Journal of the Neurological Sciences 359 (2015) 5966

Contents lists available at ScienceDirect

Journal of the Neurological Sciences

journal homepage: www.elsevier.com/locate/jns

Review article

Neuropsychological impairment in childhood absence epilepsy: Review

of the literature
A. Verrotti a,, S. Matricardi b, V.E. Rinaldi a, G. Prezioso b, G. Coppola c
a
Department of Paediatrics, University of Perugia, Italy
b
Department of Paediatrics, University of Chieti, Italy
c
Department of Child Neuropsychiatry, University of Salerno, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Aim: Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence
Received 23 June 2015 seizures in school age children. Although it is commonly considered to have a good prognosis, with a good
Received in revised form 14 October 2015 response to antiepileptic drugs, recent studies questioned this traditional view of a benign disorder, in
Accepted 15 October 2015 particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological
Available online 23 October 2015
involvement in patients affected by CAE.
Methods: A literature search was carried out in PubMed's and Medline's databases for all relevant studies published
Keywords:
Absence seizures
between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specic review
Childhood absence epilepsy (CAE) articles, systematic reviews, textbooks and case reports were examined for any further publications.
Cognitive function Results: In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ
Neuropsychology scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions
General cognition have been reported to be mildly impaired. Data regarding memory are still conicting.
Discussion: Given the neuropsychological decits in many CAE patients which signicantly affect their quality of
life, CAE should not be considered entirely benign. An early identication of neuropsychological dysfunction in
CAE children is essential for appropriate treatment.
2015 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
2. Intellectual functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3. Language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
4. Learning disabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
5. Attention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
6. Motor skills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
7. Executive functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
8. Memory functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
9. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Financial disclosure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Potential conicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

Abbreviations: CAE, childhood absence epilepsy; TAS, typical absence seizures; IGE, idiopathic generalized epilepsies; AEDs, anti-epileptic drugs; IQ, intelligence quotient; WISC,
Wechsler Intelligence Scale for Children; NIH, National Institutes of Health; NINDS, National Institute of Neurological Disorders and Stroke; FSIQ, Full Scale Intelligence Quotient; HCs,
healthy controls; VIQ, verbal intelligence quotient; BECTS, benign epilepsy with centro-temporal spikes; PGE, primary generalized epilepsy; CPS, complex partial seizures; AERP, auditory
event-related potential; MRI, magnetic resonance imaging; VPA, valproic acid; ADHD, attention decit and hyperactivity disorder; ESX, ethosuximide; LTG, lamotrigine; CBCL, Childhood
behaviour checklist test.
Corresponding author at: Ospedale S. Maria della Misericordia, Str. S. Andrea delle Fratte, 06132 Perugia, Italy.
E-mail address: averrott@unich.it (A. Verrotti).

http://dx.doi.org/10.1016/j.jns.2015.10.035
0022-510X/ 2015 Elsevier B.V. All rights reserved.
60 A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
1. Introduction
Childhood absence epilepsy (CAE) is a well-known paediatric
epileptic syndrome, which generally responds to medical treatment.
According to the proposed diagnostic scheme of the currently valid clas-
sication and terminology of the International League Against Epilepsy,
[1] CAE is a syndrome within the Idiopathic Generalized Epilepsies (IGE)
showing Typical Absence Seizures (TAS).
CAE accounts for 1017% of all cases of childhood-onset epilepsy,
and in children's cohorts the prevalence has been estimated to range
from 0.4 to 0.7 per 1000 people and, with some exceptions, it is more
frequent in girls than in boys (11.4% vs 2.5%) [2]. This syndrome is
characterized by daily, frequent but brief staring spells which typically
begin at 410 years of age in an otherwise apparently healthy child
[3]. Absence seizures are clinically characterized by impairment of
consciousness without major motor symptoms, and a typical EEG
pattern of generalized, bilateral, synchronous, symmetrical spike
wave discharges of 34 Hz. Childhood absence epilepsy generally has
a good prognosis as regards the disappearance of seizures and the
possibility to discontinue therapy with antiepileptic drugs (AEDs)
[4,5]. However, within this syndrome there are many variables that
can signicantly modify its clinical outcome as CAE is probably geneti-
cally heterogeneous, but the precise mode of inheritance and the
genes involved are incompletely understood [6].
Children with epilepsy, particularly CAE, suffer from attention and
executive functions problems and these impairments often persist
even when seizures are treated [7]. Although CAE is historically believed
to be a benign disorder, children affected by CAE may have a poor
psychosocial adjustment. This theory disagrees with the traditional
view of CAE as a benign disorder [8].
In order to summarize the current ndings on neurocognitive
impairment in CAE, this review examines the effects of this syndrome
in seven main domains: intellectual functioning, language, learning
disabilities, attention, motor skills, executive functions, memory func-
tioning. Scientic knowledge regarding cognitive involvement in child-
hood epilepsies is rapidly expanding but it is in continuous need of
further investigation and we outline areas of consensus as well as
areas of uncertainty that may indicate directions for future research.
Data for this review were identied with Medline and PubMed
surveys for studies dealing with absence seizures, references from rele-
vant articles and research from authors' les. Research was performed
including papers published from 1924 to 2015. We sought to identify
evidence published in English; specic review articles, systematic
reviews, textbooks and case reports were examined for any further
publications, as were the reference sections of all articles identied by
the literature search. Only publications containing the most relevant
results for this investigation were included (Table 1).
2. Intellectual functioning
Many study groups have focused on searching for a possible biolog-
ical basis to explain CAE comorbidities in terms of abnormalities in brain
regions implicated in behaviour, emotions, cognition and language.
Intelligence tests are considered the rst-line tool for assessing
cognitive problems in children. Results from intelligence quotient (IQ)
tests help guide diagnosis, treatment, and educational planning, and
are used by clinicians and researchers alike. The Wechsler Intelligence
Scale for Children Fourth Edition (WISC-IV, Wechsler, 2003a) is a
sensitive tool for the evaluation of epilepsy-related cognitive impair-
ments in clinically referred children with a high seizure burden [9].
