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Epileptiform EEG discharges in benign childhood epilepsy with centrotemporal spikes: Reactivity and transitory cognitive impairment
Epilepsy & Behavior 11 (2007) 65–70 www.elsevier.com/locate/yebeh
Epileptiform EEG discharges in benign childhood epilepsy with centrotemporal spikes: Reactivity and transitory cognitive impairment Lineu C. Fonseca a b
a,*
, Gloria M.A.S. Tedrus a, Elisabeth M.C. Pacheco
b
Department of Neurology, Pontifı´cia Universidade Cato´lica de Campinas (PUC-Campinas), Campinas-SP, Brazil Department of Psychology, Pontifı´cia Universidade Cato´lica de Campinas (PUC-Campinas), Campinas-SP, Brazil Received 21 January 2007; revised 4 March 2007; accepted 2 April 2007 Available online 22 May 2007
Abstract The reactivity of rolandic spikes (RS) and the occurrence of transitory cognitive impairment (TCI) during RSs were assessed in 33 children with benign childhood epilepsy with centrotemporal spikes (BECTS). The children were assessed simultaneously with EEG and computerized neuropsychological testing in a visual discrimination between words and pseudowords task (DWPT). In 20 (60.6%) children, there were insufficient RS to assess the occurrence of TCI. Of 13 children with RS between stimulus presentation and response, only 2 (15.4%) made a significantly greater proportion of errors during RS than during RS-free periods, characterizing the occurrence of TCI. The RS appear to be easily inhibited by the DWPT. TCI occurred in a limited number of cases and did not impair school performance. There is a need to study other tasks and search for other factors influencing cognitive abilities in children with BECTS. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Benign childhood epilepsy with centrotemporal spikes; Rolandic epilepsy; Epileptiform activity; Subclinical epileptiform EEG discharges; Transitory cognitive impairment; EEG and cognition; Rolandic spikes; Reading
1. Introduction Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common form of focal idiopathic epilepsy in childhood. In general, the prognosis is good and the seizures disappear by 15 years of age, with normalization of the electroencephalogram (EEG) [1]. In the interictal period, the baseline EEG activity is normal, with epileptiform activity characterized by spikes located mainly in the central and midtemporal regions— centrotemporal spikes or rolandic spikes (RS). The RS are unilateral in 60% of cases and activated during sleep. Despite having an IQ within the limits of normality, approximately 15–30% of affected children show some degree of cognitive deficit during the active epileptic phase
*
Corresponding author. Fax: +55 19 32322730. E-mail address: [email protected] (L.C. Fonseca).
1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.04.001
[2]. Slight neuropsychological alterations have been described for language [3–9], attention [7,10], executive functions [11], memory [7,11,12], visuospatial orientation [4], and phonological processing [12]. These cognitive deficits may be associated with learning difficulties and a fall in school performance [3,6,9,10,13,14], which longitudinal studies have shown to be transitory in the majority of cases [13]. Various arguments favor the hypothesis that the epileptiform EEG discharges have an important connection with the cognitive alterations observed in BECTS, either due to the tendency to find specific deficits according to the side of the focus [15–18] or due to the temporal relationships between larger number of RS and neuropsychological disturbances [3,4,6–8]. Such relationships between the side of the focus and specific cognitive deficits were not, however, observed in some studies [10,12,13], and in the studies on the relationship between number of RS and neuropsychological difficulties,
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the association frequently failed to attain statistical significance [3] or there was no assessment of specific neuropsychological aspects [4,6]. One of the mechanisms suggested to explain the relationship between RS and cognitive alterations is the occurrence of transitory cognitive impairment (TCI) during the short period of RS on the EEG [19], in the absence of evidence of an epileptic seizure, similar to observations made in other epileptic syndromes [20–24]. Studies on TCI in children with BECTS are surprisingly rare, refer to a small number of individuals, and do not represent typical series in children with BECTS [19,21], indicating the need for more profound knowledge, choosing a relevant aspect to be assessed in an adequate task. Various authors have reported reading difficulties in children with BECTS [2,5,12,14]. In a recent study [14], compared with normal children, children with BECTS were observed to perform at an inferior level more often, especially in reading; also, this inferior performance was associated with a larger number of RS per minute than average and superior performance. Number of correct answers and reaction time to discriminate words from pseudowords have been used in reading assessment [25], simultaneously with EEG data [18,26]. In research on TCI, some aspects of the tasks, such as visual input mode, longer test duration, and high information processing, may favor the detection of TCI [27]. Inhibition of epileptiform EEG discharges by the activities developed in the tests may also be important [21,27]. Thus, the objective of this research was to assess the reactivity of RS and the occurrence of associated TCI, in a task of visual discrimination between words and pseudowords.
