Abstracts
Children with epilepsy present significant problems concerning attention and comorbidity with attention deficit hyperactivity disorder (ADHD).
Objective
To determine the prevalence of attention complaints, ADHD diagnosis and attention profile in a sample of children and adolescents with idiopathic epilepsy.
Method
36 children and adolescents with idiopathic epilepsy and 37 genre and age matched healthy controls underwent several procedures to diagnose their neuropsychological profile and comorbidity with ADHD.
Results
The prevalence of ADHD was higher in patients with epilepsy [χ2= 4.1, p = 0.043, 6 (16.7%) vs 1 (2.7%)], with worse results in attention related WISC items and factors in patients with epilepsy comparing to the controls, but not between patients with and without ADHD. Clinical characteristics did not influence those results.
Conclusion
This study found a greater prevalence of problems wih attention in pediatric patients with idiopathic epilepsy, but not a distinct profile between those with or without ADHD.
epilepsy; attention; ADHD; childhood; adolescence
Crianças com epilepsia podem apresentar problemas de atenção e comorbidade com transtorno de atenção e hiperatividade (TDAH).
Objetivo
Determinar a prevalência de queixas de atenção, diagnóstico de TDAH e perfil atentivo em uma amostra de crianças e adolescentes com epilepsia idiopática.
Método
36 crianças e adolescentes com epilepsia idiopática e 37 controles saudáveis foram submetidos a vários procedimentos para diagnosticar perfil neuropsicológico e comorbidade com TDAH.
Resultados
A prevalência de TDAH foi maior em pacientes com epilepsia [χ2 = 4,1, p = 0,043, 6 ( 16,7%) vs 1 (2,7%)] , que também apresentaram piores resultados em itens e fatores dependentes de atenção do WISC. Não foram observadas diferenças entre pacientes com e sem TDAH. As características clínicas não influenciaram resultados.
Conclusão
Este estudo encontrou uma maior prevalência de problemas com atenção em pacientes pediátricos com epilepsia idiopática , mas não um perfil distinto entre aqueles com ou sem TDAH.
epilepsia; atenção; TDAH; infância; adolescência
Children and adolescents with epilepsy have more problems with attention, and therefore,
more behavioral complaints and learning deficits11 Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D,
Faraone SV et al. Psychiatric disorders and behavioral characteristics of
pediatric patients with both epilepsy and attention-deficit hyperactivity
disorder. Epilepsy Behav. 2007;10(3):384-8.
http://dx.doi.org/10.1016/j.yebeh.2007.01.010
https://doi.org/10.1016/j.yebeh.2007.01....
,22 Aldenkamp AP, Weber B, Overweg-Plandsoen WC, Reijs R, Mil S.
Educational underachievement in children with epilepsy: a model to predict the
effects of epilepsy on educational achievement. J Child Neurol.
2005;20(3):175-80.
http://dx.doi.org/10.1177/08830738050200030101
https://doi.org/10.1177/0883073805020003...
. In addition to epilepsy-related variables, many comorbidities
contribute to attention deficits in this population, such as learning and psychiatric
(mood and anxiety) disorders and attention deficit hyperactivity disorder (ADHD)11 Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D,
Faraone SV et al. Psychiatric disorders and behavioral characteristics of
pediatric patients with both epilepsy and attention-deficit hyperactivity
disorder. Epilepsy Behav. 2007;10(3):384-8.
http://dx.doi.org/10.1016/j.yebeh.2007.01.010
https://doi.org/10.1016/j.yebeh.2007.01....
.
ADHD is the most prevalent neuropsychiatric disorder among children in school age (5% in
Brazilian sutides)33 Polanczyk G, Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide
prevalence of ADHD: a systematic review and metaregression analysis. Am J
Psychiatry. 2007;164(6):942-8.
http://dx.doi.org/10.1176/appi.ajp.164.6.942
https://doi.org/10.1176/appi.ajp.164.6.9...
,44 Rohde LA, Biederman J, Busnello EA, Zimmermann H, Schmitz M, Martins
S et al. ADHD in a school sample of Bra zilian adolescents: a study of
prevalence, comorbid conditions, and impair ments. J Am Acad Child Adolesc
Psychiatry. 1999;38(6):716-22.
http://dx.doi.org/10.1097/00004583-199906000-00019
https://doi.org/10.1097/00004583-1999060...
. The prevalence of ADHD is higher in
children with epilepsy, ranging from 28.6% to 37.7%11 Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D,
Faraone SV et al. Psychiatric disorders and behavioral characteristics of
pediatric patients with both epilepsy and attention-deficit hyperactivity
disorder. Epilepsy Behav. 2007;10(3):384-8.
http://dx.doi.org/10.1016/j.yebeh.2007.01.010
https://doi.org/10.1016/j.yebeh.2007.01....
,55 Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in
childhood. Dev Med Child Neurol. 2003;45(1):50-4.
http://dx.doi.org/10.1111/j.1469-8749.2003.tb00859.x
https://doi.org/10.1111/j.1469-8749.2003...
,66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
.
Some authors argue that this prevalence must be equal of the general population (3%-5%)
when only patients with normal intelligence and controlled seizures were analyzed77 Kim GH, Kim JY, Byeon JH, Eun BL, Rhie YJ, Seo WH et al. Attention
deficit hyperactivity disorder in epileptic children. J Korean Med Sci.
