Epilepsy & Behavior 13 (2008) 614–619

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Epilepsy & Behavior

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

Residual cognitive effects of uncomplicated idiopathic and cryptogenic epilepsy q

Anne T. Berg a,*, John T. Langfitt b, Francine M. Testa c,d, Susan R. Levy c,d, Francis DiMario e,
Michael Westerveld f, Joseph Kulas e
a
Department of Biology, Northern Illinois University, DeKalb, IL 60115, USA
b
Department of Neurology, University of Rochester, Rochester, NY 14642, USA
c
Department of Pediatrics, Yale Medical School, New Haven, CT 06520, USA
d
Department of Neurology, Yale Medical School, New Haven, CT 06520, USA
e
Departments of Pediatrics and Neurology, University of Connecticut, and Connecticut Children’s Medical Center, Hartford, CT 06106, USA
f
Department of Neurosurgery, Yale Medical School, New Haven, CT 06520, USA

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

Article history: We assessed residual cognitive deficits in young people with idiopathic and cryptogenic epilepsy. In the
Received 18 May 2008 setting of an ongoing prospective study, we invited participants initially diagnosed and enrolled in the
Revised 16 July 2008 cohort 8–9 years earlier to undergo standardized neuropsychological assessment. Sibling controls were
Accepted 21 July 2008
invited when available. We analyzed 143 pairs in which cases had idiopathic or cryptogenic epilepsy
Available online 19 August 2008
and both case and control had normal intelligence. Compared with that for siblings, the Full Scale IQ
for cases was 3.3 points lower (P = 0.01) mainly due to slower processing speed, which was 5.6 points
Keywords:
lower (P = 0.0004). Word reading (P = 0.04) and spelling (P = 0.01), but not other scores, were also lower
Epilepsy
Neuropsychology
in cases. Remission status and drug use did not influence findings. In young people of normal intelligence
Cognitive deficit with idiopathic or cryptogenic childhood-onset epilepsy, substantial residual effects of epilepsy appear to
Children be confined largely to slower processing speed.
Epidemiology Ó 2008 Elsevier Inc. All rights reserved.
Prognosis

1. Introduction
Epilepsy is associated with cognitive difficulties for a variety of
reasons including the underlying symptomatic causes of epilepsy,
the transient effects of seizures and interictal discharges, the
cumulative effects of repeated seizures on brain function and
structure, and the drugs used to suppress seizures [1–3]. The idio-
pathic and cryptogenic epilepsies may themselves be associated
with some degree of behavioral and cognitive impairment inde-
pendent of seizures and antiepileptic drugs (AEDs) and even prior
to the onset of seizures [4,5].
It is not known whether the functional disturbances that cause
epilepsy also cause cognitive impairment, just by themselves. To
determine this, it is necessary to take into account the other known
causes of cognitive disturbance that occur with varying frequency
in persons with epilepsy (e.g., perinatal stroke, other brain lesions,
mental retardation, active seizures, and AEDs). Many prior studies
that performed detailed neuropsychological evaluations reported
significant case–control differences across broad cognitive do-
mains. These studies often focused on small groups [6–12]. Pa-
q
This work was funded by a grant from the National Institutes of Health, National
Institute of Neurological Disorders and Stroke RO1/R37-NS31146.
* Corresponding author.
E-mail address: atberg@niu.edu (A.T. Berg).
tients typically were studied during the active phase of their
disorder, many while on AEDs [6,7,9–17]. Several studies enrolled
prevalent cases with epilepsy, often from specialty centers, raising
concerns that more severe or intractable cases were overrepre-
sented [8,12,13,18], and some studies included individuals who
would be considered to have mild mental retardation (i.e., Full
Scale IQ < 70) [13,14] or did not state whether they were excluded
[15]. In contrast, the National Collaborative Perinatal Project
(NCPP) found little difference between cases and sibling controls
tested at 7 years, provided both case and control were judged neu-
rologically normal [19].
It is worth noting that in small clinical studies, even syndromes
such as benign rolandic epilepsy, a form of epilepsy with a near-
100% chance of complete seizure remission [20], are associated with
evidence of subtle but significant cognitive difficulties [8–11,16].
Current literature does not adequately address whether there are
substantial differences among specific forms of idiopathic epilepsy
with respect to the nature and severity of cognitive difficulties.
It remains unclear whether there is an association between epi-
lepsy and cognitive difficulties that is independent of the effects of
other associated causes of cognitive impairment, seizures, and
medications. To test whether such an association exists, we exam-
ined cognitive function in a sample of neurologically normal indi-
viduals with epilepsy and generally normal intelligence, who were
participating in a large prospective cohort study of individuals with

