Journal of Child Psychology and Psychiatry 43:1 (2002), pp 103±131

Childhood epilepsy in relation to mental handicap

and behavioural disorders
Frank M.C. Besag
Bedfordshire and Luton Community NHS Trust, UK and University of Luton, UK

Epidemiological studies indicate that there is a high rate of mental retardation and behavioural
problems in children with epilepsy. In some cases both the epilepsy and the mental retardation will have
a common cause, such as a metabolic disorder or brain trauma. However, in other children, the epilepsy
itself may cause either temporary or permanent learning problems. When permanent learning disability
can be prevented it is important to treat the epilepsy early and effectively. Children with specific learning
difficulties and memory problems can benefit greatly from appropriate management. There are many
causes of behavioural disturbance in children with epilepsy. These causes include the epilepsy itself,
treatment of the epilepsy, reactions to the epilepsy, associated brain damage/dysfunction and causes
that are equally applicable to children who do not have epilepsy. Identifying the cause or causes in each
child allows rational management to be provided. Antiepileptic treatment with medication or surgery
can either improve the situation or make matters worse. The treatment should be tailored to the needs of
the individual child. If surgery is required, there is a strong argument for performing this early in life,
both to allow the greatest opportunity for brain plasticity and also to allow the child full benefit from the
important developmental and educational years, without the problems that can be associated with the
epilepsy. Skilled management of children with epilepsy who have mental retardation and/or
behavioural problems can be very rewarding both for the family and for the professionals involved.
Keywords: Behaviour problems, cognition, epilepsy, learning difficulties, mental handicap.

There is a tendency to adopt extreme attitudes to
learning and behavioural problems in children with
epilepsy: either to state that they have no problems
at all or to consider that the situation is necessarily
disastrous. Neither extreme is appropriate. The aim
of this paper is to provide a balanced view.
Discussions of the de®nitions of mental handicap
and behavioural disorders can occupy much space
without throwing much light on the fundamental
issues. Furthermore, terminology used to designate
mental handicap often has more to do with current
usage, some might say fashion, and political cor-
rectness than underlying science or practical issues.
The de®nition of mental handicap most widely ac-
cepted is that of IQ < 70, based on the fact that this is
approximately 2 standard deviations below IQ 100.
However, wider de®nitions of impairment may be
appropriate so as to include speci®c de®cits. It is also
very important to note any loss of skills, even if the
®nal IQ remains above 70. It could be argued that
the concept of `schooling dif®culty', although more
vague, has more practical importance.
With regard to behavioural disturbance, it is usual
to refer to standardised behavioural scales such as
the Rutter, Connors or Achenbach scales, although
measures of more speci®c behaviours may be
necessary. These scales may overlook more subtle
but nevertheless important behavioural changes.
Detailed de®nitions of epilepsy, seizure types and
seizure syndromes are provided in other publica-
tions (O'Donohoe, 1985; Henriksen, 1996; Commis-
Ó Association for Child Psychology and Psychiatry, 2002.
Published by Blackwell Publishers, 108 Cowley Road, Oxford OX4 1JF, UK and 350 Main Street, Malden, MA 02148, USA
sion on Classi®cation and Terminology of the
International League Against Epilepsy, 1981, 1989;
Oxbury & Duchowny, 2000). The importance of
correct diagnosis cannot be overemphasised.
Part I Epilepsy and mental handicap
Epidemiological studies on learning
The current author (Besag, 1994a) has previously
reviewed several of the studies on epilepsy and
learning. Many of these were on selected populations
rather than being true epidemiological studies.
However, they have added to the overall impression
of a relationship between learning problems and
epilepsy. Pond and Bidwell (1960) surveyed 14 gen-
eral practices and identi®ed 39 children of school age
with epilepsy. Fourteen of these were having dif®-
culties in education, especially as a result of beha-
vioural disorders. The classical study is that of
Rutter, Graham, and Yule (1970) carried out on the
Isle of Wight. They found an excess of reading re-
tardation of 2 years or more in children with epi-
lepsy, even if they were of normal or above-normal
intelligence. This was a true epidemiological study,
examining all the children around 10 years of age in
a de®ned geographical area. Holdsworth and Whit-
more (1974a, 1974b) attempted to locate all the
children attending ordinary schools in a particular
area. However, they excluded children attending
special schools. Eighty-®ve children with epilepsy
104 Frank M.C. Besag
ful®lled their criteria of attending a mainstream
school and having had a seizure during the previous
twelve months (52 children) or having been treated
with antiepileptic drugs over that period (33 chil-
dren). This yielded a low prevalence ®gure of 1.6 per
thousand in primary schools and 2.4 per thousand
in secondary schools, probably because they exclu-
ded children who were not attending mainstream
schooling. They classi®ed 64 of the children into
three groups, based on educational performance.
Twenty-®ve (31%) were maintaining an average or
superior level of performance, 35 (53%) were `holding
their own at a below-average level' and 10 (16%) were
seriously behind. Their data did not suggest that
poor attendance was a cause of the educational dif-
®culties. The frequency of the seizures did not seem
to affect educational outcome or school attendance.
Three of the 4 children with absence seizures alone
were progressing well.
Pazzaglia and Frank-Pazzaglia (1976) found 38
children with epilepsy in a population of 13,000
school-age children 6±14 years of age in the area
around Cesena in Italy. This yielded a prevalence of
approximately 3 per thousand, which is close to
what other studies have found. Twenty-seven of the
38 children were of normal intelligence and 11 (29%)
were `retarded', de®ned as an IQ < 80, although it
should be noted that 10 of the 11 children had an IQ
< 70. About half the children had a normal school
record, 17% were behind their grade in school and
36% were in special schools.
The National Child Development Study in the UK
was a true epidemiological study of a cohort of
17,733 children born in the week 3±9 March 1958 in
England, Scotland and Wales. Of the original chil-
dren, 15,496 were traced and alive at 11 years of age,
yielding an epilepsy prevalence of 4.1 per thousand.
This suggests that few, if any, cases escaped identi-
®cation. The authors were particularly careful about
the inclusion criteria. At 11 years of age there were
346 possible cases of epilepsy but the diagnosis was
®rmly established in only 64. Of these, 22 (34%) were
in special education by the age of 16. Even those who
remained within mainstream schooling tended to
have lower reading and mathematics scores than the
age-matched general population. Most of the chil-
dren who were in special schools were there because
of intellectual impairment rather than because of the
epilepsy itself. This study led to a number of valuable
papers (Ross, Peckham, West, & Butler, 1980; Ver-
ity, Ross, & Golding, 1992; Kurtz, Tookey, & Ross,
1998).
Ellenberg, Hirtz, and Nelson (1986), in the US,
examined children with epilepsy as part of the
national collaborative perinatal project of the
National Institute of Neurological and Communica-
tive Disorders and Stroke (NCCP). This study
followed the outcome of 54,000 pregnancies in 1959.
They identi®ed 518 children who had one or more
non-febrile seizures after the newborn period; 368 of
these had intelligence tests at 7 years of age. Ninety-
eight children with non-febrile seizures had at least
one sibling in the study. Using sibling controls, the
authors concluded that, although the mean IQ score
of 91.5 was less than that of the general population,
it was not signi®cantly different from that of sibling
controls. Nevertheless, their results imply a poor
intellectual performance of children with epilepsy,
compared with those who did not have epilepsy in
the general population. This paper raises the
important question of whether the poorer intellectual
performance of the children with epilepsy re¯ects
some pre-existing, genetically determined de®cit or
whether it is a consequence of the epilepsy. This
issue will be discussed in later sections.
McDermott, Mani, and Krishnaswami, (1995)
carried out a population-based study in the US using
data collected in the 1988 National Health Interview
Survey (NHIS). The NHIS staff carried out personal
interviews with approximately 45,000 households
containing 150,000 individuals. Of the 121 children
with parent-reported seizures, 22% had develop-
mental delays and 28% had repeated a grade in
school. Of the children who had both seizures and
behavioural problems, 57% were in special educa-
tion classes. The authors have pointed out a number
of limitations. In particular, the results were based
solely on parental interviews carried out by the NHIS
staff. Furthermore, the care exercised in ensuring a
rigorous diagnosis of epilepsy in the UK national
child development study did not apply to this sam-
ple, in which broader inclusion criteria were used.
Outstanding epidemiological work has been car-
ried out in Finland by SillanpaÈaÈ. In one of these
studies (SillanpaÈaÈ, 1992) he identi®ed 143 children
with epilepsy out of a population of 21,104 children
4±15 years of age, a prevalence of 6.8 per thousand.
He found that the most frequent neurological
impairments were mental retardation, de®ned as an
IQ < 70, which was present in 31.4%, speech disor-
ders (27.5%) and speci®c learning disorders (23.1%).
He concluded that there was a 22-fold risk of occur-
rence of a handicap in children with epilepsy
compared with controls. In his earlier reviews
(SillanpaÈ aÈ, 1990, 1983) he concluded that 27.5% of
children with epilepsy did not complete their basic
education or required schooling in establishments for
learning disability. He subsequently (SillanpaÈ aÈ et al.,
1998) followed up these children to determine the
long-term prognosis of seizures with childhood onset.
Of the original 245 children identi®ed between 1961
and 1964, suf®cient data were available on 220 (90%)
in 1992; 176 were alive and 46 had died. The re-
maining 25 could not be traced or would not parti-
cipate. The 99 patients who had uncomplicated
epilepsy nevertheless had signi®cantly worse out-
comes for most social and educational variables,
despite having similar socio-economic status. The
remaining 76 patients with epilepsy and other dis-
abilities, as expected, had poor outcomes on these
 Childhood epilepsy in relation to mental handicap and behavioural disorders
measures. The poorer outcome was despite the fact
that a large proportion went into remission, with 70%
having been seizure free for more than 20 years.
In a recent study carried out by O'Neill and co-
workers (Besag, O'Neill, & Ross, 1999) in the inner
London Borough of Lambeth, parents of children
with epilepsy were asked to ®ll out questionnaires.
Using multiple ascertainment methods, the preval-
ence of epilepsy in school-age children (n ˆ 127) was
found to be 4.2 per thousand, suggesting that most
were identi®ed; 60% of parents completed question-
naires. Of these, 65% reported some learning dif®-
culty in their children. Although parental perception
is not a rigorous measure of educational failure, this
®gure is consistent with the general conclusion that
children with epilepsy are highly likely to have
schooling dif®culties.
A different approach is to examine the prevalence
of epilepsy in children with mental retardation. Air-
aksinen et al. (2000) have recently reported such a
study. They identi®ed 151 children with mental re-
tardation by screening four birth cohorts of nearly
13,000 in one Finnish province at 9±10 years of age.
All of these children and 101 randomly selected age-
matched controls were studied by a multidisciplinary
team. They used a variety of psychometric tests and
de®ned mental retardation as a score of more than 2
standard deviations below the mean. By 10 years of
age, 29 of the 151 (19%) had epilepsy. The cumulative
risk for epilepsy at 22 years of age was 21%, that is,
32 of the 151 subjects were having recurrent, un-
provoked epileptic seizures. The ®gure for the 77
subjects with severe mental retardation, de®ned as
IQ < 55 or 3 standard deviations below the mean, was
35%. The prevalence in those with mild mental re-
tardation was, in contrast, only 7%. The difference in
prevalence was highly statistically signi®cant (p <
.0005). Mild mental retardation was de®ned as being
more than 2 standard deviations but less than 3
standard deviations below the mean for IQ. There
have been a number of past studies on the prevalence
of epilepsy in people with mental handicap, although
relatively few of these have been in children.
Gustavson, Holmgren, Jansell, Son, and Blom-
quist (1977) carried out a study in children aged
5±16 years with mental retardation in northern
Sweden. They found that 84 of 161 children (52%)
who had severe mental retardation (IQ < 50) also had
epilepsy. In the same area and age group, in those
with mild mental retardation (IQ ³ 50), 36 of 171
(21%) had epilepsy.
Richardson, Koller, Katz, and McLaren (1980) ex-
amined ®gures for the occurrence of one or more
epileptic seizures in patients with mental retarda-
tion, using two control groups, one with borderline
intelligence and another with normal intelligence,
matched for age and sex. The ®gures were 27%, 11%
and 4% respectively.
Steffenburg, Hagberg, Viggedal, and Kyllerman,
(1995) examined data on all children with mental
105
retardation, 6±13 years in a geographical area of
Sweden. Of 378 children, 98 (26%) had `active' epi-
lepsy; 15% of those with mild mental retardation and
45% of those with severe mental retardation had
epilepsy.
Forsgren, Edvinsson, Blomquist, Heijbel, and
Sidenvall (1990) studied a mixed sample of children
and adults with mental retardation in a northern
Swedish county and found that 20% had `active'
epilepsy; 23% of those with severe mental retarda-
tion had epilepsy and 11% of those with mild mental
retardation.
Goulden, Shinnar, Koller, Katz, and Richardson,
(1991) carried out a prospective study in a cohort of
221 children with mental retardation and reported
that 33 (15%) had epilepsy. An additional 16 (7%)
had a single febrile or afebrile seizure by 22 years of
age. The cumulative incidence of epilepsy was 9%,
11%, 13% and 15% at 5, 10, 15 and 22 years
respectively.
The conclusion from these studies is clear. First, a
high proportion of children with epilepsy have global
or speci®c learning problems. Second, in general, the
greater the degree of pre-existing mental retardation,
the higher the risk of developing epilepsy.
Although it should be noted that febrile convul-
sions are not a form of epilepsy, they may be asso-
ciated with an increased risk of epilepsy and are
listed in the International League Against Epilepsy
classi®cation. Furthermore, febrile seizures are
common, occurring in 2±4% of the general popula-
tion (Wallace, 1988), and it would appear appropri-
ate to discuss the cognitive effects of this childhood
condition in the present paper. Verity, Greenwood,
and Golding (1998) identi®ed 398 children with
febrile convulsions among 14,676 subjects enrolled
in the Child Health and Education study which was
a national population-based study in the United
Kingdom of children born in one week in April 1970.
