Benign childhood epilepsy with centro-temporal spikes: correlation between clinical, cognitive and EEG aspects

Epilepsia benigna da infância com pontas centrotemporais: correlação entre aspectos clínicos, eletrencefalográficos e cognitivos

Lineu Corrêa Fonseca^I; Glória Maria A.S. Tedrus^I; Elisabeth Marinelli de Camargo Pacheco^II; Marcela Fernanda Berretta^III; Amanda Augusta Campregher^III; Débora Macedo Costa^III

^IProfessor of Neurology

^IIProfessor of Psychology. Pontifícia Universidade Católica de Campinas, Campinas SP, Brazil (PUC-Campinas)

^IIIScholarship holders PIBIC/CNPq, FAPIC/Reitoria PUC-Campinas and FAPESP, respectively

ABSTRACT

Benign childhood epilepsy with centro-temporal spikes (BECTS) is a form of epilepsy with no demonstrable anatomical lesion showing spontaneous seizure remission. During the active phase of the disease the children may show cognitive deficits. The objective of this study was to assess, in children with BECTS, the relationship between clinical-EEG aspects and performance in the school performance test (SPT), Raven's progressive matrixes test and the Wechsler Intelligence Scale for Children (WISC-III). Forty-two 7 to 11 year old children were included and the following tests carried out: anamnesis, neurological examination, electroencephalogram (EEG), SPT, Raven's test and WISC-III. The children with BECTS had normal IQ values but showed inferior performance in the SPT more frequently than "healthy" children, paired with respect to age and maternal scholastic level. There was moderate positive correlation between WISC-III results and the age when the seizures started and the educational level of the parents. On the other hand, aspects linked to the epileptic nature of BECTS, such as the number of seizures, time since last seizure and the number and lateralization of the centro-temporal spikes on the EEG, showed no correlation with the neuropsychological tests.

Key words: benign childhood epilepsy, epileptiform activity, electroencephalogram, cognition.

RESUMO

A epilepsia benigna da infância com pontas centrotemporais (EBICT) é uma forma de epilepsia na qual não existem lesões anatômicas demonstráveis e há remissão espontânea das crises. Na fase ativa da epilepsia as crianças podem apresentar déficits cognitivos. O objetivo deste estudo foi avaliar, em crianças com EBICT, a relação entre aspectos clínico-eletrencefalográficos e o desempenho no teste de desempenho escolar (TDE), no teste das matrizes progressivas de Raven e na Escala Wechsler de Inteligência para Crianças (WISC-III). Foram incluídas 42 crianças de 7 a 11 anos de idade. Foram realizados: anamnese, exame neurológico, eletrencefalograma (EEG), TDE, teste de Raven e WISC-III. As crianças com EBICT tiveram valores normais de QI e apresentaram desempenho inferior no TDE mais freqüentemente que crianças "sadias" pareadas quanto à idade e à escolaridade materna. Houve correlação positiva moderada entre idade de início das crises e escolaridade dos pais com resultados do WISC-III. Por outro lado, aspectos ligados à natureza epiléptica da EBICT como número de crises, tempo decorrido da última crise, número e lateralidade das pontas centrotemporais ao EEG não mostraram correlação com os resultados dos testes neuropsicológicos.

Palavras-chave: epilepsia focal benigna, atividade epileptiforme, eletrencefalograma, cognição.

Benign childhood epilepsy with centro-temporal spikes (BECTS) is the most common form of focal idiopathic epilepsy in childhood, showing no demonstrable anatomical lesions. In general the prognosis is good and the seizures disappear by 15 years of age, with normalization of the electroencephalogram (EEG)¹. During the interictal period, the baseline brain electrical activity is normal, showing epileptiform activity (EA) characterised by spikes located mainly in the central and midtemporal regions – centro-temporal spikes (CTS). CTS are unilateral in 60% of the cases and activated during sleep. There is no correlation between the number of CTS and seizure frequency¹.