1525-5050/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2008.07.007
 A.T. Berg et al. / Epilepsy & Behavior 13 (2008) 614–619
childhood and adolescent-onset epilepsy. We used tests of general
intelligence, attention, and memory, cognitive domains that are of-
ten affected by epilepsy and medications.
2. Methods
2.1. Recruitment
The Connecticut Study of Epilepsy prospectively enrolled chil-
dren (ages 1 month up to 16 years) during 1993–1997. Intensive
follow-up has been ongoing since then. Etiology, seizure types,
and epilepsy syndromes were classified according to internation-
ally recommended criteria at the beginning of the study [21,22]
and reclassified over the years as new information accrued. Details
of the methods, including the initial response rate for recruitment
into the cohort (80%), were reported previously [23,24]. Clinical
neuroimaging, particularly with MRI, was common in this cohort
at the time of initial diagnosis [25]. Over the years more imaging
was done, and during the 9-year assessment phase, we offered a
research imaging study to cohort members. In all, 85% of the entire
cohort had at least one MRI study.
2.2. Standardized cognitive assessments
During the period 2002–2006, at approximately 8–9 years after
initial study entry for each child, all families were invited to partici-
pate in a standardized assessment protocol that included a neuro-
psychological test battery. When available, we also enrolled a
neurologically normal full-sibling control without epilepsy or
unprovoked seizures. Tests were administered by a licensed psy-
chologist or trained psychometrician. Either Wechsler’s child
(Wechsler Intelligence Scale for Children III, WISC-III [26]) or adult
(Wechsler Adult Intelligence Scales III, WAIS-III [27]) scale, as appro-
priate for the subject’s age, was used to measure general cognitive
function. We used an abbreviated form of the WISC-III that preserves
the four-factor structure of the full battery [28] and, to facilitate
comparability, a modified form of the WAIS-III consistent with the
WISC-III short form to estimate IQ and index scores. Full Scale IQ
(FSIQ) scores provide a global measure of intelligence. The index
scores assess four key components of intelligence, derived by factor
analysis performed by the test developers. Verbal memory was as-
sessed with the California Verbal Learning Test (child [29] or adult
[30] version, CVLT); visual memory with the Rey Complex Figure test
(CFT) [31]; and attention with the Continuous Performance Test
(CPT) [32]. The Wide Range Achievement Test, Revision 3 (WRAT-
3) [33], was used to measure academic achievement. Age-adjusted,
standardized scores obtained from the test manuals were used in
all analyses.
2.3. Eligibility for analysis
Primary analyses involved pairs in which the case had uncom-
plicated epilepsy (i.e., idiopathic or cryptogenic epilepsy, no epilep-
tic encephalopathy) and both case and control had intelligence in
the low-average range or higher (i.e., FSIQ P 80). Pairs were ex-
cluded from these analyses if the case had an epileptic encephalop-
athy or remote symptomatic epilepsy or if either the case or
control had a FSIQ < 80. Cases with structural abnormalities on
MRI (other than incidental findings) were by definition excluded
from the group with idiopathic and cryptogenic epilepsy. The FSIQ
exclusion reflected our goal of assessing the effect of epilepsy inde-
pendent of other neurological conditions including coexisting
mental retardation. Because we used a short form of the IQ tests
and to be conservative, we excluded anyone whose FSIQ fell in
the borderline range (70–79) and below.
615
