Influence of sleep disturbance on quality of
life of patients with epilepsy
Charitomeni Piperidoua, Anna Karlovasitoub, Nikolaos Triantafyllouc,
Aikaterini Terzoudia, Theodoros Constantinidisd,
Konstantinos Vadikoliasa,*, Ioannis Heliopoulosa,
Dimitrios Vassilopoulosc, Stavros Balogiannisb
aDepartment of Neurology, Democritus University of Thrace, University - General Hospital,
b1st Department of Neurology, Aristotle University of Thessaloniki, AHEPA Hospital, Greece
cDepartment of Neurology, Athens National University, Aeginition Hospital, Greece
dDepartment of Epidemiology, Democritus University of Thrace, Greece
Received 14 September 2007; received in revised form 17 January 2008; accepted 29 February 2008
Poor sleep is a common complaint that can have a
huge impact on patients’ quality of life (QoL) and
Seizure (2008) 17, 588—594
Quality of life
impact onqualityoflife(QoL)havebeen documentedin afew reports, andthe results
are conflicting. We identified 124 consecutive epilepsy out-patients who visited the
epilepsy out-patient clinics at the University Hospital of Alexandroupolis, the AHEPA
Hospital in Thessaloniki and the Aeginitio Hospital in Athens. We measured excessive
daytime sleepiness (EDS) with the Epworth Sleepiness Scale (ESS), obstructive sleep
apnea (OSA) with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-
SDQ), and insomnia with the Athens Insomnia Scale (AIS). We evaluated quality of life
by the Quality of Life in Epilepsy Inventory (QOLIE-31). EDS was found in 16.9% (21/
124) of epileptic patients, OSA in 28.2% (35/124), and insomnia in 24.6% (30/122). In
multivariate analysis, we found that insomnia was an independent negative factor for
Total score (p < 0.001), Overall QoL (p = 0.002), Emotional well-being (p < 0.001),
Energy/fatigue (p < 0.001), Cognitive functioning (p = 0.04) and Social functioning
(p = 0.03), and OSA only for Cognitive functioning (p = 0.01). According to our
findings, EDS, OSA, and insomnia are frequent in epileptic patients. Epileptic patients
with sleep disturbance, mainly insomnia, have significant QoL impairment.
# 2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
The frequency of sleep disturbances in patients with epilepsy and their
* Corresponding author. Tel.: +30 2551030491.
E-mail addresses: firstname.lastname@example.org,
email@example.com (K. Vadikolias).
1059-1311/$ — see front matter # 2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
ability to function.1Several studies have confirmed
that excessive daytime sleepiness (EDS) and sleep
disturbances are common in epilepsy,2—4with the
exception of a recent study that revealed similar
frequency of sleep disorders in a unselected popula-
tion of epilepsy patients, compared to controls.5
Studies have shown that epileptic patients have
disrupted sleep with increased latency to sleep
onset, increased number and duration of awaken-
Furthermore, epilepsy coexists with obstructive
sleep apnea (OSA), as has been documented in
several case series.7—9The sleep disorders in
patients with epilepsy are commonly attributed to
the effects of antiepileptic drugs (AEDs) or to sei-
In recent studies, the importance of sleep dis-
turbance as a predictor of quality of life in patients
with epilepsy has been reported.10,11
The aim of this work was to determine in adult
nia, and OSA and their potential impact on QoL.
Over a period of 10 months, consecutive epilepsy
out-patients were selected from the out-patient
clinics of the University Hospital of Alexandroupolis,
the 1st Department of Neurology of AHEPA Hospital
in Thessaloniki and the Department of Neurology of
the Eginitio Hospital in Athens. All centers receive
is almost representative of the population of
Greece. During their routine visits, an experienced
neurologist interviewed the patients and assessed
the demographic and clinical characteristics, which
included seizure frequency, seizure type, and dura-
tion of disease.