Approximately a quarter of the children show some degree of cognitive deficit during the active epilepsy phase². Slight neuropsychological alterations have been described for language^3-9, attention^7,10, executive functions¹¹, memory^7,11,12, visuospatial orientation⁴, phonological processing¹² and school performance¹³. It has been discussed in the literature whether the cognitive deficit occurs due to the location of the EA in the centro-temporal region, side of the CTS, the number of CTS or even to a deficit in brain maturity, which interferes with the functional organization of the developing brain, or if it is due to activity of the focus^{3,4,6,8,14-17}. A previous study showed a relationship between immaturity in the development of brain electrical activity in children with BECTS¹⁸, represented by findings in the quantitative EEG, and inferior cognitive performance in the WISC-III. However, few studies have widely investigated the relation between clinical aspects of this epileptic syndrome, such as the age when the seizures started, the total number and type of seizure and the duration of the epilepsy phase, and the observed cognitive deficits. Thus greater knowledge of possible correlations between the clinical aspects and performance in neuropsychological tests could provide subsidies for a better knowledge of the factors related to the neuropsychological alterations observed in this syndrome.

The objective of this study was therefore to assess the relationship between clinical, EEG and neuropsychological aspects in children with BECTS, as assessed by the school performance test (SPT), Raven's progressively coloured matrix test and the Wechsler Intelligence Scale for Children (WISC-III).

METHOD

Forty-two 7 to 11 year old children diagnosed with BECTS according to the International Classification of Epilepsies and Epileptic Syndromes¹⁹ and the Dalla Bernardina et al.²⁰ criteria, were included in this study. The children were sent by the Child Neurology Outpatients Department and the Electroencephalography Department of The Celso Pierro General Hospital and Maternity, PUC-Campinas. Children were only included after the parents and/or guardians gave their consent.

The following procedures were carried out:

1.

Medical history and examination of the medical file with the clinical and laboratory data.

2. Traditional neurological examination. 3. School Performance Test (SPT)²¹ - a standardized psychometric instrument, favourably considered by the Psychological Tests Evaluation System (Brazilian Federal Council Of Psychology), which offers an evaluation of the fundamental capacities for school performance in writing, reading, arithmetic and overall ability, per school year, classifying the performance as superior, average or inferior. 4. The Raven test for progressively coloured Matrixes, Special Scale - a standardised instrument adapted to Brazilian reality, destined to measure overall intelligence. The results were expressed in percentages and grades that varied from 1 to 5, grade 1 being obtained by intellectually superior subjects and grade 5 by intellectually deficient subjects. 5. Assessment of lateral dominance using the Edinburgh Inventory - an instrument that assesses the lateral specificity of the examinee. 6.

The Wechsler Intelligence Scale for Children (WISC-III) - widely used measure of general intelligence for children aged 6-16 years. The WISC-III is organized into three IQ scores (Verbal, Performance, and Full Scale) and further divided into four factorially derived index scores including the Verbal comprehension, Processing Speed, Freedom from Distractibility and Perceptual Organization. Each of the IQ scores and factor indexes yield standard scores with a mean of 100 and a S. D. of 15.

7.

Digital Electroencephalogram - brain electrical activity was recorded using the Braintech 3.0 equipment (EMSA Equipamentos Médicos), with a resolution of 12 bits, 0.5 and 35 Hz filters, analysing 200 samples per second. Impedance was maintained below 10kW. The electrodes were placed according to the 10-20 international system and the reference consisted of inter-connected auricular electrodes. The recording was carried out while resting, hyperventilation for three minutes and, when possible, during spontaneous sleep.

The location and the side of the EA was assessed and also the number of CTS per minute.

The project was approved by the Ethics in Research with Human Beings Committee of PUC-Campinas.

Data analysis – The relationship between the clinical and electroencephalographic aspects and cognitive aspects obtained using SPT, Raven's test and the WISC-III, was studied.

Chi-Square test, Spearman rank correlation, and T Student´s test were used for statistical analysis; p values less than o.o5 were considered significant.