In secondary analyses, we included those pairs with uncompli-
cated epilepsy in which either the case or control had a FSIQ of 60–
79, to compare our results with studies that included such patients
or did not specify IQ inclusion/exclusion criteria.
2.4. Analytic approach and methods
For both primary and secondary analyses, we performed a ser-
ies of matched tests to determine the presence and magnitude of
case–control difference for overall intelligence, index scores, other
cognitive functions, and school achievement. We also determined
whether the case’s medication, remission status, or syndrome type
might explain any case–control differences observed.
Matched t tests were used for bivariate analyses. Multiple linear
regression techniques were used with the difference score as the
outcome variable to determine whether there were case–sibling
differences, as represented by the intercept term in the model,
and the extent to which remission and treatment status might ex-
plain those differences.
All tests had 90% power to detect an approximately one-third
standard deviation difference between cases and controls with an
a error of P = 0.05. Because the cognitive measures are intercorre-
lated, two-tailed P values unadjusted for multiple testing are re-
ported in the tables and text. They are conservatively interpreted,
however, in light of the multiple comparisons and with reference
to the threshold needed with a Bonferroni correction.
2.5. Ethics approval
All procedures were approved at each phase of the study by the
institutional review boards of all participating institutions and
conform to all state and federal laws and international standards.
Written informed consent parental permission and child assent
or subject consent were obtained.
3. Results
A total of 613 children were originally enrolled in the cohort.
Fig. 1 provides the derivation of the analytic sample for these anal-
yses. During the time of recruitment for the testing, 530 cohort
members were actively followed. Of those, 389 (73%) had idio-
pathic or cryptogenic epilepsy and intellectual function known or
estimated to be within or above the mildly retarded range
(IQ > 60), based on prior review of all information in their medical
and education records to date [34]. Of these, 272 (70%) had neuro-
psychological testing. We compared the 272 eligible tested cases
with the 117 who were not tested (Table 1). These comparisons
suggest that those who were tested were reasonably comparable
to those who were not with respect to potentially important fac-
tors that we could reliably ascertain, although there was a ten-
dency for participating compared with nonparticipating cases to
have parents who had attained higher levels of education.
Matched sibling controls were tested for 172 of 272 (63%) cases.
Controls for 100 cases were not obtained because there was no full
sibling (N = 38), the only sibling was too young (N = 5), or the only
sibling had epilepsy or another severe neurological condition
(N = 8). In the remaining 49 cases, there were only 7 absolute refus-
als. In the other instances, controls lived out of state, worked, or were
in school (including college). Scheduling difficulties and travel con-
cerns ultimately precluded their participation in neuropsychological
testing.
Of the 172 cases, all but 3 had undergone at least one MRI study.
In 154 instances (89.5%) this was a research MRI scan obtained un-
der a standardized seizure protocol.
Of the 172 matched pairs, 29 pairs had either a case (N = 23,
13%) or control (N = 9, 5%) with a FSIQ < 80. In three pairs both
616 A.T. Berg et al. / Epilepsy & Behavior 13 (2008) 614–619