Most of the available data show that although presenting an average
IQ, roughly one fourth of all children affected by CAE have subtle
cognitive difculties. A signicantly lower mean Full Scale Intelligence
Quotient (FSIQ) score in CAE patients compared to healthy controls
(HCs) was reported in Caplan's et al.'s studies [8,1013]. The normal
control group in Caplan et al.'s studies had a high mean FSIQ. Similarly
Vega et al. [14] and Pavone et al. [15] observed lower FSIQ scores in
CAE patients compared to controls, although the scores were within
the normal range, and these studies both included a small number of
patients. According to Jones et al. [16], eight out of 25 cases of CAE
patients had a FSIQ below the average whereas the remaining CAE
children had a lower FSIQ than HCs. Jones et al. however, used the
same subjects already studied by Caplan et al. in previous studies; it is
therefore possible to consider these results redundant. Similar results
were seen during follow-up in each of the three groups, even though
IQ appeared to be signicantly related to baseline seizure variables in
the group with an average IQ.
Frequent seizures were documented in a prospective consecutive
study by Nolan et al. [17] as a negative prognostic factor for cognitive
functioning. Signicant associations were also seen between lower
FSIQ and younger age of epilepsy onset [17], poor seizure control
[10,18] and formal thought disorder [10], supporting the hypothesis
that IQ might reect the impact of epilepsy on cognition and language
abilities.
Moreover, Caplan et al. [12] pointed out that CAE children with a
lower IQ had signicantly more social difculties. The correlation
between poorer IQ performances and behavioural problems was also
highlighted by Hermann et al. [19] These authors pointed out that the
presence of behavioural comorbidities might be associated with a
signicantly worse cognitive development.
General cognition in CAE children has often been related to that of
other epileptic syndromes, generally resulting in higher IQ scores in
comparison to children with complex partial seizures (CPS) [11,20] or
with symptomatic epilepsy [18], but lower than in syndromes like
benign epilepsy with centro-temporal spikes (BECTS) [21].
In a study by Mandelbaum et al. [22] a cognitive composite score
elaborated after the administration of a battery of tests, detected that
at baseline, children with CAE performed worse than subjects with
partial or generalized convulsive seizures. Analysis of the subjects'
performance after 6 and 12 months of antiepileptic therapy showed
no signicant deterioration attributable to medication.
Sirn et al. in a small prospective clinical study [23] hypothesized a
positive role of AEDs on cognitive functions: cessation of seizures
induced by antiepileptic medication positively inuenced neurocognitive
functioning in children with newly diagnosed CAE. The IQ score was
within the normal range in both CAE patients and in the control group.
During the follow-up after AED introduction, a signicantly benecial
effect was reported in the study group in terms of motor uency, mem-
ory and attention. However, in 2003, Nolan et al. [17] reported that the
use of more than two anticonvulsant drugs was associated with lower
IQ scores in a population of 169 children of whom 17 had CAE with a
median of 1 antiepileptic drug. Similar data were obtained the following
year [18] by assessing neuropsychological skills in 13 children with CAE
of whom 5 were treated with one and 8 with two AEDS. However,
because of the small size of these study groups it is not possible gener-
alize these ndings to all children with CAE.
A smaller number of papers did not nd any signicant differences
in general cognition between CAE children, HCs, and CPS patients,
even though patients mean IQ scores were often lower than normal
mean values [7,17,24,25,26]. However several authors only recruited
children with an IQ score N 70, a choice that might have limited the
generalization of these studies.
3. Language
Although literature data are conicting, most studies investigating
verbal IQ (VIQ, a component of FSIQ) and language skills, found worse
performances in CAE children than in normal children [26]. In particular,
Caplan et al. detected lower VIQ and language mean scores in a CAE
sample [11] and in a group of children and adolescents with CAE or
CPS epilepsy [27], compared to HCs. Similar ndings were reported by
Jones et al. [16] and Henkin et al. [28].
 A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
Evidence of verbal rather than non-verbal impairment was found in
auditory event-related potential (AERP) data of the same cohort of
patients evaluated by Henkin et al. [29]. AERPs are measures of electrical
brain activity that may be used to assess higher-level cognitive process-
ing [30]. They are considered markers of specic aspects or stages of
information processing; for this reason, AERPs have been used exten-
sively to study brain mechanisms underlying cognition and to charac-
terize information processing in healthy and cognitively impaired
individuals. In this study, average AERPs waveform peaks were identi-
ed for each subject and for each experimental condition, based on
the order of their appearance (N1 was dened as the rst and largest
negative peak; N2 as the second largest negative peak; P2 and P3
were dened as the largest positive peaks after N2). Children affected
by CAE showed an increased use of attention resources for phonetic
and semantic processing, highlighted by increased N2 amplitudes.
Prolonged P3 latencies were observed in semantic processing, in
contrast with those evoked by the non-linguistic tonal task, and with
N1 and N2 latencies, suggesting that a semantic decit inuenced the
later phase of perceptual processing. In addition, different patterns of
brain-activity lateralization associated with linguistic stimuli were
found in both epileptic groups.
Some authors reported decits limited only to certain elds of
language such as verbal uency. In particular, signicant differences
regarding phonological and category uency between CAE patients
and healthy subjects were reported by D'Agati et al. [7] whereas no
differences were found in VIQ scores among these subjects.
Nolan et al. [18] highlighted a higher VIQ performance of CAE
children compared to those affected by temporal lobe epilepsy. More
generally, Nolan et al. [17] found that the generalized idiopathic epilepsy
group, including CAE patients, scored better than other epilepsy
syndrome groups in terms of VIQ.
Hommet et al. [21], focused on the relation between lateralized
hemispheric functions such as language, and on the topography of
paroxysmal anomalies, revealing no differences among CAE patients,
BECTS cases and healthy children. Moreover no differences in the cere-
bral organisation pattern for language were seen in CAE patients.
4. Learning disabilities
The risk factors for language and learning impairment that showed
greater signicance in primary generalized epilepsy syndromes (PGE),
were: young age of onset, higher seizure frequency, lower IQ scores,
male gender, longer duration of illness, and the use of more than one
AED [10,16,18,19,27,24,25]. These data have been conrmed by studies
focused on CAE [11].
With the help of functional MRI morphometry, it has been possible
to characterize the different brain circuits involved in language and
learning processes. However, variables such as family factors, pre-
existing learning problems, psychopathology and neuropsychological
impairments were also often signicant in inuencing academic under-
achievement and cognitive defects in epileptic children [16].
In some of Caplan et al.'s. [24,12] studies, thought disorder scores,
school scores and VIQ did not appear signicantly related to different
age, gender, ethnicity and socioeconomic status in CPS and PGE patients,
even though these patients performed worse than HCs.
5. Attention
Attention problems are commonly reported in children with epilepsy,
particularly CAE [7].They can interfere with children's academic
performances and daily lives [14]. Attention seems to be particularly
vulnerable to epileptic activity [31] and evaluating the effects of epilepsy
on the development of cognitive functions is complex because of the
many variables that can affect cognitive abilities.