With the objective of making a comparative analysis of the SPT results of the children with BECTS, a control group was formed, consisting of 42 children paired with respect to age and maternal scholastic level, presenting no antecedents suggestive of pathologies involving the CNS or alterations in the neurological examination or EEG.

RESULTS

Clinical aspects – Of the 42 children studied (24 female), 5 had only had one seizure, 24 had had from two to five seizures and 13 more than six seizures.

The epileptic seizures were focal in 35 cases, with oro-pharyngeal manifestation in 28, motor in 4, versive in 3 and generalised tonic-clonic with no description of initial focal aspects in 7 cases. The seizures only occurred while sleeping in 16 cases.

Twenty-five children were using anti-epileptic drugs (carbamazepine, phenobarbital or valproic acid).

Five (11.9%) children presented a prior history of febrile seizures.

The scholastic level of the fathers was variable, with 27 fathers (64.3%) having up to 8 years of schooling (complete or incomplete basic education), 10 (23.8%) with up to eleven years of schooling (secondary education) and 5 (11,9%) with higher education. For maternal scholastic level, one mother was illiterate (2.4%), 23 (54.7%) had complete or incomplete basic education, 15 (35.7%) with secondary education and 3 (7.1%) had completed higher education.

Electroencephalographic aspects – At rest, all the children showed normal EEG baseline activity. CTS were centrally located in one case, mid-temporal in 10 cases and central and mid-temporal in 27 cases. On the day of the cognitive assessment, four children showed no CTS on the EEG. The CTS were exclusively or predominantly in the right hemisphere in 17 cases, in the left hemisphere in 16 cases, bilateral with no predominance in 3 cases and median in 2 cases. The number of CTS per minute was from 1 to 6 in 27 children and more than 6 in 11 cases.

Cognitive aspects –Table 1 shows the distribution of the children according to the WISC-III classification.

Their performance in the Raven progressive matrixes test was superior or average in 31 (73.8%) cases and inferior in 11 (26.2%) cases.

When the SPT results for the children with BECTS were compared with those of the control group, it was shown that the children with BECTS showed inferior performance more frequently, and in a statistically significant way, in the overall SPT and in the reading and writing subtests (c²; p<0.01) (Table 2).

Relationship with WISC-III – There was no correlation between the results of the WISC-III and the gender or age of the children.

Statistically significant (Spearman's test) positive correlation was found between the age when the first epileptic seizure occurred and performance IQ (p=0.013), full-scale IQ (p=0.013), processing speed (p=0.023) and perceptual organization (p=0.026) (Table 3). Thus for these variables, the later the start of the seizures, the higher the values observed in the WISC-III.

No statistically significant relationship was found between the WISC-III values and the time since the last seizure, total number and type of seizure, prior febrile seizures, CTS lateralisation and number of CTS on the EEG, or with the use of anti-epileptic drugs (Table 3).

Statistically significant correlation (Spearman's correlation coefficient) was found between higher scholastic level of the father and better performance of the child in the verbal IQ (p=0.012), in the factor-based indexes for verbal comprehension (p=0.016) and freedom from distractibility (p=0.010), and also between higher maternal scholastic level and full-scale (p=0.023), verbal (p=0.046) and performance (p=0.022) IQ values and in the factorial indexes (FI) for freedom from distractability (p=0.020) and perceptual organization (p=0.011) (Table 4).

There was a significant association between better performance in the Raven test and the WISC-III quotients and indexes (Spearman's correlation coefficient; p<0.001).

In the relationship between WISC-III and the SPT test, on comparing the results of the WISC-III for the children with higher or average performance in the SPT with those of the group showing inferior performance, the subjects with inferior performance in the subtest for writing in the SPT showed statistically significantly lower values for verbal IQ (T test, p=0.038), whilst inferior performance in the arithmetic subtest was associated with a lower value in the freedom from distractibility index (T test, p=0.027) (Table 5).

