Frontal Lobe Dysfunction in Children With
Temporal Lobe Epilepsy
Patrícia Rzezak, BSc*, Daniel Fuentes, PhD*, Catarina A. Guimarães, PhD†,
Sigride Thome-Souza, MD‡§, Evelyn Kuczynski, MD, PhD§, Li M. Li, MD, PhD†,
Renata C. Franzon, MD, PhD†, Claudia C. Leite, MD, PhD¶, Marilisa Guerreiro, MD, PhD†,
and Kette D. Valente, MD, PhD‡§
There is evidence that adults with temporal lobe
epilepsy present executive impairments. However,
there is limited information in children, especially
when using a comprehensive neuropsychologic bat-
tery. We aimed to: 1) investigate the presence and
severity of executive dysfunctions in children with
temporal lobe epilepsy, and 2) determine the impli-
cations of clinical variables (including etiology) in
the occurrence and severity of executive dysfunction,
using eight paradigms. Thirty-one children with
temporal lobe epilepsy were evaluated and com-
pared with 21 age-matched controls. Patients with
temporal lobe epilepsy had significantly worse per-
formance than controls. Intragroup analysis indi-
cated that patients with symptomatic epilepsy were
more impaired than those with cryptogenic epilepsy.
In the former group, patients with mesial lesions
performed worse than those with lateral lesions.
Regarding the severity of executive dysfunction,
83.87% manifested severe to moderate executive
impairment. Early age of onset, longer duration of
epilepsy, and use of polytherapy were correlated with
worse executive dysfunction. These findings indicated
the presence of frontal lobe dysfunction in children
with temporal lobe epilepsy, with worse performance
in those with mesial temporal lobe epilepsy, early
onset, longer duration of disease, and use of polythe-
rapy. Our study corroborates the hypothesis that tem-
poral lobe epileptogenic activity affects the extratem-
poral regions that mediate attentional and executive
functions. © 2007 by Elsevier Inc. All rights reserved.
From the *Psychology and Neuropsychology Unit, Institute of
Psychiatry, Clinical Hospital, Medical School, University of São
Paulo, São Paulo, Brazil; †Department of Neurology, University of
Campinas, Campinas, Brazil; and ‡Laboratory of Clinical
Neurophysiology, Institute of Psychiatry and Department of
Psychiatry, §Project for the Study of Psychiatric Disorders in Children
and Adolescents with Epilepsy, Institute of Psychiatry, and ¶Institute
and Department of Radiology, Clinical Hospital, Medical School,
University of São Paulo, São Paulo, Brazil.
176 PEDIATRIC NEUROLOGY Vol. 37 No. 3
doi:10.1016/j.pediatrneurol.2007.05.009 ● 0887-8994/07/$—see front matter
Rzezak P, Fuentes D, Guimarães CA, Thome-Souza S,
Kuczynski E, Li LM, Franzon RC, Leite CC, Guerreiro M,
Valente KD. Frontal lobe dysfunction in children with
temporal lobe epilepsy. Pediatr Neurol 2007;37:176-185.
Introduction
In temporal lobe epilepsy, the presence of specific
cognitive deficits, such as learning and memory impair-
ments (functions known to be associated with the temporal
lobes), are fully recognized as part of the typical clinical
picture [1-3].
In addition, some studies demonstrated the occurrence
of frontal lobe dysfunction, characterized by executive
malfunctioning, in adults with temporal lobe epilepsy.
These patients show perseverative responding and impair-
ments in abstraction and problem-solving abilities [4-7].
Two hypotheses were postulated to explain this execu-
tive dysfunction in patients with temporal lobe epilepsy.
According to Corcoran and Upton [8], perseverative re-
sponding could be explained by an impairment of working
memory, determined by the involvement of the hippocam-
pus per se. In their study, patients with hippocampal
sclerosis performed poorly in a modified version of the
Wisconsin Card Sorting Test compared with patients with
either temporal neocortical lesions or frontal lobe lesions.
On the other hand, Hermann and Seidenberg [5] proposed
that temporal lobe epileptogenic activity might disrupt the
extratemporal lobe connections responsible for executive
Communications should be addressed to:
Dr. Valente; Rua Jesuíno Arruda 901/51; São Paulo,
04532-082 São Paulo, Brazil.
E-mail: kettevalente@msn.com
Received July 31, 2006; accepted May 25, 2007.
© 2007 by Elsevier Inc. All rights reserved.
skills, based on a correlation between performance and
seizure control, but not with etiology.
In children with temporal lobe epilepsy, many neuro-
psychologic aspects are unclear, even when considering
extensively studied temporal lobe functions, such as mem-
ory. For instance, there is evidence of memory deficits
when these patients are compared with normal controls
[9-14]. However, whether children and adolescents with
temporal lobe epilepsy do [15-18] or do not [19,20] have
hemispheric specialization for verbal and visual memory
remains controversial.
Hernandez et al. [21] analyzed frontal lobe dysfunction
(planning abilities, working memory, impulse control,
attention, and certain aspects of motor coordination) in
children with frontal lobe epilepsy by using children with
temporal lobe epilepsy, with idiopathic generalized epi-
lepsy (typical absences) and normal controls for compar-
ison. Children with frontal lobe epilepsy exhibited deficits
in planning and impulse control, and more coordination
problems than the others. A further study [22], with
similar characteristics, corroborated these findings, i.e.,
children with frontal lobe epilepsy had worse performance
in executive function tests, whereas temporal lobe epilepsy
only showed impairments in memory tests.
These findings, revealing worse performance in executive
tests in children with frontal lobe epilepsy compared with
children with temporal lobe epilepsy, were expected, but do
not exclude subtle executive dysfunctions in temporal lobe
epilepsy that could impair children’s daily-life performance.
Therefore, the importance of studying executive functions in
temporal lobe epilepsy is crucial, because these executive
deficits may remain undervalued in these children.
The only study that specifically addressed frontal lobe
dysfunction in children with temporal lobe epilepsy [23]
found poor performance in executing and planning tasks in
children with hippocampal sclerosis compared with lateral
temporal lobe or frontal lobe lesions, when using one
paradigm: the Wisconsin Card Sorting Test.
To date, no studies have used a comprehensive neuro-
psychologic battery to evaluate executive functions in
children with temporal lobe epilepsy compared with age-
matched, normal controls. For this reason, we aimed to:
1) investigate the presence and severity of executive
dysfunctions in children with temporal lobe epilepsy, and
2) determine the implications of clinical variables of
epilepsy and etiology on the occurrence and severity of
executive dysfunction, by using an extensive neuropsy-
chologic evaluation consisting of eight paradigms.
Methods
Patients
We prospectively evaluated 31 consecutive children and adolescents
with temporal lobe epilepsy, followed in the Ambulatory of Epilepsy in
the Clinics Hospital of the University of São Paulo from 2005 to 2007.
The group was made up of 17 boys (54.84%) with a mean age of 11.84
years (range, 8 to 16 years old; standard deviation, 4.59 years), and a
mean estimated intelligence quotient (IQ), based on the Block Design
and Vocabulary subtests of the Wechsler Intelligence Scale for Children-
III [24], of 95.78 (range, 71 to 135; standard deviation, 12.57).
Twenty-four patients (77.42%) had symptomatic temporal lobe epi-
lepsy. Symptomatic temporal lobe epilepsy was defined as a lesion
restricted to the temporal lobe region (mesial or lateral), and demon-
strated with a 1.5T magnetic resonance image.
We also included seven patients (22.58%) with cryptogenic temporal
lobe epilepsy determined by ictal and interictal electroencephalogram
findings. Patients with extratemporal epileptic activity were excluded
from this group. Demographic and clinical information for each individ-
ual is presented in Table 1.
Temporal Lobe Epilepsy Groups
The symptomatic temporal lobe epilepsy groups included:
(1) Mesial temporal lobe epilepsy group: composed of 18 patients
(75%), including 13 boys (72.22%), 15 with hippocampal sclerosis,
two with a mesial temporal tumor, and one with gliosis of the
parahippocampal gyrus, at a mean age of 12.35 years (standard
deviation, 2.29 years) and mean estimated intelligence quotient of
95.36 (standard deviation, 14.25).
(2) Lateral temporal lobe epilepsy group: composed of six patients
(25%), including two boys (33.33%), three with temporal dysplasia,
one with temporal cysts, one with a temporal tuber, and one with a
temporal cavernoma, at a mean age of 11.57 years (standard
deviation, 2.57) and mean estimated intelligence quotient of 93.18
(standard deviation, 12.11).
The cryptogenic temporal lobe epilepsy group: Seven patients, includ-
ing two boys (28.57%), with a mean age of 11.86 years (standard
deviation, 2.03), and mean estimated intelligence quotient of 98.92
(standard deviation, 9.64).
Controls
Healthy volunteers were recruited among students from a public
school. These children were matched to study subjects in terms of age,
and socio-demographic and educational background, had neither psychi-
atric diagnosis according to the Diagnostic and Statistical Manual of
Mental Disorders-IV [25], nor previous or current history of neurologic
disorders.
Twenty-one healthy children (7 boys), at a mean age of 11.8 years
(range, 9-16 years old; standard deviation, 2.4), were selected. Mean
estimated intelligence quotient, based on the Block Design and Vocab-
ulary subtests of the Wechsler Intelligence Scale for Children-III [24],
was 108 (range, 83 to 135; standard deviation, 15.0).
The exclusion criteria for patients and controls included: an estimated
intelligence quotient below 70; clinical signs of drug intoxication or any
other condition that could lead to cognitive impairment; diagnosis of
psychiatric illness; alcohol or drug abuse; any brain-related surgical
intervention; and not being in school.
The elapsed time between last seizure and the moment of neuropsy-
chologic evaluation was at least 48 hours. Three patients who experi-
enced seizures during testing were reevaluated 1 week later.
Performance in Attention and Executive Tests
Evaluation was completed during the course of two sessions, during
which a battery of attention and executive tests was performed with each
child. Tests were administered by a trained neuropsychologist in a quiet
laboratory and in a standard sequence. Applied tests and cognitive
assessed functions included:
Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy 177
Table 1. Demographic description of patients with temporal lobe epilepsy

