Epilepsia, 53(12):2156–2163, 2012
doi: 10.1111/j.1528-1167.2012.03706.x
FULL-LENGTH ORIGINAL RESEARCH
Neurocognitive profiles in children with epilepsy
*Claudia L. Kernan, *yRobert Asarnow, *Prabha Siddarth, zSuresh Gurbani, xErin K. Lanphier,
{Raman Sankar, and *Rochelle Caplan
*Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California, U.S.A.; yDepartment of Psychology,
UCLA, Los Angeles, California, U.S.A.; zDepartment of Neurology, Kaiser Permanente, Anaheim, California, U.S.A.;
xDepartment of Psychology, Arizona State University, Tempe, Arizona, U.S.A.; and {Department of Pediatrics, UCLA,
Los Angeles, California, U.S.A.
SUMMARY
Purpose: The presence of specific neurocognitive deficits
may help explain why school achievement and psychoso-
cial functioning are often worse in children with epilepsy
than would be predicted by their global intellectual func-
tioning. This study compared children with two forms of
epilepsy: localization-related epilepsy with complex par-
tial seizures (CPS) and childhood absence epilepsy (CAE),
to determine whether they display distinct neurocogni-
tive profiles.
Methods: Fifty-one children with CPS, 31 children with
CAE, and 51 controls underwent neuropsychological test-
ing assessing verbal memory, visual memory, and execu-
tive functioning. Groups were compared in these
cognitive domains. Within-group analyses were also con-
ducted to examine seizure-related factors that may be
related to neuropsychological test performance.
Although a significant proportion of children with severe
forms of epilepsy score below average on intelligence tests,
the majority of children with epilepsy have intellectual func-
tioning within the average range (Berg et al., 2008). Despite
their mostly intact global intellectual functioning, however,
children with epilepsy as a group are at high risk for poor
academic functioning (Sillanpaa, 2004; Aldenkamp et al.,
2005; Fastenau et al., 2008) and negative psychosocial
outcomes (Wirrell et al., 1997; Sillanpaa et al., 1998).
Researchers have therefore highlighted the importance of
neuropsychological testing in children with epilepsy, positing
that specific cognitive deficits in domains other than general
intelligence may help explain why school achievement and
psychosocial functioning are often worse than would be pre-
dicted by their intelligence scores alone (Nolan et al., 2004;
Jocic-Jakubi & Jovic, 2006; Fastenau et al., 2008).
Accepted August 16, 2012; Early View publication November 5, 2012.
Address correspondence to Claudia L. Kernan, Semel Institute for Neu-
roscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA
90024, U.S.A. E-mail: ckernan@mednet.ucla.edu
Wiley Periodicals, Inc.
ª 2012 International League Against Epilepsy
2156
Key Findings: When compared to controls, children with
CPS showed a mild generalized cognitive deficit, whereas
children with CAE did not. When we controlled for intelli-
gent quotient (IQ), both epilepsy groups showed poorer
performance relative to controls in the domain of verbal
memory. When the epilepsy groups were compared to one
another, the CPS group performed significantly poorer
than the CAE group on a test of generalized cognitive func-
tioning. However, in the specific domains of executive func-
tioning, verbal memory, and visual memory the epilepsy
groups did not differ when compared to one another.
Significance: Neurocognitive deficits present in the
context of grossly intact global intellectual functioning
highlight the importance of neuropsychological screening
in both children with CPS and children with CAE.
KEY WORDS: Childhood absence epilepsy, Complex
partial seizures, Neuropsychology, Memory, Executive
functions, Child.
