maintain attention over a prolonged period during which infrequent response-demanding events occur. Selective attention is defined as the ability to focus attention in the face of distracting or competing stimuli. Divided attention requires a simultaneous response to multiple tasks or multiple task demands. Although selective attention, impulsivity, focused attention, and divided attention are regarded as aspects of selectivity of attention, arousal and vigilance represent expressions of intensity of attention [6]. Our study analyzed various components of attention in 21 children with BCECTS and 21 healthy children. Some epilepsy-related variables that could have an impact on attentional functioning, such as age at onset of epilepsy and the spike index, were also evaluated. The results of this study clearly indicate impairment in selectivity (impulsivity, focused attention, selective attention, aspects of divided attention) and in one measure of intensity (arousal) of attention in children with rolandic epilepsy. The other measure of intensity of attention (vigilance) showed no impairment in the patients with BCECTS. These results did not correlate with the electroclinical variables of age at onset of seizures and spike index on sleep EEGs. Few studies have evaluated the impact of age at onset of seizures on the development of attentional processes. The results of the study of Deltour et al. suggest the presence of short-term memory or attentional capacity limitation, regardless of the modality, in children with earlier onset of seizures [13]. According to our results, age at onset of seizures does not appear to influence the development of other executive and attentional processes. Other studies have demonstrated a correlation between the frequency of epileptiform discharges on waking and/or sleep EEGs and cognitive difficulties [14,16,18,33]. Conversely, we found no correlation between the results of the tests we used and the sleeping spike rate. Our data demonstrate that EEG centrotemporal spikes during sleep are not sufficient to impair attention. Similarly, Titomanlio et al. compared 16 children aged 10–16 years in remission from BCECTS with control children, using computerized tasks. Patients made significantly more errors than controls on the double-choice reaction time task, which suggests that some subtle cognitive deficits could therefore persist over time despite normalization of electroclinical performance [34]. Finally, one difficulty in assessing studies of attention may be confusion over the definition of attention. It is not clear in some studies of attention and BCECTS if attention is being evaluated, or whether the existence of attention deficit hyperactivity disorder (ADHD) is being evaluated. The diagnosis of ADHD according to DSMIV-TR [22] criteria was excluded in all of our study participants. The distinction between these two conditions is important. Recent findings in attention research in children and adults, using functional magnetic resonance imaging (fMRI) and an attention network test,

demonstrate that the impairments associated with attention are localized in distinct brain networks and are probably not associated with ADHD [35]. However, these distinctions are only now becoming appreciated, and confusion between the two disorders remains in the literature. In conclusion, our data confirm an impact of BCECTS on attentional ability. In our children with BCECTS, the impairment in the selectivity of attention seems to be due to the impulsivity of these subjects; in fact, they make more commission errors than healthy children. In the alertness tasks, a measure of arousal, our patients show slow reaction time compared with controls. Prospective studies looking systematically at the different aspects of attention in its modalities are needed, because often the quality of study design and the extreme variation of methodology strongly contribute to the lack of a clear and specific neuropsychological profile in children with BCECTS. References [1] Dalla Bernardina B, Sgro V, Fejerman N. Epilepsy with centro-temporal spikes and related syndromes. In: Roger J, Bureau M, Dravet Ch, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 4th ed. Montrouge: John Libbey Eurotext; 2005. [2] Fejerman N. Benign childhood epilepsy with centrotemporal spikes. In: Fejerman N, Caraballo RH, editors. Epilepsy: a comprehensive textbook. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2008. [3] Watanabe K. Benign partial epilepsies. In: Wallace SJ, Farrell K, editors. Epilepsy in children. 2nd ed. London: Edward Arnold; 2004. [4] Giordani B, Caveney AF, Laughrin D, et al. Cognition and behavior in children with benign epilepsy with centrotemporal spikes (BECTS). Epilepsy Res 2006;70: 89–94. [5] Mirsky AF, Anthony BJ, Duncan CC, Ahearn MB, Kellam SG. Analysis of the elements of attention: a neuropsychological approach. Neuropsychol Rev 1991;2: 109–45. [6] Van Zomeren AH, Brouwer WH. Clinical neuropsychology of attention. New York: Oxford Univ. Press; 1994. [7] Clarke T, Strug LJ, Murphy PL, et al. High risk of reading disability and speech sound disorder in rolandic epilepsy families: case–control study. Epilepsia 2007;48: 2258–65. [8] 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. [9] Chalmers I, Altman DG. Systematic reviews. London: BMJ Publ. Group; 1995. [10] Glaszious P, Irwing L, Bain C, Colditz G. Systematic review in health care: a practical guide. Cambridge: Cambridge Univ. Press; 2001. [11] D'Alessandro P, Piccirilli M, Tiacci, et al. Neuropsychological features of benign partial epilepsy in children. It J Neurol Sci 1990;11:265–9. [12] Piccirilli M, D'Alessandro P, Sciarma T, et al. Attention problems in epilepsy: possible significance of the epileptogenic focus. Epilepsia 1994;35:1091–6. [13] Deltour L, Quaglino V, Barathon M, De Broca A, Berquin P. Clinical evaluation of attentional processes in children with benign childhood epilepsy with centrotemporal spikes (BCECTS). Epileptic Disord 2007;9:424–31. [14] Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures. Dev Med Child Neurol 1997;39:646–51. [15] Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language profile of children with benign rolandic epilepsy. Epilepsia 2005;46:924–30. [16] Sanchez-Carpintero R, Neville BG. Attentional ability in children with epilepsy. Epilepsia 2003;44:1340–9. [17] 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. [18] Baglietto MG, Battaglia FM, Nobili L, 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. [19] Posner MI, Dehaene S. Attentional networks. Trends Neurosci 1994;17:75–9. [20] Zimmermann P, Fimm B. A test battery for attentional performance. In: Leclercq M, Zimmermann P, editors. Applied neuropsychology of attention: theory, diagnosis and rehabilitation. New York: Psychology Press; 2002. [21] Wechsler D. Wechsler Intelligence Scale for Children. 3rd ed. San Antonio: Psychological Corp; 2006. [22] Diagnostic and statistical manual of mental disorders. 4th ed. text rev. Washington: APA; 2000. [23] Nobili L, Ferrillo F, Baglietto MG, et al. Relationship of sleep interictal epileptiform discharges to sigma activity (12–16 Hz) in benign epilepsy of childhood with rolandic spikes. Clin Neurophysiol 1999;110:39–46. [24] Zimmermann P, Fimm B. Testbatterie zur Aufmerksamkeitsprüfung (TAP) [A computerized neuropsychological assessment of attention deficits]. Leipzig: Thieme; 1993.

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