Seizure frequency was determined from a seizure
diary completedbythe patient,whichwas reviewed
at routine clinical visit. Seizure frequency per
month was determined as the mean seizure fre-
quency during at least the last 12 months prior to
enrollment. Patients were divided into three sei-
zures frequency groups: fewer then one seizure per
month, one to five seizures per month, and more
than five seizures per month. Seizure type was
classified according to the International Classifica-
tion of Epilepsies and Epileptic Syndromes12into
two groups: generalized seizures (GS), and partial
seizures (PS) with or without secondary generaliza-
tion. Duration of disease was defined by the present
age and the age at diagnosis.
All patients were ?18 years old, had been diag-
nosed with epilepsy (at least two unprovoked sei-
zures) for at least 1 year, their epilepsy had been
and had been taking AED at the time of recruitment.
Exclusion criteria were any serious cognitive dys-
function (like dementia or learning disability), psy-
chiatric disorders and neurological disorders that
would further impair QoL (stroke, brain tumor).
From 317 examined patients in three centers (76,
104, 137, respectively), 124 fulfilled the inclusion
complete the questionnaires, twenty-four had
learning disabilities, nineteen presented a type of
dementia, twenty-six were <18 years old, sixteen
had stroke, twelve had cerebral tumors and the
remainder had unstable epilepsy.
We measured the patient’s QoL with the Quality of
completed questionnaire designed for epileptic
patients that has recently been translated and vali-
dated in Greek language.13The Athens Insomnia
Scale (AIS), a self-assessment psychometric tool
that has shown high consistency, reliability and
external validity for the evaluation of the intensity
of sleep difficulty, was used to establish the diag-
nosis of insomnia.14Patients with a score of 6 or
higher were diagnosed as insomniacs. The presence
of EDS was estimated by the Greek version of the
Epworth Sleepiness Scale (ESS),15the most common
measure of EDS used in the evaluation of patients
with epilepsy. The ESS is a self-administered, eight-
item questionnaire designed to ascertain sleep pro-
pensity in a variety of everyday situations.16A score
of 10 or higher is considered abnormal. We used the
Sleep Apnea scale of the Sleep Disorders Question-
naire (SA-SDQ), translated into Greek. It is a 12-item
measure of sleep-related breathing disorders, for
the diagnosis of OSA, which has been validated in a
large number of patients with OSA.17In the general
population, the cut-off score of SA-SDQ is 32 for
women and 36 for men. We used cut-off points of 29
epileptic patients by Weatherwax, which yielded a
sensitivity of 75% and a specificity of 65% for men
and 80% and 67%, for women.8
We established a database so that the accuracy of
each parameter could be easily controlled. Conse-
quently, we tested if normal distribution goodness
accords with all quantitative variables by the
Influence of sleep disturbance on quality of life of patients with epilepsy589
Kolmogorov—Smirnov test. All variables of the study
were found to fit normal distribution. Means and
standard deviation scores (m ? S.D.) were calcu-
lated for each variable. We also performed multiple
regression analysis between dependent variable
(EDS, OSA, insomnia; Fig. 1) and independent ones
seizures) and also between demographic, clinical
characteristics, sleep disturbances and subscales of
QOLIE-31. We used Student’s t-test or ANOVA for
independent samples. We also evaluated correla-
tion coefficients between quantitative variables.
The Statistical Package for Social Sciences (SPSS
for Windows) was used for all statistical analyses.
Values of p < 0.05 were considered statistically sig-
Of 124 patients included, 55 (43.7%) were male. The
mean age was 35.4 ? 12.9 (18—70), and mean dura-
tion of epilepsy was 13 ? 11.3 (1—51). Epileptic
seizures were generalized in 35/122 (28.7%) of
patients and localisation-related (including secon-
darily generalized) in 87/122 (71.3%). Two patients
590C. Piperidou et al.
EDS: Excessive Daytime Sleepiness; & with OSA, EDS, Insomnia; ~ without OSA, EDS, Insomnia; ~, & statistical
had unclassified epileptic seizures. Ninety-two
(74.2%) had <1 seizures per month, 16.1% 1—5 sei-
zures per month, and 9.7% >5 seizures per month.