Patient Sex Age (yr) IQ Subgroup Lesion Education (yr) Age of Onset (yr)

1 F 15 83 Cryptogenic No lesion 6 6
2 M 15 122 Lateral Posterior temporal dysplasia 8 6
3 F 10 80 Lateral Hippocampal dysplasia, R 4 1
4 M 15 71 Mesial MTS, R 5 1
5 M 12 80 Mesial MTS, L 5 1
6 F 14 109 Cryptogenic No lesion 8 9
7 M 15 103 Mesial DNET, L 10 7
8 F 12 85 Lateral Wernick dysplasia, R 3 2
9 F 11 103 Cryptogenic No lesion 5 3
10 F 12 97 Mesial HA bilateral 6 7
11 F 12 85 Mesial MTS, R 6 8
12 M 11 94 Mesial MTS, L 6 2
13 M 9 135 Mesial MTS, L 4 3
14 M 14 77 Mesial MTS, R 5 5
15 F 11 106 Cryptogenic No lesion 5 2
16 F 11 103 Cryptogenic No lesion 2 2
17 M 9 85 Cryptogenic No lesion 4 2
18 F 10 109 Mesial MTS, R 3 2
19 M 15 103 Mesial Parahippocampal gyrus lesion 5 1
20 M 9 94 Mesial Hippocampal rotation 4 2
21 F 13 86 Mesial MTS, R 4 5
22 M 12 106 Cryptogenic No lesion 7 10
23 F 8 100 Mesial MTS, R 2 2
24 M 13 117 Mesial MTS, L 7 6
25 M 9 100 Lateral Temporal cavernoma, L 3 7
26 M 15 91 Mesial MTS, L 9 4
27 M 13 103 Mesial HA, R 5 10
28 M 14 85 Mesial MTSR 7 3
29 F 9 94 Lateral Temporal cyst, R 3 2
30 F 11 91 Lateral Temporal tubers bilateral 4 1
31 M 15 94 Mesial Amygdala tumor, R 6 6