Cerminara et al. [32] prospectively investigated the attentional func-
tioning of twenty-four children with clinically diagnosed CAE from a
61
multicomponent perspective using several test procedures that mea-
sure different aspects of attention. Results showed that compared to
healthy controls, patients with CAE were markedly impaired in some
measures of alertness, divided attention, impulsivity, and selective
attention. With regard to focused attention, however, no differences
were observed between the two groups.
Caplan et al. [11] in 2008 found that 26% of CAE patients suffered
from Attention Decit and Hyperactivity Disorder (ADHD) and 37.5%
showed attention problems, compared respectively with 6% and 4.9%
of the controls. Vega et al. [14] also supported these results. There is
evidence that points to a complex relationship between ADHD and
seizure disorders. In particular, the ndings of high prevalence of
ADHD in recent onset idiopathic epilepsy, and the appearance of
ADHD symptoms prior to the rst recognized seizure suggest that recur-
rent seizures and their treatment may not represent the core etiological
factor underlying ADHD in children with epilepsy. [33].
By administering specic attention tests, signicant differences
compared to HCs were detected in many studies [7,20,25,26,28]. Never-
theless, Bhise et al. [34] that patients suffering from absences scored
higher than others with different seizure types in the Test of Variables
of Attention and in the Trail Making Test.
Overall, neuroimaging studies demonstrate impaired attention and
network connectivity in childhood absence epilepsy consisting of a
decreased activation of anterior insula of the medial frontal cortex
[35]. Accordingly, a functional magnetic resonance study carried out
while a CAE patient performed a sustained attention task, revealed
impaired functioning of an attention network that included the anterior
insula/frontal operculum and medial frontal cortex [36].
As far as it concerns the effects of anticonvulsant treatment on atten-
tion skills in children with CAE, most studies reported a higher rate of
attention dysfunction in patients treated with VPA compared to those
treated with ESX or LTG. In fact, Glauser et al. [36], by comparing the
efcacy of VPA, ethosuximide (ESX) and lamotrigine (LTG) in a
double-blind, randomized, controlled clinical trial, reported a higher
rate of attention dysfunction in the group treated with VPA compared
to the ESX or LTG groups at 1620 weeks, conrmed on 12 months
follow-up. These results were further conrmed by Thio [37] in a large
cohort study in which a total of 49% of studied CAE children treated
with VPA for 1620 weeks had attention problems. In comparison 32%
of children treated with ethosuximide and 24% of children treated
with lamotrigine had attention problems after 1620 weeks. Moreover,
children treated with valproic acid were less likely to show improved
attention than those treated with ethosuximide or lamotrigine. The
same conclusions were reported by Masur et al. [38].
Monotherapy with levetiracetam could also be an effective and well
tolerated strategy in patients with childhood absence epilepsy and
juvenile absence epilepsy [39]. In this prospective study twenty-one
participants with typical absence seizures were enrolled and carefully
evaluated at 6 months from baseline. Twelve patients were also re-
evaluated at 12 months after the beginning of therapy with levetirace-
tam. At the 6-month evaluation, out of 21 patients studied, 11 were
seizure free and one showed decreased seizures; at the 12-month
evaluation, 10 patients were completely seizure free. However, clini-
cians must consider that Levetiracetam should not be the rst choice
treatment in patients with CAE and mood or attention disorders.
6. Motor skills
There is more evidence for the alteration of executive functions
[7,21,26], as well as ne motor speed and motor uency [26,28] in
CAE patients. Henkin et al. found a diminished right-hand superiority
in children with CAE, in accordance with their deviant laterality patterns
of the P3 component compared to controls of the authors' previous
study [29].
More recently, Guerrini et al. [40] observed over a 7-year period, that
age-related dysgraphia occurred at a signicantly higher rate in children

Table 1
Reviewed articles.
Authors, year Demographics
Bhise et al., 2009 57 pts. with new-onset idiopathic epilepsy; 5 with generalized
convulsive, 18 with generalized non-convulsive, 34 with focal;
mean age: 10.1 2.7 years.
Caplan et al., 2002 92 CPS pts. and 51 PGE pts. vs 117 HCs, aged 5.116.9 years.
PGE: 12% no AED, 78% mono, 10% poly.
Caplan et al., 2005 100 CPS pts., 71 CAE pts. vs 93 HCs; mean age 10.3 2.74
CAE: 36% no AED, 9% mono, 55% poly.
Caplan et al., 2005 90 CPS pts. and 62 CAE pts. of vs 91 HCs, aged 516 years
CAE: 15% no AED, 69% mono, 16% poly.
Caplan et al., 2006 93 CPS pts. and 56 PGE pts., aged 5.116.3 years
PGE: 9% no AED, 79% mono, 12% poly.
Caplan et al., 2008 69 CAE pts. vs 103 HCs, aged 9.6 2.49 years
CAE: 12% no AED, 76% mono, 13% poly.
Caplan et al., 2009 26 pts. with CAE vs 37 HCs; aged 7.511.8 years
CAE: 8% no AED, 74% mono, 18% poly.
Caplan et al., 2009 182 epileptic pts., 78 with CAE, 104 with CPS, aged 6.315.2 years;
compared to 102 HCs, aged 6.615-5 years. Three age-related
subgroups: young, intermediate and youth.
Mostly in therapy.
Conant et al., 2010 16 CAE pts. and 14
children with T1D vs 15 HCs.
CAE: 6% no AED, 9% mono, 1% poly.
D'Agati et al., 2012 15 CAE pts., mean age: 11.4 2.2 years compared to 15 HCs,
mean age 10.7 2.0 years. All treated with VPA.
Fastenau et al., 2009 282 pts. with a rst recognized seizure, 13.8% with generalized
absences, mean age: 9.7 2.5; compared to
147 HCs, mean age: 10.8 2.9.
Glauser et al., 2010 453 CAE pts. randomly assigned to treatment with ETM (156),
LMT (149), or VPA (148).
Henkin et al., 2003 24 pts., 12 with GTCS, aged 1216.3, and 12 with AS, aged
1116.3, uniformly treated with VPA, vs 20 HCs, aged 10.616.
Henkin et al., 2005 24 pts. on VPA therapy, 14 with GTCS, mean age 14.3 1.6, 14
with AS, mean age 14.4 1.83, compared to 20 HCs, mean age
14.4 1.86.