Fifty patients (41.7%) had seizures during sleep, but
none reported seizures during sleep only (Table 1).
Prevalence of sleep disorders
The frequency of EDS was 16.9% (21/124) in epilep-
tic patients (12.8% in women and 20.6% in male).
There was no correlation between EDS and demo-
graphic and clinical characteristics.
Based on SA-SDQ scale, 35/124 (28.2%) of
patients had OSA (24.3% in women and 33.3% in
male). Frequency of OSA was significantly higher
in men and older patients (p < 0.01). There was
no significant correlation between EDS and OSA.
The frequency of insomnia was 24.6% (30/122),
19.4% in women and 30.9% in men. There was sig-
insomnia and seizure frequency (p = 0.02) (Table 2).
Sleep disorders and quality of life
Epileptic patients with EDS had significantly lower
score in Total score and all domains of QOLIE-31
(p < 0.05), except the Social functioning and Med-
ication effects (Table 3).
Patients with OSA had significantly lower score
only in Cognitive functioning (p < 0.01) (Table 3).
Patients with insomnia had significantly lower
score in Total score and all domains (p < 0.01)
In multivariate analysis, we found that insomnia
was an independent negative factor for Total
score (p < 0.001), Overall QoL (p = 0.002), Emo-
tional well-being(p < 0.001), Energy/fatigue
Influence of sleep disturbance on quality of life of patients with epilepsy591
Demographic and clinical characteristics
VariableN (%) or mean ? S.D.
35.4 ? 12.9
13 ? 11.3
Duration of epilepsy (years)
Seizure frequency in past year
<1 pre month
1—5 per month
>1 per month
Seizures during sleepc
aTwo patients had unclassified epileptic seizures.
bIncluding secondarily generalized.
cNumber of patients varies because of missing data.
Mean (S.D.) QOLIE-31 subscales score in relation to EDS, OSA, insomnia
ESSa<10ESS ? 10
Mean S.D.Mean S.D.
pWithout OSA With OSApAISb<6 AIS ? 6
MeanS.D. Mean S.D.Mean S.D.
Energy/fatigue 74.37 22.01 54.17 30.59 0.009 67.97 21.55 67.86 26.02 0.981 76.01 16.74 47.11 25.01 0.000
Medical effects 78.68 28.56 68.37 35.07 0.279 66.55 34.02 64.51 38.83 0.776 75.46 31.88 41.37 32.23 0.000
79.00 15.21 63.60 20.51 0.004 72.43 16.57 66.35 23.48 0.109 77.25 14.02 53.41 21.46 0.000
69.71 24.78 43.87 34.36 0.003 62.81 28.64 55.14 34.51 0.210 67.13 28.87 43.78 28.05 0.000
72.36 15.03 59.58 17.58 0.011 69.16 15.10 66.57 21.50 0.453 73.50 13.22 53.35 19.22 0.000
70.77 18.22 51.92 29.11 0.005 68.25 18.00 64.66 24.71 0.374 73.81 14.45 50.09 24.31 0.000
87.56 19.03 72.43 23.30 0.019 81.18 19.84 68.56 28.05 0.006 83.94 18.70 62.44 27.21 0.000
84.94 24.29 76.23 28.80 0.277 79.77 23.67 77.63 30.23 0.679 85.54 20.80 62.28 31.51 0.000
EDS: excessive daytime sleepiness. OSA: obstructive sleep apnea. Bold values mean statistical significance.
aESS ? 10 indicates EDS.
Multiple regression analysis between demographic and clinical characteristics and EDS, OSA and insomnia
Duration of epilepsy
Frequency of seizures
Type of seizures
Bold values mean statistical significance.
(p < 0.001), Cognitive functioning (p = 0.04) and
Social functioning (p = 0.03), and OSA only for Cog-
nitive functioning (p = 0.01) (Table 4).