Past research has indicated that children with epilepsy
display specific cognitive weaknesses, with a number of
studies demonstrating deficits in the domains of memory
and executive functioning (Jambaque et al., 1993; Bailet &
Turk, 2000; Lassonde et al., 2000; Pavone et al., 2001;
Culhane-Shelburne et al., 2002; Nolan et al., 2004; Henkin
et al., 2005; Hoie et al., 2005; Borden et al., 2006; Hermann
et al., 2006; Hommet et al., 2006; Jocic-Jakubi & Jovic,
2006; MacAllister & Schaffer, 2007; Parrish et al., 2007;
Seidenberg et al., 2007; Hermann et al., 2008; Pulsipher
et al., 2009). However, the question of whether children
with different types of seizures or epilepsy syndromes show
distinct cognitive profiles has yet to be resolved in the litera-
ture. Most studies to date looking at cognitive functioning in
children with epilepsy have compared children with epi-
lepsy to a healthy control group or standard scores. The epi-
lepsy groups in these studies have been heterogeneous,
limiting the conclusions that can be drawn in terms of delin-
eating distinct cognitive profiles. Although several recent
studies have directly compared children with different types
of seizures and epilepsy syndromes, findings have been
mixed with regard to whether there are differences among
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Neurocognitive Profiles in Pediatric Epilepsy

epilepsy groups. In addition, children have been grouped studies of neurocognitive functioning in children with epi-
together using different criteria in terms of type of seizure lepsy, a healthy control group, and groups with comparable
and epilepsy syndrome, making comparisons across studies demographic variables. If patterns specific to epilepsy
difficult. group and clinical seizure variables can be identified, this
For example, some studies have compared children with could aid in the early identification of children at risk of
generalized seizures to children with focal epilepsies and developing cognitive problems and in tailoring interven-
found that children with focal epilepsies perform poorer on tions that address their specific needs.
tests of memory (Jambaque et al., 1993; Nolan et al., 2004).
Other studies comparing children with localization-related
epilepsies to children with generalized seizures have not
Methods
found significant differences in memory functioning (Wil- Subjects
liams et al., 1998, 2001; Hermann et al., 2006). In the The current study included 51 children with CPS, 31 chil-
domain of executive functioning, some studies comparing dren with CAE, and 51 controls, aged 6–16 years with IQ
children with localization-related epilepsy to children with scores between 70 and 130. Table 1 presents demographic
idiopathic generalized epilepsy have found no or small dif- features of the sample and the recruitment sites of the sub-
ferences between the groups (Hermann et al., 2006; Parrish jects. We determined socioeconomic status (SES) using the
et al., 2007). Similarly, a study comparing children with Hollingshead 2 factor index (Hollingshead, 1973), based on
absence seizures to children with complex partial seizures parental occupational and educational status. As summa-
found no differences among the groups in executive func- rized in Table 1, there were significantly more Caucasian
tioning (Williams et al., 1998). In contrast, a study compar- subjects in the CPS group than in the CAE and control
ing children with juvenile myoclonic epilepsy (JME) to groups (v2 = 6.5, p < 0.05). There were no significant dif-
children with benign childhood epilepsy with centrotempo- ferences in the demographic variables of the CPS, CAE, and
ral spikes (BCETS) found children with JME to have signifi- control groups.
cant executive dysfunction, whereas children with BCECTS The primary study inclusion criterion for each epilepsy
did not show the same pattern (Pulsipher et al., 2009). subject was that he/she had a diagnosis of epilepsy (CPS or
In addition to seizure type and epilepsy syndrome, a num- CAE) and at least one seizure in the year prior to participa-
ber of other seizure-related variables have been identified as tion in the study. At each site a pediatric neurologist made
contributing to variability in cognitive outcomes for chil- the diagnosis of CPS or CAE based on clinical history and
dren with epilepsy. Age at onset of epilepsy has been shown electroencephalography (EEG) findings, according to the
to predict later cognitive ability, with younger age of onset International Classification of Epilepsy (Commission,
associated with poorer cognitive outcomes (Jambaque 1989). Children with a clinical history of CPS but no EEG
et al., 1993; Schoenfeld et al., 1999; Pavone et al., 2001; evidence of epileptic activity were also included in this
Nolan et al., 2004; Hoie et al., 2006; Jocic-Jakubi & Jovic, study. All CAE patients had EEG evidence of 3 Hz spike
2006). Other disease-related factors such as longer duration and wave in addition to absence seizures induced by hyper-
of illness (Nolan et al., 2004), greater numbers of seizures ventilation. We excluded patients with a mixed seizure dis-
(Hoie et al., 2006; Jocic-Jakubi & Jovic, 2006; Fastenau order, previous epilepsy surgery, atypical spike and wave
et al., 2009), and treatment with one or more antiepileptic complexes, juvenile myoclonic epilepsy, generalized tonic–
drugs (AEDs) (Schoenfeld et al., 1999; Nolan et al., 2004; clonic seizures, a neurologic illness other than epilepsy,
Fastenau et al., 2009) have also been associated with
increased cognitive difficulties.