Abbreviations:
CPS ⫽ Complex partial seizure
DNET ⫽ Dysembryoplastic neuroepithelial tumor
F ⫽ Female
FH ⫽ Familiar history of epilepsy
FS ⫽ Febrile seizures
GTCS ⫽ Generalized tonic-clonic seizure
HA ⫽ Hippocampal atrophy

(1) Auditory attention and short-term retention capacity (Digit Span,
Wechsler Intelligence Scale for Children-III [24], and Number and
Letter, Wide Range Assessment of Memory and Learning [26]);
(2) Visual attention and short-term retention capacity (Finger Windows,
Wide Range Assessment of Memory and Learning [26]);
(3) Complex visual scanning, visual attention, mental flexibility, and
inhibitory control (Trail Making Test, Children’s Version [27]);
(4) Semantic naming, response initiation, verbal search, and production
of individual words under restrictive search conditions (Word
Fluency, Animals and Foods) [27];
(5) Abstract behavior, set shifting, response inhibition, and mental
flexibility at the cognitive level (Wisconsin Card Sorting Test [28]);
and
(6) Impulse control (Matching Familiar Figures Test-20 [29]).
Correlation With Clinical Variables
therapy and polytherapy, and seizure control status at the moment of
neuropsychologic evaluation.
Severity of Executive Dysfunction
We adopted clinical criteria to measure the severity of executive
dysfunction in our patients with temporal lobe epilepsy. We considered
an executive function to be impaired when the patient had a bad
performance (lower than 1 standard deviation) in at least two executive
paradigms compared with controls.
Degrees of severity for the comprehensive battery of eight executive
paradigms were classified as mild when deficits occurred in two
executive tests, moderate if impairment occurred in 3 to 4 executive tests,
and severe when there was failure in 5 out of 8 executive paradigms.

Clinical variables included: etiology (symptomatic versus crypto- Statistical Analysis

genic), location (mesial temporal lobe epilepsy and lateral temporal lobe
epilepsy in the symptomatic group), laterality (right versus left), age of
onset, duration of epilepsy, seizure type, presence of secondary general-
ization, frequency of seizures, history of status epilepticus, history of
previous neurological insult, family history of epilepsy, use of mono-
Descriptive analysis consisted of means and standard deviations of
each variable. Demographic variables (age, sex, and education) of
patients and controls were compared using the chi-square test to verify if
both groups could be matched.

178 PEDIATRIC NEUROLOGY Vol. 37 No. 3

Table 1. Continued

Duration (yr) SE FH FS Frequency Number of AEDs Seizure Type

9 No Yes No Weekly 1 CPS

9 Yes Yes No Without seizures 1 CPS, GTCS
9 No Yes No Without seizures 2 CPS
14 Yes Yes Yes Biweekly 2 SPS, CPS, GTCS
12 No Yes Yes Weekly 1 CPS
5 No Yes No Without seizures 0 CPS
8 Yes No No Weekly 0 SPS, CPS, GTCS
10 No Yes No Without seizures 1 CPS
8 No Yes No Monthly 1 SPS
5 No Yes Yes Weekly 2 SPS, CPS, GTCS
4 Yes Yes No Daily 2 SPS
9 Yes No Yes Without seizures 2 SPS, CPS
6 No Yes No Daily 1 SPS
9 No No No Weekly 2 SPS
9 No No No Without seizures 1 SPS, CPS, GTCS
8 No Yes No Without seizures 0 CPS
7 No Yes No Without seizures 1 SPS, CPS
8 Yes Yes Yes Daily 1 SPS, CPS
14 Yes No No Daily 1 SPS, CPS
7 No Yes No Without seizures 1 SPS, CPS
8 Yes No Yes Daily 1 SPS, CPS
2 No Yes No Without sizures 1 CPS
6 No Yes No Without seizures 1 CPS
7 No Yes No Without seizures 1 SPS, CPS
2 Yes No Yes Monthly 1 SPS, CPS
11 No No Yes Monthly 2 CPS
3 Yes No No Weekly 2 SPS, CPS, GTCS
9 No Yes Yes Without seizures 1 SPS, CPS
6 No Yes No Without seizures 1 SPS, CPS
9 No No No Without seizures 1 CPS, GTCS
9 No No No Weekly 1 SPS, CPS

IQ ⫽ Intelligence quotient
L ⫽ Left
M ⫽ Male
MTS ⫽ Mesial temporal sclerosis
R ⫽ Right
SE ⫽ Status epilepticus
SPS ⫽ Simple partial seizure

Regarding neuropsychologic performance, patients and controls were
compared by t test. A nonparametric Mann-Whitney test was used to
compare groups (symptomatic, cryptogenic, and controls) because of the
small number of subjects in each group.
Finally, analysis of variance was used to evaluate the influence of
clinical variables on executive functions. Significance was set at P ⫽
0.05. For statistical analysis, the SPSS 11.0 software package was used.
Results
No statistical difference was found between the tempo-
ral lobe epilepsy groups and controls regarding sex (F ⫽
1.596, P ⫽ 0.087), and years of education (F ⫽ 0.466,
P ⫽ 0.335). However, differences were observed regard-
ing chronological age (F ⫽ 0.051, P ⫽ 0.035), with
controls being younger.
Performances in Attention and Executive Tests
Patients with temporal lobe epilepsy had a worse perfor-
mance compared with controls in the following tests: Wis-
consin Card Sorting Test (number of categories achieved,
P ⫽ 0.002, number of perseverative errors, P ⫽ 0.035; and
number of perseverative responses, P ⫽ 0.045); Digit For-
ward (Wechsler Intelligence Scale for Children-III, P ⫽
0.003); Matching Familiar Figures Test (number of errors,
P ⫽ 0.033; and total index, P ⫽ 0.042); Trail Making Test
(numbers of errors in trial A, P ⫽ 0.040; time to accomplish
in trial B, P ⫽ 0.038; and number of errors in trial B, P ⫽
0.006); Word Fluency (animals, P ⫽ 0.035); Finger Window
(Wide Range Assessment of Memory and Learning, P ⫽
0.014); and Number and Letter (Wide Range Assessment of
Memory and Learning, P ⫽ 0.007) (Table 2).
There were no differences between patients with tem-
poral lobe epilepsy and controls in the Wisconsin Card
Sorting Test (number of nonperseverative errors, and
failure to maintain set); Digit Back-Forward (Wechsler
Intelligence Scale for Children-III); Matching Familiar
Figures Test (latency time); Trail Making Test (time to
accomplish trial A); and Word Fluency (foods) (Table 2).

Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy 179

Table 2. Means, standard deviations, and P values of the difference in temporal lobe epilepsy patients’ and controls’ performance in
executive functions tests (t test)

Temporal Lobe Temporal Lobe Epilepsy, Controls, Standard

Tests Epilepsy, Mean Standard Deviation Controls, Mean Deviation t P Value

WCST (categ.) 4.07 2.82 6.35 2.35 ⫺2.997 0.020

WCST (PE) 29.77 21.16 20.25 10.74 1.854 0.035
WCST (NPE) 25.13 16.95 19.55 10.74 1.314 0.097
WCST (PR) 36.43 29.13 24.40 13.04 1.731 0.045
WCST (MS) 0.93 1.01 0.85 0.88 0.30 0.380
DF (WISC-III) 6.73 2.15 7.90 1.70 ⫺2.853 0.003
DB (WISC-III) 4.53 2.01 4.81 1.25 ⫺0.557 0.290
MFFT errors 20.00 11.28 14.15 8.39 1.876 0.033
MFFT time 216.31 129.71 227.00 148.97 ⫺0.235 0.407
MFFT total 3178.86 1936.81 2339.05 1094.82 1.757 0.042
TM A time 37.73 38.61 28.19 13.20 1.086 0.141
TM A errors 0.23 0.50 0.05 0.22 1.792 0.040
TM B time 63.00 26.33 49.14 27.09 1.815 0.038
TM B errors 0.55 0.87 0.10 0.30 2.619 0.006
WF foods 10.61 4.26 14.14 4.61 ⫺1.064 0.146
WF animals 12.71 4.87 14.48 5.18 ⫺2.836 0.035
Finger Windows 13.07 5.16 15.71 3.32 ⫺2.248 0.014
Number-Letter 7.80 3.12 10.62 4.91 ⫺2.543 0.007

Abbreviations:
DB ⫽ Digit Back-Forward
DF ⫽ Digit Forward
MFFT ⫽ Matching Familiar Figures Test
TM ⫽ Trail Making Test
WCST ⫽ Wisconsin Card Sorting Test
WCST (categ.) ⫽ Wisconsin Card Sorting Test (number of categories achieved)
WCST (MS) ⫽ Wisconsin Card Sorting Test (failure in maintenance of set)
WCST (NPE) ⫽ Wisconsin Card Sorting Test (nonperseverative errors)
WCST (PE) ⫽ Wisconsin Card Sorting Test (perseverative errors)
WCST (PR) ⫽ Wisconsin Card Sorting Test (perseverative responses)
WF ⫽ Word Fluency
Boldface indicates statistical significance.

Correlation With Clinical Variables
We observed that the existence of a temporal lobe lesion
(in the mesial or lateral structures), as visualized on
magnetic resonance imaging, determined a worse perfor-
mance of children with symptomatic temporal lobe epi-
lepsy in executive functions tests compared with patients
with cryptogenic temporal lobe epilepsy and controls
(Table 3). In addition, patients with lesions in mesial
temporal lobe structures had a worse performance in a
higher number of tests than those with lateral temporal
lobe lesions (Table 3).
Patients with an early age of epilepsy onset, longer
duration of epilepsy, and polytherapy had a statistically
significantly worse performance in a large number of
subtests (Table 4). History of status epilepticus, family
history of epilepsy, seizure control, frequency of seizures,
and presence of secondary generalization had a smaller
influence on executive performance, considering the num-
ber of subtests (ⱕ2 subtests) (Table 4).
executive dysfunction. In terms of the severity of this
dysfunction, we estimated that:
● 2 patients (7.14%) had a mild executive dysfunction
(two with cryptogenic temporal lobe epilepsy);
● 11 patients (39.28%) had a moderate executive dysfunc-
tion (seven with mesial temporal lobe epilepsy, one with
lateral temporal lobe epilepsy, and three with crypto-
genic temporal lobe epilepsy); and
● 15 patients (53.57%) had a severe executive dysfunction
(nine with mesial temporal lobe epilepsy, four with
lateral temporal lobe epilepsy, and two with cryptogenic
temporal lobe epilepsy).
Therefore, 28 patients (90.32%) had some degree of
executive dysfunction, and 26 (83.87%) of 31 evaluated
patients had an executive dysfunction classified as mod-
erate or severe.
Discussion

Severity of Executive Dysfunction Frontal lobe dysfunction includes difficulties in antici-

pating, planning and organizing, initiating action plans,
Based on the adopted clinical criteria, 28 (90.32%) of inhibiting distractions and interference, monitoring a pro-
31 patients with temporal lobe epilepsy exhibited an cess, shifting flexibility to new actions when necessary,