Complicated
83 Lost to follow- N=31 (27%)
up (includes 13
deaths)
Uncomplicated
N=52 (63%)

613 originally
recruited Not tested
1993-97 N=80
Complicated
N=140 (26%)
Tested
530 actively N=60
followed in
2002-06 Case&control
Not tested FSIQ>=80
N=118 (30%) Sib-control N=143
Uncomplicated
N=390 (74%) N=172 (63%)
Tested
N=272 (70%) No control Case or control
N=100 (37%) FSIQ<80
N=29

Fig. 1. Derivation of analytic sample.

Table 1
Comparisons of potential differences between eligible cases who were tested and those who were not tested

Not tested (N = 118) Tested (N = 272) P value (df for v2)

Highest level of parental education
<High school (N = 12) 7 (6%) 5 (2%) 0.05 (2)
Completed high school (N = 210) 66 (56%) 144 (53%)
Completed college (N = 168) 44 (37%) 123 (45%)
Subject’s race/ethnicity
Caucasian (N = 333) 100 (85%) 232 (85%) 0.76 (3)
African-American (N = 33) 8 (7%) 25 (9%)
Hispanic (N = 21) 8 (7%) 13 (5%)
Other (N = 3) 1 (1%) 2 (1%)
Sex
Female (N = 193) 56 (47%) 137 (50%) 0.65 (1)
Male (N = 197) 61 (53%) 135 (50%)
Age at study entry
<5 years (N = 124) 33 (28%) 90 (33%) 0.19 (2)
5–9 years (N = 179) 62 (53%) 117 (43%)
P10 years (N = 87) 22 (19%) 65 (24%)
Epilepsy syndrome group
Idiopathic localization related 20 (17%) 43 (16%) 0.67 (3)
Cryptogenic focal 50 (42%) 133 (49%)
Idiopathic generalized 37 (31%) 79 (29%)
Undetermined 10 (8%) 17 (29%)
Any special education
No (N = 195) 61 (52%) 134 (49%) 0.60 (1)
Yes (N = 195) 56 (48%) 138 (51%)
Remission status*
<5 years seizure free (N = 128) 31 (26%) 96 (35%) 0.09 (1)
P5 years seizure free (N = 262) 86 (74%) 176 (65%)
Taking AEDsa
No (N = 275) 88 (75%) 187 (69%) 0.20 (1)
Yes (N = 115) 29 (25%) 85 (31%)
a
Assessed at the time of testing for those tested, or at the time of the global cognitive assessment if study neuropsychological testing was not performed.

were borderline. Thus, there were 143 pairs for our primary anal-
ysis of case–control differences in uncomplicated epilepsy in indi-
viduals with FSIQs P 80.
In these 143 pairs, the mean age at testing was 15.0 years
for cases and 15.6 years for controls. Females constituted 49%
of the cases and 57% of the controls. Ninety-five (66%) cases
were at least 5 years seizure free; 99 (69%) were no longer tak-
ing AEDs; 88 (61.5%) were both seizure free and off AEDs. Only
9 (6.2%) cases were taking more than one AED. In the case
group, 20 (14%) had idiopathic focal, 71 (50%) cryptogenic focal,
40 (28%) idiopathic generalized, and 12 (8%) unclassified
epilepsy.
In 49 pairs, both case and control completed the WAIS-III; in 68
pairs, both completed the WISC-III; in 26 pairs, they were discor-
dant for test version (in 17 pairs, case WISC-III/control WAIS-III;
in 9 pairs the converse).
 A.T. Berg et al. / Epilepsy & Behavior 13 (2008) 614–619 617