The children were comprehensively assessed at the
age of 10. Sixteen children were excluded because
they had neurodevelopmental problems before the
®rst febrile convulsion and 1 child was said to be
atypical, leaving 381 children. Of these, 287 had
simple febrile convulsions and 94 complex febrile
convulsions, de®ned as a convulsion that lasted
longer than 15 minutes, that was focal or that
occurred more than once during an episode of fever.
Only 4 of the 102 outcome measures appeared to be
statistically signi®cantly different from the control
group. The results indicated that the children with
the febrile convulsions were more impulsive or
excitable, less skilled in gymnastics, more anxious
and had better reading skills than the controls. The
last ®nding, that children with the febrile convul-
sions performed better than those without, was an
unexpected result. However, it is quite possible to
have 4 apparently statistically signi®cant results out
of 102 measures by chance. Of the 334 children with
febrile convulsions, 305 had normal intellectual
106 Frank M.C. Besag
ability (91.3%) which was very close to the ®gure
for the 12,017 control children, namely 92.4%. The
results for the subgroups of children who had simple
febrile convulsions and complex febrile convulsions
were also similar. They concluded that the intellec-
tual and behavioural outcome for the group with
complex febrile convulsions was as good as that of
the rest of the cohort and that their results should be
considered as reassuring both for parents and for
physicians.
Chang, Guo, Huang, Wang, and Tsai (2000) fol-
lowed up 103 children who had febrile convulsions
under 3 years of age in a population-based study of
4,340 live births in Taiwan. The children were fol-
lowed up at least until 6 years of age. They con®rmed
that febrile convulsions did not have adverse effects
on behaviour or scholastic performance. A surpri-
sing result was that the children with a history of a
febrile convulsion seemed to have signi®cantly better
control of distractibility and attention.
It is interesting to view these results in the light of
the classical paper by Annegers, Hauser, Shirts, and
Kurland (1987) who concluded that the risk for
subsequent epilepsy after febrile seizures was as
follows: after focal seizures 8%, after repeated or
prolonged seizures 22% and after focal and pro-
longed seizures 49%. This would suggest that febrile
seizures, particularly those that are focal, repeated
and prolonged, might have signi®cant sequelae. With
regard to the outcome of children who have pro-
longed febrile seizures, Shinnar et al. (2001) have
recently published a study of 180 children aged
1 month±10 years who had febrile status epilepticus.
They de®ned febrile status epilepticus as being a
febrile seizure lasting longer than 30 minutes. They
compared this group with 244 children, including
168 who had had simple febrile seizures and 76
with complex febrile seizures that lasted less than
30 minutes. They concluded that the short-term
morbidity and mortality of febrile status epilepticus
in their series was extremely low. The follow-up as-
sessment was at 1 month. They pointed out that
there were no IQ measurements in this study, nor
any immediate neuro-imaging. They indicated that
there were plans to examine neuro-imaging in the
entire cohort, in particular to determine factors that
might be associated with the development of hippo-
campal sclerosis. It should be noted that prolonged
febrile seizures have, in the past, been associated
with hippocampal sclerosis but there is much debate
about whether this association represents some
preceding underlying abnormality or whether the
hippocampal sclerosis is a true consequence of the
prolonged seizure (Shinnar, 1998).
What conclusions should be drawn from these
studies? Wallace (1988, 1996b) has provided a very
full discussion of the major issues. Taking into ac-
count both earlier and more recent work, it would
appear that most febrile convulsions do not result in
serious sequelae and that there is little evidence for
early damage after some prolonged febrile convul-
sions. However, it would be very unwise to be com-
placent about febrile convulsions because it would
appear that a single prolonged convulsion can
sometimes cause permanent impairment. The safest
approach is to view any prolonged convulsion as
being a medical emergency that should be treated
promptly.
The various relationships between epilepsy and
mental handicap will be discussed in the section
on causes of learning problems in children with
epilepsy.
Studies on selected populations. Stores and
co-workers have published a number of papers
reporting work on various aspects of educational
dif®culties in children with epilepsy (Stores, 1971,
1973; Stores & Hart, 1975; Stores, 1976, 1978;
Stores, Hart, & Piran 1978; Stores & Piran, 1978;
Bennett-Levy & Stores, 1984). Stores and Hart
(1975) studied the reading skills in children with
generalised epileptiform discharges and focal dis-
charges. Seventeen subjects (10 boys, 7 girls) with
generalised discharges were matched for age and sex
with 17 who had persistent focal discharges on
either side and also with children who did not have
epilepsy. No difference was found between the
reading skills of children with the generalised dis-
charges and matched controls who did not have
epilepsy. However, those with persistent focal spike
discharges tended to have a lower reading ability
than matched controls, especially with regard to
accuracy. These effects were generally related to left
hemisphere focal spikes. It is interesting to note that
the reading skills of boys with epilepsy, whatever the
type, were worse than those of girls with epilepsy.
This sex difference was not found in control children
who did not have epilepsy. In another study, Stores
et al. (1978) measured inattentiveness in 36 boys
and 35 girls with epilepsy. Again, the boys performed
more poorly than the girls but no sex difference was
seen in any of the measures in the control children
who did not have epilepsy. A particularly interesting
result was that the distraction applied to children
during a distractibility test lowered the scores in
controls, as expected, but the performance improved
in those who had epilepsy, suggesting that these
children were in some way under-aroused and de-
rived bene®t from the alerting effect of the noise.
Another unexpected result was that children with 3
per second spike-wave discharges, commonly seen
in absence seizures, were less impaired on vigilance
and distractibility tests than other subgroups.
Aldenkamp and his co-workers have carried out a
number of studies to determine the effect of epilepsy
on learning. For example, Aldenkamp, Overweg-
Plandsoen, and Arends (1999) studied a selected
sample comprising 123 children who were referred to
their epilepsy centre in Holland. The inclusion cri-
teria were: referral to the epilepsy programme for
 Childhood epilepsy in relation to mental handicap and behavioural disorders
neurological assessment and assessment of learning
and behaviour, aged 6±12 years, in normal schooling
(i.e., excluding those in special education), mild
global learning impairment, de®ned as a retardation
of educational achievement between 6 months and
1 year, based on school reports and a school
achievement test, and a recon®rmed diagnosis of
epilepsy. Exclusion criteria were the presence of
dyslexia or dyscalculia, full-scale IQ < 70, speci®c
cognitive impairment associated with attention-de-
®cit hyperactivity disorder (ADHD) or neurological
impairments other than epilepsy. Thirty-one pa-
tients ful®lled the inclusion criteria. These were split
into two groups: group A had epilepsy and mild
global learning impairment preceded by develop-
mental delay (17 patients) and group B had epilepsy
and sudden unexpected mild global learning im-
pairment (14 patients). There was a control group of
13 patients who had mild global learning impair-
ments without epilepsy or other neurological prob-
lems. The children in group B showed more frequent
neuropsychological impairment (p ˆ .04). They con-
cluded that the key ®nding of this group might be the
relatively frequent demonstration of subtle seizures,
which could explain both the decline of school re-
sults and the impairments found on neuropsycho-
logical testing. They added that these seizures could
have been overlooked for some time. They also made
the important point that unexpected decline in
school performance with lapses of concentra-
tion might be a ®rst sign of previously undiagnosed
epilepsy.
The same group (Neyens, Aldenkamp, & Meinardi
1999) carried out a prospective follow-up study of
the intellectual development of children with recent
onset of epilepsy. Eleven children aged 7±15 years
with a mean duration of epilepsy of 2 years and 38
control children without epilepsy were tested on the
Netherlands revised version of the Wechsler Intelli-
gence Scale for Children on three occasions. They
were also given other psychometric tests. The chil-
dren with epilepsy differed at ®rst assessment with a
full-scale IQ of 94.2 compared with 107.3 for the
controls. The children with epilepsy also showed a
lower rate of increase in the full-scale IQ score with
time. They were tested on three occasions with a
test-retest interval of approximately 6 months. The
gain in full-scale IQ score was 12 points in the
controls and 5 points in the children with epilepsy.
The performance IQ also showed a trend towards
difference over time with the lower gain in the epi-
lepsy group. The gain in the full-scale IQ score in
children with a duration of epilepsy of less than 2
years was also signi®cantly lower than that of the
children who had a longer duration of epilepsy, 2±3
years. The authors argued that the impact of epi-
lepsy might be greater during the period of devel-
opment below 10 years of age. However, they pointed
out a number of limitations in this study. The
experimental group was small. There was also
107
considerable variation in the type of epilepsy/seiz-
ure type. The development of children is not neces-
sarily smooth but may be `by leaps'. Perhaps the
greatest drawback of the study is that the two
groups did not have the same starting point in terms
of IQ score. The argument for epilepsy causing de-
terioration would be much greater if a prospective
study showed a difference after both the epilepsy
and control groups had initial psychometric as-
sessment showing the same cognitive level. It should
be noted that both the studies of Aldenkamp (1999)
and Neyens et al. (1999) were open studies but it
might be dif®cult to design a proper blinded study in
which both the assessors and those analysing the
results were unaware of whether the children had
epilepsy or not.
Bulteau et al. (2000) carried out a retrospective
study of the relationship between epilepsy syn-
dromes and educational factors in 251 children aged
3±17 years referred to their specialist service in
Paris. Although this was a selected group of children
and some of the classi®cations might be open to
debate, the results are of great interest. As expected,
the children with `idiopathic' generalised epilepsies
had a higher IQ (mean 83.7) than those with symp-
tomatic/cryptogenic epilepsies (mean 63.3). Multiple
regression analysis showed that there was a signi®-
cant relationship between IQ and epileptic syndrome
(using four broad categories), age of onset and
number of antiepileptic drugs. Although the num-
bers in some of the groups were relatively small,
there were also some interesting cognitive pro®les
associated with particular types of epilepsy. The
most striking de®cits were for frontal lobe epilepsy,
in arithmetic and coding, and for occipital epilepsy,
in image completion and coding. As might have been
expected, overall performance was poor for multifo-
cal epilepsy. As stated elsewhere in this paper, a
syndrome-based approach to the effects of epilepsy
on learning would appear to be the best way of
viewing the whole subject but there remains a lack of
good epidemiological evidence to con®rm this.
An issue that is central to the relationship between
epilepsy and learning has been raised by Cole
(2000), who asked the question: `Is epilepsy a pro-
gressive disease?' He discussed the possible neuro-
biological consequences of epilepsy. He illustrated
these with a number of case reports. From the case
reports he concluded that status epilepticus may
have devastating consequences and recurrent sei-
zures over many years may be associated with
delayed neurocognitive dysfunction. Seizures may,
however, continue for many years without evidence
of progressive neurological symptoms and even a
single seizure may be suf®cient to cause injury with
prolonged consequences. He discussed a number of
neurobiological consequences of seizures that might
have a role to play in causing cognitive impairments,
including ionic ¯uxes, kinase activation, immediate
early gene expression, late gene expression, protein
108 Frank M.C. Besag
expression, protein modi®cation, mossy ®bre
sprouting and synaptic reorganisation, cell loss, gli-
osis, neo-neurogenesis, and increased susceptibility
to recurrent seizures. He discussed the limitation of
the animal models on which these mechanisms are
based. It is not clear how these might apply to people
with epilepsy.
Deterioration of cognitive skills in a child is a
major cause for concern. Any child who deteriorates,
i.e., has actually lost skills, without obvious cause,
must be investigated thoroughly. However, a falling
IQ does not necessarily imply loss of skills. IQ de-
cline in epilepsy has been discussed by Besag,
Fowler, and Pool (1991). They showed that the ma-
jority of children in their series who had any falling
IQ did not decline in absolute ability. The mental age
calculated from the raw scores of the cognitive tests
continued to improve, but at a rate that lagged be-
hind the increase in chronological age, with the re-
sult that their IQ, which is a quotient depending on
mental age and chronological age, declined. This si-
tuation is what some would call `stagnation' rather
than `deterioration'. Nevertheless, the fact that the
child is not developing at the expected rate is a cause
for concern and any intervention that might allow
the child to develop at a more normal rate would be
very worthwhile.
There are still many unanswered questions with
regard to memory impairment and epilepsy. This
subject has recently been reviewed by Helmstaedter
and Kurthen (2001). Poor memory seems to be a fre-
quent complaint among adult patients but formal
testing often reveals no de®cits. This could re¯ect the
shortcomings of the tests used or it could indicate that
many people think that their memory is poor but in-
dividuals with a neurological condition such as epi-
lepsy have more reason to imagine that they have
particular problems in this area. Two recent studies
(Elixhauser, Leidy, Meador, Means, & Willian, 1999;
Sawrie et al., 1999) have suggested that complaints of
poor memory may be related more to depressed mood
than to impairment of memory itself. In contrast,
Blake, Wroe, Breen, and McCarthy (2000) showed
accelerated forgetting in patients with epilepsy who
seemed unimpaired in usual memory tests.
There is a lack of studies on memory in children
and teenagers with epilepsy. It could be argued that
it is particularly important to determine such de®cits
in an age group in which education plays such a
major role, especially in view of reports of `under-
achievement' in young people with epilepsy and a
normal IQ. The majority of the studies have been on
small numbers of patients with temporal lobe epi-
lepsy before and after surgery. Occasional papers
have examined other types of epilepsy or have been
based on multicentre data.
Pavone et al. (2001) carried out detailed psycho-
logical testing of 16 right-handed children with ab-
sence epilepsy and 16 matched controls without
epilepsy. The children with absence epilepsy had
lower scores for general cognitive function and visuo-
spatial skills. There were selective de®cits in non-
verbal memory and delayed recall but verbal memory
and language skills were relatively preserved. They
commented that earlier age of seizure onset seemed
to be associated with more severe cognitive decline.