2012;27(10):1229-32.
http://dx.doi.org/10.3346/jkms.2012.27.10.1229
https://doi.org/10.3346/jkms.2012.27.10....
. Even though, recent population based
studies supports the first hospital-based findings of a greater prevalence88 Cohen R, Senecky Y, Shuper A, Inbar D, Chodick G, Shalev V et al.
Prevalence of epilepsy and attention-deficit hyperactivity (ADHD) disorder: a
population-based study. J Child Neurol. 2013;28(1):120-3.
http://dx.doi.org/10.1177/0883073812440327
https://doi.org/10.1177/0883073812440327...
. Inattention symptoms may indeed
precede the diagnosis of epilepsy in some children99 Hesdorffer DC, Ludvigsson P, Olafsson E, Gudmundsson G, Kjartansson
O, Hauser WA et al. ADHD as a risk factor for incident unprovoked seizures and
epilepsy in children. Arch Gen Psychiatry. 2004;61(7):731-36.
http://dx.doi.org/10.1001/archpsyc.61.7.731
https://doi.org/10.1001/archpsyc.61.7.73...
. Chou et al described a bidirectional association between
ADHD and epilepsy in a longitudinal population based study, with greater hazard risks
for ADHD in children with epilepsy and of epilepsy in those with ADHD during a 7,5 year
follow-up1010 Chou IC, Chang YT, Chin ZN, Muo CH, Sung FC, Kuo HT et al.
Correlation between epilepsy and attention deficit hyperactivity disorder: a
population-based cohort study. PLoS ONE. 2013;8(3):e57926.
http://dx.doi.org/10.1371/journal.pone.0057926
https://doi.org/10.1371/journal.pone.005...
. Children with ADHD
and epilepsy differ from other samples of children with ADHD for having equal gender
prevalence and for having predominantly attention disorders rather than hyperactivity
ones88 Cohen R, Senecky Y, Shuper A, Inbar D, Chodick G, Shalev V et al.
Prevalence of epilepsy and attention-deficit hyperactivity (ADHD) disorder: a
population-based study. J Child Neurol. 2013;28(1):120-3.
http://dx.doi.org/10.1177/0883073812440327
https://doi.org/10.1177/0883073812440327...
,1010 Chou IC, Chang YT, Chin ZN, Muo CH, Sung FC, Kuo HT et al.
Correlation between epilepsy and attention deficit hyperactivity disorder: a
population-based cohort study. PLoS ONE. 2013;8(3):e57926.
http://dx.doi.org/10.1371/journal.pone.0057926
https://doi.org/10.1371/journal.pone.005...
. A Brazilian study reported a higher
prevalence of hyperactivity symptoms1111 Loutfi KS, Carvalho AM, Lamounier JA, Nascimento JA. ADHD and
epilepsy: contributions from the use of behavioral rating scales to investigate
psychiatric comorbidities. Epilepsy Behav. 2011;20(3):484-9.
http://dx.doi.org/10.1016/j.yebeh.2010.12.043
https://doi.org/10.1016/j.yebeh.2010.12....
.
Studies involving attention problems in children with epilepsy show great
heterogeneity11 Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D,
Faraone SV et al. Psychiatric disorders and behavioral characteristics of
pediatric patients with both epilepsy and attention-deficit hyperactivity
disorder. Epilepsy Behav. 2007;10(3):384-8.
http://dx.doi.org/10.1016/j.yebeh.2007.01.010
https://doi.org/10.1016/j.yebeh.2007.01....
,55 Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in
childhood. Dev Med Child Neurol. 2003;45(1):50-4.
http://dx.doi.org/10.1111/j.1469-8749.2003.tb00859.x
https://doi.org/10.1111/j.1469-8749.2003...
,66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
,1212 Caplan R, Siddarth P, Stahl L, Lanphier E, Vona P, Gurbani S et al.
Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.
Epilepsia. 2008;49(11):1838-46.
http://dx.doi.org/10.1111/j.1528-1167.2008.01680.x
https://doi.org/10.1111/j.1528-1167.2008...
,1313 Vega C, Vestal M, DeSalvo M, Berman R, Chumg M, Blumenfeld H et al.
Differentiation of attention-related problems in childhood absence epilepsy.
Epilepsy Behav. 2010;19(1):82-5.
http://dx.doi.org/10.1016/j.yebeh.2010.06.010
https://doi.org/10.1016/j.yebeh.2010.06....
concerning design, inclusion criteria, sample size,
neuropsychological and clinical batteries, which interferes in drawing precise
conclusions about the kind of relation between cognitive dysfunction and epilepsy: is it
a predominant causal condition or is it a matter of comorbidity and similar
neurobiological background? The study of a sample with normal intelligence and
idiopathic epilepsy must favor the understanding of direct relationships between
epilepsy and ADHD. It’s also important to search for specific cognitive profile
for these children, both aims of this cross sectional study. A broader approach to the
children with well controled epilepsy must include a thorough behavioral and cognitive
assessment, since problems in those areas may occur irrespective of seizure control
status. Researches must address these questions in order to improve clinical
decisions.