3.1. Primary analyses: Case–control differences—uncomplicated
epilepsy and FSIQ P80 (N = 143 pairs)
Cases scored slightly worse than controls on average on all of
the 16 scales from five different tests that were compared. This dif-
ference was substantial for processing speed only. Cases scored an
average of 5.6 points lower than sibling controls (P = 0.0004) (Table
2a). The critical value for a Bonferroni correction is 0.003. The case,
control, and differences scores were all consistent with a normal
distribution and the average difference was not due to a few outli-
ers. In all, 29% of cases had scores that fell > 1 SD beneath control
values, whereas only 10% of cases had scores > 1 SD above control
values.
In a series of multiple regression analyses, we tested whether
the case–control differences were substantially influenced by
adjustment for remission status, AED status of the case, and the
case’s syndrome. None was.
We also considered whether test version might influence the
findings. We first adjusted for whether the case and control within
each pair underwent the same or different IQ tests. This did not
influence results. We limited the analyses to pairs in which the
case and control were concordant for the IQ test version. None of
the findings was substantially altered. Most importantly, the
case–control difference for processing speed did not vary signifi-
cantly as a function of test version ( 5.0, P = 0.04, for pairs tested
with the WISC-III, and 6.3, P = 0.009, for pairs tested with the
WAIS-III). In the subgroup in which cases were 5 years seizure free
and off AEDs (N = 90 pairs), this processing speed difference per-
sisted ( 6.0, P = 0.004).
3.2. Secondary analyses: Inclusion of cases and controls with
borderline intelligence or mild mental retardation (FSIQ = 60–79)
When we included the 29 pairs in which either the case or con-
trol or both had a FSIQ of 60–79, we found much stronger evidence
of case–control differences (Table 2b). This is not surprising as
more cases (13%) than controls (5%) fell in that range. Cases scored
worse than their sibling controls on most cognitive indices, mem-
ory tasks, and school achievement, but not on attention scores
(CPT). Even with a corrected critical value of 0.003, several of the
differences would still be considered significant. In a series of t
tests and multiple linear regression analyses, we tested whether
remission status (<5 vs > 5 years seizure free) or current AED use
explained case–control differences, represented by the intercept
in the regression model. Remission status and AED use did contrib-
ute to some case–control differences. Cases still scored signifi-
cantly worse than their controls even after adjustment for these
factors.
4. Discussion
No prior published study to our knowledge has determined
whether epilepsy alone has an impact on cognition, independent
of associated factors and causes of epilepsy that can by themselves
adversely affect cognitive function. In young people of normal
intelligence (FSIQ P80) and normal neurological status, we found
little evidence indicating substantial residual impairment in either
general or specific cognitive functioning. Although overall intelli-
gence, measured by the FSIQ, was significantly lower in cases than
controls, almost all of this effect was due to processing speed,
which remained substantially lower in cases despite overall intel-
ligence in the ‘‘normal range.” The cases’ remission and medication
status did not explain this finding.
References to slowed mental processing have been noted since
antiquity in descriptions of persons with epilepsy. Formal studies
have documented slowed reaction time relative to controls, but
have been confounded by the effects of medications, which also
slow processing [35]. One study of children with recently diag-
nosed epilepsy reported that psychomotor function, measured in
part by the coding subtest from the WISC, also used in processing
speed, was most affected [15]. Slowed processing speed is a non-
specific finding associated with diffuse brain dysfunction and one
of the earliest presenting neurocognitive deficits in disorders
affecting primarily white matter early in the course of the disease

Table 2
Case–control differences when (A) both case and control have a FSIQ > 80 and (B) either case or control may have a FSIQ of 60–79