Table 1. Demographics
The purpose of the present study was to compare neuro-
cognitive functioning in children with localization-related Diagnosis
epilepsy with complex partial seizures (CPS), usually Variables Control CPS CAE
thought to involve cognitive impairment (particularly mem- n 51 53 31
ory), and children with childhood absence epilepsy (CAE), Male (%) 51 49 45
often regarded as a benign disorder without cognitive or Female (%) 49 51 55
other comorbidities. Children with general cognitive func- Chronological age (year) (SD) 10 (3) 10 (3) 9 (2)
Ethnicity (%)
tioning in the average range were compared on neuropsy- Caucasiana 39 62 39
chological measures of verbal memory, visual memory, and Non-Caucasian 61 38 61
executive functioning. We also investigated the effects of Socioeconomic status (%)
clinical variables on neurocognitive functioning in this pop- High 29 33 26
ulation, including age at seizure onset, duration of illness, Low 71 67 74
seizure frequency, number of AEDs, as well as lateralization CPS, complex partial seizures; CAE, childhood absence epilepsy.
a
Significantly more Caucasian subjects in CPS group than in CAE and
and localization of epileptic activity on EEG. The current Control group, p < 0.05.
study included a larger sample size than in most previous
Epilepsia, 53(12):2156–2163, 2012
doi: 10.1111/j.1528-1167.2012.03706.x
2158
C. L. Kernan et al.

chronic medical illness, imaging evidence for structural and diagnosis of each CAE subject from the different
brain abnormalities, a metabolic disorder, a hearing disor- recruitment sites. If he did not concur with the diagnosis
der, mental retardation based on school/classroom place- or EEG findings, the child was not included in the study.
ment, and bilingual speakers of American English who did The parents and children’s medical records provided
not attend English speaking schools or speak English at information on seizure-related variables, including seizure
home. frequency, current AEDs, age of onset, and illness duration
We recruited 42% of the CPS and 33% of the CAE (Table 2). EEG recordings done around the time of diagno-
subjects from tertiary centers (i.e., UCLA- and USC-based sis indicated left, right, bilateral, and no lateralization in
clinics) and 58% of the CPS and 67% of the CAE from 28%, 20%, 28%, and 24% of the CPS subjects, respectively.
community services (i.e., Los Angeles and Anaheim The localization of epileptic activity was temporal in 36%,
Kaiser Permanente, the Los Angeles and San Diego Chap- frontotemporal in 30%, and not localized in 34% of the CPS
ters of the Epilepsy Foundation of America, and private subjects. Thirteen of the CPS children had secondary gener-
practices). There were no differences between the CPS alization.
group and the CAE group in terms of recruitment site To include children from a wide range of ethnic and
(Table 2). UCLA institutional review board (IRB)– socioeconomic status backgrounds similar to that of the
approved recruitment flyers were available for parents of CPS and CAE group, we recruited the control subjects from
children with CPS and CAE at each recruitment site. Par- four public and two private schools in the Los Angeles com-
ents who decided to enter their children into the study munity. The study coordinator screened potential partici-
contacted the study coordinator who provided information pants for neurological, psychiatric, language, and hearing
about the study and used a UCLA IRB–approved tele- disorders through a telephone conversation with a parent.
phone script to determine if the children met the study’s We excluded children with diagnoses of these disorders in
inclusionary but none of the exclusionary criteria. The the past from the study.