Our main research hypothesis to be tested were: there was higher prevalence of attention complaints and ADHD diagnosis in children and adolescents with epilepsy; the attention profile of patients with epilepsy is worse than controls; there is an association between clinical characteristics of epilepsy (disease duration, seizure frequency, type of seizure and polytherapy) and clinical complaints/attention profile; the attention profile and academic achievement of patients with epilepsy and ADHD were worse that those patients with epilepsy without this comorbidity.
METHOD
Subjects
Thirty six children of an original sample of 53 consecutively seen (February 2009
- February 2010) pediatric patients treated in the Pediatric Neurology clinic of
the Hospital Universitário Antônio Pedro, located in
the city of Niterói (Rio de Janeiro, Brazil), were selected according to
the following criteria: having diagnosis of idiopathic epilepsy syndrome
criteria (1981, 1989)1414 Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, VaEmde Bas
W et al. Revised terminology and concepts for organization of seizures and
epilepsies: report of the ILAE Commission on Classification and Terminology,
2005-2009. Epilepsia. 2010;51(4):676-85.
http://dx.doi.org/10.1111/j.1528-1167.2010.02522.x
https://doi.org/10.1111/j.1528-1167.2010...
;
formal testing of intellectual functioning (WISC III) with intelligence quocient
(IQ) > = 80; having normal clinical neurological examination and
neuroimaging exams. The main reason for discarding 17 patients was IQ. The
caregivers of children and adolescents with epilepsy were interviewed for
informed consent and medical information concerning epilepsy. The seizure types
were classified according to International League Against Epilepsy (ILAE)
criteria1414 Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, VaEmde Bas
W et al. Revised terminology and concepts for organization of seizures and
epilepsies: report of the ILAE Commission on Classification and Terminology,
2005-2009. Epilepsia. 2010;51(4):676-85.
http://dx.doi.org/10.1111/j.1528-1167.2010.02522.x
https://doi.org/10.1111/j.1528-1167.2010...
. Regarding the
frequency of seizures, the patients were classified into three groups: no
seizures (patients without any seizures in the last year), few seizures
(patients with one to eleven seizures per year), and many seizures (patients
with more than eleven attacks a year). Thirty seven healthy controls, matched in
terms of age and gender were analyzed using the same clinical and
neuropsychological batteries. Those controls had the same socioeconomical and
cultural background (same region of habitation) and attended a nearby primary
school. Their healthy status was assessed by a thorough clinical examination and
interview with parentes by one of the authors (HSMF). The difference between the
number of patients and controls is due to asymmetric losses because of low
IQ.
There was no significant difference in the average age (11.2 ± 2.1 vs. 11.4 ± 2.1 years), gender distribution (55.5% vs. 64.9% males) and level of education (5.9 ± 2.2 vs. 6.1 ± 2.3 years of study) between patients and healthy controls. There was a significant difference between educational levels of caregivers, which were higher in the health control sample (9.3 ± 4.3 vs. 12.1 ± 3.9 years of studying informed by them; p = 0.006). The duration of epilepsy ranged from 10 to 120 months, with an average of 49.1 months (standard deviation (SD) 27.2). Family history of epilepsy was negative in 27 patients (75%). Twenty-three patients (63.9%) had no seizures in the last year and 8 patients (22.2%) had a few seizures. Nineteen patients (52.8%) had generalized seizures, 13 patients (35.3%) had focal seizures and 4 patients (11.9%) had more than one kind of seizure. Thirty-one patients (86.1%) used only one antiepileptic drug (AED), 4 patients (11.1%) used more than one AED and one patient (2.8%) did not go under drug treatment.
Assessment
Cross sectional study. All the measures were done in two visits to the hospital with one week interval. Children and adolescents with epilepsy have undergone neuropsychological evaluation to determine intellectual level, attention profile and academic achievement. The tests used were Weschler Intelligence Scale for Children 3rd edition – WISC-III1515 Wechsler, DW. WISC III: escala de Inteligencia Wechsler para crianças: manual. 3a ed. São Paulo: Casa do Psicologo; 2002. (total IQ, verbal and performance IQ; processing speed and freedom from distractibility factors; age-corrected values of subtests of the folowwing subtests: Coding, Arithmetic, Symbol Search and Digit Spam), Raven’s Progressive Matrices1616 Raven, JC. Matrizes progressivas: escala geral. Rio de Janeiro: CEPA; 1997. (RPM; raw scores), Sustained Attention Test (SAT; raw scores)1717 Cambraia SV. Atenção concentrada (AC): manual. São Paulo: Vetor; 2003., TAVIS-III – Test of Visual Attention – 3rd Edition (raw scores)1818 Duchesne M, Mattos P. Normatização de um teste computadorizado de atenção visual. Arq Neuropsiquiatr. 1997;55(1):62-9. and School Performance Test – SPT1919 Stein LM. TDE: Teste de desempenho escolar: manual para aplicação e interpretação. São Paulo: Casa do Psicólogo; 1994. (raw scores). The WISC-III consists of 13 subtests organized into two groups: verbal and performance IQ. The results of children in subtest results in three IQ scales (verbal IQ, performance IQ and total IQ) and four optional scores named index factors (processing speed, perceptual organization, freedoom from distractibility and verbal comprehension)1515 Wechsler, DW. WISC III: escala de Inteligencia Wechsler para crianças: manual. 3a ed. São Paulo: Casa do Psicologo; 2002.. RPM is a test of non-verbal intelligence, with a strong influence of attention and executive functions1616 Raven, JC. Matrizes progressivas: escala geral. Rio de Janeiro: CEPA; 1997.. SAT is a kind of cancellation test that analyzes sustained and selective attention. TAVIS-III is computerized Brazilian test that analyzes sustained, selective and alternating attention1818 Duchesne M, Mattos P. Normatização de um teste computadorizado de atenção visual. Arq Neuropsiquiatr. 1997;55(1):62-9.. SPT provides an objective assessment of the essential abilities to school performance, more specifically, writing, arithmetics and reading, according to school age and Brazilian school policies1919 Stein LM. TDE: Teste de desempenho escolar: manual para aplicação e interpretação. São Paulo: Casa do Psicólogo; 1994..