Lendt, Helmstaedter, and Elger (1999) performed
memory, attention, language and visuoconstructive
tests on 20 children (10±16 years) before and at three
and 12 month intervals after temporal resection (10
right, 10 left). The outcome was compared with 30
healthy age-matched control children. No preopera-
tive differences were found between patients and
controls with regard to verbal and ®gural memory
performance. Memory performance did not change
after surgery. However, language performance and
attention improved signi®cantly three months and
one year after surgery respectively. Individual eval-
uations of memory revealed that ®ve children im-
proved and four deteriorated. The deterioration in
memory appeared to be related to poor seizure con-
trol. They concluded that hemispheric differences in
postoperative memory were less in children than in
adults, possibly because children are capable of
greater brain plasticity.
Dlugos, Moss, Duhaime, and Brooks-Kayal (1999)
carried out comprehensive neuropsychological test-
ing on eight children (11 years 10 months±16 years)
who underwent temporal lobectomy (®ve left, two
right) for temporal lobe epilepsy. They tested IQ,
verbal learning, naming, visual memory, sight word
recognition, reading comprehension and calculation.
All of their ®ve children who underwent left temporal
lobectomy had signi®cant language-related cognitive
de®cits on postoperative testing. Four of the patients
had verbal learning de®cits. The authors pointed out
that IQ testing alone did not reliably identify these
de®cits.
Williams, Griebel, Sharp and Boop (1998) tested
nine children under 16 years of age who had a tem-
poral lobectomy (®ve left, four right). Paired t tests
did not reveal marked changes in cognitive function
after surgery. However, there were decreases in
delayed verbal memory.
Szabo et al. (1998) performed neuropsychological
tests on 14 children (7±12 years) undergoing tem-
poral lobe resection for refractory epilepsy. Immedi-
ate verbal memory decreased signi®cantly in
children who performed above the median preoper-
atively and tended to decrease in children who had a
left temporal lobe resection. The whole group had a
statistically signi®cant decrease in delayed verbal
memory.
There seems to be considerable evidence for the
suggestion that left (dominant) temporal lobectomy
is associated with verbal memory de®cits, although
this is generally considered to be a small price to pay
for the advantages of freedom from seizures. Right
(non-dominant) temporal lobectomy does not seem
to be associated with the same degree of non-verbal
 Childhood epilepsy in relation to mental handicap and behavioural disorders
de®cit, and memory de®cits in children appear to be
less than in adults (Lendt et al., 1999). The degree of
memory impairment following temporal lobectomy
may depend on a number of factors, including the
presence of a clear abnormality such as gross hip-
pocampal sclerosis in the removed temporal lobe, the
age of seizure onset, the age at surgery and the
surgical technique. The role of antiepileptic drugs
and memory is much less clear. Results from larger
numbers of children are required. This will almost
certainly imply cooperation between multiple centres
using standardised protocols in prospective studies.
Causes of learning problems in children
with epilepsy
Relationships between epilepsy and learning. It is
important to distinguish between three possible in-
terrelationships between epilepsy and learning:
1. brain damage or dysfunction causing epilepsy
and also causing learning disability (Figure 1a);
2. epilepsy causing brain damage or dysfunction
which, in turn, results in learning disability
(Figure 1b);
3. epilepsy directly causing learning disability
(Figure 1c).
The ®rst situation in which brain damage or dys-
function causes epilepsy and also, independently,
results in learning disability can result from a large
number of different causes. These causes include all
the usual main categories, such as genetic/chromo-
somal, in¯ammatory, infectious, neoplastic and
traumatic. A full discussion of each of the causes is
beyond the scope of this paper. For example, the
Oxford genetics database lists several hundred con-
ditions associated with seizures or epilepsy, most of
which are also associated with learning disability.
Figure 1 The possible relationships between epilepsy
and learning disability
109
The increasing role of genetics in de®ning the causes
of both epilepsy and learning disability has been both
clari®ed and clouded by the extraordinary advances
in this area over recent years. There is a steady
stream of individual genetic disorders that are being
identi®ed in individuals or families, resulting in the
combination of epilepsy and learning disability.
There is also an attempt to isolate genes responsible
for the combination of epilepsy and learning disabil-
ity. As more and more information is gathered it has
become increasingly apparent that what seems to be
a single phenotype may be the result of more than one
genetic abnormality and that a single genetic abnor-
mality may result in a tremendous variation in phe-
notype. An example of the latter is tuberous sclerosis,
which is inherited as an autosomal dominant, al-
though many cases are spontaneous mutations. The
gene is noted for highly variable expressivity: within
the same family one member may have neither epi-
lepsy nor learning disability whereas another may
have severe, disabling epilepsy and profound learn-
ing disability. The genetic heterogeneity is illustrated
by the fact that at least two genes have been identi®ed
as being responsible for tuberous sclerosis, on chro-
mosome 16 and chromosome 9.
A particularly interesting development over recent
years has been the identi®cation of genetic disorders
leading to cortical malformations, which result in
both epilepsy and learning disability. For example,
Allen and Walsh (1999) have identi®ed a speci®c
gene `doublecortin' that is mutated in patients who
have a condition known as subcortical band het-
erotopia in which an abnormal band of neurones in
the white matter underlies the relatively normal
cortex, giving an appearance of a second layer of
cortex deep to the usual position, generally bilater-
ally. Allen and Walsh have pointed out that in the
same families double cortex may occur in females
whereas males have the much more severe condition
of lissencephaly which is characterised by an
abnormally thickened cortex with decreased or even
absent surface convolutions. There is increasing
evidence that a number of other cortical malforma-
tions may have a genetic origin. Duncan (1997) has
provided an excellent overview of cortical malforma-
tions and their role in epilepsy. Reviews of the role of
genetics in epilepsy include those by Bate and
Gardiner (1999) and Berkovic and Scheffer (1997).
Berkovic and Mulley (1996) identi®ed the ®rst gene
for an `idiopathic' epilepsy. This work implies that
not only the terminology but also the underlying
concept behind so-called idiopathic epilepsy will
need to be reconsidered. It appears that many of the
epilepsies that were previously classi®ed as `idio-
pathic' will need to be reclassi®ed as `symptomatic',
in other words they will be reclassi®ed from `cause
unknown' to `cause known', as research in the gen-
etics of the epilepsies expands (Besag, 1999b).
As stated in the previous section on epidemiologi-
cal studies, in general, the greater the degree of
110 Frank M.C. Besag
mental handicap, the more likely epilepsy becomes.
This implies that those chromosomal and genetic
disorders that result in severe or profound mental
handicap will be associated with a high incidence of
epilepsy. This trend appears to be con®rmed by data
(see section on epidemiological studies), although
it is interesting to note that some conditions, for
example Down syndrome, generally result in severe
learning disability but cause only a relatively modest
increase in the likelihood of epilepsy (Johannsen,
Christensen, Goldstein, Nielsen, & Mai, 1996).
Chromosomal abnormalities and a dominantly-
inherited condition (tuberous sclerosis) have already
been discussed brie¯y. There are several single case
reports appearing in the literature of syndromes that
result from a genetic defect and are associated with
both learning disability and epilepsy with no obvious
metabolic abnormality. Most of these are autosomal
recessive conditions. In addition, metabolic condi-
tions may cause learning disability and epilepsy. The
classical example is phenylketonuria. This is a par-
ticularly interesting example because dietary mani-
pulation, using a low phenylalanine diet, can reduce
or prevent the learning disability. Epilepsy is repor-
ted to occur in a high proportion of untreated cases,
typically 25% (Aicardi, 1992). This is only one
example of many hundred rare metabolic disorders
that can cause epilepsy and learning disability.
There are several syndromes that include learning
disability and a high prevalence of epilepsy but do
not have an identi®ed genetic disorder. However, the
situation is changing rapidly. For example, the
MECP2 gene for Rett syndrome has recently been
identi®ed (Amir et al., 1999) and has been localised
to the distal long arm of the X chromosome. Rett
syndrome is characterised by abnormal hand
movements, loss of hand skills, mental retardation
and epilepsy. The classical form of Rett syndrome
occurs only in females. In contrast, no speci®c uni-
versal gene defect has yet been found for Sturge-
Weber syndrome which consists of a vascular
malformation of the face (`port-wine stain') and
the meninges, often accompanied by epilepsy and
mental retardation.
Epilepsy as a cause of learning problems. The
obvious situation in which epilepsy may cause
learning problems is that in which a child has pro-
longed, brain-damaging status epilepticus. The
brain damage, in turn, results in learning disability.
The situation is represented in Figure 1b. Can epi-
lepsy lead directly to learning disability without
causing brain damage? In order to answer this
question satisfactorily it may be helpful to introduce
the concept of state-dependent learning disability. It
is very important to distinguish permanent learning
disability, on one hand, from state-dependent
learning disability on the other. Permanent learning
disability may arise from any of the causes discussed
earlier in this paper. The term state-dependent
learning disability refers to learning disability that is
caused by factors currently affecting the individual
that are potentially reversible or treatable (Besag,
2001c). With regard to children who have epilepsy,
the two main factors that may cause state-depend-
ent learning disability are antiepileptic medication
and the epilepsy itself. Because state-dependent
learning disability is potentially reversible and
treatable, failure to recognise it and manage the
situation appropriately is failure to serve the patient
adequately. The ®rst step in managing state-
dependent learning disability is to think of the
diagnosis. Unfortunately this ®rst step is often not
taken and the result is that the condition is neither
recognised nor treated.
The effects of epilepsy on learning can be placed in
the subcategories of pre-ictal, ictal and post-ictal. A
more complete discussion of the peri-ictal effects in
general appears later in the section on the beha-
vioural effects of epilepsy. There appear to be no
formal studies on the effects of prodrome or aura on
learning, although prodrome, because it can affect
mood and sometimes lasts for days, probably also
affects performance in the classroom. Multiple auras
can be very anxiety provoking (see later) and this
could also affect the performance of the child at
school.
A dramatic example of ictal state-dependent
learning disability is the situation of nonconvulsive
status epilepticus. Some children have periods of
time in which the normal EEG is replaced by either
continuous spike-wave epileptiform discharges or
such frequent discharges that the clinical effect is
continuous. The classical form of nonconvulsive
status epilepticus is accompanied by generalised
spike-wave discharges. However, complex partial
seizure status epilepticus may also occur. In these
circumstances the EEG changes may be less obvious.
Nonconvulsive status epilepticus often responds
promptly to treatment with an intravenous benzo-
diazepine, such as diazemuls. Rarely the condition
may last for long periods. It may even continue in-
de®nitely and be unresponsive to treatment. Some-
times the manifestations of nonconvulsive status
epilepticus can be remarkably subtle. The child may
be able to interact with his or her surroundings,
although less well than normally. Nonconvulsive
status epilepticus causes a spectrum of disability
from the child who appears relatively alert to one who
is in a zombie-like state, hypotonic, unable to re-
spond and unable to walk. The extent of the epilep-
tiform discharges on the EEG do not appear to
correlate directly with the degree of impairment;
some children with less frequent epileptiform dis-
charges may be grossly impaired by them whereas
others who have continuous discharges may never-
theless be able to walk and to respond in a primitive
way to questioning. It is clearly important to recog-
nise this condition and to diagnose it by carrying out
an emergency EEG. If the EEG con®rms the diagno-
 Childhood epilepsy in relation to mental handicap and behavioural disorders
sis then it may be appropriate to treat immediately
with intravenous medication such as diazemuls. The
longer-term antiepileptic drug treatment should also
be reviewed if the child is subject to repeated bouts of
nonconvulsive status epilepticus. In the author's
experience, lamotrigine seems to be highly effective
in preventing recurrent attacks in at least some
children.
Frequent absence seizures may affect attention
and learning. Infrequent absence seizures are usu-
ally associated with a good outcome for learning.
However, as shown by the current author, absence
seizures sometimes occur thousands of times daily
(Besag, 1995a). In these circumstances learning and
social interaction are grossly impaired.
Transitory cognitive impairment. The basic con-
cept of transitory cognitive impairment is that an
epileptiform discharge that does not manifest as a
seizure by simple observation may nevertheless im-
pair cognitive function. If these discharges occur
frequently then they may at least lead to frustration
in the classroom. Observation of videotapes of young
people undergoing testing during transitory cognitive
impairment has demonstrated the obvious frustra-
tion that they experience. Although the cognitive
impairment itself may be transitory there may be an
ongoing effect on con®dence in the classroom, which
may affect learning.
Binnie and colleagues have carried out a number
of studies on transitory cognitive impairment (Aarts,
Binnie, Smit, & Wilkins, 1984; Binnie & Marston,
1992; Marston, Besag, Binnie, & Fowler, 1993). They
showed clearly that left-sided (dominant) discharges
impaired verbal tasks and right sided (non-domin-
ant) discharges affected a test of visuo-spatial func-
tion (Aarts et al., 1984; Binnie, 1989). This subject
has been reviewed by Binnie (1989; Binnie & Mar-
ston, 1992). Marston et al. (1993) found that an-
tiepileptic drug treatment of children with transitory
cognitive impairment was associated with an im-
provement of psychosocial function. The treatment
of obvious seizures was thought to have been optimal
before the addition of antiepileptic medication to
treat the epileptiform discharges. However, the
additional treatment resulted not only in a reduction
of the epileptiform discharges but also in a reduction
of the frequency of obvious seizures. The reduction of
the obvious seizures was considered to be a con-
founding factor in this study. Ronen, Richards,
Cunningham, Secord, and Rosenbloom (2000) failed
to demonstrate any improvement in learning when a
small group of 8 children, aged 6±12 years, who had
epileptiform discharges were treated with sodium
valproate. In contrast, treatment with valproate was
associated with reduced performance on verbal
memory tasks, increased delays on attentional tasks
and increased parental reports of internalising
problems. It should be pointed out that, in addition
to the fact that this was a small and heterogeneous
111
sample of children, the paroxysmal EEG discharges
improved in only four of the eight children. In three
the number of discharges was similar on treatment
and in the remaining case the number increased.
This paper illustrates the multifactorial in¯uences
on learning and behaviour in children with epilepsy.