180 PEDIATRIC NEUROLOGY Vol. 37 No. 3

and working memory. These abilities are attributed to
executive functioning [6,7,30].
This study is the first to analyze executive functions in
children with temporal lobe epilepsy by means of a broad
neuropsychologic battery. The absence of significant dif-
ferences between performances in several tests in our
study underscores their complementary nature, and rein-
forces the concept of executive functions as a multidimen-
sional phenomenon comprising a wide spectrum of abili-
ties, not all of which are measured by the same tests.
Moreover, groups of subjects with impairments of these
functions are heterogeneous, and neuropsychologic mea-
sures address independent and complementary compo-
nents.
The Wisconsin Card Sorting Test is the most frequently
used test to examine executive functions in patients with
epilepsy [23,31-33]. For patients with frontal lobe lesions
and severe executive impairment, there is a consensus that
this test is as sensitive as any other [23,34-36]. However,
there are many controversies regarding the degree of
executive impairment in patients with subtle executive
dysfunctions, such as in temporal lobe patients. It was
postulated [1,6,37] that these controversies may be the
result of a widespread use of the Wisconsin Card Sorting
Test, which may be insufficient to evaluate all of these
deficits.
In studies of children, the prefrontal region became fully
functional only in late childhood or preadolescence [38-
40]. Developmental changes were described in a cross-
sectional study by Igarashi and Kato [41], using the
Wisconsin Card Sorting Test on normal children. These
authors found that the adult pattern was achieved after 12
years of age. Our results with the Wisconsin Card
Sorting Test, in children with temporal lobe epilepsy,
corroborate those observed in adults [5,8,31], demon-
strating that, even in children, some of the executive
functions measured by the Wisconsin Card Sorting Test
are compromised, despite the presence of mechanisms
of neural plasticity.
In our series, using a more comprehensive battery for
executive functions, we observed that children and ado-
lescents with temporal lobe epilepsy had impairments not
completely measured by the Wisconsin Card Sorting Test
in mental flexibility and set shifting, perseveration, inhib-
itory control, verbal fluency, and maintenance of attention,
reinforcing our hypothesis that a more comprehensive and
extensive neuropsychologic battery is necessary to assess
these complex cognitive functions.
The importance of studying children and adolescents
was emphasized by Martin et al. [31]. Although children
and adults with temporal lobe epilepsy have the same
underlying pathology, children and adolescents have not
yet undergone the effects of long-lasting epilepsy, and
have substantially fewer years of seizure activity. Our
results suggest that temporal lobe involvement per se is
important, because this pattern of extensive cognitive
impairment, as reported elsewhere [1,5,8,31] in adults, can
also be observed in early stages of life. Patients with early
epilepsy onset had a worse performance, corroborating the
recent study of Cormack et al. [42], which demonstrated
that age of onset was the best predictor of intellectual
dysfunction, suggesting that the first year of life represents
a critical period for the development of intellectual abili-
ties. However, it must be emphasized that our patients
with a longer duration of epilepsy had more extensive
cognitive impairment, corroborating the idea that early
intervention is necessary.
In terms of etiology, patients with symptomatic tempo-
ral lobe epilepsy had a worse performance in tests of
executive function than those with cryptogenic temporal
lobe epilepsy and controls. Moreover, patients with lesions
in mesial structures had a worse performance in a higher
number of tests compared with patients with lateral tem-
poral lesions. However, the number of children in this
group was low (six patients), which could represent a
limiting factor to this analysis.
Based on our findings, we partially agree with Corcoran
and Upton [8] that the hippocampus acts like a comparator
of actions, wherein lesions determine the existence of a
prefrontal lobe dysfunction. Nevertheless, it is important
to emphasize that patients with lateral temporal lobe
epilepsy also displayed executive dysfunction. For that
reason, we believe in a wide anatomical and functional
network connecting temporal and frontal lobes, and allow-
ing the temporal epileptogenic zone to affect the frontal
and prefrontal regions [23,31,32].
In accordance with this hypothesis, recent functional
neuroimaging studies demonstrated hypometabolism in
the prefrontal regions of patients with temporal lobe
epilepsy [43,44]. Nelissen et al. [43], using single-photon
emission computed tomography and positron emission
tomography, found interictal hypometabolism in the fron-
tal lobe cortex of adults with temporal lobe epilepsy. The
authors suggested a dynamic process of frontal lobe
function inhibition, which could represent a process of
protection against epileptiform-discharge propagation, but
which could also be responsible for the functional deficits
presented by these patients. In a structural imaging study,
using voxel-based morphometry, Cormack et al. [45]
found a reduction in grey-matter density ipsilateral to the
seizure focus in the hippocampus, lateral temporal lobe,
and extratemporal regions, including the thalamus, poste-
rior cingulate cortex, cerebellum, and frontal and parietal
opercular cortex, which, according to these authors, could
reflect a structural change determined by the disruption of
cortical development by recurrent seizures and by a loss of
functional input from the sclerotic hippocampus. This
finding suggests more than a functional intermittent
change [43], and would explain our findings of worse
performance in earlier and longer-duration epilepsy.
The severity of executive dysfunction in temporal lobe
epilepsy patients was not previously evaluated. Here, we
elaborate upon clinical criteria with which we could
determine that 83.87% of those children and adolescents
Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy 181
Table 3. Differences in executive performance of temporal lobe epilepsy patients (mesial, lateral, and cryptogenic) and controls (Z and P
values) (Mann-Whitney test)

Mesial Lateral
Tests ␮ (SD) Z P ␮ (SD) Z P

WCST (categ.) 3.67 (2.56) ⫺2.282 0.002 3.5 (2.88) ⫺2.180 0.014
WCST (PE) 32.89 (24.10) ⫺1.639 0.050 30.50 (11.40) ⫺1.768 0.038
WCST (NPE) 26.06 (19.36) ⫺0.585 0.279 28.00 (11.90) ⫺1.615 0.053
WCST (PR) 40.72 (33.73) ⫺1.434 0.076 36.67 (12.52) ⫺1.951 0.025
WCST (MS) 0.72 (0.89) ⫺0.520 0.301 1.17 (0.41) ⫺1.160 0.123
DF (WISC-III) 7.00 (2.17) ⫺2.410 0.008 6.67 (1.97) ⫺1.677 0.047
DB (WISC-III) 4.39 (1.54) ⫺1.091 0.137 4.00 (3.10) ⫺1.071 0.142
MFFT errors 18.82 (11.17) ⫺1.444 0.126 20.17 (11.65) ⫺1.251 0.100
MFFT time 228.22 (140.80) 0.000 0.500 247.67 (105.66) ⫺0.292 0.385
MFFT total 2943.12 (1081.29) ⫺0.412 0.340 4576.50 (3463.55) ⫺2.313 0.010
TM A 31.38 (16.36) ⫺0.412 0.340 66.17 (79.76) ⫺1.343 0.089
Time
TM A errors 0.24 (0.42) ⫺1.679 0.046 0.33 (0.82) ⫺1.027 0.152
TM B 65.06 (27.56) ⫺1.718 0.043 70.40 (37.42) ⫺1.204 0.114
Time
TM B errors 0.76 (1.00) ⫺2.664 0.004 0.00 (0.00) ⫺0.704 0.240
WF 12.67 (4.47) ⫺2.675 0.003 10.00 (5.33) ⫺1.961 0.028
Foods
WF animals 10.39 (3.87) ⫺1.202 0.114 9.67 (3.98) ⫺1.908 0.025
Finger Windows 12.67 (4.57) ⫺1.982 0.023 10.50 (6.35) ⫺2.495 0.006
Number Letter 7.39 (2.66) ⫺2.557 0.005 7.00 (3.58) ⫺2.208 0.013

Abbreviations:
DB ⫽ Digit Back-Forward
DF ⫽ Digit Forward
MFFT ⫽ Matching Familiar Figures Test
␮ ⫽ Mean
SD ⫽ Standard deviation
TM ⫽ Trail Making Test
Boldface indicates statistical significance.