Hermann et al., 2008 52 pts. with new-onset epilepsy (among whom 7 CAE and JAE
pts), aged 818 years, divided in a comorbidity + group
(AP/ADHD) and a comorbidity- group, compared to 48 HCs.
Cognitive tests
KBIT, WRAML, CVLT, SCWT, TOVA, TMT A and B, GPT for
Dominant and Non-Dominant Hands, CBCL, CDI, RCMAS-2.
WISC-R, K-FTDS, Holliday and Hasan's analysis of cohesion, Story
Game (with Caplan and colleagues modications).
WISC-R, WISC-3, K-SADS, TOLD, CBCL, CDI, MASC.
WISC-R, WISC-3, CBCL, K-SADS, TOLD, K-FTDS, Story Game (with
Caplan and colleagues modications).
WISC-R, WISC-3, K-FTDS, TOLD, K-SADS, CBCL, WIAT.
WISC-3, WISC-R, TOLD, TOAL, K-SADS, CBCL.
WISC-3.
WISC-R, WISC-3, K-SADS, TOLD-2, TOAL, WIAT.
WISC-3, WRAT-3, WRAML, Finger Tapping, KABC-HM, VMI, TOL,
WCST, COWA, CF -Animal Naming test, GDS, CBCL, MTRT.
WISC-3, TOL, FAS, CAT, F-DIGIT span, B-DIGIT span, CBTT, TMT-A
e B.
WISC-3, CELF-3, CTOPP, CPT, WCST, WRAML, WJ-R.
CPT-2, K-CPT, WISC-3 E 4, TONI, PPVT-3, BEERY VMI, WRAT,
WCST, WJ-3.
WISC-R, AERP.
WISC-R, CVLT, ROCF, FTT.
WISC-3, WASI, WRAT-3, BNT, EVT, PPVT-3, D-KEFS, CMS, CPT.
62
Major outcomes
1) PGEs verbal scores lower than focal epilepsy pts.
2) PGEs: lower memory scores and higher attention scores.
1) CPSs IQ b PGEs IQ b HCs IQ; correlation FSIQ/seizure control
and formal thought disorders.
2) PGEs: poorer language scores than HCs and TLEs.
1) CAEs IQ b HCs IQ; lower IQ in pts. with psychiatric problems.
A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
1) CAEs IQ b HCs IQ.
2) CAEs school score and VIQ = CPSs b HCs.
1) No differences between CAEs IQ and HCs IQ.
2) No differences in thought disorders between CPSs and PGEs;
seizure frequency, age of onset, duration of illness = predictors;
positive role of VPA therapy.
1) CAEs IQ b HCs IQ.
2) CAEs VIQ b HCs VIQ.
3) Within the CAE group: 26% ADHD; 37.5% attention problems.
1) CAEs IQ lower but average; smaller grey matter volumes in
frontal and temporal lobes.
1) CAE predicts lower verbal scores in the young group.
1) No differences between CAEs IQ and HCs IQ.
2) No differences in acad. ach.
3) Impaired problem solving, visuomotor planning/integration,
and attention in CAE pts.; no differences in memory, ne motor
and processing speed.
1) No differences between CAEs IQ and HCs IQ.
2) Phonological and category uency lower than HCs.
3) Lower planning and attention scores in CAE pts.; no differences
in memory.
1) No differences between CAEs IQ and HCs IQ.
2) CAEs language scores b LRI epilepsies; CAEs acad. ach. in
writing N GTCSs and LRI epilepsies; AED therapy is a risk factor.
3) Lower scores in attention, executive functions and
construction skills in CAE pts.; VPA lead to lower processing
speed scores.
1) Pts on VPA had higher attention dysfunctions.
1) AERPs suggestive for verbal impairment and different
lateralization of brain activity in CAEs.
1) CAEs and GTCSs verbal uency b HCs.
2) Lower attention, verbal memory and ne motor response scores
in AS pts.; no differences in non-verbal memory and retention skills.
1) Comorbidity + group: worse cognitive performances.
2) Comorbidity + group: worse verbal scores.
3) Comorbidity + group: worse memory and executive functions
scores.
Hommet et al., 2001 23 pts. in total recovery from BECTS, vs 33 HCs and 10 pts. with
complete resolution of CAE; mean age: 21 years.
CAE: 100% mono
Jones et al., 2010 39 CPS pts., 25 CAE pts., 27 HCs; aged 7.6 to 16.1 years. The
sample was
divided into three groups based on Full Scale IQ at baseline:
below average, average, and controls. Follow-up: 22.9 6.5
months. Mostly in therapy.
Kernan et al., 2012 51 CPS pts., 31 CAE pts., and 51 HCs; aged 616 years
CAE: 6% no AED, 68% mono, 26% poly.
Lagae et al., 2001 23 new-onset CAE pts., 13 with classical absences, mean age 8.0
years, and 10 with frontal absences, mean age 8.6 years.
Lopes et al., 2014 90 pts., (30 with frontal lobe epilepsy, 30 with CAE, 30 with BECT
and 30 controls).
WISC-R, WMS-R, WCST, TMT, SCWT. 1) CAEs IQ b BECTSs IQ.
2) CAEs VIQ = BECTSs VIQ = HCs VIQ.
3) Lower PIQ scores and impaired motor skills and visuospatial
integration in CAE pts.; no differences in executive functions.
CBCL, K-SADS, CDI, MASC, WISC3, TOLD2, TOAL, WIAT screener. 1) 8 CAEs pts. in the below-average group.
2) Average group VIQ b HCs VIQ; no effect of time on acad. ach.
and language; benecial effects of AEDs on below-average group.
WISC-3, SCWT, TOMAL, CVLT-C, DPT. 1) CPSs IQ b CAEs IQ b HCs IQ.
2) Lower executive functions, attention, and verbal memory
scores in CAE pts.; age of onset as a predictor for executive
functions impairment.
Questionnaire. 1) IQ b 85 in 1/13 pts. with classical absences and in 3/10 pts.
with frontal spikes.
2) Learning disabilities in pts. with frontal spikes.
Memory tests (Coimbra's Neuropsychological Assessment 1) Frontal lobe epilepsy: greater risk of memory problems.
battery). 2) Memory decits in all epilepsies N during learning phase.
3) BECTS have major attention problems.

A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966

4) Longer duration of active epilepsy predicts memory
difculties.