The clinical assessment of ADHD comorbidity has been carried out with both
SNAP-IV2020 Mattos, P, Serra-Pinheiro MA, Rhode LA, Pinto D.
Apresentação de uma versão em português para uso no Brasil
do instrumento MTA-SNAP-IV de avaliação de sintomas de transtorno do
déficit de atenção/hiperatividade e sintomas de transtorno
desafiador e de oposição. Rev Psiquiatr Rio Gd Sul.
2006;28,(3):290-97.
http://dx.doi.org/10.1590/S0101-81082006000300008
https://doi.org/10.1590/S0101-8108200600...
, which was
filled by caregivers and teachers, and clinical interview with caregivers based
on the DSM-IV criteria for ADHD. The neuropsychology team were blinded for the
ADHD diagnosis.
Data Analysis
The Statistical Package for Social Sciences Release (SPSS 16.0) for Windows was used to analyze data. The demographic, clinical, neuropsychological assessment and school performance data were all presented in descriptive statistics. The hypothesis tests were made within the specific goals and selected according to the variable type in use, categorical, continuous and discrete quantity. Frequency distributions were used to describe qualitative data (dichotomous and polychotomous categorical).
The results of attention were analyzed in relation to clinical, intelligence and academic achievement data. Neuropsychological and academic data were compared between patients and controls and between patients with and without ADHD. The following non-parametric statistical tests were used (sample didn't pass the normalty hypothesis by the Kolmogorov-Smirnov test): Mann-Whitney, Kruskal-Wallis and Spearman (p-value lower than 0.05 is considered significant, reported for two-tailed test).
RESULTS
Neuropsychological evaluation
Table 1 describes data on IQ, WISC attention dependent subtests, nonverbal intelligence and academic performance of children and adolescentes with epilepsy and healthy controls. Children and adolescents with epilepsy have lower mean results of perfromance IQ, processing speed and freedom from distractibility factors and weighted points of Coding, Symbol Search and Digit Spam than healthy controls. Table 2 describes the results of SAT and TAVIS. There is no differences between groups for the results of these attention tests.
Attention complaints and ADHD diagnosis
Table 3 describes the average results of the SNAP-IV which have been filled by caregivers and teachers. Table 4 describes ADHD diagnosis. Among the six diagnosed cases of ADHD in patients with epilepsy, 3 (50%) presented the inattentive subtype and 3 (50%) presented the combined subtype. Patients with epilepsy and ADHD had focal or generalized seizures in equal proportions. There was no significant difference between patients with epilepsy with or without ADHD in relation to age, genre, level of education or epilepsy duration. The single case of ADHD in the control group presented the combined subtype.
Comparing clinical data and neuropsychological profile
There were no significant associations between clinical aspects of epilepsy (focal x generaized seizures, disease duration, seizure frequency and number of AED) and neuropsychological profile (IQ factors or subtests; attention), except for two: more seizures and difficulty in alternate attention; focal seizures and difficulty in sustained attention (reaction time 0.72 ± 0.35 vs. 0.53 ± 0.26; p = 0.04).
Comparing academic achievement and neuropsychological profile/ADHD diagnosis
Table 5 shows comparisons of academic achievement and neuropsychological profile among patients with and without ADHD. There were no significant differences except for two WISC items (Coding and Symbol Search). Because we found only one healthy control with ADHD we cannot test differences of the neuropschological among subgroups of cases and controls with or without ADHD.
DISCUSSION
The present study reveals that the prevalence of ADHD was higher in children and
adolescents with epilepsy (16.7%) than in controls (2.7%), which was consistent with
several studies found in literature. Although such consistency has been found, our
results showed lower prevalence rates than the ones found in literature. Other
studies dealed with more heterogenic or less seizure controlled samples of epilepsy,
maybe leading to higher rate of attentional problems. Herman et al.66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
found in their sample 31% of
patients with ADHD compared to 6% of controls. The authors evaluated 75 children
with newly diagnosed idiopathic epilepsy and found no association between attention
deficits and clinical variables of epilepsy, similarly to the results found in this
study. A Brazilian study, with a similar sample size (n = 30) and no controls found
a prevalence of 53.3%1111 Loutfi KS, Carvalho AM, Lamounier JA, Nascimento JA. ADHD and
epilepsy: contributions from the use of behavioral rating scales to investigate
psychiatric comorbidities. Epilepsy Behav. 2011;20(3):484-9.
http://dx.doi.org/10.1016/j.yebeh.2010.12.043
https://doi.org/10.1016/j.yebeh.2010.12....