There was no statistically significant correlation between the other IQ values and factor-based indexes and the SPT values (overall and subtests).

Relationship with SPT – There was no statistically significant difference between the results for SPT and the age when the first seizure occurred, the time since the last seizure, the total number of seizures, the number of CTS on the EEG and the use of anti-epileptic drugs (AED) (T test).

The children with mothers who studied for more than 8 years, showed median and superior performance in the sub-test for reading and the overall score in the SPT (c², p=0.039 and p=0.039, respectively). There was no significant correlation between the scholastic level of the father and the SPT performance.

DISCUSSION

Clinical, EEG and cognitive aspects – The present patients studied showed clinical and electroencephalographic characteristics suggestive of a typical BECTS population, with a low seizure frequency, predomination of focal seizures with sensitive/motor oro-pharyngeal manifestation, an age for the appearance of the first seizure between 2 and 10, brain activity with a normal base response and no serious behavioural or cognitive complaints⁷.

With respect to the WISC-III results, more than 10% of the children assessed in the present study showed values slightly below those expected for their age.

In comparative studies of the WISC-III results between children with BECTS and healthy controls, although within the normal limits, some authors found a significant reduction in IQ for children with BECTS^6,10, although others did not^4,22.

Weglage et al.¹⁰ showed a reduction in performance IQ in children with BECTS, but not in verbal IQ. In the majority of the studies, no abnormalities were observed in the verbal tasks of WISC².

Scholastic difficulties, although cited in the initial description of BECTS¹, have only recently been recognised and approached. Greater attention has been given to specific neuropsychological tests such as language, attention and visuospatial perception¹⁶.

Learning difficulties in children with BECTS have been pointed out by their teachers^3,23,24 and transitory stagnation or regression in cognitive abilities such as reading and writing, have also been described¹⁶. In BECTS children with a high proportion of atypical epileptic seizures, educational problems were reported in about 50% of the cases⁹.

In earlier studies¹³, the SPT instrument was applied to evaluate fundamental abilities in school performance. Frequently and in a statistically significant way, inferior performance was observed in the reading subtest as compared to a control group paired for age and maternal scholastic level. There was also a statistical tendency for lower performance in writing and overall SPT score.

In the present study, with different patients, the inferior performance was statistically significant for reading, writing and overall SPT, similar to the observations made by Misiara²⁵.

Correlation of the EEG and cognitive aspects – Similar to observations made by other authors^2,5,10,25, no significant association was observed in the present study between inferior performance in the WISC, in the Raven and SPT tests and the total number and type of epileptic seizure. In addition, no significant relationship was observed between inferior performance and the use of AED, this being in agreement with various studies on cognition in children with BECTS^2,3,16,26.

Correlation was encountered between the age of the child when he had his first seizure and performance in the performance and full-scale IQ, and also with processing speed and perceptual organisation (WISC-III). One hypothesis that may explain this correlation is that an earlier start to epilepsy could coincide with the period in which certain abilities are starting to be acquired¹⁶. One factor affecting the finding of a correlation between age for the first seizure and performance IQ, but not with verbal IQ, could be the fact that the verbal tasks making up the verbal IQ use material that is learnt and highly consolidated, which is less vulnerable to brain alterations, whilst the non-verbal tasks used in the performance IQ use material that demands strategy formulation to emit an adequate response²⁷.

Monjauze et al.²⁶ found no correlation between age at first seizure and specific language aspects such as morpho-syntax and special reading abilities, and raised the hypothesis that this did not occur because these abilities were acquired later in life. In idiopathic epilepsy, the functional alterations, when intense, can lead to important cognitive impairment²⁸.

In the present study, there was no significant correlation between low SPT scores and the age of the child at the first seizure, a result in agreement with Miziara²⁵.