Mandelbaum et al., 1997 Pts. with new-onset seizure: 43 at baseline (20 with AS, mean COGNITIVE COMPOSITE SCORE: WISC, BGT, WRAT, DTLA, CBCL. 1) ASs IQ b PSs and GSs IQ only at baseline.
age 9.92 3.71), 26 at 6-month follow-up (11 with AS, mean age
10.04 0.85), and 26 at 12-month follow-up (6 with AS, mean
age 9.64 1.24).
At baseline: 36/43 in monotherapy.
Nolan et al., 2003 169 epileptic pts. with GIE (22, 17 of whom with CAE), GSE (25), GMDS, DAS, WISC-III, WAIS-R. 1) CAEs IQ N GSEs IQ; seizure control and number of AEDs
CE (16), TLE (40), FLE (34), PE (32); aged 0 to 18 years. correlate with IQ.
5% no AED, 37% mono, 57% poly. 2) CAEs verbal scores N than other epilepsy syndromes.
Nolan et al., 2004 70 pts. with CAE, FLE or TLE; aged 6 to 18 years. The CAE sample WRAML, WISC-3, SB 4, WAIS-R. 1) No differences between CAEs IQ and FLEs or TLEs IQ; young age
included 13 pts. at onset, frequent seizures, number of AEDs correlate with IQ.
5 on mono, 8 on poly. 2) CAEs verbal learning = HCs N TLEs; duration of epilepsy as a
predictor.
3) Lower memory scores in CAE pts.; AEDs did not correlate with
memory.
Pavone et al., 2001 16 pts. with AS, aged 616 years. WISC-R, RPM, RCFT, TOMAL. 1) ASs pts. IQ lower but average.
11 on VPA, 2 on ETX, 3 on VPA + ETX. 2) CAEs language scores = HCs.
3) Selective decits in memory; age of onset as a predictor for
visuospatial skills impairment.
Sirn et al., 2007 11 pts., 10 with newly diagnosed CAE and 1 with JAE, vs 10 FTT, IQ, WISC-R, WPPSI-R, tests for attention, visual and spatial 1) No differences between CAEs IQ and controls IQ; no difference
controls with mild asthma memory. after AED introduction.
VPA, ETM or VPA + ETM therapy. 2) AED introduction improved ne motor speed, attention, and
visual memory.
3) Duration of discharges and clinical absence seizure at rst
assessment correlate with visual memory impairment.
Thio et al., 2013 446 pts. with newly diagnosed CAE. Neuropsychological tests. 1) 49% of pts. treated with VPA: attention problems.
2) 32% of pts. treated with ethosuximide and 24% of pts. treated
with lamotrigine: attention problems.
Tosun et al., 2011 24 CAE pts., aged 5.515.8 years, vs 28 HCs WISC-3. 1) CAEs IQ lower but average; use of different brain regions.
3 no AEDs, 14 mono, 7 poly. 2) CAEs VIQ b Hcs IQ; fMRI: different brain regions for language.
Vega et al., 2010 38 CAE pts. vs 46 HCs; aged 6 to 16 years. BASC, ATT, HYP, WASI. 1) CAEs IQ b HCs IQ.
5% no AED, 66% mono, 27.7% poly. 2) CAE pts.: increased risk for ADHD.

63
64 A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
with absence epilepsy than in a control population. Clinical and neuro-
physiological ndings, in this particular population, were consistent
with an age-related dystonic origin of dysgraphia. Considering that
children spend 30% to 60% of their school day performing handwriting
and other ne motor tasks, handwriting difculties may seriously affect
their daily life. However, after observing a favourable outcome in older
children with longer follow-up, the authors suggested that not only
epilepsy but also dysgraphia would eventually disappear.
7. Executive functions
Executive functions consist in a set of higher-order cognitive abilities
necessary to make decisions and to undertake goal-directed and specic
behaviours. Most data in literature [19,20,25] highlight a decit in this
functioning within all epileptic subjects, and particularly in CAE sub-
jects. Hommet et al. [21] found no differences in executive functioning
between patients no longer affected by BECTS, CAE and HCs.
Risk factors for frontal functioning impairment have been investi-
gated by several authors, but further studies are required. The potential
risk factor most frequently reported was the age of seizure onset [20,
14]. Hermann et al. [19] in their longitudinal study highlighted that
time had negative effects only on the Continuous Performance Task
omission and commission errors, which increased over time in patients
with comorbidities, specically among children with ADHD. This study
however included children with different types of epilepsy and only few
patients were affected by CAE.
Conant et al. [26] described signicant differences regarding execu-
tive functions in CAE children compared to HCs. Cases appeared to
have difculty when having to shift in type of response to changing
external demands but their processing speed and inhibition abilities
appeared to be normal. Furthermore, Fastenau et al. [25] in their large,
prospective, community-based study, detected that children suffering
from generalized epilepsy with absences performed worse on a
composite measure that included attention, executive functions, and
visuoconstruction.
Increasing evidence of frontal cortex involvement in CAE drew many
authors to investigate on executive functions such as frontal cognitive
domains, like attention, problem solving and decision making, planning
and working memory. In particular, working memory appears to be
involved in frontal circuit impairment. Working memory was dened
by Baddeley as a brain system that provides temporary storage and
manipulation of the information necessary for such complex cognitive
tasks as language comprehension, learning, and reasoning [41].
The increasing evidence for a primary role of the frontal cortex in
CAE genesis has been linked to the neurocognitive involvement that
characterizes this syndrome: imaging studies on CAE subjects revealed,
in association with both average and lower FSIQ scores, signicantly
smaller grey matter volumes and abnormal age-related changes of
the cortex. In particular, Caplan et al. [8] compared frontotemporal
Magnetic Resonance Imaging (MRI) brain volumes in 26 children with
CAE with 37 HCs: grey matter volumes of the left orbital frontal gyrus
as well as both left and right temporal lobes were signicantly smaller
in CAE children compared with the controls. The differences in IQ scores
between CAE patients and HCs did not account for the signicantly
smaller CAE volumes. Nevertheless, it was not possible to rule out an
association of volume ndings with psychopathology, given the hetero-
geneity of the epilepsy group in terms of different psychiatric diagnosis
and the exclusion of control subjects with a psychiatric diagnosis. In
accordance with previous results, Tosun et al. [42] demonstrated
through surface based morphometry that CAE patients did not have a
normal age-related decrease in cortical thickness and increase in sulcal
depth in certain brain areas (the left frontal lobe, the somatosensory
region, and the superior temporal gyrus). None of the seizure variables,
including age of onset, seizure frequency, and AEDs had a signicant
effect on the association between age and cortical morphometry
measures in the CAE population. These ndings, combined with the
signicant group differences in the relationship between IQ and cortical
morphometry measures, demonstrated that, compared to HCs, CAE
patients used different brain areas to perform cognitive functions.