Table 4. Influence of clinical variables in temporal lobe epilepsy on executive function tests (analysis of variance)

Test/Variable (P Value) Lesion Laterality Age of Onset (yr) Duration (yr) SE FH FS

WCST (categ.) 0.933 0.281 0.680 0.392 0.142 0.462 0.435

WCST (PE) 0.731 0.729 0.925 0.260 0.010 0.045 0.626
WCST (NPE) 0.525 0.184 0.827 0.437 0.812 0.114 0.877
WCST (PR) 0.746 0.644 0.806 0.273 0.090 0.044 0.525
WCST (MS) 0.248 0.001 0.302 0.128 0.282 0.805 0.758
DF (WISC-III) 0.860 0.099 0.953 0.016 0.993 0.501 0.482
DB (WISC-III) 0.891 0.700 0.025 0.266 0.171 0.027 0.107
MFFT errors 0.832 0.069 0.609 0.750 0.714 0.979 0.223
MFFT time 0.939 0.323 0.976 0.988 0.403 0.899 0.348
MFFT total 0.268 0.286 0.494 0.995 0.851 0.347 0.826
TM A time 0.968 0.449 0.438 0.801 0.629 0.689 0.680
TM A errors 0.528 0.168 0.574 0.614 0.610 0.339 0.323
TM B time 0.493 0.582 0.311 0.161 0.534 0.376 0.964
TM B errors 0.225 0.939 0.781 0.527 0.151 0.902 0.283
WF foods 0.666 0.183 0.164 0.494 0.827 0.289 0.478
WF animals 0.272 0.383 0.278 0.582 0.614 0.262 0.933
Finger Windows 0.070 0.289 0.153 0.871 0.049 0.641 0.839
Number-Letter 0.117 0.002 0.866 0.352 0.336 0.819 0.366

Abbreviations:
DB ⫽ Digit Back-Forward
DF ⫽ Digit Forward
FH ⫽ Familiar history of epilepsy
FS ⫽ Febrile seizures
MFFT ⫽ Matching Familiar Figures Test
SE ⫽ Status epilepticus
TM ⫽ Trail Making Test
Boldface indicates statistical significance.

182 PEDIATRIC NEUROLOGY Vol. 37 No. 3

Table 3. Continued

Cryptogenic Controls
␮ (SD) Z P ␮ (SD)

5.83 (2.99) ⫺0.308 0.379 6.35 (2.35)

19.67 (10.48) ⫺0.305 0.380 20.25 (10.74)
19.50 (10.52) ⫺0.061 0.475 19.55 (10.74)
23.33 (13.94) ⫺0.518 0.302 24.40 (13.04)
1.33 (1.63) ⫺0.452 0.325 0.85 (0.88)
6.00 (2.10) ⫺1.944 0.026 7.90 (1.70)
5.50 (2.17) ⫺0.537 0.295 4.81 (1.25)
21.67 (10.65) ⫺1.524 0.064 14.15 (8.39)
157.00 (70.59) ⫺0.700 0.242 227.00 (148.97)
2401.50 (973.90) ⫺0.122 0.451 2339.05 (1094.82)
27.57 (12.07) ⫺0.133 0.447 28.19 (13.20)

0.14 (0.38) ⫺0.832 0.202 0.05 (0.22)

52.71 (22.31) ⫺0.451 0.326 49.14 (27.09)

0.43 (0.53) ⫺1.958 0.025 0.10 (0.3)

15.14 (5.52) ⫺0.772 0.440 14.14 (4.61)

12.00 (5.97) ⫺0.133 0.894 14.48 (5.18)

16.43 (4.58) ⫺0.641 0.261 15.71 (3.32)
9.57 (3.36) ⫺0.134 0.447 10.62 (4.91)

WCST ⫽ Wisconsin Card Sorting Test

WCST (categ.) ⫽ Wisconsin Card Sorting Test (number of categories achieved)
WCST (MS) ⫽ Wisconsin Card Sorting Test (failure in maintenance of set)
WCST (NPE) ⫽ Wisconsin Card Sorting Test (nonperseverative errors)
WCST (PE) ⫽ Wisconsin Card Sorting Test (perseverative errors)
WCST (PR) ⫽ Wisconsin Card Sorting Test (perseverative responses)
WF ⫽ Word Fluency

Table 4. Continued

Frequency Frequent Versus Infrequent Seizure Control Number of AEDs Seizure Type Secondary Generalization

0.228 0.219 0.419 0.036 0.533 0.992

0.255 0.191 0.073 0.538 0.570 0.815
0.296 0.836 0.576 0.983 0.844 0.799
0.227 0.184 0.065 0.593 0.672 0.881
0.085 0.013 0.003 0.825 0.452 0.477
0.642 0.501 0.668 0.290 0.761 0.723
0.222 0.914 0.691 0.179 0.496 0.591
0.606 0.410 0.089 0.936 0.596 0.007
0.664 0.593 0.954 0.444 0.649 0.039
0.249 0.493 0.409 0.310 0.760 0.944
0.466 0.196 0.108 0.279 0.919 0.412
0.171 0.441 0.836 0.701 0.832 0.302
0.514 0.162 0.300 0.692 0.906 0.266
0.283 0.357 0.493 0.368 0.342 0.606
0.469 0.253 0.296 0.711 0.783 0.985
0.771 0.683 0.941 0.915 0.045 0.058
0.309 0.480 0.682 0.336 0.339 0.156
0.945 0.773 0.980 0.363 0.270 0.619