The mother and father's scholastic levels were an important factor in performance in the WISC-III test. Correlation was found between lower paternal scholastic level and inferior performance of the child in the verbal IQ and in the fator-based index for verbal comprehension and freedom from distractibility, as also between lower maternal scholastic level and inferior performance in the IQs (full-scale, verbal and performance) and in fator-based indexes (resistance to distraction and perceptual organization). These findings suggest that cultural limitations of the parents can be additional adverse factors for children with BECTS, and can influence in the formation of their perceptive abilities, in the processing of activities and in performance.

With respect to the relationship between EA and cognitive performance, greater numbers of CTS are also associated with a lower IQ^6,10 and inferior performance in reading in the School Performance Test¹³. However, the relationship between the number of CTS and cognition did not reach statistical significance³ or there was no assessment of specific neuropsychological aspects^4,6.

A possible mechanism for transitory cognitive difficulty during CTS in the genesis of cognitive difficulties and behaviour, has surprisingly been little assessed in the literature²³ and, in recent research, only 15% of the children showed alterations, and even this was limited^29,30.

In the present study, no relationship was found between the number of CTS and the results in the WISC-III and SPT.

With respect to CTS lateralization and neuropsychological aspects, involvement of the right hemisphere would be connected to difficulties in visuospatial processing, and of the left hemisphere with language dysfunctions^4,17,31.

As in other studies^10,12,16, there was no significant correlation in the present study between inferior performance in WISC-III and in the Raven test and CTS lateralization.

Final considerations – Inferior performance was found in the School Performance Test in important proportions in children with BECTS. The time for the first seizure was a factor in the neuropsychological results, as also with the parents scholastic level. On the other hand, factors connected to the epileptic nature of BECTS, such as the number of seizures, time since the last seizure and the CTS number and lateralization, showed no correlation with the results in the neuropsychological tests, suggesting the existence of other factors to be better investigated, such as an eventual immaturity or brain dysfunction¹⁴, which could be expressed in basal brain electrical activity elements¹⁸.

Received 16 January 2007, received in final form 27 March 2007. Accepted 4 May 2007.

Dr. Lineu Corrêa Fonseca - Rua Sebastião de Souza 205 / 122 - 13013-910 Campinas SP - Brasil.