Test score A. Case and control FSIQ > 80 (N = 143 pairs) B. Case or control FSIQ < 80 (N = 172 pairs)
a
Case mean (SD) Control mean (SD) P value Case mean (SD) Control mean (SD) P valuea
b
FSIQ 104.3 (13.9) 107.6 (12.7) 0.01 99.4 (17.6) 104.9 (14.3) <0.0001
Index scoresb
Verbal comprehension 108.2 (15.2) 110.5 (14.9) 0.09 103.6 (17.8) 108.0 (16.7) 0.001
Perceptual organization 106.4 (14.5) 106.8 (14.3) 0.78 101.8 (17.9) 104.4 (15.4) 0.09
Working memory 101.9 (14.5) 104.2 (13.2) 0.11 98.2 (16.4) 102.3 (13.8) 0.004
Processing speed 99.1 (15.2) 104.7 (13.6) 0.0004 96.4 (16.3) 103.4 (14.0) <0.0001
CVLT
List A 1–5c 52.6 (10.9) 53.5 (11.2) 0.47 51.0 (11.5) 53.1 (11.1) 0.07
Short-delay free recalld 0.10 (1.00) 0.18 (0.98) 0.45 0.08 (1.13) 0.15 (0.94) 0.03
Long-delay free recalld 0.12 (0.98) 0.27 (0.91) 0.20 0.01 (1.03) 0.23 (0.88) 0.03
Rey Complex Figure
Immediate recall 49.4 (14.4) 51.1 (14.1) 0.30 46.7 (15.4) 50.7 (14.1) 0.01
Delayed recall 48.7 (14.3) 50.0 (13.8) 0.43 45.8 (15.4) 49.6 (13.7) 0.008
CPT
Omissions 49.7 (15.4) 48.2 (9.2) 0.28 50.3 (15.0) 48.6 (9.8) 0.14
Commissions 50.6 (11.8) 49.3 (11.6) 0.33 50.9 (11.7) 49.9 (11.6) 0.39
Reaction time 46.9 (10.4) 46.6 (10.8) 0.79 47.5 (10.6) 46.9 (10.9) 0.52
WRAT
Reading 103.4 (12.9) 105.7 (9.0) 0.04 100.1 (14.8) 104.0 (10.1) 0.0005
Spelling 102.9 (13.1) 105.9 (10.5) 0.01 99.7 (14.9) 104.3 (11.1) 0.0001
Arithmetic 98.2 (18.0) 100.9 (13.3) 0.09 94.7 (19.0) 99.8 (13.3) 0.0009
a
Based on matched t test.
b
Scaled to a mean of 100 and SD of 15.
c
T scores, mean = 50, SD = 10.
d
Z score, mean = 0, SD = 1.
618 A.T. Berg et al. / Epilepsy & Behavior 13 (2008) 614–619
(e.g., multiple sclerosis, multi-infarct dementia) [36–38]. Poten-
tially, the disturbances themselves that lead to idiopathic and
cryptogenic epilepsy persist in the form of relative inefficiency of
processing, even in cognitively and neurologically normal individ-
uals whose epilepsy is in remission.
These findings differ from those in the current literature that
suggest substantial cognitive impairments in young people with
idiopathic and cryptogenic epilepsy. There are several potential
reasons for this.
First, by using full siblings as controls we were able to assess the
impact associated with epilepsy after adjustment for the two
greatest determinants of cognitive function, genetic and environ-
mental factors [39]. This was not the case in other studies with
the exception of one with several methodological similarities to
our own. In that study, after excluding those with IQ scores <80,
no difference was found in FSIQ when comparing cases with
matched sibling controls [19].
Second, most of the literature focuses on patients with active
epilepsy on treatment. In one often-cited study of 251 prevalent
cases, 94% of patients were on treatment, with 58% taking two or
more drugs [13]. In a study of 53 children with recent-onset epi-
lepsy, 77% of cases were taking AEDs when tested (15). Antiepilep-
tic drugs have a substantial impact on cognitive function [3,40–43].
Additionally, interictal abnormalities, even without seizures, may
impair cognitive function transiently [1]. This suggests that the ac-
tive stage of epilepsy may be the most vulnerable period for expe-
riencing cognitive deficits.
Third, some studies included subjects with FSIQs < 80. We ini-
tially excluded these to isolate the effects of epilepsy itself from
other factors that might cause both seizures and subnormal intel-
lectual function. When we later included them, our results were
more consistent with published reports. This suggests that some
findings in the literature may reflect inclusion of individuals whose
overall level of cognitive function falls below the normal range.
It is possible that some studies included children with structural
brain abnormalities, the presence of which is often not suspected
prior to the onset of seizures and which cannot be determined with-
out appropriate neuroimaging. For example, Byars et al. recently
demonstrated that children with such previously unsuspected le-
sions performed less well on a battery of neuropsychological tests
than did children with negative imaging studies [44].
Epidemiologists consider mental retardation alone as sufficient
grounds for classifying the cause of epilepsy as ‘‘remote symptom-
atic” (symptomatic) [22]. Technically, this includes anyone with a
FSIQ < 70. The basis for this is an older retrospective, chart review
study of patients diagnosed from 1935 to 1974 in which mental
retardation was defined as a FSIQ < 70. No information was avail-
able, however, about whether cognitive testing was performed or
if this designation was simply based on clinical impressions at
the time of initial diagnosis. Infants and young children with mild