It would be reasonable to suggest that at least some
children with transitory cognitive impairment might
improve with the right type of antiepileptic medica-
tion that reduces the epileptiform discharges without
adding signi®cant drug-related impairments.
Frequent focal discharges. The role of frequent lo-
calised epileptiform discharges, not amounting to
nonconvulsive status epilepticus but suf®cient to
cause non-transitory impairments, has been unsat-
isfactorily described in the literature. Frequent
frontal discharges can result in highly disinhibited
behaviour. This type of behaviour is very liable to
affect both formal classroom learning and the ability
to learn from social situations.
Left temporal discharges may affect verbal abilit-
ies, as shown by a number of studies, including
those of Stores and co-workers (Stores & Hart,
1975). When the source of frequent left temporal
epileptiform discharges is removed, speech may im-
prove in some cases.
Frequent hemispheric discharges. A gross example
of frequent localised discharges is the situation in
which the individual has an abnormal hemisphere
which is a continuous source of a torrent of these
discharges. Many different pathological conditions
can result in this situation, including hemimegal-
encephaly and Rasmussen's encephalitis. Congen-
ital malformations such as porencephalic cysts can
also cause frequent hemispheric discharges. Hemi-
spherectomy, which involves either the removal or
disconnection of the cerebral cortex on the entire
affected side, can abolish the discharges and in-
crease learning. (See later section on surgery and
learning.)
Post-ictal state-dependent learning disability. At
®rst, the concept of post-ictal state-dependent
learning disability might appear to be both obvious
and unimportant. However, in some cases it is nei-
ther. If a person is having very frequent seizures,
they may not have time to recover from one seizure
before they have another. The result is that they are
in a constant post-ictal state. Treating the seizures,
so that they are not so frequent, allows the person to
emerge from the constant post-ictal state and to
function at a much higher level. Even people who are
experienced in managing epilepsy may incorrectly
assume that learning disability is permanent when it
may be state-dependent, treatable and reversible.
Another example of post-ictal effects on learning is
the child who has frequent nocturnal seizures. In a
series of 15 patients examined by the author's team,
112 Frank M.C. Besag
a large number of nocturnal seizures were recorded
by video telemetry. These seizures had generally
been unobserved and unsuspected by awake night
staff. In one case, 208 seizures were recorded in a
single night on the video telemetry. Frequent noc-
turnal seizures may affect daytime performance,
both through direct post-ictal effects and through
the effect of a broken night's sleep.
A particularly interesting example of post-ictal
state-dependent learning disability is the situation of
a child who has very frequent epileptiform dischar-
ges overnight. This situation is known as continuous
spike-wave during slow wave sleep (CSWS) or elec-
trical status epilepticus of slow wave sleep (ESES).
To satisfy the diagnostic criteria of ESES, at least
85% of slow-wave sleep must be occupied by spike-
wave discharges. The classical manifestation of
ESES is the Landau-Kleffner syndrome of acquired
epileptic aphasia (Landau & Kleffner, 1957). In this
condition the child develops an auditory agnosia and
loses the ability to understand speech. In some cases
the ability to interpret environmental sounds such
as birdsong may also be lost. Because these children
cannot understand their own speech they may be-
come mute. Although the progress of this condition
varies greatly from one child to another and may, in
some cases, resolve spontaneously there is a grave
concern that in some children permanent speech
de®cits occur. Treatments include antiepileptic me-
dication such as sodium valproate and lamotrigine,
steroid treatment and neurosurgery. The role of
neurosurgery in this condition is discussed in a later
section.
Gordon (2000) has recently reviewed the effect of
epilepsy on language function. He concluded that
there seems to be no doubt that language develop-
ment can be adversely affected by the presence of
epileptic activity as demonstrated by spike-wave
discharges in the EEG. He also concluded that the
same activity can cause disintegration of language
function, although he stated that further research
may be needed to establish the exact correlation. It
was pointed out that other aspects of learning may
also be impaired selectively by electrical status epi-
lepticus of slow wave sleep. These conclusions have
considerable implications with regard to early treat-
ment of children who present with continuous spike-
wave discharges in slow wave sleep or electrical
status epilepticus of slow wave sleep. (Also see sec-
tion on surgery for ESES.)
Aldenkamp et al. (1996) have suggested that epi-
leptiform discharges may have a post-ictal effect on
cognitive function without causing transitory cogni-
tive impairment. They compared four groups, aged
9±21 years: three with epilepsy and a control group.
The ®rst group were age-matched `non-neurological'
normal controls, the second group were patients
with established epilepsy who had no epileptiform
discharges or seizures during testing, the third
group had epileptiform discharges but no detectable
seizures over the period of testing and the fourth
group had both epileptiform discharges and one or
several seizures during the test sessions. It should
be emphasised, however, that no obvious seizures
occurred: the seizures were brief and subtle. They
were only detected after extensive analysis of the
video recordings. Patients and parents were unaware
of these seizures. There were some possible con-
founding factors in this study, such as differences in
the types of seizures and medication between the
groups. The results showed signi®cant differences in
the performance on intelligence subtests and tests of
complex information processing between the control
group and the fourth group, i.e., the group with both
epileptiform discharges and subtle seizures. The
authors discussed in some detail the possible rea-
sons for these differences and concluded that they
were probably the effects of both ictal and post-ictal
changes. It would have been of great interest if these
authors could have shown an improvement in this
particular group of subjects at other times when they
were in another state with regard to the presence of
subtle seizures or epileptiform discharges. Ideally
this same group of people would have been tested in
four states: with both discharges and subtle sei-
zures, with subtle seizures and no discharges, with
discharges but no subtle seizures and with neither
discharges nor subtle seizures. Although this would
have given a very informative set of test results, it is
highly unlikely that these different states could
all have been achieved in the same group of real
patients.
All these studies point to the fact that post-ictal
effects on learning in children with epilepsy have
probably been underestimated and have often been
ignored. Successful treatment of the epilepsy, pro-
vided the treatment itself does not lead to cognitive
problems, should result in considerable bene®ts to
learning. This opportunity should not be missed. The
adverse and bene®cial effects of antiepileptic treat-
ment are discussed in the next section.
Antiepileptic treatment and learning
Antiepileptic drug treatment. Parents and physi-
cians are naturally concerned about the possibility
that any treatment might affect learning adversely.
The sedative effects of the wrong type of antiepileptic
medication or excessive doses may be all too obvi-
ous. In children, a paradoxical effect may be seen
with drugs such as phenobarbital, the benzodiaze-
pines and vigabatrin. These drugs may cause a
condition mimicking attention de®cit disorder. The
correct management is not to prescribe stimulant
drugs such as methylphenidate but to use a different
antiepileptic drug that does not have this very un-
desirable adverse effect. Antiepileptic drugs may af-
fect schooling in more subtle ways. For example,
excessively high blood levels of carbamazepine may
cause diplopia which, in turn, may make it dif®cult
 Childhood epilepsy in relation to mental handicap and behavioural disorders
for the child to perform adequately in reading or
writing.
There have been many studies on the effect of
antiepileptic drugs on cognition. Most of these have
been on adults but some have been on children.
Trimble and co-workers have made a notable con-
tribution to this ®eld (Trimble, 1979, 1987a; Trimble
& Cull, 1988). Meador (Meador, Loring, Huh, Galla-
gher, & King, 1990; Nichols, Meador, & Loring, 1993;
Meador, 1998, 2000) and Aldenkamp (Aldenkamp
et al., 1993; Tonnby et al., 1994; Aldenkamp et al.,
1994; Vermeulen & Aldenkamp, 1995) have also
contributed signi®cantly. Vermeulen and Aldenk-
amp (1995) have reviewed the cognitive adverse ef-
fects of chronic antiepileptic drug treatment but
again much of this review is based on data collected
from adults. They have correctly pointed out that
many of the studies were on a relatively small
number of patients, with the implication that ®nding
`no difference' between groups may simply have been
a re¯ection of a lack of power of the study. Studies on
children include those by Calandre, Dominguez-
Granados, Gomez-Rubio, and Molina-Font (1990),
Forsythe, Butler, Berg, and McGuire (1991) and
Aldenkamp et al. (1993). Most of these studies were
on relatively small numbers of children. Vermeulen
and Aldenkamp concluded that, although over 90
investigations had been conducted over the pre-
ceding 25 years to determine what effect antiepilep-
tic drugs have on cognition, no satisfactory answer
to the question could be given, primarily because of
poor methodology, design and analysis. They were
not of the opinion that they could provide a clear
answer to the question of whether antiepileptic drugs
in therapeutic doses had any cognitive effects at all,
good or bad. If the studies reviewed were limited to
those that were using monotherapy in patients with
epilepsy and had control group data for comparison
with appropriate repeated measures analysis and
good information, only 4 studies remained (some
reporting on multiple drugs), 2 on phenobarbitone, 3
on valproate, 3 on carbamazepine and 1 on pheny-
toin (Calandre et al., 1990; Ronnberg, Samuelsson,
& Soderfeldt, 1992; Helmstaedter, Wagner, & Elger,
1993; Tonnby et al., 1994). Only 2 of these studies
were on children. However, all of these studies had
low numbers of subjects in the subgroups apart from
the Tonnby et al. (1994) study that had 56 school-
age children in the carbamazepine group. Even this
study had only small numbers in the phenytoin
group (10 children) and the valproate group (17
children). Vermeulen and Aldenkamp have also
concluded that not even the methodology for ap-
proaching this area has been decided. They do,
however, make a number of recommendations for
research into the cognitive effects of antiepileptic
drugs, the details of which remain open to debate.
Aldenkamp et al. (1998) carried out a multicentre,
controlled, parallel-group, non-randomised clinical
investigation of cognitive complaints of seizure-free
113
children with epilepsy before and after drug discon-
tinuation. The inclusion criteria were age between 7
and 18 years, a diagnosis of epilepsy, seizure free-
dom for at least 1 year and monotherapy antiepi-
leptic drug treatment. The children were compared
with matched healthy controls. One hundred and
two eligible children entered the study but 19 were
regarded as dropouts, leaving 83 children and their
controls. They concluded that there were clear dif-
ferences between the reports made by the children
themselves and those made by the parents in that
the children did not report more complaints during
treatment in comparison to the matched controls
and also did not report changes in cognitive com-
plaints after drug discontinuation, except for being
less tired. The parents, however, did report signi®-
cant improvements after drug discontinuation, pri-
marily related to alertness. It is dif®cult to draw ®rm
conclusions about a study that uses subjective
measures. On one hand, these may be more relevant
in measuring quality of life but on the other hand
they appear less scienti®cally rigorous than objective
measures. Perhaps the best solution would be to use
a combination of subjective, questionnaire-based
measures and objective cognitive tests.
A particularly interesting paper is that of Jamb-
aqueÂ, Chiron, Dumas, Mumford, and Dulac (2000)
who examined the mental and behavioural outcome
of infantile epilepsy treated with vigabatrin in chil-
dren who had tuberous sclerosis. Vigabatrin is
highly effective in treating infantile spasms in chil-
dren who have tuberous sclerosis. They found that in
those children with infantile spasms whose spasms
came under control, the mental score increased
signi®cantly and the behaviour improved, although
most of them continued to have partial seizures. In
contrast, patients with partial epilepsy and no
spasms had more subtle improvements in behaviour
but no change in mental score. The whole group
consisted of 13 children who underwent psycho-
metric and behaviour evaluation before vigabatrin
was commenced and after a mean of 3 years on
vigabatrin; 7 had infantile spasms and were all free
of these seizures before 2 years of age, and 5 con-
tinued to have rare partial seizures. The authors
concluded that the cessation of spasms with vig-
abatrin is associated with signi®cant improvement in
cognition and behaviour in children with tuberous
sclerosis. Infantile spasms are associated with a
gross EEG abnormality, hypsarrhythmia. It seems
highly likely that such a gross disturbance of elec-
trical function in the brain is responsible, at least in
part, for the cognitive decline seen when babies de-
velop infantile spasms. A number of workers, inclu-
ding the current author, surmised that the effective
treatment of infantile spasms would lead to a pro-
nounced improvement in intellectual outcome. It is
pleasing to note that the study of Jambaque et al.
seems to con®rm this. Their results also add weight
to the comments made earlier about state-dependent
114 Frank M.C. Besag
learning disability. It would appear that this is an
example in which the epilepsy may cause learning
disability directly but if the abnormal discharges and
infantile spasms are allowed to continue untreated
then permanent cognitive impairment may result. It
would be valuable to gain more research data to
con®rm this important hypothesis because it has
major implications both for treating and preventing
learning disability.
It is somewhat paradoxical that vigabatrin, a drug
that is so useful for treating infantile spasms, can
probably cause learning problems in older children
when it is used to treat partial seizures. There is
considerable anecdotal evidence that vigabatrin can
cause attention problems and overactivity in chil-
dren, especially those who already have a degree of
learning disability (Wallace, 1996a; Besag, 2001b). It
would appear that the same drug can be very useful
in treating and preventing learning disability in
children who have infantile spasms whereas it may
cause or exacerbate schooling problems in older
children treated for partial seizures. In any case,
vigabatrin is currently recommended primarily for
infantile spasms and is avoided in treating partial
seizures unless there is no other reasonable alter-
native because it may cause visual ®eld constriction
(Eke, Talbot, & Lawden, 1997; Luchetti, Amadi,
Gobbi, & Bertani 2000; Hardus, Engelsman, Van
Veelen, & Stilma, 2000). The debate about the role
for vigabatrin continues, however. Prasad, Penney,
and Buckley (2001) treated 73 children with vig-
abatrin over a 7-year period and concluded that
vigabatrin was effective in producing a signi®cant
reduction in seizure frequency. This led them to state
that, despite emerging concerns regarding visual
®eld constriction, vigabatrin retains an important
role in the medical management of childhood epi-
lepsy. This was a mixed group of patients aged 5±257
months when vigabatrin treatment was initiated.
Only 12 could undergo static threshold perimetry
and 2 of these had the well-described visual ®eld
constriction.