2. Method
service of the Celso Pierro Hospital of PUC-Campinas. Table 1 outlines the distribution of the 33 children with respect to age and gender. The average age at onset of epilepsy was 6.9 years (SD = 4.3), and the average number of seizures was 4.4 (SD = 4.0). The mean time since the last seizure was 1.47 years (SD = 2.1). Twenty-one children were not taking medication at the time of the assessment, and 12 were on antiepileptic drugs (carbamazepine, n = 9; valproate, n = 3). They had normal or corrected-to-normal vision. The average Full Scale IQ (Wechsler Intelligence Scale for Children, WISC-III) was 109.5 (SD = 22.3). Three children were left-handed as confirmed by the Edinburgh Handedness Inventory [31]. There were no serious behavioral or cognitive complaints. No children were mentally retarded (IQ < 70), as determined by the WISC-III.
2.2. Procedures
2.2.1. School performance test (SPT) [32] This standardized psychometric instrument, approved by the Brazilian Federal Council of Psychology, is used to evaluate fundamental capacity for school performance in writing, reading, and arithmetic, as well as overall ability, per school year. Performance is classified as superior, average, or inferior. 2.2.2. Electroencephalogram Brain electrical activity was recorded using Braintech 3.0 equipment (EMSA Equipamentos Me´dicos), with a 21-channel EEG, and a resolution of 12 bits with 0.5- and 35-Hz filters, analyzing 200 samples per second. Impedance was maintained below 10 kX. The electrodes were placed according to the 10–20 international system, and the reference consisted of interconnected auricular electrodes. EEGs were obtained while resting, with hyperventilation for 3 min, and, when possible, during spontaneous sleep. The EEG was also recorded during the discrimination of words and pseudowords task. Location and side of the epileptiform activity were assessed, as was number of RS per 5 min. For the 17 children whose EEGs were recorded at rest and during the cognitive task in the same session, RS were counted for 5-min. periods in the two situations, and the means compared (t test for paired samples), with differences considered statistically significant at P < 0.05.
2.3. Discrimination between words and pseudowords task (DWPT) 2.1. Participants Thirty-three 7- to 12-year-old children were studied. All had been diagnosed with BECTS according to the International Classification of Epilepsies and Epileptic Syndromes [28,29] and the criteria of Dalla Bernadina et al. [30], and all had exhibited RS on the EEG obtained the previous month. The subjects were chosen consecutively from neurological outpatient departments and the electroencephalographic
Table 1 Distribution of the 33 children with respect to age and gender Age (years)
Male N
7 8 9 10 11 12 Total
Female %
N
Total %
N
1 0 4 6 2 1
3.0 0 12.1 18.2 6.1 3.0
0 2 5 4 7 1
0 6.1 15.1 12.1 21.2 3.0
1 2 9 10 9 2
14
42.4
19
57.5
33
% 3.0 6.1 27.3 30.3 27.3 6.1 100
A program, developed especially for this research in collaboration with EMSA Equipamentos Me´dicos, synchronized the visual presentation of the stimuli with the recording at the EEG, and recorded the type (hit or error) of response and reaction time. One hundred words and 100 pseudowords, disyllables paired with respect to number of letters and composition of the consonants and vowels, were presented randomly. High-frequency words, taken from children’s first readers, were used, [25]. A pseudoword was considered to be a group of letters forming a pronounceable unit but having no meaning, and were obtained by exchanging graphemes or making other alterations to real words. Words and pseudowords were white on a black background, and were presented for 1 s, with a 4-s interval between. During the activity there were short pauses (one to three) for resting. The child was instructed to press a previously determined key (INS or space) with one hand if the stimulus was a word, or another key (space or INS, respectively) with the other hand if it was a pseudoword. The number of cases was balanced for each type of response laterality. For the test, the child was seated in a darkened environment after prior training to check for adequate understanding of the instructions. The program used generated a file containing the type of reaction and the time taken for each response.
L.C. Fonseca et al. / Epilepsy & Behavior 11 (2007) 65–70 During the test, one of the authors of this article attentively observed the patient, looking for signs of epileptic seizures, particularly clonic facial movements. At the end of the test, he asked the patient if he or she had experienced any symptoms, such as perioral paresthesias, that could be attributed to a seizure. No symptoms or signs suggestive of epileptic seizures were observed during the DWPT. For each child, the percentages of hits and errors were determined, as were the mean reaction time for correct responses to words and pseudowords during RS-containing and RS-free intervals on the EEG. Occurrence of RS was assessed during the period between stimulus presentation and response, and errors and reaction times in the periods with and without RS were compared. The Fisher exact test or v2 test was used to compare the errors, and the t test, to compare reaction times at a significance level of 0.05. The power of the v2 test of independence of the data in the contingency tables was computed [33]. Transitory cognitive impairment was considered to have occurred when performance on the DWPT was statistically inferior in the period between stimulus and response during RS, compared with such performance during RS-free periods. The project was approved by the Ethics in Research with Human Beings Committee of PUC-Campinas, which is recognized by the National Ethics in Research Commission (CONEP/MS).