In particular the relationship between IQ and sulcal depth of the
left inferior frontal and sulcal region between the paracentral lobule
and superior frontal region, highlighted the involvement of traditional
language-related brain regions with the verbal skills of these children
and raised the hypothesis of plasticity and reorganization in absence
of a structural lesion. Therefore, the average intellectual functioning of
these children reects marked plasticity and reorganization of brain
development due to the neuropathology distribution underlying CAE.
8. Memory functioning
Memory consists of those processes that retain, retrieve and use
data about external stimuli, ideas, events and skills [37]. Measures of
memory in CAE children did not reveal uniform ndings in literature.
Several studies have shown that memory problems may be present in
other epilepsy syndromes such as frontal lobe epilepsy, and idiopathic
generalized epilepsy including childhood absence epilepsy and benign
epilepsy with centro-temporal spikes [43]. Some studies found that
especially visual memory is impaired in children with CAE [42,27]
while others did not nd signicant differences in memory functioning
in children with epileptic syndromes [20,41]. However most of the
children studied were usually integrated in a miscellaneous group that
included patients with CAE, juvenile absence seizures, juvenile
myoclonic epilepsy and grand mal seizures on awakening, integrating
several generalized idiopathic epileptic syndromes.
Bhise et al. [34] found that performance in memory was below the
average in patients suffering from absences. According to Pavone et al.
[15] CAE patients had lower scores in delayed recall, suggesting a selec-
tive memory decit probably as a consequence of impaired attention
capacities, and in specic non-verbal memory scores, possibly correlated
to the relative decits in visual-perceptual skills. On the contrary CAE
groups evaluated by Kernan et al. [20] and Henkin et al. [28] differed
signicantly from the control groups as regards to verbal memory.
Other studies disagreed with these analyses as CAE patients did not
result in being lower in global, composite, verbal or non-verbal memory
test scores [25,5,27,14].
These data suggest that suitable learning and testing strategies may
improve patients' long-term academic achievements [27].
In particular, Lopes et al. [44], after having examined 90 children
with either frontal lobe epilepsy, CAE or BECTS, found that a longer
duration of active epilepsy predicted memory difculties in the learning
phase of the list learning task. Therefore children and adolescents with
more years of active epilepsy were more likely to have problems with
the acquisition and consolidation of knowledge with a consequent
impact on school results.
Furthermore, the inuence of AEDs therapy on memory abilities is
not clear yet. Although Siren et al. [23] detected an improvement in
visual memory after 713 months of AED treatment in children with
absence seizures, no correlation between the number of AEDs adminis-
tered and memory tests was found. [17]. According to Nolan et al. [17],
FSIQ had a signicant positive correlation with all memory tests except
visual retention. Contrary to the FSIQ scores, the number of AEDs taken
did not correlate with memory tests. On the other hand, Siren et al. [23]
detected that only the duration of epileptic discharges and clinical
absence seizures during the rst assessment correlated signicantly
with performance during the visual memory task.
There is growing evidence that sleep in general and specic sleep
stages such as REM and slow wave sleep (SWS) are involved in memory
formation and cognitive performances [45]. SWS particularly enhances
declarative memories, whereas REM sleep preferentially supports
procedural and emotional memory aspects [46].
Sleep disorders frequently coexist in patients with epilepsy [47].
Whether sleep affects epilepsy or epilepsy modies sleep has been
 A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
extensively evaluated but very little literature exists concerning this
topic in the paediatric population [48]. It is however possible to hypoth-
esize that epileptiform activity may interfere with neuroplasticity pro-
cesses when it occurs in a specic area involved in learning activity
during sleep, thus disturbing the natural occurrence of learning-
dependent slow wave activity or spindle activity [49].
An early recognition and therapeutic intervention, with a careful
choice of AEDs, could therefore help in stabilizing sleep structure, and
preventing one of the many negative effects of epilepsy on cognitive
functioning in children.
9. Conclusions
An increasing number of data in literature demonstrate that a mild
neuropsychological impairment is widespread among children with
CAE. In particular, CAE can impair multiple cognitive functions and
lead to academic and other functional difculties. The early detection
of children at risk of developing neuropsychological problems to
make the tailored interventions that address their specic needs
might prevent worse school achievement and psychosocial functioning
[6].
Overall CAE patients appear to perform worse than HCs, even if
scores are predominantly higher than in patients affected by other
epilepsy syndromes like CPS.
An impaired intellectual functioning was evidenced by a signicantly
lower mean FSIQ in CAE patients, but several studies only detected a
FSIQ within the lower limits of the normal range.
CAE also seems to affect verbal intellectual abilities, therefore
expressive/receptive speech and language development in CAE patients
is particularly important. Social communication decits may reect
negatively in social and academic achievement, as in behavioural
problems.
Interesting data derive from the analysis of attention, motor skills
and executive functions. Subtle impairment especially in attention,
problem solving, executive functions, and visuo-spatial integration has
been reported in literature. Data are still conicting concerning memory
ndings, in particular visual memory seems to be mainly affected in
these patients. These reports, supported by neuroimaging evidence,
are in agreement with the new theory of system epilepsy, and high-
light both a negative alteration of normal thalamo-frontal circuits
and a positive reorganization of the bordering cortical areas, in order
to preserve the basic functions.
Therefore, despite the fact that CAE has been believed a benign
epilepsy for a long time, neuropsychological studies questioned this
view, at least in a subgroup of patients with evidence of cognitive
decits signicantly affecting their quality of life. There are many vari-
ables that can signicantly affect the evolution of CAE, also concerning
neuropsychological aspects: and early age of onset, high frequency of
seizures, insufcient response to the rst drug, particular ictal and
interictal EEG characteristics and a longer duration of illness. It would
be advisable for these patients to be carefully evaluated in order to
promptly identify the cases at risk for neuropsychological impairment.
This might allow management with a specic support, with the aim
of preventing worsening of school achievement and psychosocial
functioning.
The high rate of comorbidities including impaired neuropsychologi-
cal skills should alert clinicians to the necessity of an early identication
and treatment of children with CAE. This particularly concerns children
with a longer duration of illness, uncontrolled seizures, and AED
treatment.