study coordinator also contacted the child’s pediatric neu-
rologist to confirm the child’s diagnosis and to rule out Procedures
exclusionary criteria. One UCLA pediatric neurology This study was conducted in accordance with the policies
investigator (W.D.S.) reviewed the history, EEG records, of the University of California, Los Angeles Human Sub-
jects Protection Committees. Informed assents and consents
were obtained from all subjects and their parents, respec-
Table 2. Recruitment location and seizure tively.
characteristics
Diagnosis
Neuropsychological assessment
All subjects were administered neuropsychological tests
Variables CPS CAE
by individuals trained in standardized testing procedures.
n 53 31 For safety reasons, testers were not blind to whether the sub-
Recruitment location (%)
Tertiary 42 33
jects had epilepsy, but testers were blind to the epilepsy
Community 58 67 group (CPS or CAE) and all other seizure variables. The
Seizure frequency (log) (SD)a,b 3 (2) 6 (3) Wechsler Intelligence Scale for Children-Third Edition
Antiepileptic drugs (%) (WISC-III) was administered to children to obtain a mea-
None 2 6 sure of global intellectual functioning (Wechsler, 1991).
Monotherapy 75 68
Polytherapy 23 26
The Full Scale IQ score was generated from each test. Exec-
Age of onset (year) (SD) 6 (3) 6 (2) utive functioning was assessed with subtests from the
Duration of epilepsy (year) (SD) 4 (2) 3 (2) Stroop Color-Word Test (Stroop Color Naming, Stroop
Seizure lateralization (%) Interference) (Golden, 1975), the Wisconsin Card Sorting
Left 28 N/A Test (Total Errors, Perseverative Errors)(Heaton et al.,
Right 20 N/A
Bilateral 28 N/A
1993), and the Test of Memory and Learning (TOMAL;
No lateralization 24 N/A Digits Forward, Digits Backwards) (Reynolds & Bigler,
Seizure localization (%) 1994). Verbal memory was assessed with subtests from the
Temporal 36 N/A California Verbal Learning Test-Children’s Version
Frontotemporal 30 N/A (CVLT-C; CVLT-C Total, Long-Delay Free Recall, Reten-
Not localized 34 N/A
Secondary generalization (%) 25 0
tion, and Discriminability) (Delis et al., 1994), the TOMAL
(Memory for Stories, Memory for Stories-Delayed), and the
N/A, not applicable.
a
CAE significantly different than CPS, p < 0.0001. Doors and People Test (Auditory Name Recall, Long-
b
Log-transformed seizure frequency was used in the analyses because the Delayed Auditory Name Recall, Visual Name Recall, and
seizure frequency ranged from 1–50,000 seizures per year in the CAE Auditory Retention) (Baddeley et al., 1994). Visual mem-
subjects.
ory was assessed with subtests from the Doors People Test
Epilepsia, 53(12):2156–2163, 2012
doi: 10.1111/j.1528-1167.2012.03706.x

(Door Recall, Shapes Recall, Long Delayed Shapes Recall,
and Visual Retention).
Data analysis
A multivariate analysis of variance (MANOVA) was
used to compare the CPS, CAE, and control groups in the
domain of verbal memory. Standardized scores were used
for this analysis. Because standardized test scores were not
uniformly available for all neurocognitive tests within the
executive functioning and visual memory domains (i.e.,
Stroop, and Doors and People tests), multivariate analyses
of covariance (MANCOVAs) using raw scores, controlling
for age, were used to compare the CPS, CAE, and control
groups on neurocognitive tests in these domains. For all
MANOVAs and MANCOVAs, subjects missing data were
excluded. Significant MANOVA and MANCOVA effects
were subsequently analyzed using univariate analysis of
variance (ANOVA) and post hoc comparisons when appro-
priate. To determine whether demographic variables con-
founded results, we analyzed the relationship between
gender, SES, and ethnicity on neurocognitive tests scores
using separate ANOVAs. Gender, SES, and ethnicity did
not significantly influence test scores for any of the three
groups, and were therefore not controlled for in the analyses
described above.