3. Results 3.1. Reactivity of RS to the DWPT An EEG at rest with RS was obtained for 17 of the 33 children in the same session and immediately before the DWPT. There was a statistically significant reduction in the mean number of RS per 5 min during the DWPT, compared with the number of RS on the EEG recorded at rest (Table 2). No RS occurred during the DWPT in 5 (29.5%) patients. There was no difference in reactivity of the RS with respect to the side of the brain in which they occurred and also no significant difference in the frequency of RS between the initial, middle, and final thirds of the DWPT. 3.2. Transitory cognitive impairment In the present study, of the 33 children who took the DWPT, RS were not recorded in 20 (60.6%), or were too rare to allow for an assessment of the occurrence of TCI. RS occurred between stimulus presentation and response in only 13 (39.4) cases, allowing analysis for detection of TCI. Table 3 lists the characteristics of these children with respect to age, side of unilateral or predominantly unilateTable 2 EEG at rest and during discrimination between words and pseudowords: percentage of patients with RS and mean number of RS per 5 min EEG
% of patients with RSs
Mean number of RSs per 5 min
Rest Discrimination between words and pseudowords
100 70.1
36.2a 24.83a
a
Statistically significant, P < 0.05, t test for paired samples.
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ral RS, number of RS per minute, and percentages of hits and reaction times in RS-containing and RS-free periods throughout the trial. TCI, characterized by a statistically significant greater proportion of errors during RS-containing than during RS-free periods, was observed in only two (15.4%) children (cases 3 and 4) (Table 3). However, for the remaining children in whom TCI was not observed, the power of the statistical analysis was low (<0.50) because of the small number of RS between stimulus and response; hence the risk of false negative results was high. With respect to reaction time, there was no statistically significant difference between stimuli with and without RS. For the 11 children without TCI, overall school performance was superior for one, average for six, and inferior for four, and reading performance was superior for two, average for six, and inferior for five. Of the two children with TCI, for case 3, all categories of school performance test were superior, and for case 4, reading performance was inferior and performance in other categories average. Parents of patient 3 considered the school performance to be good, and parents of case 4, satisfactory. These two children were both taking carbamazepine. 4. Discussion There is a complex interaction between cognition and RS: RS can be inhibited by cognitive activity, but RS can also affect cognition. 4.1. Reactivity of the RS In an the present study, RS did not register or were rare during the DWPT in the majority of cases (about 60%). When RS were counted at rest and during the DWPT in the same session, the mean number of RS per 5 min was smaller during DWPT and RS did not occur at all during this phase in 30% of the children. These findings suggest that the occurrence of RS is significantly inhibited by functional brain activation, in agreement with observations of epileptiform activity in other locations [20–22,27]. Among the inhibitory factors are not only the complexity of the task [20], but also the functional specificity of the brain region involved. In an assessment of the influence of movement, tactile stimulation, and cognitive tests on the rate of discharge of RS, tongue movements were observed to cause a reduction in the mean number of spikes per minute, and the silent reading test was observed to cause a less marked reduction [34]. Presumably, the activity of normal neurons in the vicinity of the RS generator provokes a reduction in interictal discharges. As RS occur in regions superimposed on the cortical areas for language, it is possible that the occurrence of RS is inhibited by tasks involving language, such as reading. While studying children with focal epilepsy, Aldenkamp and Arends [27] also noted a significant reduction in
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Table 3 Characteristics of the EEGs of the 13 children during the DWPT Case
Age
Rolandic spikes Side
Number/min
RS
No RS
RS
No RS
1 2 3 4 5 6 7 8 9 10 11 12 13
10 9 9 8 9 10 10 10 11 11 11 7 12
La R L R L L L R R R L L L
3 7 16 33 2 4 11 37 2 2 3 22 4
0 39 13b 16b 0 33 31 33 0 0 0 11 0
2 26 3 6 4 43 27 41 11 6 11 10 4
1138 2121 1163 1159 900 1168 793 2573 2010 1993 864 1067 768
1186 2229 1054 1137 879 1105 776 2376 2070 1316 840 1029 824
a b
% Errors
Reaction time (ms)
R, right hemisphere; L, left hemisphere. Significant difference in error rate between trials with and without RS, v2 test, P < 0.05.