The present study showed that EDS and OSA, but
not insomnia, are more frequent in patients with
epilepsy than in the general population. Mainly
insomnia and, secondarily, OSA were found as inde-
pendent negative factors of QOL in patients with
The frequency of EDS in our epileptic patients
was higher than in the general population, in accor-
dance with a large study covering 10 countries in
four continents1(16.9% vs. 11.6%). Data on the
literature concerning the frequency of EDS in
patients with epilepsy are contradictory. In all stu-
dies, the frequency is higher than in controls, yet
the difference is significant in some,3,18,19but not in
all.5,10,20,21This discrepancy may be attributed to
differences in patient samples (patients referred to
a sleep center,8medically refractory patients,7
unselected patients5) and possibly differences in
treatment, given that a number of CNS drugs is
positively associated with EDS.22Data on predictors
of EDS in patients with epilepsy is not clear. Seizures
EDS has been documented in patients with epilepsy
before starting any medical treatment or after its
discontinuation.23Other studies could show that
coexisting symptoms, such as OSA and restless leg
syndrome are stronger predictors of subjective EDS
than AEDs or type and frequency of seizures.24The
present work found no correlation between EDS and
demographic or clinical variables. Furthermore it
was shown that OSA did not predict EDS. These
findings are in agreement with Khatami et al.5but
in contrast to other studies.20,24These data indicate
that pathogenesis of EDS in epileptic patients is a
complex phenomenon, which needs careful evalua-
lower QOLIE-31 in Total score and all domains,
except Medication effects and Social functioning.
However, in multivariate analysis EDS was not found
to act as an independent factor on QoL. The impact
of sleep disturbances on QoL in epileptic patient has
been reported in two studies.11,10Our findings
regarding EDS are not comparable with the results
include EDS in the study by Alanis-Guevara et al.11
and QoL was measured by a different questionnaire
(SF-36) in the other.10
Based on SA-SDQ scale, frequency of OSA in our
sample was 28.2% (24.3% in women and 33.3% in
men). The prevalence of OSA has been reported to
be between 16% and 24%, for men, and 5% and 9%,
for women, in the general population.25—27Our
results are in agreement with a previous study in
unselected epileptic patients, which used the same
cut-off score (30%)5but lower than in studies on
patients with refractory epilepsy (35%)7and epi-
lepsy patients referred to a sleep center (45% and
52%).28In the study by Manni et al. the frequency of
OSA was 14.1%, when patients were investigated
with symptom checklist.9The difference could be
attributed to the use of different questionnaires. In
the same study, the frequency was 10.2% when
patients underwent polysomnographic monitoring.
These different results support the viewthat the SA-
SDQ is not a diagnostic tool and should only be used
to screen individuals for OSA.8
In our patients, the frequency of OSA was posi-
tively correlated withage and male gender,as in the
general population. There was no correlation
A recent report found a possible relationship
between onset of OSA symptoms and increase in
seizure frequency, first onset of seizures and new
onset of status epilepticus.29CPAP therapy has also
been shown to reduce seizure frequency.24,29—31
Nevertheless, the number of patients was small,
and, as suggested by Ho ¨llinger et al.29multicenter
randomized placebo-controlled studies are needed
592C. Piperidou et al.
Multiple regression analysis between demographic, clinical characteristics and sleep disturbances and
Total scoreSeizure worry Overall QoLEmotional
Betap Betap Betap BetapBetapBetapBetapBetap
Frequency ?0.166 0.153 ?0.228 0.110 ?0.214 0.088 ?0.156 0.211 ?0.082 0.454 ?0.124 0.349
EDS0.011 0.919 ?0.063 0.644
?0.239 0.072 ?0.134 0.407 ?0.177 0.213 ?0.033 0.813
?0.516 0.000 ?0.169 0.274 ?0.440 0.002 ?0.524 0.000 ?0.645 0.000 ?0.289 0.049 ?0.274 0.106 ?0.332 0.038
Bold values mean statistical significance.