Within the domain of executive functioning, Persevera-
tive Errors on the WSCT were not included in the data anal-
yses, because an error in data recording during test
administration resulted in loss of data for this variable. In
the domain of verbal memory, a separate MANCOVA using
raw scores controlling for age was conducted comparing the
groups on verbal memory subtests from the Doors and
People test, because significantly fewer subjects (N = 48)
completed this test. This was because the Doors and People
test was added to our battery later in the study. Doors and
People completers did not differ from the rest of the sample
in terms of demographics.
In addition, to determine whether neuropsychological
testing discriminated between the epilepsy and control
groups above and beyond what would be predicted by their
general intellectual functioning, the between-group analy-
ses described above were also conducted controlling for IQ.
For only those cognitive domains on which the groups
differed significantly, within-group analyses were per-
formed to explore the association of seizure-related vari-
ables (age of onset, log seizure frequency, lateralization
and localization, and number of AEDs) and neurocogni-
tive domains. Specifically, for the executive functioning
and verbal memory domains, within-group MANCOVAs
were conducted with the neurocognitive test scores as the
dependent variables and the seizure variables as predic-
tors, controlling for age. Significant MANCOVA effects
were subsequently analyzed using univariate analysis of
variance (ANOVA) and post hoc comparisons when
appropriate.
2159
Neurocognitive Profiles in Pediatric Epilepsy
Results
Comparisons between the control and epilepsy groups
Table 3 summarizes the means and standard deviations
for each of the three groups on the global intellectual func-
tioning, executive functioning, verbal memory, and visual
memory variables. There were significant differences
among the groups in terms of global intellectual function-
ing. Specifically, the ANCOVA comparing the CPS, CAE,
and control groups, with age as a covariate revealed signifi-
cant group differences: F2,135 = 10.29, p £ 0.0001, with the
control group and the CAE group scoring significantly
higher than the CPS group (mean difference = )13, 95% CI
[)17 to )8] and mean difference = )7, 95% CI [)11 to
)0.2]), respectively).
For the executive functioning tests, the MANCOVA
comparing the CAE, CPS, and control group scores, with
age as a covariate, yielded a significant effect of group:
F10,218 = 2.24, p < 0.05. Univariate analyses yielded signif-
icant group differences for Stroop Color Naming Time:
F3,117 = 5.72, p < 0.01; and WCST Total Errors:
F3,117 = 3.98, p < 0.05. Post hoc tests revealed that the CPS
group performed more poorly than the controls on Stroop
Color Naming Time (mean difference = 16, 95% CI [7–
24]) and WCST Total Errors (mean difference = 13, 95%
CI [5–19]). The CAE group performed more poorly than the
controls on WCST Total Errors only (mean difference = 8,
95% CI [)1 to 17]).
In the domain of verbal memory, the MANOVA compar-
ing the groups on the CVLT and TOMAL measures yielded
a significant effect for group: F10,252 = 3.86, p < 0.0001.
Univariate analyses yielded significant group differences
for CVLT Total: F2,133 = 6.63, p < 0.01; CVLT Long Delay
Free Recall: F2,133 = 8.7, p < 0.01; CVLT Discriminability:
F2,133 = 4, p < 0.05; TOMAL Memory for Stories:
F2,133 = 8.93, p < 0.01; and TOMAL Memory for Stories
Delayed: F2,133 = 15.43, p < 0.0001. Post hoc tests revealed
that the CPS group performed more poorly than the controls
on CVLT Total: mean difference = )8, 95% CI ()11 to )5);
CVLT Long-Delay Free Recall: mean difference = )0.9,
95% CI ()1 to )0.5); CVLT Discriminability: mean differ-
ence = )0.7, 95% CI ()1 to )0.3); TOMAL Memory for
Stories: mean difference = )2, 95% CI ()3 to )1); and
TOMAL Memory for Stories Delayed: mean differ-
ence = )3, 95% CI ()4 to )2). The CAE group performed
more poorly than the controls on CVLT Total: mean differ-
ence = )5, 95% CI ()9 to )1); TOMAL Memory for Stories:
mean difference = )2, 95% CI ()3 to )1); and TOMAL
Memory for Stories Delayed: mean difference = )2, 95% CI
()4 to )1). For the Doors and People verbal memory tests,
the MANCOVA did not yield a significant effect.