discharges with reading, and demonstrated that this inhibition was greater than that induced by simple visual activities, epileptiform activity being recorded in 82.4% of children during simple visual activities and in 47.1% of cases during reading. The inhibition of RS by cognitive tasks revealed by EEGs suggests that this also occurs during everyday activities, decreasing the possibility that RS have a significant cognitive impact. 4.2. Transitory cognitive impairment Assessment of function during short periods of epileptiform activity, without evidence of epileptic seizures, has revealed that TCI is associated with the epileptiform activity in some patients (30–50%) [35,36]. This association was evident at greater frequency with generalized epileptiform activity, but could also be observed in focal discharges, and the nature of the TCI was dependent on the hemisphere affected: the right hemisphere was associated with impairment in spatial tasks, and the left hemisphere with impairment in verbal tasks [22,37]. For BECTS, the reference study with respect to TCI is that of Binnie and Marsten [19], who assessed eight children using a test of short-term memory for spatial material. Four (50%) children had a significantly higher error rate in the trials accompanied by RS. However, the authors pointed out that this series was not typical, as the children had cognitive or behavioral problems, and psychosocial problems may have prompted referral. The 33 patients studied here had clinical and electroencephalographic data characteristic of a typical BECTS population [7], with low seizure frequency, predominance of focal seizures with sensory/motor oropharyngeal manifestations, occurrence of first seizure between 3 and 10 years of age, EEG with normal baseline activity, and no serious behavioral or cognitive complaints.
Of the 13 children in whom the presence of TCI could be assessed, only 2 (15.3%) were assessed as having TCI in the reading task. TCI was not demonstrated in the other children. However, because the power of the statistical analysis was low, due to the small number of RS between stimulus presentation and response, the risk of false negatives was high. This percentage of TCI (15.3%) is lower than that observed by Binnie and Marston (50.0%) [19], but probably represents more adequately the typical profile of BECTS, as it was a nonselected population. We were unable to find a similar study in the literature on BECTS and reading activities, but in children with focal epilepsies, Aldenkamp and Arends [27] reported a similar finding of 14% TCI in a simple reading exercise. Although reaction time was greater during RS, this increase did not reach the level of significance. In one of the patients with TCI, the RS occurred in the right hemisphere, and in the other patient, in the left hemisphere, suggesting that the occurrence of TCI is not linked to a specific hemisphere. The impact of TCI on various aspects of daily life, such as school activities and behavioral problems, has been considered [22,23,38], leading to therapy with the objective of suppressing epileptiform activity [39]. Good results have been obtained with respect to behavior in children with epilepsy and behavioral problems [40]. In assessing a typical group of children with BECTS, the present study failed to provide important support in favor of the hypothesis that TCI is a preponderant factor in the genesis of neuropsychological alterations in BECTS. The findings of this study suggest that RS are easily inhibited by cognitive activities, that TCI occurs in only a small proportion of cases, and that this may not be associated with impairment of school performance. To understand the cognitive difficulties observed in children with BECTS, TCI should be studied during other types of activity, and other hypotheses for its genesis, such
L.C. Fonseca et al. / Epilepsy & Behavior 11 (2007) 65–70
as the cerebral immaturity associated with BECTS [41] and the cognitive immaturity resulting from an active epileptic focus [8], should be assessed. There should also be an attempt to study TCI using longitudinal methodology [42]. Among the topics to be assessed are the diffuse alterations in the absolute and relative theta powers in the quantitative EEG [43–45] for children with BECTS, indicating diffuse functional modifications possibly related to immaturity and not simply restricted to the regions involved in epileptiform activity. Future studies on the relationship between these alterations in baseline cerebral electrical activity and the cognitive deficits observed in children with BECTS could eventually provide new insights into their interrelationships. Acknowledgments The authors are grateful to EMSA Equipamentos Medicos for the technical support in elaborating stimulation programs, and to Valeria Lopes Ximenes (scholarship holder, FAPESP, Sa˜o Paulo, Brazil) for her participation in part of the research. References [1] Beaussart M. Benign epilepsy of children with rolandic (centrotemporal) paroxysmal foci. Epilepsia 1972;13:795–811. [2] Pinton F, Ducot B, Motte J, et al. Cognitive functions in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Epileptic Disord 2006;8:11–23. [3] Staden U, Isaaca E, Boyd SG, Brandl U, Nevillle BGR. Language dysfunction in children with rolandic epilepsy. Neuropediatrics 1998;29:242–8. [4] D’Alessandro P, Piccirilli M, Tiacci C, et al. Neuropsychological features of benign partial epilepsy in children. Ital J Neurol Sci 1990;11:265–9. [5] Carlsson G, Igelbrink-Schulze N, Neuabauer BA, Stephani U. Neuropsychological long-term outcome of rolandic EEG traits. Epileptic Disord 2000;2(Suppl. 1):63–6. [6] Baglietto MG, Battaglia FM, Tortonelli S, 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. [7] Massa R, de Saint-Martin A, Carcangiu R, et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology 2001;57:1071–9. [8] Papavasiliou A, Mattheou D, Bazigou H, Kotsalis C, Parakevoulakos E. Written language skills in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2005;6:50–8. [9] Vinayan KP, Biji V, Thomas SV. Educational problems with underlying neuropsychological impairment are common in children with benign epilepsy of childhood with centrotemporal spikes (BECTS). Seizure 2005;14:207–12. [10] Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual and behavioral findings in patients with centrotemporal spikes with or without seizures. Dev Med Child Neurol 1997;39:646–51. [11] Croona C, Kihlgren M, Lundrerg S. EEG-Olofsson KE. Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes. Dev Med Child Neurol 1999;41:813–8. [12] Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language profile of children with benign rolandic epilepsy. Epilepsia 2005;46:924–30.