. Cohen et
al., in a population based study with 284,419 children found a prevalence of 5 out
of 1,000 children, 27.7% of them also have epilepsy88 Cohen R, Senecky Y, Shuper A, Inbar D, Chodick G, Shalev V et al.
Prevalence of epilepsy and attention-deficit hyperactivity (ADHD) disorder: a
population-based study. J Child Neurol. 2013;28(1):120-3.
http://dx.doi.org/10.1177/0883073812440327
https://doi.org/10.1177/0883073812440327...
.
We found a similar distribution of combined and inattentive subtypes of ADHD,
consistent with the previously mentioned authors, but different from the specific
literature concerning ADHD, where there is a predominance of the combined subtype
(2/3) in relation to the inattentive subtype33 Polanczyk G, Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide
prevalence of ADHD: a systematic review and metaregression analysis. Am J
Psychiatry. 2007;164(6):942-8.
http://dx.doi.org/10.1176/appi.ajp.164.6.942
https://doi.org/10.1176/appi.ajp.164.6.9...
. In a smaller study with a prospective design,
Bennett-Back et al. analyzed 40 children and their siblings, and also found a higher
prevalence of ADHD in children with epilepsy (70% vs 16.7%). They found more
children with the inattentive subtype2121 Bennett-Back O, Keren A, Zelnik N. Attention-deficit hyperactivity
disorder in children with benign epilepsy and their siblings. Pediatr Neurol.
2011;44(3):187-92.
http://dx.doi.org/10.1016/j.pediatrneurol.2010.10.003
https://doi.org/10.1016/j.pediatrneurol....
. The greater prevalence of attentional problems must imply
a clinical profile more prone to academic than behavioral problems and a greater
need of scholar support. Vega et al.1313 Vega C, Vestal M, DeSalvo M, Berman R, Chumg M, Blumenfeld H et al.
Differentiation of attention-related problems in childhood absence epilepsy.
Epilepsy Behav. 2010;19(1):82-5.
http://dx.doi.org/10.1016/j.yebeh.2010.06.010
https://doi.org/10.1016/j.yebeh.2010.06....
are the ones to quote a higher prevalence of hyperactivity
in samples with absence epilepsy. The scales of ADHD-related symptoms did not differ
between samples on average. This may be related to the low total number of cases of
ADHD in both samples. Kim et al. argued that this higher prevalence of ADHD
diagnosis in children with epilepsy must be a bias of severe cases, finding a 6.9%
prevalence of ADHD in a sample of 102 children with normal intelligence and well
controlled seizures77 Kim GH, Kim JY, Byeon JH, Eun BL, Rhie YJ, Seo WH et al. Attention
deficit hyperactivity disorder in epileptic children. J Korean Med Sci.
2012;27(10):1229-32.
http://dx.doi.org/10.3346/jkms.2012.27.10.1229
https://doi.org/10.3346/jkms.2012.27.10....
, but the
previous mentioned studies were on benign cases. Our study endorses the overall
tendency to find a higher prevalence of ADHD in this population, enrolling a similar
population as Kim et al.77 Kim GH, Kim JY, Byeon JH, Eun BL, Rhie YJ, Seo WH et al. Attention
deficit hyperactivity disorder in epileptic children. J Korean Med Sci.
2012;27(10):1229-32.
http://dx.doi.org/10.3346/jkms.2012.27.10.1229
https://doi.org/10.3346/jkms.2012.27.10....
. Another
Brazilian study1111 Loutfi KS, Carvalho AM, Lamounier JA, Nascimento JA. ADHD and
epilepsy: contributions from the use of behavioral rating scales to investigate
psychiatric comorbidities. Epilepsy Behav. 2011;20(3):484-9.
http://dx.doi.org/10.1016/j.yebeh.2010.12.043
https://doi.org/10.1016/j.yebeh.2010.12....
sought an
agreement regarding the completion of the scales for ADHD by parents and teachers of
children with epilepsy. The scales filled by teachers are more negative for
inattention, showing a greater number of symptoms of hyperactivity and impulsivity.
Another Brazilian study also found a predominance of hyperactivity symptoms1111 Loutfi KS, Carvalho AM, Lamounier JA, Nascimento JA. ADHD and
epilepsy: contributions from the use of behavioral rating scales to investigate
psychiatric comorbidities. Epilepsy Behav. 2011;20(3):484-9.
http://dx.doi.org/10.1016/j.yebeh.2010.12.043
https://doi.org/10.1016/j.yebeh.2010.12....
. Polanczyk et al., in a
metanalysis about the prevalence of ADHD in general population affirms that the
variation in the prevalence is more related to methodological characteristics of the
various studies than to geographical diferences33 Polanczyk G, Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide
prevalence of ADHD: a systematic review and metaregression analysis. Am J
Psychiatry. 2007;164(6):942-8.
http://dx.doi.org/10.1176/appi.ajp.164.6.942
https://doi.org/10.1176/appi.ajp.164.6.9...