References

• 1. Beaussart M. Benign epilepsy of children with rolandic (centro-temporal) paroxysmal foci. Epilepsia 1972;13:795-781.
• 2. Pinton F, Ducot B, Motte J, et al. Cognitive functions in children with benign childhood with centrotemporal spikes (BECTS) Epileptic Disord 2006;8:11-23.
• 3. Staden U, Isaaca E, Boyd SG, Brandl U, Neville BGR. Language dysfunction in children with rolandic epilepsy. Neuropediatrics 1998; 29:242-248.
• 4. D'Alessandro P, Piccirilli M, Tiacci C. Neuropsychological features of benign partial epilepsy in children. It J Neurol Sci 1990;11:265-269
• 5. Carlsson G, Igelbrink-Schulze N, Neuabauer BA, Stephani U. Neuropsychological long-term outcome of rolandic EEG traits. Epileptic Disord 2000;2(Suppl 1):S63-S66.
• 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;43:407-412.
• 7. Massa R, Saint-Martin A, Carcangiu R et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology 2001; 57:1071-1079.
• 8. Papavasiliou A, Mattheou, Bazigou H, Kotsalis C, Paraskevoulakos E. Written language skills in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 2005;6:50-58.
• 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. Seizure 2005;14: 207-212.
• 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: 646-651.
• 11. Croona C, Kihlgren M, Lundrerg S, Eeg-Olofsson O, Eeg-Olofsson KE. Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes. Dev Med Child Neurol 1999;41: 813-818.
• 12. Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language of children with benign rolandic epilepsy. Epilepsia 2005; 46:924-930.
• 13. Fonseca LC, Tedrus GMAS, Tonelotto JMF, Antunes TA, Chiodi MG. Desempenho escolar em crianças com epilepsia benigna da infância com pontas centrotemporais. Arq Neuropsiquiatr 2004; 62:459-462.
• 14. Doose H, Neubauer B, Carlsson G. Children with benign focal sharp waves in the EEG development disorders and epilepsy. Neuropediatrics 1996;27:227-241.
• 15. Papazian O, Alfonso I, Garcia-Galarreta V. Efecto de las descargas epileptiformes interictales sobre las funciones cognitivas en niños con epilepsia idiopática. Rev Neurol 2003; 36:282-284.
• 16. Deonna T, Roulet-Perez E. Cognitive and behavioural disorders of epileptic origin in children. London:Cambridge University Press, 2005: 81-96.
• 17. Wolff M, Weiskopf N, Serra E, Preissl H, Birbaumer N, Kraegeloh-Mann. Benign partial epilepsy in childhood: selective cognitive deficits are related to the location of focal spikes determined by combined EEG/MEG. Epilepsia 2005;46:1661-1667.
• 18. Tedrus GMAS, Fonseca LC, Tonelotto JMF, Costa RM, Chiodi MG. Benign childhood epilepsy with centro-temporal spikes: quantitative EEG and the Weschsler Intelligence Scale for children (WISC-III). Clin EEG Neurosci 2006;37:193-196.
• 19. Commission on Classification and Teminology of the International League against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-399.
• 20. Dalla Bernardina B, Sgro V, Fejerman N. Epilepsy with centro-temporal spikes and related syndromes. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P (Eds). Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey & Company Ltd, 2002: 181-202.
• 21. Stein LM. Teste de Desempenho Escolar: Manual para Aplicação e Interpretação. São Paulo: Casa do Psicólogo Livraria e Editora Ltda, 1994.
• 22. Gunduz E, Demirbilek V, Korkmaz B. Benign rolandic epilepsy: neuropsychological finding. Seizure 1999;8:246-249.
• 23. Binnie CD, Marston D. Cognitive correlates of interictal discharges. Epilepsia 1992;33(Suppl):S11-S19
• 24. Morooka K, Arimoto K, Takagi K, Hoshino K, Kanzaki M. Developmental disabilities in benign childhood epilepsy with centrotemporal spikes. Epilepsia 1995;36(Suppl): S127.
• 25. Miziara CSMG. Avaliação das funções cognitivas na epilepsia focal benigna da infância com descargas centrotemporais. Tese Doutorado. FMUSP, São Paulo. 2003.
• 26. Monjauze C, Tuller L, Hommet C, Barthez MA, Khomsi A. Language in benign childhood epilepsy with centrotemporal spikes abbreviated form: rolandic epilepsy and language. Brain Lang 2005;92:300-308.
• 27. Mayes SD, Calhoun SL. Similarities and differences in Wechsler Intelligence Scale for Children-Third Edition (WISC-III) profiles: support for subtest analysis in clinical referrals. Clin Neuropsychol 2004;18: 559-572.
• 28. Hommet C, Sauerwein HC, Toffol B, Lassonde M. Idiopathic epileptic syndromes and cognition. Neurosci Biobehav Rev 2006;30:85-96.
• 29. Aldenkamp AP, Arends J, Verspeek S, Berting M. The cognitive impact of epileptiform EEG-discharges; relationship with type of cognitive task. Child Neuropsychol 2004;10:297-305.
• 30. Fonseca LC, Tedrus GMAS, Ximenes V. Transient cognitive impairment (TCI) in children with benign childhood epilepsy with centrotemporal spikes. Clin Neurophysiol 2006;117(Suppl):S1-S2.
• 31. Piccirilli M, D'Alessandro P, Tiacci C, Ferroni A. Language lateralization in children with benign partial epilepsy. Epilepsia 1988;29:19-25.

Benign childhood epilepsy with centro-temporal spikes: correlation between clinical, cognitive and EEG aspects

Epilepsia benigna da infância com pontas centrotemporais: correlação entre aspectos clínicos, eletrencefalográficos e cognitivos

Publication Dates

• Publication in this collection
  10 Sept 2007
• Date of issue
  Sept 2007

History

• Accepted
  04 May 2007
• Received
  27 Mar 2007