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Epileptiform EEG discharges in benign childhood epilepsy with centrotemporal spikes: Reactivity and transitory cognitive impairment Lineu C. Fonseca a b
a,*
, Gloria M.A.S. Tedrus a, Elisabeth M.C. Pacheco
b
Department of Neurology, Pontifı´cia Universidade Cato´lica de Campinas (PUC-Campinas), Campinas-SP, Brazil Department of Psychology, Pontifı´cia Universidade Cato´lica de Campinas (PUC-Campinas), Campinas-SP, Brazil Received 21 January 2007; revised 4 March 2007; accepted 2 April 2007 Available online 22 May 2007
Abstract The reactivity of rolandic spikes (RS) and the occurrence of transitory cognitive impairment (TCI) during RSs were assessed in 33 children with benign childhood epilepsy with centrotemporal spikes (BECTS). The children were assessed simultaneously with EEG and computerized neuropsychological testing in a visual discrimination between words and pseudowords task (DWPT). In 20 (60.6%) children, there were insufficient RS to assess the occurrence of TCI. Of 13 children with RS between stimulus presentation and response, only 2 (15.4%) made a significantly greater proportion of errors during RS than during RS-free periods, characterizing the occurrence of TCI. The RS appear to be easily inhibited by the DWPT. TCI occurred in a limited number of cases and did not impair school performance. There is a need to study other tasks and search for other factors influencing cognitive abilities in children with BECTS. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Benign childhood epilepsy with centrotemporal spikes; Rolandic epilepsy; Epileptiform activity; Subclinical epileptiform EEG discharges; Transitory cognitive impairment; EEG and cognition; Rolandic spikes; Reading
1. Introduction Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common form of focal idiopathic epilepsy in childhood. In general, the prognosis is good and the seizures disappear by 15 years of age, with normalization of the electroencephalogram (EEG) [1]. In the interictal period, the baseline EEG activity is normal, with epileptiform activity characterized by spikes located mainly in the central and midtemporal regions— centrotemporal spikes or rolandic spikes (RS). The RS are unilateral in 60% of cases and activated during sleep. Despite having an IQ within the limits of normality, approximately 15–30% of affected children show some degree of cognitive deficit during the active epileptic phase
*
Corresponding author. Fax: +55 19 32322730. E-mail address: [email protected] (L.C. Fonseca).
1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.04.001
[2]. Slight neuropsychological alterations have been described for language [3–9], attention [7,10], executive functions [11], memory [7,11,12], visuospatial orientation [4], and phonological processing [12]. These cognitive deficits may be associated with learning difficulties and a fall in school performance [3,6,9,10,13,14], which longitudinal studies have shown to be transitory in the majority of cases [13]. Various arguments favor the hypothesis that the epileptiform EEG discharges have an important connection with the cognitive alterations observed in BECTS, either due to the tendency to find specific deficits according to the side of the focus [15–18] or due to the temporal relationships between larger number of RS and neuropsychological disturbances [3,4,6–8]. Such relationships between the side of the focus and specific cognitive deficits were not, however, observed in some studies [10,12,13], and in the studies on the relationship between number of RS and neuropsychological difficulties,
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the association frequently failed to attain statistical significance [3] or there was no assessment of specific neuropsychological aspects [4,6]. One of the mechanisms suggested to explain the relationship between RS and cognitive alterations is the occurrence of transitory cognitive impairment (TCI) during the short period of RS on the EEG [19], in the absence of evidence of an epileptic seizure, similar to observations made in other epileptic syndromes [20–24]. Studies on TCI in children with BECTS are surprisingly rare, refer to a small number of individuals, and do not represent typical series in children with BECTS [19,21], indicating the need for more profound knowledge, choosing a relevant aspect to be assessed in an adequate task. Various authors have reported reading difficulties in children with BECTS [2,5,12,14]. In a recent study [14], compared with normal children, children with BECTS were observed to perform at an inferior level more often, especially in reading; also, this inferior performance was associated with a larger number of RS per minute than average and superior performance. Number of correct answers and reaction time to discriminate words from pseudowords have been used in reading assessment [25], simultaneously with EEG data [18,26]. In research on TCI, some aspects of the tasks, such as visual input mode, longer test duration, and high information processing, may favor the detection of TCI [27]. Inhibition of epileptiform EEG discharges by the activities developed in the tests may also be important [21,27]. Thus, the objective of this research was to assess the reactivity of RS and the occurrence of associated TCI, in a task of visual discrimination between words and pseudowords.