WCST ⫽ Wisconsin Card Sorting Test

WCST (categ.) ⫽ Wisconsin Card Sorting Test (number of categories achieved)
WCST (MS) ⫽ Wisconsin Card Sorting Test (failure in maintenance of set)
WCST (NPE) ⫽ Wisconsin Card Sorting Test (nonperseverative errors)
WCST (PE) ⫽ Wisconsin Card Sorting Test (perseverative errors)
WCST (PR) ⫽ Wisconsin Card Sorting Test (perseverative responses)
WF ⫽ Word Fluency

Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy 183

with temporal lobe epilepsy exhibited a moderate or
severe executive dysfunction, with an undeniable effect on
their quality of life, because these children were still
receiving their education.
It is common to assume that memory impairments are
responsible for the poor performance of those children
in cognitive tests. Even so, the influence of attentional
skills in memory functions is well-known [46]. Thus,
we believe that memory deficits, widely described in
the literature, could be partially explained by executive
dysfunctions.
Furthermore, it is important to keep in mind the influ-
ence of clinical variables of epilepsy on cognitive func-
tioning. In our study, we observed the important roles of
the existence of a lesion, early age of onset, longer
duration of epilepsy, and use of polytherapy. These find-
ings corroborate those of Hermann et al. [32] regarding the
influence of age of onset of epilepsy on executive func-
tioning. Therefore, our data suggest that temporal lobe
involvement per se is an important variable that could
determine the presence of an executive dysfunction, and
that early interventions are necessary, because the exten-
sive cognitive impairment pattern observed by Hermann
and Seidenberg [5] in adults can already be seen in the first
stages of life, and could be aggravated by longer duration
of epilepsy and the use of polytherapy.
In conclusion, our data indicate the need for compre-
hensive batteries to assess executive functions, and for
clinical criteria to classify degrees of executive dysfunc-
tion in children and adolescents, because some of the most
widely used executive-function tests are not sensitive
enough to detect minor impairments. Our study also
confirms that children and adolescents with temporal lobe
lesions have extratemporal cognitive deficits, despite their
shorter duration of epilepsy. In addition, we corroborate
the notion that the abnormal epileptogenic activity of the
temporal lobe affects extratemporal areas of the frontal
lobe, responsible for executive functions, emphasizing the
existence of a neural network linking both the temporal
and frontal lobes. We also think that the existence of
frontal lobe dysfunction in patients with lateral lesions
could be related to the great number of patients with
cortical dysplasia, suggesting the existence of a microdys-
genesis not visualized by routine extratemporal neuroim-
aging examinations. Moreover, the hypothesis of a neural
network and the existence of invisible structural abnor-
malities in the frontal cortex are not mutually exclusive,
but could be coexistent and correlated.
We are grateful to the staff members of the Clinical Neurophysiology
Laboratory and the Psychology and Neuropsychology Unit, and espe-
cially Bernardo Moreira, MD, Lia Arno Fiore, MD, Flavio Alóe, MD,
Juliana Góis, BSc, Sylvie Paes, BSc, and Pedro Zuccolo, BSc, for their
ongoing assistance. This work was supported by Fundação de Amparo à
Pesquisa do Estado de São Paulo grants 03/06025-3 and 05/03489-4.
184 PEDIATRIC NEUROLOGY Vol. 37 No. 3
References
[1] Hermann BP, Seidenberg M, Schoenfeld J, Davies K. Neuro-
psychologic characteristics of the syndrome of mesial temporal lobe
epilepsy. Arch Neurol 1997;54:369-76.
[2] Bell BD, Hermann BP, Woodard AR, et al. Object naming and
semantic knowledge in temporal lobe epilepsy. Neuropsychology 2001;
15:434-43.
[3] Blume WT. Diagnosis and management of epilepsy. Can Med
Assoc J 2003;168:441-8.
[4] Trenery M, Jack CR. Wisconsin Card Sorting Test performance
before and after temporal lobectomy. J Epilepsy 1994;7:313-7.
[5] Hermann BP, Seidenberg M. Executive system dysfunction in
temporal lobe epilepsy: Effects of nociferous cortex versus hippocampal
pathology. J Clin Exp Neuropsychol 1995;7:809-19.
[6] Doval O, Gavira M, Kanner MA. Frontal lobe dysfunction in
epilepsy. In: Ettinger AB, Kanner MA, eds. Psychiatric issues in
epilepsy—practical guide to diagnosis and treatment. Philadelphia:
Lippincott Williams and Wilkins, 2001:261-71.
[7] Gioia GA, Isquith PK, Retzlaff PD, Espy KA. Confirmatory
factor analysis of Behavior Rating Inventory of Executive Function
(BRIEF) in a clinical sample. Child Neuropsychol 2002;8:249-57.
[8] Corcoran R, Upton D. A role for the hippocampus in card
sorting? Cortex 1993;29:293-304.
[9] Camfield PR, Gates R, Ronen G, Camfield C, Ferguson A,
MacDonald GW. Comparison of cognitive ability, personality profile and
school success in epileptic children: Pure right versus left temporal lobe
EEG foci. Ann Neurol 1984;15:122-6.
[10] Adams CBT, Beardsworth ED, Oxbury SM, Oxbury JM,
Fenwick PB. Temporal lobectomy in 44 children: Outcome and neuro-
psychologic follow-up. J Epilepsy 1990;3 (Suppl.):157-68.
[11] Williams D, Mateer CA. Developmental impact of frontal lobe
injury in middle childhood. Brain Cogn 1992;20:196-204.
[12] Hershey T, Craft S, Glauser TA, Hale S. Short-term and
long-term memory in early temporal lobe dysfunction. Neuropsychology
1998;12:52-64.
[13] Lendt M, Helmstaedter C, Elger CE. Pre-and postoperative
neuropsychologic profiles in children and adolescents with temporal lobe