In the domain of visual memory, MANCOVA comparing
the groups on the Doors and People measures yielded a sig-
nificant effect for group: F8,82 = 1.83, p < 0.05; however,
univariate analyses did not yield significant effects.
Epilepsia, 53(12):2156–2163, 2012
doi: 10.1111/j.1528-1167.2012.03706.x
2160
C. L. Kernan et al.

Table 3. Neurocognitive performances in control, CPS, and CAE groupsa

CPS CAE
Control
Mean (SD) Mean (SD) 95% CI Mean (SD) 95% CI
Full Scale IQb***c* 107 (12) 94 (15) )17 to )8 101 (16) )11 to 0.2
Attention and executive functioning
Stroop Color Namingb* 53 (15) 69 (30) 7 to 24 65 (23) 4 to 20
Stroop Interference 43 (30) 37 (29) )14 to 2 50 (35) )6 to 50
WCST Total Errorsb*d* 30 (21) 43 (24) 5 to 19 38 (24) )1 to 17
Digits Forward 39 (17) 34 (21) )11 to 1 28 (12) )16 to )7
Digits Backward 23 (13) 16 (15) )10 to )2 18 (13) )9 to 0.4
Verbal memory
CVLT Total (T score)b**d* 56 (9) 48 (11) )11 to )5 51 (11) )9 to )1
CVLT Long-Delay Free (z-score)b* 1 (1) )0.4 (1) )1 to 0 0.03 (1) )1 to )0.1
Discriminability (z-score)b* 1 (1) )0.1 (1) )1 to 0 0.2 (1) )1 to )0.01
TOMAL Memory for Stories 12 (3) 10 (3) )3 to )1 10 (3) )3 to )1
(standard score)b**d**
TOMAL Memory for Stories- Delayed 11 (3) 8 (3) )4 to )2 9 (3) )4 to )1
(standard score)b**d**
Verbal Memory (Doors and People)
Auditory Name Recall 23 (7) 19 (8) )7 to 0.1 20 (7) )7 to 1
Long-Delay Auditory Name Recall 9 (3) 6 (4) )4 to )1 8 (3) )2 to 1
Visual Name Recall 16 (6) 13 (7) )7 to 0.2 17 (5) )2 to 3
E–F Difference (Auditory Retention) 1 (2) 3 (2) 0.1 to 2 1 (2) )1 to 1
Visual memory
Door Recall 17 (4) 15 (5) )5 to )0.3 18 (3) )1 to 2
Shapes Recall 32 (5) 26 (9) )10 to )1 31 (4) )4 to 2
Long Delayed Shapes 11 (2) 10 (2) )2 to 0.1 11 (1) )0.4 to 1
G–H Difference (Visual Retention) 0.2 (2) 1 (2) )1 to 2 0.4 (1) )1 to 1
*p < 0.05.
**p < 0.01.
***p < 0.0001.
a
Raw scores are reported unless otherwise indicated. Lower scores indicate better performance for Stroop Color Naming, Stroop Interference, and WCST
Total Errors. For all other tests, higher scores indicate better performance.
b
Significant difference between CPS and controls.
c
Significant difference between CPS and CAE.
d
Significant difference between CAE and controls.

Comparisons between the control and epilepsy groups,
controlling for IQ
For the executive functioning tests, the MANCOVA
comparing the CAE, CPS, and control group scores, with
age and IQ as a covariates, did not yield a significant effect:
F10,236 = 1.01, p = 0.44. For the Doors and People tests,
neither visual memory nor verbal memory MANCOVA
yielded a significant effect: F8,88 = 1.83, p = 0.08, and
F8,104 = 1.07, p = 0.39, respectively.