2. Method
service of the Celso Pierro Hospital of PUC-Campinas. Table 1 outlines the distribution of the 33 children with respect to age and gender. The average age at onset of epilepsy was 6.9 years (SD = 4.3), and the average number of seizures was 4.4 (SD = 4.0). The mean time since the last seizure was 1.47 years (SD = 2.1). Twenty-one children were not taking medication at the time of the assessment, and 12 were on antiepileptic drugs (carbamazepine, n = 9; valproate, n = 3). They had normal or corrected-to-normal vision. The average Full Scale IQ (Wechsler Intelligence Scale for Children, WISC-III) was 109.5 (SD = 22.3). Three children were left-handed as confirmed by the Edinburgh Handedness Inventory [31]. There were no serious behavioral or cognitive complaints. No children were mentally retarded (IQ < 70), as determined by the WISC-III.
2.2. Procedures
2.2.1. School performance test (SPT) [32] This standardized psychometric instrument, approved by the Brazilian Federal Council of Psychology, is used to evaluate fundamental capacity for school performance in writing, reading, and arithmetic, as well as overall ability, per school year. Performance is classified as superior, average, or inferior. 2.2.2. Electroencephalogram Brain electrical activity was recorded using Braintech 3.0 equipment (EMSA Equipamentos Me´dicos), with a 21-channel EEG, and a resolution of 12 bits with 0.5- and 35-Hz filters, analyzing 200 samples per second. Impedance was maintained below 10 kX. The electrodes were placed according to the 10–20 international system, and the reference consisted of interconnected auricular electrodes. EEGs were obtained while resting, with hyperventilation for 3 min, and, when possible, during spontaneous sleep. The EEG was also recorded during the discrimination of words and pseudowords task. Location and side of the epileptiform activity were assessed, as was number of RS per 5 min. For the 17 children whose EEGs were recorded at rest and during the cognitive task in the same session, RS were counted for 5-min. periods in the two situations, and the means compared (t test for paired samples), with differences considered statistically significant at P < 0.05.
2.3. Discrimination between words and pseudowords task (DWPT) 2.1. Participants Thirty-three 7- to 12-year-old children were studied. All had been diagnosed with BECTS according to the International Classification of Epilepsies and Epileptic Syndromes [28,29] and the criteria of Dalla Bernadina et al. [30], and all had exhibited RS on the EEG obtained the previous month. The subjects were chosen consecutively from neurological outpatient departments and the electroencephalographic
Table 1 Distribution of the 33 children with respect to age and gender Age (years)
Male N
7 8 9 10 11 12 Total
Female %
N
Total %
N
1 0 4 6 2 1
3.0 0 12.1 18.2 6.1 3.0
0 2 5 4 7 1
0 6.1 15.1 12.1 21.2 3.0
1 2 9 10 9 2
14
42.4
19
57.5
33
% 3.0 6.1 27.3 30.3 27.3 6.1 100
A program, developed especially for this research in collaboration with EMSA Equipamentos Me´dicos, synchronized the visual presentation of the stimuli with the recording at the EEG, and recorded the type (hit or error) of response and reaction time. One hundred words and 100 pseudowords, disyllables paired with respect to number of letters and composition of the consonants and vowels, were presented randomly. High-frequency words, taken from children’s first readers, were used, [25]. A pseudoword was considered to be a group of letters forming a pronounceable unit but having no meaning, and were obtained by exchanging graphemes or making other alterations to real words. Words and pseudowords were white on a black background, and were presented for 1 s, with a 4-s interval between. During the activity there were short pauses (one to three) for resting. The child was instructed to press a previously determined key (INS or space) with one hand if the stimulus was a word, or another key (space or INS, respectively) with the other hand if it was a pseudoword. The number of cases was balanced for each type of response laterality. For the test, the child was seated in a darkened environment after prior training to check for adequate understanding of the instructions. The program used generated a file containing the type of reaction and the time taken for each response.
L.C. Fonseca et al. / Epilepsy & Behavior 11 (2007) 65–70 During the test, one of the authors of this article attentively observed the patient, looking for signs of epileptic seizures, particularly clonic facial movements. At the end of the test, he asked the patient if he or she had experienced any symptoms, such as perioral paresthesias, that could be attributed to a seizure. No symptoms or signs suggestive of epileptic seizures were observed during the DWPT. For each child, the percentages of hits and errors were determined, as were the mean reaction time for correct responses to words and pseudowords during RS-containing and RS-free intervals on the EEG. Occurrence of RS was assessed during the period between stimulus presentation and response, and errors and reaction times in the periods with and without RS were compared. The Fisher exact test or v2 test was used to compare the errors, and the t test, to compare reaction times at a significance level of 0.05. The power of the v2 test of independence of the data in the contingency tables was computed [33]. Transitory cognitive impairment was considered to have occurred when performance on the DWPT was statistically inferior in the period between stimulus and response during RS, compared with such performance during RS-free periods. The project was approved by the Ethics in Research with Human Beings Committee of PUC-Campinas, which is recognized by the National Ethics in Research Commission (CONEP/MS).