epilepsy. Epilepsia 1990;40:1543-57.
[14] Bigel MG, Smith ML. The impact of different neuropathologies
on pre- and postsurgical neuropsychologic functioning in children with
temporal lobe epilepsy. Brain Cogn 2001;46:46-9.
[15] Fedio P, Mirsky AF. Selective intellectual deficits in children
with temporal lobe or centrencephalic epilepsy. Neuropsychologia 1969;
7:287-300.
[16] Cohen M. Auditory/verbal and visual/spatial memory in chil-
dren with complex partial epilepsy of temporal origin. Brain Cogn
1992;20:315-26.
[17] Jambaque I, Dellatolas G, Dulac O, Ponsot G, Signoret JL.
Verbal and visual memory impairment in children with epilepsy. Neu-
ropsychologia 1993;31:1321-37.
[18] Schoenfeld J, Seidenberg M, Woodard A, et al. Neuropsycho-
logic and behavioral status of children with complex partial seizures. Dev
Med Child Neurol 1999;41:724-31.
[19] Aynaci FM, Ozdirim E, Saatci I, et al. Clinical, electrophysio-
logical and neuropsychologic findings of twenty-two children with
mesial temporal sclerosis. Turk J Pediatr 2003;45:221-30.
[20] Nolan MA, Redoblado MA, Lah S, et al. Memory function in
childhood epilepsy syndromes. J Paediatr Child Health 2004;40:20-7.
[21] Hernandez MT, Sauerwein HC, Jambaqué I, et al. Deficits in
executive functions and motor coordination in children with frontal lobe
epilepsy. Neuropsychologia 2002;40:384-400.
[22] Culhane-Shelburne K, Chapieski L, Hiscock M, Glaze D.
Executive functions in children with frontal and temporal lobe epilepsy.
JINS 2002;8:623-32.
[23] Igarashi K, Oguni H, Osawa M, et al. Wisconsin Card Sorting
Test in children with temporal lobe epilepsy. Brain Dev 2002;24:174-8.
[24] Wechsler D. Wechsler intelligence scale for children (WISC-
III). (3rd ed.). São Paulo: Casa do Psicólogo, 1991:1-322.
 [25] American Psychiatric Association. Diagnostic and statistical
manual of mental disorders. 4th ed. Washington, DC:American Psychi-
atric Association, 1994:1-943.
[26] Sheslow D, Adams W. Wide range assessment of memory and
learning—administration manual. Wilmington: Wide Range, Inc., 1990:
1-154.
[27] Spreen O, Strauss E. A compendium of neuropsychologic
tests—administration, norms and commentary. New York: Oxford Uni-
versity Press, 1991:1-442.
[28] Heaton RK, Chelune GJ, Talley JL, Kay G, Curtiss G.
Wisconsin Card Sorting Test manual—revised and expanded. Psy-
chological assessment resource. São Paulo: Casa do Paiscólogo,
1993:1-331.
[29] Cairns ED, Cammock J. Development of a more reliable
version of Matching Familiar Figures Test. Dev Psychol 1978;13:555-60.
[30] Lezak MD. Neuropsychologic assessment. New York: Oxford
University Press, 1995:1-1026.
[31] Martin RC, Sawrie SM, Gilliam FG, et al. Wisconsin card
sorting performance in patients with temporal lobe epilepsy: Clinical and
neuroanatomical correlates. Epilepsia 2000;41:1626-32.
[32] Hermann BP, Seidenberg M, Bell B. The neurodevelopmental
impact of childhood-onset temporal lobe epilepsy on brain structure and
function and the risk of progressive cognitive effects. Epilepsia 2002;43:
1062-71.
[33] Oyegbile TO, Dow C, Jones J, et al. The nature and course of
neuropsychologic morbidity in chronic temporal lobe epilepsy. Neurol-
ogy 2004;62:1736-42.
[34] Goldstein B, Obrzut JE, John C, Ledakis G, Armstrong CL.
The impact of frontal and non-frontal brain tumor lesions on Wisconsin
Card Sorting Test performance. Brain Cogn 2004;54:110-6.
[35] Meyer SE, Carlson GA, Wiggs EA. A prospective study of the
association among impaired executive functioning, childhood attentional
problems, and development of bipolar disorder. Dev Psychopathol
2004;16:461-76.
[36] Romine CB, Lee D, Wolfe ME, Homack S, George C, Riccio
CA. Wisconsin Card Sorting Test with children: A meta-analytic study of
sensitivity and specificity. Arch Clin Neuropsychol 2004;19:1027-41.
[37] Horner MD, Flashmian LA, Freides D. Focal epilepsy and the
Wisconsin Card Sorting Test. J Clin Exp Neuropsychol 1989;11:74.
[38] Goldman PS. An alternative to developmental plasticity: Het-
erology of CNS in infants and adults. In: Stein D, Rosen J, Butters N,
editors. Plasticity and recovery of function in the central nervous system.
New York: Academic Press, 1974:149-74.
[39] Golden CJ. The Luria-Nebraska children’s battery: Theory and
formulation.In: Hynd GW, Obrzut JE, eds. Neuropsychologic assessment
and the school-age children. New York: Grune & Stratton, 1981:277-
302.
[40] Grattan LM, Eslinger PL. Frontal lobe damage in children and
adults: A comparative review. Dev Neuropsychol 1991;7:283-326.
[41] Igarashi K, Kato M. Developmental change in working mem-
ory. In: Osaka N, ed. Brain and working memory. Kyoto: Kyoto
University Press, 2000:299-308.
[42] Cormack F, Cross JH, Isaacs E, et al. The development of
intellectual abilities in pediatric temporal lobe epilepsy. Epilepsia 2007;
48:201-4.
[43] Nelissen N, Van Paesschen W, Baete K, et al. Correlations of
interictal FDF-PET metabolism and octal SPECT perfusion changes in
human temporal lobe epilepsy with hippocampal sclerosis. Neuroimage
2006;32:684-95.
[44] Takaya S, Hanakawa T, Hashikawa K, et al. Prefrontal hypo-
function in patients with intractable mesial temporal lobe epilepsy.
Neurology 2006;61:1674-6.
[45] Cormack F, Gadian DG, Vargha-Khadem F, Cross JH, Connelly
A, Baldewega T. Extra-hippocampal grey matter density abnormalities in
paediatric mesial temporal sclerosis Neuroimage 2005;27:635-43.
[46] Gil R. Distúrbios de memória. In: Gil R, ed. Neuropsicologia.
São Paulo: Livraria Santos Editora, Ltda., 2003:171-96.
Rzezak et al: Executive Dysfunction and Temporal Lobe Epilepsy 185