, we can assume the same for variations in ADHD
subtypes.
Due to the reduced sample used in this study, it was possible to compare only focal
and generalized epilepsy, but not specific seizure subtypes or epileptic syndromes,
with no differences in neuropsychological profile. Dafoulis et al. described less
behavioral problems in benign focal epilepsy than generalized epilepsy2222 Dafoulis V, Kalyva E. Factors associated with behavioral problems in
children with idiopathic epilepsy. Epilepsy Res. 2012;100(1-2):104-12.
http://dx.doi.org/10.1016/j.eplepsyres.2012.01.014
https://doi.org/10.1016/j.eplepsyres.201...
. Alonso et al.2323 Alonso-Pietro E, Álvarez MA, Reyes-Berazain A, Rojas-Massipe E,
Romero-García C, Pando A. [Attention disorders in a sample of complex
partial epileptic children]. Rev Neurol. 2001;33(10):991-3.
Spanish., found an association between
attention and frequency of seizures in patients with focal seizures with impairment
of consciouness/awareness. In this study, a worse alternate attention in TAVIS-III
in patients with less controlled seizures could be found. Other authors found
greater inattention in specific groups of idiopathic epilepsy, such as absence
epilepsy1212 Caplan R, Siddarth P, Stahl L, Lanphier E, Vona P, Gurbani S et al.
Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.
Epilepsia. 2008;49(11):1838-46.
http://dx.doi.org/10.1111/j.1528-1167.2008.01680.x
https://doi.org/10.1111/j.1528-1167.2008...
,1313 Vega C, Vestal M, DeSalvo M, Berman R, Chumg M, Blumenfeld H et al.
Differentiation of attention-related problems in childhood absence epilepsy.
Epilepsy Behav. 2010;19(1):82-5.
http://dx.doi.org/10.1016/j.yebeh.2010.06.010
https://doi.org/10.1016/j.yebeh.2010.06....
. For the same reason (few
patients in polytheraphy and high seizure frequency), we couldn't find any
relation of the cognitive profile with these variables. Dafoulis et al. described
worse behavior problems, including symptoms of ADHD in chronic idiopathic epilepsy,
related to age of onset of epilepsy (later), number of antiepileptic drugs
(polytherapy) and gender (male), but not seizure frequency or age2222 Dafoulis V, Kalyva E. Factors associated with behavioral problems in
children with idiopathic epilepsy. Epilepsy Res. 2012;100(1-2):104-12.
http://dx.doi.org/10.1016/j.eplepsyres.2012.01.014
https://doi.org/10.1016/j.eplepsyres.201...
. Our results endorses the
assumption that the absence of clinical variables of gravity must not preclude the
clinician of a comprehensive search of cognitive problems in all patients with
epilepsy.
Regarding demographic data, one should also mention that there was a higher level of education in healthy control caregivers, a difference of approximately three years. Despite this difference, we found no potential influences, once the academic achievement of the two samples was similar. We found no studies that investigate the influence of this factor on all samples of epilepsy, although the relation between a child's academic performance and the educational level of parents is known.
No significant differences between IQ of patients and controls were found, once this
is a sample with idiopathic epilepsy where, by definition, there are no severe
neurological deficits. However, there were lower scores on IQ factors and additional
factors related to attention and executive functioning (performance IQ, processing
speed and freedom from distractibility factors), as well as specific WISC-III
subtests which are more dependent on attention (Coding, Symbol Search) and working
memory (Digit Spam). The studies using the WISC (in its revised version, WISC-R, in
the majority) have explored further full scale IQ than factors and subtests66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
. Alonso et al. describe compromise
in the various subtests of the WISC-R for patients compared to controls2323 Alonso-Pietro E, Álvarez MA, Reyes-Berazain A, Rojas-Massipe E,
Romero-García C, Pando A. [Attention disorders in a sample of complex
partial epileptic children]. Rev Neurol. 2001;33(10):991-3.
Spanish.. It is, though, important to
mention that they only analyzed epilepsy with focal seizures with impairment of
consciouness (previously classified as focal complex). Hermann et al.66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
analyzed the subtest Coding with a
larger battery of executive functions, finding difficulties in patients with
idiopathic epilepsy (there is no reference if generalized or focal). Again, the
diversity of methods hinders a more accurate comparison of data found in the
literature. In contrast, the specific assessment of attention showed no significant
differences between patients and controls. Several studies have shown significant
differences using various tests of attention, all with similar characteristics as
the ones found in this study, evaluating visual attention in selective and sustained
modalities. The best known test is CPT (Continuous Performance Test) used by Hermann
et al.66 Hermann B, Jones J, Dabbs K, Allen CA, Sheth R, Fine J et al. The
frequency, complications and aetiology of ADHD in new onset paediatric epilepsy.
Brain. 2007;130(12):3135-48.
http://dx.doi.org/10.1093/brain/awm227
https://doi.org/10.1093/brain/awm227...
. TAVIS III has a similar
structure to CPT. On the other hand, the other tests used (SAT) are tests of
cancellation, which also evaluate the selective and sustained attention1717 Cambraia SV. Atenção concentrada (AC): manual. São
Paulo: Vetor; 2003.. TAVIS III also assesses
alternating attention1818 Duchesne M, Mattos P. Normatização de um teste
computadorizado de atenção visual. Arq Neuropsiquiatr.