3. Results 3.1. Reactivity of RS to the DWPT An EEG at rest with RS was obtained for 17 of the 33 children in the same session and immediately before the DWPT. There was a statistically significant reduction in the mean number of RS per 5 min during the DWPT, compared with the number of RS on the EEG recorded at rest (Table 2). No RS occurred during the DWPT in 5 (29.5%) patients. There was no difference in reactivity of the RS with respect to the side of the brain in which they occurred and also no significant difference in the frequency of RS between the initial, middle, and final thirds of the DWPT. 3.2. Transitory cognitive impairment In the present study, of the 33 children who took the DWPT, RS were not recorded in 20 (60.6%), or were too rare to allow for an assessment of the occurrence of TCI. RS occurred between stimulus presentation and response in only 13 (39.4) cases, allowing analysis for detection of TCI. Table 3 lists the characteristics of these children with respect to age, side of unilateral or predominantly unilateTable 2 EEG at rest and during discrimination between words and pseudowords: percentage of patients with RS and mean number of RS per 5 min EEG
% of patients with RSs
Mean number of RSs per 5 min
Rest Discrimination between words and pseudowords
100 70.1
36.2a 24.83a
a
Statistically significant, P < 0.05, t test for paired samples.
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ral RS, number of RS per minute, and percentages of hits and reaction times in RS-containing and RS-free periods throughout the trial. TCI, characterized by a statistically significant greater proportion of errors during RS-containing than during RS-free periods, was observed in only two (15.4%) children (cases 3 and 4) (Table 3). However, for the remaining children in whom TCI was not observed, the power of the statistical analysis was low (<0.50) because of the small number of RS between stimulus and response; hence the risk of false negative results was high. With respect to reaction time, there was no statistically significant difference between stimuli with and without RS. For the 11 children without TCI, overall school performance was superior for one, average for six, and inferior for four, and reading performance was superior for two, average for six, and inferior for five. Of the two children with TCI, for case 3, all categories of school performance test were superior, and for case 4, reading performance was inferior and performance in other categories average. Parents of patient 3 considered the school performance to be good, and parents of case 4, satisfactory. These two children were both taking carbamazepine. 4. Discussion There is a complex interaction between cognition and RS: RS can be inhibited by cognitive activity, but RS can also affect cognition. 4.1. Reactivity of the RS In an the present study, RS did not register or were rare during the DWPT in the majority of cases (about 60%). When RS were counted at rest and during the DWPT in the same session, the mean number of RS per 5 min was smaller during DWPT and RS did not occur at all during this phase in 30% of the children. These findings suggest that the occurrence of RS is significantly inhibited by functional brain activation, in agreement with observations of epileptiform activity in other locations [20–22,27]. Among the inhibitory factors are not only the complexity of the task [20], but also the functional specificity of the brain region involved. In an assessment of the influence of movement, tactile stimulation, and cognitive tests on the rate of discharge of RS, tongue movements were observed to cause a reduction in the mean number of spikes per minute, and the silent reading test was observed to cause a less marked reduction [34]. Presumably, the activity of normal neurons in the vicinity of the RS generator provokes a reduction in interictal discharges. As RS occur in regions superimposed on the cortical areas for language, it is possible that the occurrence of RS is inhibited by tasks involving language, such as reading. While studying children with focal epilepsy, Aldenkamp and Arends [27] also noted a significant reduction in
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Table 3 Characteristics of the EEGs of the 13 children during the DWPT Case
Age
Rolandic spikes Side
Number/min
RS
No RS
RS
No RS
1 2 3 4 5 6 7 8 9 10 11 12 13
10 9 9 8 9 10 10 10 11 11 11 7 12
La R L R L L L R R R L L L
3 7 16 33 2 4 11 37 2 2 3 22 4
0 39 13b 16b 0 33 31 33 0 0 0 11 0
2 26 3 6 4 43 27 41 11 6 11 10 4
1138 2121 1163 1159 900 1168 793 2573 2010 1993 864 1067 768
1186 2229 1054 1137 879 1105 776 2376 2070 1316 840 1029 824
a b
% Errors
Reaction time (ms)
R, right hemisphere; L, left hemisphere. Significant difference in error rate between trials with and without RS, v2 test, P < 0.05.
discharges with reading, and demonstrated that this inhibition was greater than that induced by simple visual activities, epileptiform activity being recorded in 82.4% of children during simple visual activities and in 47.1% of cases during reading. The inhibition of RS by cognitive tasks revealed by EEGs suggests that this also occurs during everyday activities, decreasing the possibility that RS have a significant cognitive impact. 4.2. Transitory cognitive impairment Assessment of function during short periods of epileptiform activity, without evidence of epileptic seizures, has revealed that TCI is associated with the epileptiform activity in some patients (30–50%) [35,36]. This association was evident at greater frequency with generalized epileptiform activity, but could also be observed in focal discharges, and the nature of the TCI was dependent on the hemisphere affected: the right hemisphere was associated with impairment in spatial tasks, and the left hemisphere with impairment in verbal tasks [22,37]. For BECTS, the reference study with respect to TCI is that of Binnie and Marsten [19], who assessed eight children using a test of short-term memory for spatial material. Four (50%) children had a significantly higher error rate in the trials accompanied by RS. However, the authors pointed out that this series was not typical, as the children had cognitive or behavioral problems, and psychosocial problems may have prompted referral. The 33 patients studied here had clinical and electroencephalographic data characteristic of a typical BECTS population [7], with low seizure frequency, predominance of focal seizures with sensory/motor oropharyngeal manifestations, occurrence of first seizure between 3 and 10 years of age, EEG with normal baseline activity, and no serious behavioral or cognitive complaints.