The earlier studies by Besag (1994b, 1995a) and a
more recent study by Eriksson, Knutsson, and Ner-
gardh (2001) have con®rmed that lamotrigine is
highly effective in treating epileptiform discharges. In
the study by Besag (1994a) 17 children and teenag-
ers who had frequent spike wave discharges were
monitored with a validated portable spike-wave
monitor (Besag, Mills, Wardale, Andrew, & Craggs,
1989b). He found that 8 of the 17 patients had a
reduction in spike-wave discharges of 80% or more.
In some cases the reduction was over 99%. Eriksson
et al. (2001) studied 12 patients aged 4±21 years
using 24-hour video-EEG recording. The recordings
were made both during placebo and drug phases.
Periods of repeated epileptiform discharges longer
than 30 seconds were reduced in length and number
during the lamotrigine phase. It should be noted that
most of these subjects had learning disability. They
concluded that their ®ndings gave some support for
the assumption that a reduction in the amount of
inter-ictal epileptiform activity was a possible reason
for the observed improvement in behaviour and
alertness. They acknowledged, however, that there
might be other reasons for increased alertness in this
group of patients.
Another of the new antiepileptic drugs, topira-
mate, has been used in treating a resistant form of
epilepsy in childhood, the so-called severe myoclonic
epilepsy in infancy or Dravet syndrome (Dravet,
Bueau, Guerrini, Giraud, & Roger, 1992). This syn-
drome is characterised by seizure onset in the ®rst
year of life, usually with febrile convulsions or gen-
eralised clonic seizures, followed by myoclonic and/
or partial and/or typical absence seizures between 2
and 3 years of age. Initially the EEG does not usually
show paroxysmal abnormalities but recordings
within the second year of life show inter-ictal gen-
eralised spike-wave complexes and/or generalised
polyspike-waves. There is delayed development from
the second year and unsteadiness is generally seen.
A recent publication by Nieto-Barrera, Candeau,
Nieto-Jiminez, Correa, and Ruiz del Portal (2000) on
18 patients aged 2±22 (mean 13.3 years) demon-
strated that over half (56%) had a reduction in seiz-
ure frequency by more than 50%. Three became
seizure free. They found that the most dramatic re-
sponse was with atypical absence seizures. This
implies that such children might improve in cogni-
tive performance, although they included no formal
testing to show such an effect in their report. More-
land, Griesemar, and Holden (1999) demonstrated a
more mixed response to this drug in 49 children with
refractory seizures. They stated that more than half
the children experienced adverse effects which could
interfere with learning at school but 20% demon-
strated increased alertness or improved behaviour.
There is a strong argument for considering the way
different childhood epilepsy syndromes affect learn-
ing. Shields (2000) has reviewed what he terms
`catastrophic epilepsy in childhood'. In his paper he
discusses not only speci®c epilepsy syndromes but
other syndromes or clinical situations that are
associated with epilepsy and learning disability. He
also discusses the important question of whether
therapy can alter outcome. Some of the syndromes,
such as severe myoclonic epilepsy of infancy and
Otahara syndrome (early infantile epileptic enceph-
alopathy with suppression-burst EEG) always
appear to be associated with learning disability.
However, early treatment in other forms of epilepsy,
notably infantile spasms (see earlier), may result in
an improved outcome for learning.
The overall conclusions with regard to the role of
antiepileptic drug treatment in relation to cognition
is that some children bene®t greatly, a middle group
do not appear to improve or decline and a third group
are made worse by the medication. A good example
would be the use of lamotrigine in the treatment of
 Childhood epilepsy in relation to mental handicap and behavioural disorders
severe myoclonic epilepsy in infancy. Guerrini et al.
(1998) have shown that lamotrigine can aggravate
seizures in severe myoclonic epilepsy infancy, almost
certainly implying a poor cognitive outcome, but
Wallace (1998) has reported that some children with
this syndrome may bene®t from the drug. It could be
argued that the children who bene®ted did not have
the true syndrome of severe myoclonic epilepsy of
infancy but it is much more likely that the difference
in results re¯ects individual variations between dif-
ferent children. It is the responsibility of the clinician
to assess each child with epilepsy and cognitive
problems as an individual and to monitor response
to treatment carefully. Children who have frequent
epileptiform discharges and/or frequent seizures
should be treated effectively and as soon as possible
because at least some have reversible cognitive
problems resulting from the epilepsy.
Does epilepsy surgery improve learning ability? In
previous sections reference has been made to the
possibility of various types of surgery improving
cognition. Examples have been given of children
undergoing hemispherectomy and left temporal lob-
ectomy, whose cognition has clearly improved after
surgery. However, the prediction of cognitive out-
come is not straightforward. Although there are
many published papers on the overall outcome of
epilepsy surgery, most of these concentrate on the
success in terms of reduction or elimination of sei-
zures rather than other measures such as cognition
or quality of life. The question of classi®cation of
outcome following epilepsy surgery has been dis-
cussed in a recent International League Against
Epilepsy Commission Report (Wieser et al., 2001).
Again, the emphasis is on remission of seizures
rather than other variables, although the authors
discuss the importance of quality of life outcome
measurement, suggesting that this should be com-
prehensive, re¯ecting behaviour, schooling, occupa-
tion, psychosocial, self-suf®ciency, marriage and
reproduction, and mental and cognitive domains.
Because temporal lobectomy is the most fre-
quently performed epilepsy surgical procedure, it
will be discussed in some detail.
In a recent review (Hennessy et al., 2001), the
outcome of surgical treatment of temporal lobe le-
sions was assessed in 80 patients, 41 of whom were
20 years of age or younger at surgery. In 75 of the 80
patients the age of onset of seizures was under 20
years of age, with the largest group, 36 patients,
having an age of seizure onset of 0±4 years. Good
outcome was particularly associated with the resec-
tion of dysembryoplastic neuroepithelial tumours.
However, the most outstanding results of this series
were those related to age at surgery and duration of
epilepsy. If patients had the temporal lobe surgery
before the age of 15 years, 84% achieved a good
outcome, compared with a rate of only 44% if the
surgery was carried out after the age of 30 years. If
115
the duration of epilepsy was less than 10 years then
the remission rate was 88% but if it was more than
20 years the remission rate fell to 57%. Ten patients
were classi®ed as learning disabled not only on the
basis of low IQ but also because they had severe
behavioural and attention dif®culties. In this group
only 37% had a remission of the seizures compared
with 74% of those who were cognitively normal.
These results seem to emphasise the importance of
early intervention. The suggestion is that if the sei-
zures are stopped early in life then the outcome in
terms of seizure control is likely to be good. However,
there are several confounding factors. For example,
early age of seizure onset may be associated with
more severe underlying brain problems that may
predispose to poor outcome.
Duncan (2001) has also emphasised that if the
rest of the brain is normal and a structural lesion is
removed then a good result is likely to be achieved,
even if the lesion is incompletely removed. Do these
results imply that surgery should not be offered to
children with learning disability? In the past, an IQ
of less than 60 or 70 was considered to be an ex-
clusion criterion by at least some clinicians. For ex-
ample, in the second edition of his highly regarded
textbook on childhood epilepsies, O'Donohoe (1985)
listed an IQ of less than 60 as being an exclusion
criterion for epilepsy surgery in children. Such an
exclusion criterion would be considered inappropri-
ate now, especially in view of the comments already
made about the possibility of cognitive improvement
following surgery. However, the analysis of Vascon-
cellos et al. (2001) of 100 patients aged 2±20 years
again con®rmed that those with lower age of onset of
epilepsy (£ 24 months of age) and lower IQ had a
poorer outcome in terms of seizure frequency after
surgery. They concluded that the poor outcome was
based on early age of seizure onset and appeared to
be independent of aetiology.
Bourgeois et al. (1999) analysed results from a
series of 200 children with epilepsy aged 1±15 years
who had surgery for a variety of brain lesions, most
commonly oligodendrogliomas, dysembryoplastic
neuroepithelial tumours and astrocytomas. Only 9
(5.2%) derived no bene®t from the surgery in terms of
seizure control. Improvement in cognitive function
was reported in 24.6%.
It is also interesting to note that psychosis is no
longer considered to be an absolute contraindica-
tion to surgery. Epilepsy-associated psychosis may
occur in teenagers ± see later, and adults. The
study by Reutens, Savard, Andermann, Dubeau,
and Olivier (1997) was in adults but the results are
probably applicable to teenagers. They concluded
that with appropriate psychiatric intervention, pa-
tients with chronic psychosis and refractory epi-
lepsy can undergo the necessary investigations for
neurosurgery and can also bene®t from the surgery.
These authors pointed out that it is often assumed
that disturbed behaviour will prevent adequate
116 Frank M.C. Besag
pre-operative evaluation but this is not necessarily
the case.
The largest study to determine whether presurgi-
cal IQ predicts seizure outcome after temporal lob-
ectomy is that by Chelune et al. in 1,034 adult
patients from 8 centres in the Bozeman consortium
(Chelune et al., 1998). They found that patients who
continued to have seizures after surgery had a
slightly lower mean IQ and that this difference was
statistically signi®cant. Seven of the 8 centres re-
ported lower pre-operative IQ scores for patients who
continued to have seizures after surgery. For IQ £ 75,
38% continued to have seizures. The ®gure for IQ
76±109 was 23.8% and for IQ ³ 110 it was 16.9%
seizure free. If a structural lesion was present then
those with IQ £ 75 had a 3.9 times increased risk for
seizures compared to those with a higher IQ.
Westerveld et al. (2000) examined the cognitive
outcome of temporal lobectomy in 82 patients, aged
6±17 years, from eight centres in the largest pub-
lished study of this type in children; 43 had a left and
39 a right temporal lobectomy. With regard to verbal
cognitive skills, 67 (82%) had no signi®cant change,
8 (10%: 5 left, 3 right) declined by more than twice
the standard error (8 points) and 7 (9%: 3 left, 4
right) improved after the surgery. For performance
IQ, 67 (82%) had no signi®cant change, 2 (2.4%: 1
left, 1 right) declined by more than twice the stand-
ard error (9 points) and 13 (16%: 10 left, 3 right)
improved after the surgery. Risk factors for signi®-
cant decline were being older at the time of the sur-
gery and the presence of a structural lesion other
than mesial temporal sclerosis. A slight improve-
ment in global intellectual function was signi®cantly
more likely to occur than a decline.
Miranda and Smith (2001) have recently published
the results of cognitive testing before and after tem-
poral lobectomy on 50 young people (age range 6.43±
18.25 years). They commented that only a small
subset of papers has seriously addressed cognitive
outcome in children after temporal lobectomy. In
their group, 25 patients underwent left and 25 right
temporal lobectomy. The grouped results showed a
small increase in performance but not verbal IQ.
Examination of individual results revealed that, of
the 50 patients, 36 (72%) had no change in verbal IQ.
Performance IQ results were available for 49 of the
patients, of whom 33 (67)% showed no signi®cant
change. Of the remaining 17 patients, 12 improved
and 4 had a lower IQ after the temporal lobectomy.
Children with dual pathology and those with a longer
follow-up interval were less likely to show an im-
proved performance IQ. In fact, none of the children
whose performance IQ improved had dual pathology.
Of the 14 patients (28%) whose verbal IQ changed
signi®cantly, half had an increase and half a de-
crease. It was interesting to note marked increases in
IQ for individual patients who initially had a full-
scale IQ < 70. A boy with full-scale IQ of 52 before a
left temporal lobectomy improved 28 points, with
gains of 24 points in verbal and 29 points in per-
formance IQ. A girl with a full-scale IQ of 64 before a
right temporal lobectomy had an increase of 15
points, with gains of 20 points in verbal and 10 in
performance IQ. Their overall results are very inter-
esting, in that they illustrate that the side of the
surgery does not seem to have a major effect on the
outcome, in contrast to the conclusions of some
previous studies. They also emphasise that low IQ
should not be considered as a contraindication
to temporal lobectomy, as well illustrated by the
two children who had the greatest gains in IQ after
surgery.
A major omission from these papers is any dis-
cussion of the role of the pre-operative EEG. It would
have been very interesting to know whether the
children who improved had very abnormal EEGs
with frequent epileptiform discharges before surgery
and whether these discharges were reduced or ab-
sent after the surgery. The present author has sug-
gested that the strongest indicator for lack of
acquisition of skills in young people with epilepsy
may be the presence of frequent epileptiform dis-
charges (Besag, 1995b), but neither Westerveld et al.
nor Miranda and Smith mention this issue. For those
who had a poor outcome there are other unanswered
questions which might relate both to seizure and
cognitive outcome. Were larger resections carried out
in patients who had structural lesions? Are secon-
dary pre-operative EEG foci important? If post-
operative EEG abnormalities are important, can
pre-operative factors predict these abnormalities?
Does the poorer IQ in patients with longer follow-up
only apply to patients with ongoing epileptiform
abnormalities, as has been suggested by some
authors (Besag, 1995b)?
Reviews of the outcome of hemispherectomy in
children (Goodman, 1986; Lindsay, Ounsted, &
Richards, 1987; Knight & Oxbury, 2000; Oxbury,
Zaiwalla, Adams, Middleton, & Oxbury, 1995) have
con®rmed that this operation is effective not only in
improving seizure control but also in improving other
aspects of function. Oxbury et al. (1995) reported an
increase in IQ on follow-up after hemispherectomy,
with an average of 15 points gain at 5 years.
Chugani and co-workers (Chugani, 1995; Chugani
et al., 1993) have demonstrated that surgery can be
of great bene®t in babies with infantile spasms if
focal metabolic abnormalities can be demonstrated
by positron emission tomography (PET). Some of
these infants underwent cortical resection or hemi-
spherectomy. He reported that cognitive outcome
was variable, with normal function in some patients.
It is interesting that a form of epilepsy that many
might previously have considered to be essentially
generalised has been shown to be focal in some cases
and that this can be the basis of successful surgical
treatment.