mental retardation would not have been tested and detected. The
study, for the most part, considered only severe mental retarda-
tion, often in association with cerebral palsy [45]. Because IQ can
reflect environmental factors as well as the effects of seizures
and medications, we required the FSIQ to be < 60 to use IQ alone
(absent abnormal motor examination, abnormal imaging, etc.) as
the basis for designating the underlying cause as ‘‘symptomatic”
[34].
The prospective identification and intensive follow-up of our
community-based cohort generally diminish concerns over selec-
tion bias that can be caused by prevalence sampling methods or
by studies that do not report their response rates at all, a failing
common in the clinical literature in this field. We were not able
to test all study subjects or recruit controls for those that we did.
Unlike most studies, however, we have been able to describe the
derivation of our analytic sample, demonstrate high response rates,
and also provide an analysis of factors that might raise concerns
about selection bias. Although individuals could self-select to par-
ticipate in the cognitive assessments, there is little evidence of ma-
jor differences between participating and nonparticipating cases.
Despite the prospective nature of this study, we do not have
longitudinal data with standardized neurocognitive testing done
at initial diagnosis and then years later. We do not know if cogni-
tive function changed from what it was 8–9 years earlier; for some,
this would have been during infancy and very early childhood.
Studies of children with new-onset epilepsy report that they score
significantly worse then controls [14,15]. These studies examine
children on medication, with recent seizures, and in the active
stages of their disorder. Had our study subjects been tested at on-
set, a similar pattern of findings might have been observed. We
think this would be unlikely. If the cases’ current levels of function
reflected substantial loss over 8–9 years that would mean that they
would have had to be functioning at a substantially higher level
than their sibling controls prior to onset, because the current dif-
ference between cases and controls is so modest. On the other
hand, cases whose FSIQ was in the borderline to very mild mental
retardation range, the ones we excluded from the primary analy-
ses, may represent a subgroup that experienced declines since on-
set. In that regard, some studies considered changes in cognitive
function from before or at onset [19,46] to about 3 years later or
during the course of chronic epilepsy [47] and found no evidence
of change. Nonetheless, declines in cognitive function cannot be
fully ruled out. They have been seen in studies that focus on severe
epilepsy and institutionalized patients [48]. Determining the exact
determinants of such changes may not be a simple matter.
These findings should be reassuring for the more than half of
individuals with uncomplicated childhood-onset epilepsy and nor-
mal intelligence. If the findings for processing speed reflect true,
residual cognitive comorbidity associated with epilepsy, this may
have implications for schooling and employment. We caution,
however, that these findings should not be used to minimize the
importance of cognitive comorbidity in young people with epi-
lepsy. In a separate analysis we reported that a quarter of the entire
cohort had borderline to severe intellectual impairment [34]. Fur-
ther, even if the effects of epilepsy appear relatively mild 8 to 9
years later in individuals with overall normal cognitive function,
the impact may have been much greater during the active phase
of the disorder; a large proportion of the idiopathic and crypto-
genic cases received special education services [49]. Our study is
not designed to test whether such interventions are effective; how-
ever, we strongly caution that our findings should not be used to
argue that they are unnecessary. Older studies with prolonged fol-
low-up of social and employment outcomes in adulthood have
suggested that young adults with childhood-onset epilepsy are rel-
atively impaired in these domains compared with their peers
[50,51]. Long-term follow-up of our cohort has the potential to
bridge the gap between manifestations of the disorder in childhood
and consequences in adulthood.
Acknowledgments
We thank all the physicians in Connecticut who have allowed
us to recruit and follow their patients. Eugene Shapiro provided
essential administrative help throughout. Shlomo Shinnar partici-
pated in earlier phases of this study. Above all, the study would
not have been possible without the generous help of the many
families who have participated over the years.
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