In the domain of verbal memory, the MANCOVA com-
paring the groups on the CVLT and TOMAL measures, con-
trolling for IQ, yielded a significant effect of group
(F10,272 = 2.34, p = 0.05). Univariate analyses yielded sig-
nificant group differences for CVLT Long Delay Free
Recall: F3,144 = 4.39, p < 0.05; TOMAL Memory for
Stories: F3,144 = 5.40, p < 0.01; and TOMAL Memory for
Stories Delayed: F3,144 = 7.10, p < 0.01. Post hoc tests
revealed that the CPS group performed more poorly than the
controls on CVLT Long Delay Free Recall (adjusted
means = )0.26 and 0.39) and TOMAL Memory for Stories
Delayed (adjusted means = 9.37 and 10.95). The CAE
group performed more poorly than the controls on TOMAL
Memory for Stories (adjusted means = 10.12 and 11.80)
and TOMAL Memory for Stories Delayed (adjusted
means = 9.07 and 10.95).
Relationship between neurocognitive performance and
seizure-related variables
In the executive functioning domain, for the CPS group,
the within-group MANCOVA exploring the association
between the seizure-related variable and the tests of neuro-
cognitive functioning did not yield a significant relationship
between seizure-related variables and tests of neurocogni-
tive functioning. For the CAE group, there was a significant
main effect for age of seizure onset (F5,20 = 7.19,
p < 0.001). Post hoc t-tests revealed that younger age of
onset was associated with poorer performance on Digits
Forward (t28 = )3.34, p < 0.05).
In the domain of verbal memory, for the CPS group, the
within-group MANCOVA exploring the association
between the seizure-related variables and the tests of neuro-
cognitive functioning in the verbal domain where there were
group differences (CVLT and TOMAL) yielded a signifi-
cant main effect for seizure frequency (F5,40 = 2.84,

Epilepsia, 53(12):2156–2163, 2012

doi: 10.1111/j.1528-1167.2012.03706.x

p < 0.03). Post hoc t-tests were performed and revealed that
greater seizure frequency was associated with poorer perfor-
mance on CVLT Total (t48 = )2.06, p < 0.05) and TOMAL
Memory for Stories Delayed Recall (t48 = )2.30, p < 0.05).
For the CAE group, the MANCOVA did not yield a signifi-
cant relationship between the seizure related variables and
neurocognitive performance on the CVLT and TOMAL.
AEDs, lateralization, and localization were not related to
neurocognitive functioning.
Discussion
The present study is one of few that compare neurocogni-
tive functioning in relatively large samples of children with
different types of epilepsy with comparable demographic
variables. When compared to each other, the CPS and CAE
group differed significantly in generalized cognitive func-
tioning, but not in the specific cognitive domains of execu-
tive functioning, verbal memory, and visual memory.
Compared to controls, children with CPS showed a mild
generalized cognitive deficit reflected by a mean Full Scale
IQ of 94 (SD = 15), whereas children with CAE did not
(mean Full Scale IQ = 102, SD = 16). Relative to controls,
both groups showed poorer performances in the domains of
executive functioning and verbal memory, with the CPS
group showing poorer across a greater range of tests. This is
consistent with a study of children with CPS, which found a
pattern of relatively diffuse and generalized cognitive dys-
function in children with CPS (Schoenfeld et al., 1999).
To determine whether neuropsychological testing could
help identify specific neurocognitive weaknesses in chil-
dren with CPS and CAE above and beyond what would be
predicted by their general intellectual functioning, we also
compared our study groups controlling for IQ. After control-
ling for IQ, no differences were found between the epilepsy
groups and the controls in the domain of executive function-
ing. However, both the CPS and CAE groups demonstrated
mild verbal memory deficits that were not associated with
deficits in generalized cognitive functioning. Specifically,
controlling for IQ, the CPS group performed poorer than the
controls on delayed verbal memory tasks (memory for word
lists and memory for stories), and the CAE performing
poorer than the control group on story memory tasks (both
immediate and delayed). The present study is among the
few to document cognitive impairments in children with
CAE. CAE has historically been considered a ‘‘benign’’ dis-
order, with little effect on neurocognitive functioning. How-
ever, increasing evidence suggests that this may not be the
case. In a prospective study with 39 children with general-
ized absence seizures, children with absence seizures per-
formed more poorly on tests of attention/executive
functioning/construction than controls (Fastenau et al.,
2009). Although we found intact nonverbal memory skills
with mild verbal memory deficits in children with CAE, two
other studies found the reverse pattern of mild nonverbal
2161
Neurocognitive Profiles in Pediatric Epilepsy
memory problems, with intact verbal memory skills (Pav-
one et al., 2001; Nolan et al., 2004). These inconsistencies
in findings may be partially due to small sample sizes and
subsequent lack of power to detect differences. Varying
degrees of seizure control in the study populations and dif-
ferences across studies in instruments used to assess verbal
and visual memory may also partially account for these dis-
crepant findings. More research is needed to better charac-
terize the factors that account for within-group variability in
cognitive functioning among children with CAE. Nonethe-
less, these findings, along with studies showing language
impairments (Caplan et al., 2009) in children with CAE
suggest that CAE is a syndrome that affects multiple cogni-
tive functions.