The novel surgical procedure known as multiple
subpial transection, pioneered by Morrell (Morrell,
 Childhood epilepsy in relation to mental handicap and behavioural disorders
Whisler, & Bleck, 1989) can be particularly effective
in some children who have the Landau-Kleffner
syndrome of acquired epileptic aphasia or who have
other de®cits arising from continuous spike-wave
during slow-wave sleep (CSWS) or electrical status
epilepticus of slow-wave sleep (ESES) (see earlier).
The particular advantage is that it can be used in
areas of the brain which could not be resected
without causing an unacceptable functional de®cit.
The principle of this treatment is to isolate the epi-
leptic focus by transecting around it, preventing the
spread of the epileptic discharges. Morrell et al.
(1989) followed up 20 of the original 32 cases, aged
5±22 years, for a period of 5 years or more. Complete
control of seizures was achieved in 11 of the 20 cases
(55%). In a subsequent study (Morrell et al., 1995),
14 children with the Landau-Kleffner syndrome of
acquired epileptic aphasia were treated; 7 of these
(50%) were said to have recovered age-appropriate
speech and were in ordinary classes in school. These
results indicated a clear improvement in speech
function. It should be noted that not all other work-
ers have had such a high success rate. In one of the
more recent studies, Mulligan, Spencer, and Spencer
(2001) reviewed 12 patients at Yale who underwent
multiple subpial transection. This was a mixed
group of children and adults (age range 8±49 years).
The outcome varied greatly from one patient to an-
other. Some of the patients had persistent de®cits or
even appeared to have improved in some functions
while deteriorating in others. Perhaps the most ex-
tensive review is that of Smith (1998) who reported
on 100 patients who underwent this procedure, of
whom two-thirds also had resections; 69 of these
patients were in Engel class 1 or 2, with regard to
seizure outcome, implying that they were either free
of disabling seizures or `almost seizure free'.
Irwin, Edwards, and Robinson (2000) recently
con®rmed the bene®ts of multiple subpial transec-
tion in ®ve children, aged 5±10 years, with the Lan-
dau-Kleffner syndrome, both in terms of speech
function and behaviour. In the same centre, Robin-
son, Baird, Robinson, and Simonoff (2001) examined
the outcome of 18 children with the Landau-Kleffner
syndrome and found that no child with electrical
status epilepticus of slow-wave sleep (ESES) lasting
longer than 36 months had normal language out-
come. They concluded that their data supported the
recommendation that ESES should be terminated
within 36 months, using multiple subpial transec-
tion if steroid treatment is ineffective or causes
unacceptable adverse effects.
The difference in outcome between the initial good
results obtained by Morrell and relatively poorer re-
sults achieved by others require explanation. Cer-
tainly early intervention to reduce the duration of the
ESES to no more than 36 months would seem ad-
visable. The surgical technique of multiple subpial
transection is not straightforward and the theory of
the procedure may be dif®cult to put into practice.
117
However, multiple subpial transection offers hope for
children who have de®cits arising from an epileptic
focus in an `eloquent area' of the brain, i.e., an area
that cannot be resected without producing an
unacceptable de®cit.
The Landau-Kleffner syndrome is an important
model demonstrating that permanent de®cits may
result from state-dependent impairment if the CSWS
or ESES continues for a long period. However, CSWS
or ESES does not necessarily cause language de®-
cits. In some cases visuo-spatial de®cits occur and
are improved with surgery.
What is the answer to the question posed at the
beginning of this section: `Does epilepsy surgery
improved learning ability?' In some cases the answer
is undoubtedly yes. In this regard, the Landau-
Kleffner syndrome, although rare, is an important
model because some children improve dramatically
with multiple subpial transection. A number of
children who undergo hemispherectomy also im-
prove with regard to cognition. What the clinician
needs to know is how to distinguish between those
children who will improve and those who will not.
Because the data from adult series cannot neces-
sarily be applied to children, some uncertainty re-
mains with regard to selection criteria for temporal
lobectomy in children with epilepsy. Complete re-
moval of abnormal tissue containing the epileptic
focus should be associated with a better outcome. If
the seizure onset is early then there is a good chance
that brain plasticity will have ensured that most
useful cognitive function resides in the normal tissue
left behind and it is less likely that the child will have
a poor cognitive outcome. This is in contrast to the
poorer prognosis, with regard to memory, for adults
who undergo removal of an apparently normal hip-
pocampus. If the child is carefully selected after
thorough investigation by a skilled multidisciplinary
team, the outcome of epilepsy neurosurgery is likely
to be good.
Management of learning problems
The ®rst aim should be to prevent learning disability,
if at all possible. This issue has been discussed in
earlier sections. As already stated, some types of
learning disability associated with epilepsy are
treatable and early treatment may not only improve
learning but may also prevent permanent learning
disability. There seems to be growing evidence that
treating children who have frequent epileptiform
discharges or chaotic EEG abnormalities may fall
into this category of leading both to an improvement
in cognition and to the prevention of longer-term
learning problems. This is almost certainly true for
some babies who have infantile spasms and some
children who have the Landau-Kleffner syndrome,
for example. It now seems extraordinary that some of
the older textbooks stated that antiepileptic treat-
ment for the Landau-Kleffner syndrome was only of
118 Frank M.C. Besag
bene®t in treating the seizures and did not affect
language development. Such conclusions were
probably based on late intervention, when perma-
nent damage had already occurred. Early energetic
treatment is to be preferred. However, this syndrome
is a good example of the complexity of the decision±
making process. Some children with Landau-Kleff-
ner syndrome seem to improve without therapy
whereas others do not. It is clear that one should not
wait for long periods before treating but what is an
unacceptably long period in this context? Is the limit
of 36 months suggested by Robinson et al. (2001) too
long? There are still unanswered questions in this
regard.
Treatment should be aimed at more than just re-
ducing seizures. There has been a recent trend to
assess children much more fully than simply by re-
cording seizure counts. A number of quality of life
measures have become available (Sabaz et al., 2000;
Cramer et al., 1999; Hoare, Mann, & Dunn, 2000). In
addition, it is evident that greater emphasis should
be placed on serial cognitive testing in children with
epilepsy to ensure that if there are underlying subtle
seizures or epileptiform activity that may be affecting
learning, the child is treated sooner rather than
later.
In addition to treatment with medication or sur-
gery, there are many useful strategies that can be
employed. The strategies should be tailored to the
needs of the individual child. It is beyond the scope
of this paper to describe speci®c strategies in detail
but these can be of tremendous value in managing
children who have a variety of de®cits, including
large verbal-performance differences, memory de-
fects and autistic features. Some of the strategies are
discussed in the section on epilepsy and behavioural
disorders.
The child with absence seizures should be man-
aged by people who realise that he or she may not be
able to register and remember speech or other events
that occur during the brief subtle seizures. Teachers
should be very sensitive to this and be prepared to
repeat what they have just said if they suspect that
the child has had an absence seizure. Children with
very frequent absence seizures will perform better on
static tasks such as jigsaw puzzles than they will in
dynamic tasks such as question-and-answer ses-
sions in class. Teachers should aim to build self-
con®dence by encouraging the child to carry out
tasks that are easily achievable, despite the absence
seizures.
Longer-term memory de®cits may be managed by
using the technique of `errorless learning' which
consists of telling the child the answer before asking
them the question. This reinforces memory much
better than `putting the child on the spot' by insisting
that they guess the answer when they do not know.
There are very many other strategies that can be
tremendously rewarding in teaching children who
have speci®c or global learning problems.
Effective treatment of both the seizures and the
epileptiform discharges by medication or surgery,
together with a number of enabling strategies dis-
cussed elsewhere in this paper, can greatly reduce
the impact of epilepsy on learning.
Part II Epilepsy and behavioural disorders
Epidemiological studies of behaviour
There has been a remarkable lack of systemic epi-
demiological studies on behaviour in children with
epilepsy since the Isle of Wight study by Rutter et al.
(1970). This showed that the rate of psychiatric dis-
order was approximately 7% in the general popula-
tion of 10±11-year-old children, rising to 10.3% for
physical disorders not affecting the nervous system,
13.3% for neurological disorders at or below the
brain stem, 28.6% for uncomplicated epilepsy,
37.5% for lesions above the brain stem without sei-
zures and 58.3% for lesions above the brain stem
associated with seizures. Most of the large epidemi-
ological studies carried out since then have concen-
trated more on education than behaviour. However,
there are a few exceptions.
McDermott et al. (1995), in their population-based
study in the US using data collected in the 1988
National Health Interview Survey (NHIS), included a
28-item instrument, the BPI, based on parent re-
ports of behavioural problems. As previously stated,
the inclusion criteria for seizures did not require a
rigorous diagnosis of epilepsy. The 121 children,
aged 5±17 years, with seizures identi®ed from ap-
proximately 45,000 households were compared with
controls and children with cardiac problems. The
adjusted odds ratio for any behavioural problem was
4.7 for the seizure group and 3.0 for the cardiac
group. The odds ratios for speci®c behaviours were:
antisocial 2.3, anxiety 3.7, headstrong 4.0, hyper-
active 7.4, peer con¯ict 3.8 and dependency 6.5
(ages 5±11 years only). Some of the limitations of this
study were discussed earlier. In particular, it de-
pended on parent questionnaires only. Huberty,
Austin, Harezlak, Dunn, and Ambrosius (2000) have
shown that mother's evaluations of problems may be
different from those of teachers and very different
from those of the child.
Lewis et al. (2000) identi®ed 392 young people,
aged 8±22 years, with intellectual disability who
were said to be representative of the general Aus-
tralian population of young people with intellectual
disability; 115 had epilepsy. Using the Develop-
mental Behaviour Checklist, they found no differ-
ence in the rates of emotional and behavioural
disturbance between those with epilepsy and con-
trols. Antiepileptic medication and seizure frequency
were not found to be associated with behavioural
disturbance either. Their paper implied that the
degree of behavioural disturbance was related solely
to the intellectual disability. This result is surprising
 Childhood epilepsy in relation to mental handicap and behavioural disorders
and emphasises the need for whole-population
studies of children with epilepsy to examine the
causes of behavioural disturbance in more detail.
In a recent study carried out by O'Neill and co-
workers (Besag et al., 1999) in the inner London
Borough of Lambeth, (also see section on epidemio-
logical studies on learning) 48% of the children with
epilepsy were found to have disturbed behaviour on
standardised Rutter scales. This compares with ap-
proximately 10% in the general population. Even if
allowance is made for the type of population in
an inner London borough, the rate of behavioural
disturbance is still high.
It is encouraging to see an increasing number of
publications on measures of quality of life or well-
being of children with epilepsy (Norrby, Carlsson,
Beckung, & Nordholm, 1999; Carpay et al., 1996;
Arunkumar, Wyllie, Kotagal, Ong, & Gilliam, 2000;
Eiser & Morse, 2001). However, there are also dif®-
culties with subjective measures.
It would be helpful to have more studies that de-
termined not only the rate of behavioural distur-
bance but also the types and causes of behavioural
disturbance.
Other studies on behavioural disturbance
in children with epilepsy
Hoare and co-workers have carried out a number of
studies on epilepsy and behavioural disturbance in
children (Hoare, 1984b, 1984a; Hoare & Kerley,
1991; Hoare & Mann, 1994). Hoare and Kerley
(1991) assessed 108 children with chronic epilepsy
attending a specialist clinic. The rates of psychiatric
disturbance on the Rutter Parent and Teacher scales
were 54% and 48% respectively. They emphasised
the importance of family factors in the management
of these children.
The publications by Stores and co-workers, referred
to earlier, considered the effects of epilepsy on learn-
ing but also dealt with some behavioural aspects.
Austin and co-workers have published a number
of papers on epilepsy and behavioural problems in
children (Dunn, Austin, & Huster, 1997; Austin,
Risinger, & Beckett, 1992; Dunn & Austin, 1999;
Austin et al., 2001). One of their earlier papers
(Austin et al., 1992), based on ®ndings from 127
children aged 8±12 years, indicated that there was a
signi®cant relationship between behavioural prob-
lems and ®ve variables: female gender, family stress,
seizure frequency and lack of both family mastery
and extended family support. In a recent study of
224 children with epilepsy and 135 healthy siblings
they found that children with previously unrecog-
nised seizures were already at risk of behavioural
problems at the time of the ®rst recognised seizure
(Austin et al., 2001). The interpretation of this im-
portant ®nding is either that the behavioural dis-
turbance is due to some underlying neurological
problem or that the children may have been having
119
unrecognised seizures before the ®rst obvious
seizure.
Herman has examined various psychosocial cor-
relates of childhood epilepsy (Hermann, 1990). In
101 children (44M, 57F, aged 6±11), the most fre-
quent and signi®cant predictor of behavioural prob-
lems was inadequate seizure control. The second
most important was divorced or separated parents
and the third was polytherapy for the epilepsy. His
group also examined social competence in 183 chil-
dren aged 6±16, using a standard questionnaire
completed by the mother (Hermann, Whitman,
Hughes, Melyn, & Dell, 1988). Social competence
was associated most strongly with good seizure
control, followed by a shorter duration of epilepsy
and higher family income. With regard to outcome
following neurosurgery, he commented on the poor
methodology of publications available at that time,
and added that measures of psychosocial outcome
were extremely sketchy (Hermann, 1990). However,
he concluded that there was considerable anecdotal
information suggesting a favourable psychosocial
outcome for focal resections in children with epi-
lepsy.
Although there is a lack of data from population-
based studies, there seems to be no doubt that a
high proportion of children with epilepsy attending
specialist services have behavioural disorders in two
particular areas, namely overactivity/attention de®-
cit and autistic spectrum disorder. These children
make very considerable demands on their families,
education authorities and providers of medical
services.