Of the 13 children in whom the presence of TCI could be assessed, only 2 (15.3%) were assessed as having TCI in the reading task. TCI was not demonstrated in the other children. However, because the power of the statistical analysis was low, due to the small number of RS between stimulus presentation and response, the risk of false negatives was high. This percentage of TCI (15.3%) is lower than that observed by Binnie and Marston (50.0%) [19], but probably represents more adequately the typical profile of BECTS, as it was a nonselected population. We were unable to find a similar study in the literature on BECTS and reading activities, but in children with focal epilepsies, Aldenkamp and Arends [27] reported a similar finding of 14% TCI in a simple reading exercise. Although reaction time was greater during RS, this increase did not reach the level of significance. In one of the patients with TCI, the RS occurred in the right hemisphere, and in the other patient, in the left hemisphere, suggesting that the occurrence of TCI is not linked to a specific hemisphere. The impact of TCI on various aspects of daily life, such as school activities and behavioral problems, has been considered [22,23,38], leading to therapy with the objective of suppressing epileptiform activity [39]. Good results have been obtained with respect to behavior in children with epilepsy and behavioral problems [40]. In assessing a typical group of children with BECTS, the present study failed to provide important support in favor of the hypothesis that TCI is a preponderant factor in the genesis of neuropsychological alterations in BECTS. The findings of this study suggest that RS are easily inhibited by cognitive activities, that TCI occurs in only a small proportion of cases, and that this may not be associated with impairment of school performance. To understand the cognitive difficulties observed in children with BECTS, TCI should be studied during other types of activity, and other hypotheses for its genesis, such
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as the cerebral immaturity associated with BECTS [41] and the cognitive immaturity resulting from an active epileptic focus [8], should be assessed. There should also be an attempt to study TCI using longitudinal methodology [42]. Among the topics to be assessed are the diffuse alterations in the absolute and relative theta powers in the quantitative EEG [43–45] for children with BECTS, indicating diffuse functional modifications possibly related to immaturity and not simply restricted to the regions involved in epileptiform activity. Future studies on the relationship between these alterations in baseline cerebral electrical activity and the cognitive deficits observed in children with BECTS could eventually provide new insights into their interrelationships. Acknowledgments The authors are grateful to EMSA Equipamentos Medicos for the technical support in elaborating stimulation programs, and to Valeria Lopes Ximenes (scholarship holder, FAPESP, Sa˜o Paulo, Brazil) for her participation in part of the research. References [1] Beaussart M. Benign epilepsy of children with rolandic (centrotemporal) paroxysmal foci. Epilepsia 1972;13:795–811. [2] Pinton F, Ducot B, Motte J, et al. Cognitive functions in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Epileptic Disord 2006;8:11–23. [3] Staden U, Isaaca E, Boyd SG, Brandl U, Nevillle BGR. Language dysfunction in children with rolandic epilepsy. Neuropediatrics 1998;29:242–8. [4] D’Alessandro P, Piccirilli M, Tiacci C, et al. Neuropsychological features of benign partial epilepsy in children. Ital J Neurol Sci 1990;11:265–9. [5] Carlsson G, Igelbrink-Schulze N, Neuabauer BA, Stephani U. Neuropsychological long-term outcome of rolandic EEG traits. Epileptic Disord 2000;2(Suppl. 1):63–6. [6] Baglietto MG, Battaglia FM, Tortonelli S, 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. [7] Massa R, de Saint-Martin A, Carcangiu R, et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology 2001;57:1071–9. [8] Papavasiliou A, Mattheou D, Bazigou H, Kotsalis C, Parakevoulakos E. Written language skills in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2005;6:50–8. [9] Vinayan KP, Biji V, Thomas SV. Educational problems with underlying neuropsychological impairment are common in children with benign epilepsy of childhood with centrotemporal spikes (BECTS). Seizure 2005;14:207–12. [10] Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual and behavioral findings in patients with centrotemporal spikes with or without seizures. Dev Med Child Neurol 1997;39:646–51. [11] Croona C, Kihlgren M, Lundrerg S. EEG-Olofsson KE. Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes. Dev Med Child Neurol 1999;41:813–8. [12] Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language profile of children with benign rolandic epilepsy. Epilepsia 2005;46:924–30.
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