These ndings also emphasize the role of the frontal lobe and the
thalamus in cognition, attention and language; the association of
seizure variables with impaired cognition and language in CAE high-
lights the need for future studies to focus on the involvement of these
brain regions in the neuropsychological comorbidities of CAE.
65
Funding source
None.
Financial disclosure
The authors have no nancial relationships relevant to this article to
disclose.
Potential conicts of interest
The authors declare the following interests: none.
Competing interests
All authors declare that there is no support from any organisation for
the submitted work, no nancial relationships with any organisations
that might have an interest in the submitted work in the previous
three years, and no other relationships or activities that could appear
to have inuenced the submitted work.
All coauthors have seen and agreed with the contents of the
manuscript.
The manuscript has not been previously published and is not being
considered for publication elsewhere.
The manuscript is an honest, accurate, and transparent account of
the study being reported; no important aspects of the study have been
omitted; and any discrepancies from the study as planned (and, if
relevant, registered) have been explained.
Ethical approval was not required (review).
Data sharing was not required (review).
References
[1] A.T. Berg, S.F. Berkovic, M.J. Brodie, J. Buchhalter, J.H. Cross, W. van Emde Boas, et al.,
Revised terminology and concepts for organisation of seizures and epilepsies: a
report of ILAE Commission on Classication and Terminology, 20052009, Epilepsia
51 (2010) 676685.
[2] P. Jallon, P. Latour, Epidemiology of idiopathic generalized epilepsies, Epilepsia 46
(2005) 1014.
[3] J. Buchhalter, Treatment of childhood absence epilepsy-an evidence-based answer
at last! Epilepsy Curr. 11 (2011) 1215.
[4] P. Loiseau, C.P. Panayiotopoulos, Childhood absence epilepsy, in: S. Gilman (Ed.),
Medlink Neurology, Arbor Publishing, San Diego, SA, 2005 (Medlink Neurology.
Gilman S (ed). San Diego, SA: Arbor Pub).
[5] P. Wolf, Childhood absence epilepsy and related syndromes, in: J. Roger, M. Bureau,
C. Dravet, P. Genton, C.A. Tassinari (Eds.), Epileptic Syndromes in Infancy, Childhood
and Adolescence, 4th ed.John Libbey Eurotext Ltd. Hirsch E, Panayiotopoulos CP,
Montrouge, FR, 2005.
[6] S. Matricardi, A. Verrotti, F. Chiarelli, C. Cerminara, P. Curatolo, Advances in child-
hood absence epilepsy, J. Pediatr. Neurol. 50 (2014) 205212.
[7] E. D'Agati, C. Cerminara, L. Casarelli, M. Pitzianti, P. Curatolo, Attention and executive
functions prole in childhood absence epilepsy, Brain Dev. 34 (2012) 812817.
[8] R. Caplan, J. Levitt, P. Siddarth, K.N. Wu, S. Gurbani, R. Sankar, W.D. Shields, Frontal
and temporal volumes in childhood absence epilepsy, Epilepsia 50 (2009)
24662472.
[9] M. Elisabeth, S. Sherman, B.L. Brooks, T.B. Fay-McClymont, W.S. MacAllister,
Detecting epilepsy-related cognitive problems in clinically referred children with
epilepsy: is the WISC-IV a useful tool? Epilepsia 53 (2012) 10601066.
[10] R. Caplan, D. Guthrie, S. Komo, P. Siddarth, S. Chayasirisobhon, H. Kornblum, R.
Sankar, R. Hansen, W. Mitchell, W.D. Shields, Social communication in children
with epilepsy, J. Child Psychol. Psychiatry 43 (2002) 245253.
[11] R. Caplan, P. Siddarth, L. Stahl, E. Lanphier, P. Vona, S. Gurbani, S. Koh, R. Sankar, W.D.
Shields, Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbid-
ities, Epilepsia 49 (2008) 18381846.
[12] R. Caplan, J. Sagun, P. Siddarth, S. Gurbani, S. Koh, R. Gowrinathan, R. Sankar, Social
competence in pediatric epilepsy: insights into underlying mechanisms, Epilepsy
Behav. 6 (2005) 218228.
[13] R. Caplan, P. Siddarth, S. Gurbani, R. Hanson, R. Sankar, W.D. Shields, Depression and
anxiety disorders in pediatric epilepsy, Epilepsia 46 (2005) 720730.
[14] C. Vega, M. Vestal, M. DeSalvo, R. Berman, M. Chung, H. Blumenfeld, M.N. Spann,
Differentiation of attention-related problems in childhood absence epilepsy,
Epilepsy Behav. 19 (2010) 8285.
[15] P. Pavone, R. Bianchini, R.R. Triletti, G. Incorpora, A. Pavone, E. Parano, Neuropsy-
chological assessment in children with absence epilepsy, Neurology 56 (2001)
10471051.
66 A. Verrotti et al. / Journal of the Neurological Sciences 359 (2015) 5966
[16] J.E. Jones, P. Siddarth, S. Gurbani, W.D. Shields, R. Caplan, Cognition, academic
achievement, language, and psychopathology in pediatric chronic epilepsy: short-
term outcomes, Epilepsy Behav. 18 (2010) 211217.
[17] M.A. Nolan, M.A. Redoblado, S. Lah, M. Sabaz, J.A. Lawson, A.M. Cunningham, A.F.
Bleasel, A.M. Bye, Intelligence in childhood epilepsy syndromes, Epilepsy Res. 53
(2003) 139150.
[18] M.A. Nolan, M.A. Redoblado, S. Lah, M. Sabaz, J.A. Lawson, A.M. Cunningham, A.F.
Bleasel, A.M. Bye, Memory function in childhood epilepsy syndromes, J. Paediatr.
Child Health 40 (2004) 2027.
[19] B.P. Hermann, J.E. Jones, R. Sheth, M. Koehn, T. Becker, J. Fine, C.A. Allen, M.
Seidenberg, Growing up with epilepsy: a two-year investigation of cognitive
development in children with new onset epilepsy, Epilepsia 49 (2008) 18471858.
[20] C.L. Kernan, R. Asarnow, P. Siddarth, S. Gurbani, E.K. Lanphier, R. Sankar, R. Caplan,
Neurocognitive proles in children with epilepsy, Epilepsia 53 (2012) 21562163.
[21] C. Hommet, C. Billard, J. Motte, G.D. Passage, D. Perrier, P. Gillet, C. Prunier, B.D.
Toffol, A. Autret, Cognitive function in adolescents and young adults in complete
remission from benign childhood epilepsy with centro-temporal spikes, Epileptic
Dis. 3 (2001) 207216.