Causes of behavioural problems in children
with epilepsy
It is very important, when faced with a child who has
epilepsy and behavioural problems, to try to deter-
mine the cause or causes. This allows professionals
to adopt a rational approach to management. In the
past there has been a tendency to assume that in-
dividuals had `epileptic behaviour'. Such an ap-
proach is to be decried. Besag (Besag, Loney,
Waudby, Fowler, & Brooks, 1989a; Besag, 1995b)
strongly recommends that a systematic approach to
determining the cause or causes of behavioural dis-
turbance in a child with epilepsy be adopted. The
scheme in Tables 1 and 2 has been suggested. This
scheme has proved to be very successful in the
practical management of children with epilepsy be-
havioural problems. The current author surveyed a
group of young people with dif®cult epilepsy at a
residential epilepsy special school, using this
scheme. However, no population-based studies have
been performed. The various causes will be dis-
cussed in more detail in the following sections.
The epilepsy itself. The ®rst category includes
the peri-ictal disturbances of prodrome, aura,
120 Frank M.C. Besag
Table 1 Possible causes of behavioural disturbance in a child
with epilepsy
1. The epilepsy itself.
2. Treatment of the epilepsy.
3. Reactions to the epilepsy.
4. Associated brain damage/dysfunction.
5. Causes which are equally applicable to those without
epilepsy.
Table 2 The epilepsy itself
1. Peri-ictal changes
Prodrome
Aura
Automatism
Post-ictal changes
Confusion
Disinhibition
Paranoid or affective states
2. Inter-ictal psychoses
Schizophreniform
Affective
3. Focal discharges
Temporal
Frontal
4. Frequent generalised discharges/absence seizures
automatism and post-ictal changes. Prodrome is a
period typically lasting from a few minutes to several
days before a seizure or cluster of seizures during
which mood and consequently behaviour may be
disturbed. The prodrome is terminated when the
seizure occurs. The parents of the child may be very
familiar with the phenomenon of prodrome but may
not be aware of the fact that this situation is well
recognised. Their child may have been criticised by
teachers or others and may have been blamed for the
mood or behavioural disturbance. Explaining to
parents the phenomenon of prodrome and providing
them with the terminology can be greatly enabling.
The author's current practice is to write such ter-
minology on a piece of paper while explaining it to
the parents and then to hand the parents the piece
of paper to take away with them. Punishing a child
for the mood disturbance of prodrome is adding
insult to injury. His or her activities may already
have been restricted by the epilepsy. Undeserved
punishment is likely to impair the self-esteem and
quality of life of the child even further.
Aura is often described as being the warning of a
seizure. An aura is, strictly speaking, not a warning
of a seizure but is itself a simple partial seizure.
Because simple partial seizures occur in full con-
sciousness, the child may ®nd the manifestation of
the seizure very distressing. The resulting anxiety
may lower the seizure threshold with the result that
further auras may occur. A vicious circle ensues with
auras causing anxiety, lowering the seizure thresh-
old causing even more auras. This situation of re-
peated auras may be interrupted by giving the child
not anxiolytic medication but additional antiepileptic
medication, typically oral diazepam or clobazam. It
should be noted, however, that in some children and
even in some teenagers, benzodiazepines may pre-
cipitate disinhibited behaviour.
Automatisms are easily misinterpreted. Although
limb-¯ailing automatisms are probably an uncom-
mon manifestation of complex partial seizures, if
someone happens to be struck by the ¯ailing limb
then the child may acquire, through no fault of his or
her own, a reputation for being violent. If the lower
limbs ¯ail and someone is kicked then the child
may gain a reputation for being very violent. Simple
explanation can avoid such misinterpretations
from occurring.
With regard to other ictal phenomena causing be-
havioural disturbance, the role of limbic seizures
continues to be debated. There is evidence in adults
that seizures arising in the amygdala may be asso-
ciated with fear or anxiety as an ictal symptom
(Cendes et al., 1994). This, in turn, may cause
behavioural disturbance.
In the immediate post-ictal phase confusion,
tiredness, irritability and even paranoid states may
occur. All of these changes can result in aggressive
behaviour. A situation that is not well recognised is
the child who has a frontal lobe complex partial
seizure followed by disinhibition resulting from de-
layed recovery of frontal lobe function. The result can
be bizarre behaviour, for example, screaming or
acting in a very immature way. A professional wit-
nessing such behaviour may correctly state that this
is not a seizure. However, it would be very misleading
to suggest that it was not epilepsy-related behaviour
because it has resulted from a disinhibited post-ictal
state.
Paranoid states may vary from brief, immediate
post-ictal periods resulting from confusion to more
prolonged psychiatric states requiring treatment
with neuroleptic medication. For example, at the
mild end of the spectrum, a person may be confused
immediately after a seizure and may mistake an offer
of assistance as being a threat. This may result in an
aggressive reaction. Such a state would be very
short-lived. On the other hand, a full-blown post-
ictal psychosis may occur. The phenomenon of post-
ictal psychosis has been reviewed by Logsdail and
Toone (1988). A post-ictal paranoid state may follow
a seizure or cluster of seizures after a `lucid interval'.
This can create uncertainty about the origin of the
psychiatric disorder, causing possible diagnostic
confusion with a functional psychosis.
Affective states may also occur in the post-ictal
period. Post-ictal depression is usually relatively
brief, lasting only a few days. It would generally be
inappropriate to treat with antidepressant medica-
tion because this would not have time to become
effective and because the condition is self-limiting.
Intensive support from carers and relatives is the
appropriate management. Elevated mood states may
 Childhood epilepsy in relation to mental handicap and behavioural disorders
also occur in the post-ictal period. Again, these are
usually brief and self-limiting.
Inter-ictal psychoses bear no speci®c time rela-
tionship to the seizures. There is a considerable
literature on this topic, including the classical study
by Slater and Beard (1995). Trimble (1987b) has
reviewed this subject. He has emphasised the role of
alternative or reciprocal psychosis. This concept
implies that the psychosis is worse when the seizures
are less frequent and the psychosis is improved when
the seizures are more frequent. The EEG equivalent is
`forced normalisation' implying that the EEG is relat-
ively normal during the psychotic state but becomes
abnormal when the patient emerges from the psy-
chosis. Inter-ictal psychoses may be either schizo-
phreniform or affective. Schizophreniform inter-ictal
psychoses differ from functional schizophrenia in the
fact that there is preservation of warmth of affect and
there is no family history of psychosis. In functional
schizophrenia there is a high risk that ®rst-degree
relatives will also have the condition.
In the author's experience the `forced normali-
sation' relationship between psychosis and EEG
abnormality does not always apply. Some patients
may have worsening rather than improvement of the
EEG when the psychosis occurs.
The psychotic and affective states discussed in the
preceding sections are generally described in adults
but can certainly occur in teenagers. Inter-ictal
psychoses may be prolonged and often require
treatment with neuroleptic medication. They may be
remitting and relapsing. It has been suggested that
antipsychotic medication should be avoided in peo-
ple with epilepsy because of the danger of precipi-
tating seizures. However, if the psychosis is putting
the patient at risk or affecting the quality of life of the
patient to a signi®cant degree then it would, in the
opinion of the author, be inappropriate to withhold
treatment. In his experience it is unusual for a
seizure exacerbation to occur when antipsychotic
medication is prescribed. On the other hand, the
patient's mental state may be dramatically improved
by the prescription of such medication. The role of
psychotropic medication in the treatment of children
with epilepsy and behavioural problems is discussed
in more detail in a later section.
Focal discharges. There is a reported association
between left temporal discharges and aggressive
behaviour (van Elst, Woermann, Lemieux, Thomp-
son, & Trimble, 2000; Devinsky et al., 1994; Amen,
Stubble®eld, Carmicheal, & Thisted, 1996; Volkow &
Tancredi, 1987). Part of this may arise from the fact
that left temporal discharges can be associated with
language dysfunction and this, in turn, can lead to
considerable frustration.
Frequent frontal discharges can lead to disinhib-
ited mood states, as already discussed in the section
on epilepsy and learning. This situation is not well
described in the literature.
121
Frequent absence seizures. Frequent absence sei-
zures may affect behaviour in a number of different
ways. As stated in the section on epilepsy and
learning, a child who is having very frequent absence
seizures cannot easily take part in activities requi-
ring rapid conversational exchange. As a result, he
may become withdrawn and avoid social situations
because he realises that he may not be able to cope.
Frequent absence seizures may also fragment con-
centration. This can mimic attention de®cit disorder.
The disjointed speech that results from frequent
lapses of awareness may be mistaken for a psycho-
sis. A third way in which absence seizures may affect
behaviour is when a child goes in and out of non-
convulsive status epilepticus. Some of these children
appear to `make up for lost time' when they are in the
phases of having fewer seizures. They are incapable
of being badly behaved when the absence seizures
are very frequent and seem to compensate during
their more able periods by being particularly badly
behaved.
As stated earlier, a high proportion of children with
epilepsy and behavioural problems attending spe-
cialist services have either overactivity/attention
de®cit or autistic spectrum disorder. The current
author has reviewed the multiple causes of overac-
tivity/attention de®cit in children with epilepsy
(unpublished). Frequent absence seizures are a
treatable cause. Management of the other causes are
discussed in the appropriate sections of this paper.
Epilepsy is common in autism, often emerging by
the teenage years in 20±40%, but there is an in-
creasing realisation that some younger children who
present with markedly autistic features have un-
suspected epileptiform discharges either during the
day or at night (electrical status epilepticus of slow
wave sleep ESES or continuous spike-wave during
slow wave sleep CSWS) (Berney, 2000; Tuchman,
Rapin, & Shinnar, 1991; Taylor, Neville, & Cross,
1999). Treating these children allows them to emerge
from their apparently autistic state. However, follow-
up of teenagers who have had very frequent epilep-
tiform discharges earlier in life has shown that they
may subsequently have autistic features when the
epileptiform discharges are no longer present (Besag,
1999a). It would appear that these young people
have been unable to interact adequately with the
world around them during a critical developmental
phase because of the frequent epileptiform dischar-
ges at that time. If they have not had the opportunity
to develop two-way social interaction during this
developmental phase they may present with a very
Asperger-like picture during teenage years. This
suggests that early treatment of the epileptiform
discharges, so as to allow the child to gain fully from
the early developmental years, may have avoided
these social impairments.
In all these circumstances the emphasis should be
on treating the generalised discharges/absence sei-
zures and then assisting the individual to gain the
122 Frank M.C. Besag
necessary skills to function competently and with
con®dence in social situations.
Treatment of the epilepsy. The behavioural effects
of the older and well-established antiepileptic drugs
are generally recognised. In particular, phenobarbi-
tone may cause gross behavioural disturbance in
younger children (de Silva et al., 1996). This situ-
ation may mimic attention de®cit hyperactivity dis-
order. Benzodiazepines can cause a similar clinical
picture. The behavioural effects of the nine new an-
tiepileptic drugs have been reviewed recently by the
current author (Besag, 2001b). The most notorious
of the new antiepileptic drugs for causing beha-
vioural disturbance is vigabatrin. This can some-
times cause a behavioural disorder similar to that
resulting from phenobarbitone or benzodiazepines.
Behavioural disturbances have also been reported
with gabapentin (Lee et al., 1996; Khurana et al.,
1996). These authors stated that, in general, dis-
turbed behaviour was seen in children who had pre-
existing hyperactivity and/or learning disability.
These ®ndings were not con®rmed by the current
author (Besag, 1996).
Fowler, Besag, Strange, and Pool (1997) reported
on 16 adolescents with epilepsy and learning dis-
ability who were assessed with Rutter Behavioural
Scales before and during treatment with topiramate.
There was a signi®cant (p < .05) increase in negative
reported behaviour on both the parents and teachers
scales. Topiramate has also been associated with
general slowing of cognition and behaviour which
could be mistaken for an affective disorder. The
concept of reciprocal or alternative psychosis has
been discussed in previous sections. If an antiepi-
leptic drug results in sudden control of the seizures
this may, in some circumstances, precipitate psy-
chosis. There have been a number of reports of
psychosis with both vigabatrin and topiramate
(Trimble, Rusch, Betts, & Crawford, 2000; Besag,
2001b). As already discussed, this situation is rel-
atively unlikely to occur in young children but may
occur in teenagers.
A further important concept is that of the so-called
`release phenomenon'. If a person has been relatively
disabled by very frequent seizures and suddenly
becomes more able because the seizures are better
controlled, he or she may not know how to use their
new-found ability appropriately. The result may be
very unacceptable behaviour. The correct way of
managing the situation is not to stop the antiepi-
leptic drug but to provide the necessary professional
input to teach the individual how to use the new-
found skills to good advantage in a socially accept-
able way. Such interventions can be very valuable
indeed. The alternative of withdrawing the medica-
tion and allowing the young person to return to a
disabled state is not a good one.
Surgery may occasionally result in worsening of
behaviour rather than improvement. In some adult
patients, there have been reports of individuals who
did not have psychosis before temporal lobectomy
but developed a psychosis after the surgery (Mace &
Trimble, 1991). It is not clear whether a similar
situation might apply to some children.
Reactions to the epilepsy. Limitations placed on the
child or teenager because of the epilepsy may be very
damaging to self-esteem. The general principle
should be to restrict the child as little as possible but
to ensure adequate supervision to provide a rea-
sonable degree of safety. For example, swimming
should not be discouraged but must be adequately
supervised. This implies supervision tailored to the
individual circumstances (Besag, 2001a).
Teasing may be very damaging to the child's self-
esteem, resulting in both mood and behavioural
disturbance. Tonic-clonic seizures may be frighten-
ing for the onlooker and may lead to teasing. Com-
plex partial seizures, although less dramatic, may be
even more liable to cause teasing because the auto-
matisms that often occur in these seizures may be
viewed by other children as being very bizarre
behaviour. Ironically, the involuntary behaviour of
the automatism may result in teasing which has, as
its consequence, voluntary behavioural disturbance,
because the child is so upset by the teasing. The
approach to this situation should be education both
of the child who has the seizures and of the other
children in the class or school. Educating teachers
and parents is also mandatory in such circum-
stances. As is the case for teasing in general, the
child should be provided with strategies that help
them to feel in control. Some children or teenagers
develop remarkably effective strategies for them-
selves.