The literature is somewhat inconclusive regarding the
relationship between seizure variables and cognitive func-
tioning in children with epilepsy, with some studies finding
relationships and others not (Schoenfeld et al., 1999;
Williams et al., 2001; Nolan et al., 2004; Hermann et al.,
2006; Jocic-Jakubi & Jovic, 2006; Fastenau et al., 2009;
Austin & Fastenau, 2010; see Jambaque et al., 1993). In our
sample, seizure frequency was associated with cognitive
test performance in the CPS group, but not in the CAE
group. Younger age of onset was associated with poorer per-
formance on cognitive tests for the CAE group, but not the
CPS group. It may be that the relationship between age of
seizure onset and frequency and neurocognitive perfor-
mance differs depending on type of epilepsy and involved
brain regions. However, the literature does not adequately
address this question, and further exploration of the mecha-
nisms underlying the association between these factors and
neurocognitive functioning or lack thereof is needed. In par-
ticular, large prospective studies initiated close after the
onset of epilepsy will be useful in characterizing the course
of neuropsychological functioning over time and in deter-
mining the relative contributions of seizures variables on
neuropsychological impairment (Hermann et al., 2006;
Fastenau et al., 2009; Austin & Fastenau, 2010).
Along with the cross-sectional design of this study and
the lack of power to detect differences in the visual memory
domain, other limitations should be noted. The study was
not population-based, which limits the generalizability of
the findings. Although the control group was well-matched
to the epilepsy group on demographic variables, the control
group performed better than average on many of the neuro-
psychological tests. In addition, information on lateraliza-
tion and localization of the EEG findings of the CPS group
was limited because it was based on reports of EEG record-
ings done at the time of the diagnosis of epilepsy.
Despite its limitations, the present study demonstrates
that although children with CPS and CAE may look similar
in terms of their academic and behavioral problems (Caplan
et al., 2004, 2008; Fastenau et al., 2008; Caplan et al.,
2009), the cognitive underpinnings of their functional defi-
cits may be distinct, with the CPS group showing more
Epilepsia, 53(12):2156–2163, 2012
doi: 10.1111/j.1528-1167.2012.03706.x
2162
C. L. Kernan et al.
diffuse cognitive impairment. In addition, the present study
demonstrated verbal memory deficits in children with CAE
and CPS in the context of intact global intellectual function-
ing. Although the deficits were mild in magnitude for many
of the children studied, it is important to note that, overall, a
disproportionate number of children with CPS and CAE fell
more than one standard deviation below controls, even
when controlling for IQ. There is clearly a subset of children
who are at risk for academic and functional difficulties due
to memory problems. More research is needed to determine
whether these memory difficulties may be present in the
nonverbal domain, as the present study was underpowered
to detect visual memory differences. Because neuropsycho-
logical testing is costly in terms of both time and financial
resources, findings may be useful for designing more
targeted memory screenings of children with epilepsy.
Acknowledgments
This study was supported by grants NS32070 (RC) and MH 67187 (RC).
Disclosure
None of the authors has any conflicts of interest to disclose. We confirm
that we have read the Journal’s position on issues involved in ethical publi-
cation and affirm that this report is consistent with those guidelines.
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