[22] D.E. Mandelbaum, G.D. Burack, The effect of seizure type and medication on
cognitive and behavioral functioning in children with idiopathic epilepsy, Dev.
Med. Child Neurol. 39 (1997) 731735.
[23] A. Sirn, A. Kylliinen, M. Tenhunen, K. Hirvonen, T. Riita, M. Koivikko, Benecial
effects of antiepileptic medication on absence seizures and cognitive functioning
in children, Epilepsy Behav. 11 (2007) 8591.
[24] R. Caplan, P. Siddarth, C.E. Bailey, E.K. Lanphier, S. Gurbani, W. Donald Shields, R.
Sankar, Thought disorder: a developmental disability in pediatric epilepsy, Epilepsy
Behav. 8 (2006) 726735.
[25] P.S. Fastenau, C.S. Johnson, S.M. Perkins, A.W. Byars, T.J. deGrauw, J.K. Austin, D.W.
Dunn, Neuropsychological status at seizure onset in children: risk factors for early
cognitive decits, Neurology 73 (2009) 526534.
[26] L.L. Conant, A. Wilfong, C. Inglese, A. Schwarte, Dysfunction of executive and
related processes in childhood absence epilepsy, J. Exp. Child Psychol. 18 (2010)
414423.
[27] R. Caplan, P. Siddarth, P. Vona, L. Stahl, C. Bailey, S. Gurbani, R. Sankar, S.W. Donald,
Language in pediatric epilepsy, Epilepsia 50 (2009) 23972407.
[28] Y. Henkin, M. Sadeh, S. Kivity, E. Shabtai, L. Kishon-Rabin, N. Gadoth, Cognitive
function in idiopathic generalized epilepsy of childhood, Dev. Med. Child Neurol.
47 (2005) 126132.
[29] Y. Henkin, L. Kishon-Rabin, H. Pratt, S. Kivity, M. Sadeh, N. Gadoth, Linguistic
processing in idiopathic generalized epilepsy: an auditory event-related potential
study, Epilepsia 44 (2003) 12071217.
[30] S.A. Hillyard, T.W. Picton, F. Plum, Electrophysiology of cognition, Handbook of
Physiology, Section 1: The Nervous System: Higher Functions of the Nervous
System, American Physiological Society, Bethesda 1987, pp. 519584.
[31] R. Sanchez-Carpintero, B.G. Neville, Attentional ability in children with epilepsy,
Epilepsia 44 (2003) 13401349.
[32] C. Cerminara, E. D'Agati, L. Casarelli, I. Kaunzinger, K.W. Lange, M. Pitzianti, P. Parisi,
O. Tucha, P. Curatolo, Attention impairment in childhood absence epilepsy: an
impulsivity problem? Epilepsy Behav. 27 (2013) 337341.
[33] P. Parisi, R. Moavero, A. Verrotti, P. Curatolo, Attention decit hyperactivity disorder
in children with epilepsy, Brain Dev. 32 (2010) 1016.
[34] V.V. Bhise, G.D. Burack, D.E. Mandelbaum, Baseline cognition, behavior, and motor
skills in children with new-onset, idiopathic epilepsy, Dev. Med. Child Neurol. 52
(2010) 2226.
[35] B.D. Killory, X. Bai, M. Negishi, et al., Impaired attention and network connectivity in
childhood absence epilepsy, NeuroImage 56 (2011) 22092217.
[36] T.A. Glauser, A. Cnaan, S. Shinnar, D.G. Hirtz, D. Dlugos, et al., Ethosuximide, valproic
acid, and lamotrigine in childhood absence epilepsy, N. Engl. J. Med. 362 (2010)
790799.
[37] L.L. Thio, Childhood absence epilepsy: poor attention is more than seizures,
Neurology 81 (2013) 138139.
[38] D1. Masur, S. Shinnar, A. Cnaan, R.C. Shinnar, P. Clark, J. Wang, E.F. Weiss, D.G. Hirtz,
T.A. Glauser, Childhood Absence Epilepsy Study Group, Pretreatment cognitive
decits and treatment effects on attention in childhood absence epilepsy, Neurology
81 (2013) 15721580.
[39] A. Verrotti, C. Cerminara, S. Domizio, A. Mohn, E. Franzoni, G. Coppola, N. Zamponi,
P. Parisi, P. Iannetti, P. Curatolo, Levetiracetam in absence epilepsy, Dev. Med. Child
Neurol. 50 (2008) 850853.
[40] R. Guerrini, F. Melani, C. Brancati, A.R. Ferrari, P. Brovedani, A. Biggeri, L. Grisotto, S.
Pellacani, Dysgraphia as a mild expression of dystonia in children with absence
epilepsy, PLoS ONE 10 (2015), e0130883, http://dx.doi.org/10.1371/journal.pone.
0130883. eCollection 2015.
[41] A. Baddeley, Working memory, Science 255 (1992) 556559.
[42] D. Tosun, P. Siddarth, A.W. Toga, B. Hermann, R. Caplan, Effects of childhood absence
epilepsy on associations between regional cortical morphometry and aging and
cognitive abilities, Hum. Brain Mapp. 32 (2011) 580591.
[43] L. Lagae, J. Pauwels, C.P. Mont, B. Verhelle, I. Vervisch, Frontal absences in children,
Eur. J. Paediatr. Neurol. 5 (2001) 243251.
[44] A.F. Lopes, J.P. Monteiro, M.J. Fonseca, C. Robalo, M.R. Simoes, Memory functioning
in children with epilepsy: frontal lobe epilepsy, childhood absence epilepsy and
benign epilepsy with centrotemporal spikes, Behav. Neurol. 218637 (2014).
[45] P. Panayiotopoulos, Typical absence seizures and related epileptic syndromes:
assessment of current state and directions for future research, Epilepsia 49 (2008)
21312147.
[46] P. Parisi, O. Bruni, M.P. Villa, A. Verrotti, S. Miano, A. Luchetti, P. Curatolo, The
relationship between sleep and epilepsy: the effect on cognitive functioning in
children, Dev. Med. Child Neurol. 52 (2010) 805810.
[47] R. Huber, M.F. Ghilardi, M. Massimini, G. Tononi, Local sleep and learning, Nature
430 (2004) 7881.
[48] C.W. Bazil, Sleep and epilepsy, Curr. Opin. Neurol. 132 (2000) 171175.
[49] S.V. Kothare, J. Keleyias, Sleep and epilepsy in children and adolescents, Sleep Med.
11 (2010) 674685.