1997;55(1):62-9.. The use
of raw scores and the small sample may hinder more accurate results on attention
deficits.
When comparing patients with epilepsy in relation to neuropsychological variables and
the diagnosis of ADHD, we found a significant difference only in the result of
Raven's Progressive Matrices1616 Raven, JC. Matrizes progressivas: escala geral. Rio de Janeiro:
CEPA; 1997. and two WISC items (Coding and Symbol Search), and a worse
result for those with comorbidity. Raven's is a test of nonverbal intelligence
with great dependence on attention, as well as visual perception55 Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in
childhood. Dev Med Child Neurol. 2003;45(1):50-4.
http://dx.doi.org/10.1111/j.1469-8749.2003.tb00859.x
https://doi.org/10.1111/j.1469-8749.2003...
, as those two WISC items.
Semrud-Clikeman et al.2424 Semrud-Clikeman M, Wical B. Components of attention in children with
complex partial seizures with and without ADHD. Epilepsia. 1999;40(2):211-5.
http://dx.doi.org/10.1111/j.1528-1157.1999.tb02077.x
https://doi.org/10.1111/j.1528-1157.1999...
, studiyng
a diferente group patients with epilepsy (complex focal seizures), described that
patients with epilepsy had worse results on tests of attention regardless of having
comorbidity with ADHD, although this comorbidity was associated with worse outcomes.
Other studies evaluate separately the prevalence of ADHD and neuropsychology of
attention. Macallister et al. tried to describe specific neuropsychological
endophenotypes for children with epilepsy with and with ADHD of both subtypes
inattentive and combined. Those with ADHD and epilepsy have worse results of
intellectual function, auditory attention and working memory. In a follow-up of the
patients, the authors described the negative influence of seizure frequency and
number of antiepileptic drugs on the results2525 MacAllister WS, Vasserman M, Vekaria P, Miles-Mason E, Hochsztein N,
Bender HA. Neuropsychological endophenotypes in ADHD with and without epilepsy.
Appl Neuropsychol Child. 2012 Jul;1(2):121-8.
http://dx.doi.org/10.1080/21622965.2012.709421
https://doi.org/10.1080/21622965.2012.70...
. Bechtel et al. described that children with ADHD with
or without epilepsy functions worse than health control in working memory tests,
with no specific difference, with similar results in pharmacological response and
functional neuroimaging, suggesting the view that ADHD with and without epilepsy
shares a common underlying2626 Bechtel N, Kobel M, Penner IK, Specht K, Klarhöfer M, Scheffler
K, et al. Attention-deficit/hyperactivity disorder in childhood epilepsy: a
neuropsychological and functional imaging study. Epilepsia. 2012;53(2):325-33.
http://dx.doi.org/10.1111/j.1528-1167.2011.03377.x
https://doi.org/10.1111/j.1528-1167.2011...
. We
know that many factors contribute to the results of neuropsychological tests,
specially when it comes to epilepsy. In addition, the absence of neuropsychological
evidence of deficits doesn't impedes the diagnosis of ADHD. Then, the absence
of neuropsychological differences between the two groups is not contrary to the
existence of comorbidity in this population. Furthermore, when dealing with people
with lower income and social levels, other factors may influence the cognitive
results. Our sample consisted of patients with epilepsy with little or no seizures
of unknown etiology. It presented a distinct cognitive profile in some tests
concerning attention and a higher prevalence of ADHD than controls. There has not
been found any additional difference with ADHD comorbidity. As the potential effect
of clinical variables of epilepsy on cognitive impairment is known2727 Schubert R. Attention deficit disorder and epilepsy. Pediatr Neurol.
2005;32(1):1-10.
http://dx.doi.org/10.1016/j.pediatrneurol.2004.06.007
https://doi.org/10.1016/j.pediatrneurol....
, one could postulate that these
aspects should not be exclusive determinants of cognitive impairment in these
patients.
Dealing with a sample of tertiary care patients led to a more severe cognitive
profile of the initial sample, with the exclusion of 14 patients because of low IQs.
Our final sample, therefore, were of patients with less severe epilepsy. This
precaution was important because the main objective of this study was to relate
attention difficulties clinical aspects of epilepsy and comorbid ADHD, which would
be jeopardized if we considered patients with lowered intellectual capacity. In a
review of 2009, our group found nine studies on this topic2828 Costa CRM, Maia Filho HS, Gomes MM. Epilepsia e saúde mental
infantil. J Epilepsy Clin Neurophysiol. 2006;12(2):79-88.
http://dx.doi.org/10.1590/S1676-26492006000300007
https://doi.org/10.1590/S1676-2649200600...
. Although all these studies selected patients
without mental retardation (with the exception of Gonzalez-Heydrich et al.11 Gonzalez-Heydrich J, Dodds A, Whitney J, MacMillan C, Waber D,
Faraone SV et al. Psychiatric disorders and behavioral characteristics of
pediatric patients with both epilepsy and attention-deficit hyperactivity
disorder. Epilepsy Behav. 2007;10(3):384-8.
http://dx.doi.org/10.1016/j.yebeh.2007.01.010
https://doi.org/10.1016/j.yebeh.2007.01....