?0.138 0.223 ?0.176 0.207 ?0.113 0.353 ?0.048 0.692 ?0.038 0.725 ?0.223 0.089 ?0.054 0.720 ?0.091 0.519
0.115 0.447 0.189 0.1570.248 0.126 0.223 0.2370.179 0.308
0.021 0.893 ?0.137 0.344
0.063 0.668 0.079 0.505 ?0.074 0.535 ?0.083 0.430 ?0.057 0.6560.111 0.421
0.078 0.531 ?0.375 0.016 ?0.132 0.458 ?0.144 0.383
to further investigate the interaction between OSA
The presence of OSA had a significant negative
correlation only with the Cognitive functioning sub-
scale of QOLIE-31, which, indeed, remained an
independent factor in multivariate analysis. Psycho-
logical studies in the general population have indi-
cated that OSA is associated with many cognitive
dysfunctions, regarding mainly verbal activity,
attention, short memory, learning skills and logical
reasoning.32Moreover, it is known that cognitive
functioning is more frequently impaired in people
with epilepsy than in the general population, and
the degree of cognitive impairment varies according
to the epilepsy syndrome.33Many factors have been
implicated in cognitive impairment among epileptic
patients (seizures themselves, structural brain
lesions, genetic background, and adverse effects
of AEDs).34This is, to the best of our knowledge,
the first study to show that OSA correlated with
cognitive impairment in epileptic patients. Com-
parative studies of OSA patients and healthy indivi-
duals indicate a significantly higher rate of anxiety
and depressive disorders in the former.32,35How-
ever, in a recent study patients with OSA did not
differ from the control group in terms of emotional
state.27Similarly, we found no correlation between
OSA and Emotional well-being subscale in our
patients. Because we could not find a similar study
evaluating OSA and QoL in patients with epilepsy in
the literature, we believe that we need more stu-
dies to establish the impact of OSA on QoL in epi-
Frequency of insomnia in our patients was lower
than in the general population (24.6% vs. ?30%).1
This finding is in contrast with the evidence coming
from other studies that found increased latency to
sleep onset, increased number and duration of awa-
kenings and decreased sleep efficiency and sleep
adequacy in epileptic patients.6,10Additionally,
Khatami et al.5found insomnia in 34% of patients.
We could attribute the low frequency of insomnia in
our patients to the fact that all of them had been
taking AEDs at the time of recruitment. It is known
that some AEDs (mainly benzodiazepines and barbi-
turates) produce sedation and drowsiness as side
reduce arousals and stage shifts.36
We found that insomnia strongly correlated with
frequency of seizures. Abad-Alegria et al.37also
demonstrated that early awakening, nocturnal awa-
kening and difficulty in initiating sleep were more
common in patients with poor seizure control.
Insomnia correlated significantly negatively with
all the subscales of QOLIE-31. In multivariate ana-
lysis, insomnia was an independent negative factor
for Total score and all domains except Seizure worry
and Medication effects. A recent epidemiologic sur-
vey in the general population revealed a negative
impact of insomnia on QoL.38We could not find any
other study that specifically correlates insomnia
with QoL in epileptic patients. In our results, fre-
quency of seizures was not an independent negative
factor for QoL in multivariate analysis. Therefore,
we believe that the strong correlation between
insomnia and frequency of seizures in our patients
is a confounding factor leading to underestimation
of the relationship between frequency of seizures
and impaired QoL. In almost all reports, seizure
frequency has been identified as a negative factor
for QoL in patients with epilepsy.39—42Two stu-
dies43,44did not find a relation between frequency
of seizures and QoL, but all patients in these had
symptomatic drug-resistant epilepsy.
In summary, the results of our study add further
data about the frequency and type of sleep distur-
bances in patients with epilepsy and the impact of
these on QoL. We believe that longitudinal studies
and objective sleep tests (i.e. polysomnography,
MSLT) are needed to establish these findings. Never-
theless, we suggest that clinical recognition and
treatment of sleep disturbances is important for
the improvement of QoL in patients with epilepsy.
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