Associated brain damage/dysfunction. As dis-
cussed in the section on learning, brain damage or
dysfunction may be independent of the epilepsy or
may be caused by the epilepsy. In either case, the
child or teenager can be provided with speci®c en-
abling strategies that can be highly effective. Frontal
lobe dysfunction may result in grossly disinhibited
behaviour. This usually arises because of the un-
derlying brain problem, for example injury to the
frontal lobes, rather that the epilepsy itself, although
frequent focal discharges can result in frontal lobe
dysfunction (see earlier). The disinhibition of frontal
lobe dysfunction may present with features resem-
bling attention de®cit disorder.
Dominant temporal lobe damage may result in
poor language function with accompanying frustra-
tion and behavioural disturbance. Some very
enabling strategies can be used to help such chil-
dren. For example, the child with good performance
skills but relatively poor verbal skills can be taught to
say: `Please bear with me; I know what I want to say
but I am not very good with words' or `Please show me
what you want me to do as well as telling me'.
 Childhood epilepsy in relation to mental handicap and behavioural disorders
Non-dominant hemisphere damage/dysfunction
leaves the verbal abilities intact but may result in
signi®cant visuo-spatial problems. Because there is
a tendency for people to judge an individual's ability
by the way he or she speaks, such patients may be
under enormous pressure to perform to a level that is
beyond their capabilities. If they fail, they are ac-
cused of not trying hard enough. Careful psycho-
metric assessment coupled with practical advice can
be very bene®cial in these circumstances. Contrary
to the traditional approach of telling the child not to
talk in class, these children should be encouraged to
`talk themselves through' tasks, using frequent ver-
bal cues to assist themselves in organisational tasks,
particularly those calling on their limited visuo-
spatial skills. Written, step-by-step instructions can
also be helpful in these circumstances.
Memory impairment can lead to gross frustration.
Again, many useful strategies that teachers can use
with the child and that the child can be taught, can
help to overcome this frustration. For example, the
teachers may use the technique of `errorless learn-
ing' (see earlier) with subsequent reinforcement after
appropriate periods of time and the child may be
encouraged to use diaries or other memory aids.
Causes that are equally applicable to children
without epilepsy. A diagnosis of epilepsy does not
make the child immune to all the causes of beha-
vioural disturbance that apply equally well to chil-
dren who do not have this condition. The fact that
the child has epilepsy does not necessarily imply
that this condition is the cause of the behavioural
disturbance.
Management of behavioural problems
As each cause of behavioural disturbance has been
discussed in the preceding sections, possible man-
agement strategies have been indicated. These are
not intended to be comprehensive because each
child and family is unique. The strategies should be
tailored to the individual child and family. A multi-
disciplinary approach is often required (Besag et al.,
1989a). Behavioural programmes are frequently ap-
propriate, implying that the psychologist is a key
member of the team. However, other disciplines also
play a valuable role. For example, the speech and
language therapist can greatly reduce frustrations
from communication dif®culties. The occupational
therapist can assist with social skills training. The
play specialist can help the child to learn that social
interaction with other people can be pleasurable. It is
often important to work with the whole family so that
a consistent approach can be maintained, and so
that other family members can learn the necessary
strategies required for the individual child.
There are few publications that present data on
behavioural outcome. The shortcomings of the data
on antiepileptic drugs have already been discussed.
123
It has also been mentioned that reports of outcome
after epilepsy surgery tend to concentrate on seizure
control. There have been a number of studies on
temporal lobe resections, including some classical
publications (Falconer & Taylor, 1968; Lindsay,
Ounsted, & Richards, 1984). The reviews on hemi-
spherectomy (Goodman, 1986; Lindsay et al., 1987)
indicate a good behavioural outcome in a large pro-
portion of cases. The paper by Bourgeois et al.
(1999), on a series of 200 children with epilepsy aged
1±15 years who had surgery for a variety of brain
lesions, has already been mentioned with regard to
improvements in learning. These authors reported
that behaviour improved in 31% of the children, es-
pecially in those with hyperkinetic disorders. A re-
cent paper by Lendt, Helmstaedter, Kuczaty,
Schramm, and Elger (2000) examined the early be-
havioural outcome after a mixed group of surgical
procedures on 28 children (mean age 11.5 years)
who were compared with a control group of 28 chil-
dren who also had epilepsy but did not undergo
surgery. Both groups were assessed with the child
behaviour checklist (CBCL). The surgery comprised
13 temporal and 11 extratemporal resections, two
hemispherectomies and two callosotomies. Before
the surgery 39% had signi®cant behavioural prob-
lems and a further 11% were in the borderline range.
Three months after the surgery there were signi®cant
improvements in internalising, externalising and
attention problems. The control group did not im-
prove. Good seizure control was the one signi®cant
predictor of behavioural improvement. The authors
concluded that this was because the epileptic focus
was removed. In studies such as this, it would be of
great interest to have detailed and prolonged EEG
recordings before and after the surgery to determine
whether subtle seizure activity was contributing to
the pre-surgery behavioural disturbance. There
seems to be a consensus that if epilepsy surgery is
needed then the earlier in life it is performed, the
better. Not only will this allow the child the possi-
bility of going through the important developmental
and educational years without all the drawbacks of
having seizures but it will also allow the opportunity
for maximum brain plasticity.
The role of psychotropic medication. The role of
psychotropic medication in treating behavioural and
psychiatric disorders has recently been examined by
the Psychobiology Commission of the International
League Against Epilepsy (Trimble & Cornaggia,
2001). There is an understandable reluctance to use
psychotropic medication in children with epilepsy
and behavioural problems. Most of these children
will already be taking antiepileptic drugs and there is
often a resistance to the possibility of adding further
medication during the developmental years. How-
ever, there are circumstances in which psychotropic
medication can be valuable. As indicated earlier, the
teenager with an epilepsy-associated psychosis may
124 Frank M.C. Besag
bene®t greatly from neuroleptic medication. The
newer antipsychotic drugs such as risperidone and
olanzapine are generally highly effective. Although
standard formularies, such as the British National
Formulary, recommend `caution in patients with
history of epilepsy', serious seizure exacerbations
are probably rare. There appears to be clear evidence
of seizure precipitation by clozapine in adults
(Devinsky, Honigfeld, & Patin, 1991; Devinsky &
Pacia, 1994; Pacia & Devinsky, 1994). This drug
should, in any case, only be used if absolutely
necessary because of other adverse effects, notably
agranulocytosis. However, there are reports of con-
tinued use of clozapine even when seizures have
been precipitated. The drug has been continued in
smaller doses or with antiepileptic medication. There
have been isolated case reports of seizures with
olanzapine (Lee, Crismon, & Dorson, 1999), inclu-
ding death in status epilepticus of a female adult
patient (Wyderski, Starrett, & Abou-Saif, 1999), but
the risk appears to be much less than that associ-
ated with clozapine (Beasley, Jr., Tollefson, & Tran,
1997; Schuld et al., 2000). Should neuroleptic medi-
cation be used when there is no clear diagnosis of
psychosis? Risperidone is being used to treat beha-
vioural disorders in both children and adults with
autism (Zuddas, Di Martino, Muglia, & Cianchetti,
2000; McDougle et al., 1998). There does not seem to
be clear evidence for seizure exacerbations with ris-
peridone, although there has been a report of a
seizure with an overdose of this drug (Acri & Hen-
retig, 1998). There is an argument, from the evidence
available at this time, for using risperidone for the
treatment of some children with epilepsy, beha-
vioural dif®culties and autistic spectrum disorder.
However, such treatment should only be undertaken
after careful consideration of the following factors.
First, the clinician should decide whether some other
form of management would be more appropriate. For
example, correct communication strategies, a
structured day and suitable teaching techniques
may all contribute to the avoidance of behavioural
problems in autistic children. Have subtle seizures
been excluded as a treatable cause of the autistic
features? Second, risperidone is not licensed for use
in children. Parents need to be made aware of this
before it is prescribed. Third, the need for the medi-
cation should be reviewed regularly, especially since
there are no data on possible long-term adverse
effects. Notwithstanding the reservations, risperi-
done, often in quite small doses, can be a useful
adjunct for the management of young people with
epilepsy, autistic spectrum disorder and behavioural
problems. A report of the use of quetiapine to treat 6
male children and teenagers with autistic spectrum
disorder concluded that it was not very effective and
was associated with a high incidence of adverse ef-
fects, including sedation, a possible seizure and
weight gain (Martin, Koenig, Scahill, & Bregman,
1999). There is a need for more data on the use of the
atypical antipsychotic drugs in the treatment of
behavioural disorders in suitably selected young
people with epilepsy with or without autistic spec-
trum disorder. There is also a need for further
information on the way that neuroleptic and
antiepileptic drugs interact. There is some data
indicating, as might be expected, that enzyme-
inducing drugs such as carbamazepine can reduce
the serum concentration of neuroleptic medication.
For example, carbamazepine has been shown to
reduce the concentration of both risperidone and the
active metabolite markedly (Spina et al., 2000).
Speci®c conditions such as depression or obses-
sive-compulsive disorder in teenagers may require a
selective serotonin reuptake inhibitor. Although
these drugs appear to be much less likely to preci-
pitate seizures than other antidepressant medication
(Rosenstein, Nelson, & Jacobs, 1993), the British
National Formulary states: `should be used with
caution in patients with epilepsy (avoid if poorly
controlled, discontinue if convulsions develop)'.
There is limited evidence from the literature that
selective serotonin reuptake inhibitors cause seizure
exacerbations. There are some isolated reports of
seizures in adults treated with ¯uvoxamine (Kim,
Craig, & Hawley, 2000; Trabert, Hohagen, Winkel-
mann, & Berger, 1995; Deahl & Trimble, 1991) and
one case of status epilepticus (Loo, Piau, Galinowski,
& Olie, 1987). There is a suggestion that ¯uoxetine
might even have antiepileptic properties (Favale,
Rubino, Mainardi, Lunardi, & Albano, 1995),
although this has been challenged (Gigli et al.,
1994). Fluoxetine in overdose has been associated
with seizures (Neely, 1998; Braitberg & Curry, 1995;
Riddle et al., 1989). With regard to drug interactions,
there is a report that sertraline can cause a marked
rise in lamotrigine serum levels and this can preci-
pitate toxicity (Kaufman & Gerner, 1998). Fluoxetine
is said to decrease valproic acid levels (Droulers,
Bodak, Oudjhani, Lefevre, & Bodak, 1997). Paroxe-
tine apparently does not cause changes in plasma
concentrations of carbamazepine, valproate or
phenytoin (Andersen et al., 1991). Fluoxetine and
¯uvoxamine do not appear to change plasma con-
centrations of carbamazepine. From the information
that is available at present, it would seem that se-
lective serotonin reuptake inhibitors provide a rea-
sonable treatment option for teenagers with seizures
who have some types of psychiatric disorders such
as depression and obsessive compulsive disorder.
However, particular caution should be observed
when prescribing sertraline with lamotrigine and
perhaps ¯uoxetine with valproate.
Psychotropic medication can also be of value in
treating children with epilepsy and overactivity/at-
tention de®cit. However, as stated in the section on
frequent absence seizures, there are many possible
causes for this disorder in children with epilepsy. If
frequent epileptiform discharges are responsible for
the poor attention then the treatment should be
 Childhood epilepsy in relation to mental handicap and behavioural disorders
effective antiepileptic medication. If, on the other
hand, the child is being treated with an antiepileptic
drug that can cause these symptoms, for example
phenobarbitone or one of the benzodiazepines, then
the drug responsible should be replaced by medica-
tion that is better tolerated. If causes requiring dif-
ferent management are excluded then drugs such as
methylphenidate or dexamphetamine can be highly
effective in some cases (Semrud-Clikeman & Wical,
1999; Gross-Tsur, Manor, van der Meare, Joseph, &
Shalev, 1997). Stimulant medication is said not to
exacerbate well-controlled epilepsy (Gross-Tsur
et al., 1997). However, children who do not have a
diagnosis of epilepsy but have an abnormal EEG are
at risk of having seizures with stimulant medication
(Hemmer, Pasternak, Zecker, & Trommer, 2001).
Hemmer et al. found that 10% of 30 children with
epileptiform EEGs and 17% of 12 children with Ro-
landic spikes had a seizure with stimulant medica-
tion. The seizures were not necessarily the result of
prescribing the stimulant medication. Of the 175
children who had a normal EEG only one (0.6%) had
a seizure. There is a possibility that some children
with epilepsy that is not controlled will have more
seizures when methylphenidate is prescribed (Gross-
Tsur et al., 1997). There seems to be remarkably
little information on interactions between antiepi-
leptic drugs and stimulant medication. There is a
single paper describing rapid and severe onset of
dyskinesia and bruxism when methylphenidate was
added to valproic acid (Gara & Roberts, 2000).
Although psychotropic medication can be of great
value in treating some children with epilepsy and
behavioural disorder, care should be exercised in
selecting cases that are likely to respond and exclu-
ding those for whom other management strategies
would be more appropriate.
Conclusions
The emphasis throughout this review has been on
assessing the individual child and determining
management that is appropriate, according to the
outcome of that assessment. For the child who has
learning problems, reviewing the antiepileptic treat-
ment can be of great value. In some cases this implies
less medication because it is the medication that is
causing the problem but in other cases more medi-
cation or different medication may be required be-
cause the seizures are impairing learning. Speci®c
learning disability, frontal lobe dysfunction and
memory problems can all be managed successfully
with appropriate interventions. The mainstay of
management is the provision of the right environ-
ment, especially in terms of educational and beha-
vioural input. A multidisciplinary approach is often
required. Psychotropic medication can be helpful in
carefully selected cases. Above all, children with
epilepsy should be encouraged to live as full a life as
125
possible. With skilled management much can be
achieved. The outcome can be remarkably bene®cial
for the child and very rewarding for the professionals.
Correspondence to
Frank M.C. Besag, Consultant Neuropsychiatrist and
Research Director, Specialist Medical Department,
Bedfordshire and Luton Community NHS Trust,
Milton Road, Clapham, Bedfordshire, UK; Fax:
+44 (0)1234 310584; Email: FBesag@aol.com
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