, where almost 40% of the sample had
IQ scores lower than 80), most researchers included children with very different
etiologies (idiopathic, symptomatic and cryptogenic) and level of control of
epileptic seizures, which limits the comparison of our data with the literature and
generalization of results. The strict inclusion criteria in our sample aimed at
reducing the range of possible cognitive and clinical interferences, but led to a
small sample size, hindering the statistical significance appreciation of many
findings. Kim et al. studied a similar population but of a greater sample size (102)
although there are no data about neuropsychological function77 Kim GH, Kim JY, Byeon JH, Eun BL, Rhie YJ, Seo WH et al. Attention
deficit hyperactivity disorder in epileptic children. J Korean Med Sci.
2012;27(10):1229-32.
http://dx.doi.org/10.3346/jkms.2012.27.10.1229
https://doi.org/10.3346/jkms.2012.27.10....
.
Other aspect that must be adressed is the possible comorbidities with other
neuropsychiatric disorders other than ADHD in this sample. Another study of our
group, analysing the same sample using the Child Behavior Checklist (CBCL) found
worse results in psychopathology in children with epilepsy with certain
psychopathological variables related to IQ (sluggish cognitive tempo, aggressive
behavior, attention problem and activities) and academic performance (conduct,
breaking rule behavior and school), also with no relation to clinical variables2929 Moreira FS, Lima AB, Fonseca PC, Maia Filho HS. Mental health of
children and adolescents with epilepsy: analysis of clinical and
neuropsichological aspects. Arq Neuropsiquiatr. 2014;72(8):613-8.
http://dx.doi.org/10.1590/0004-282X20140098
https://doi.org/10.1590/0004-282X2014009...
.
The complexity of these relations and the multifactor nature of cognitive dysfunction in epilepsy seem to turn the implemented methodology (cross-sectional) too limited to confirm a causal relationship between attention deficit and epilepsy versus comorbid ADHD. However, it is considered an important endeavor to further investigate this question.
In conclusion, specific reasons for attention deficit in children with epilepsy are not clearly elucidated, but there is strong evidence that the problem exists and must be identified early. The results reinforce the importance of studying cognitive comorbidity in epilepsy and also clinical and neuropsychological analysis. That would allow the creation of cognitive and educational measures suited to this population, with the objective of improving their academic performance and thus their quality of life, minimizing the effects of a disease that can often be limiting, such as epilepsy.
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22Dafoulis V, Kalyva E. Factors associated with behavioral problems in children with idiopathic epilepsy. Epilepsy Res. 2012;100(1-2):104-12. http://dx.doi.org/10.1016/j.eplepsyres.2012.01.014
» https://doi.org/10.1016/j.eplepsyres.2012.01.014 -
23Alonso-Pietro E, Álvarez MA, Reyes-Berazain A, Rojas-Massipe E, Romero-García C, Pando A. [Attention disorders in a sample of complex partial epileptic children]. Rev Neurol. 2001;33(10):991-3. Spanish.
-
24Semrud-Clikeman M, Wical B. Components of attention in children with complex partial seizures with and without ADHD. Epilepsia. 1999;40(2):211-5. http://dx.doi.org/10.1111/j.1528-1157.1999.tb02077.x
» https://doi.org/10.1111/j.1528-1157.1999.tb02077.x -
25MacAllister WS, Vasserman M, Vekaria P, Miles-Mason E, Hochsztein N, Bender HA. Neuropsychological endophenotypes in ADHD with and without epilepsy. Appl Neuropsychol Child. 2012 Jul;1(2):121-8. http://dx.doi.org/10.1080/21622965.2012.709421
» https://doi.org/10.1080/21622965.2012.709421 -
26Bechtel N, Kobel M, Penner IK, Specht K, Klarhöfer M, Scheffler K, et al. Attention-deficit/hyperactivity disorder in childhood epilepsy: a neuropsychological and functional imaging study. Epilepsia. 2012;53(2):325-33. http://dx.doi.org/10.1111/j.1528-1167.2011.03377.x
» https://doi.org/10.1111/j.1528-1167.2011.03377.x -
27Schubert R. Attention deficit disorder and epilepsy. Pediatr Neurol. 2005;32(1):1-10. http://dx.doi.org/10.1016/j.pediatrneurol.2004.06.007
» https://doi.org/10.1016/j.pediatrneurol.2004.06.007 -
28Costa CRM, Maia Filho HS, Gomes MM. Epilepsia e saúde mental infantil. J Epilepsy Clin Neurophysiol. 2006;12(2):79-88. http://dx.doi.org/10.1590/S1676-26492006000300007
» https://doi.org/10.1590/S1676-26492006000300007 -
29Moreira FS, Lima AB, Fonseca PC, Maia Filho HS. Mental health of children and adolescents with epilepsy: analysis of clinical and neuropsichological aspects. Arq Neuropsiquiatr. 2014;72(8):613-8. http://dx.doi.org/10.1590/0004-282X20140098
» https://doi.org/10.1590/0004-282X20140098
Publication Dates
-
Publication in this collection
Feb 2015
History
-
Received
22 Feb 2014 -
Reviewed
20 Oct 2014 -
Accepted
07 Nov 2014