- Email: [email protected]
Influence of sleep disturbance on quality of life of patients with epilepsy
Seizure (2008) 17, 588—594
www.elsevier.com/locate/yseiz
Influence of sleep disturbance on quality of life of patients with epilepsy Charitomeni Piperidou a, Anna Karlovasitou b, Nikolaos Triantafyllou c, Aikaterini Terzoudi a, Theodoros Constantinidis d, Konstantinos Vadikolias a,*, Ioannis Heliopoulos a, Dimitrios Vassilopoulos c, Stavros Balogiannis b a
Department of Neurology, Democritus University of Thrace, University - General Hospital, Alexandroupolis, Greece b 1st Department of Neurology, Aristotle University of Thessaloniki, AHEPA Hospital, Greece c Department of Neurology, Athens National University, Aeginition Hospital, Greece d Department of Epidemiology, Democritus University of Thrace, Greece Received 14 September 2007; received in revised form 17 January 2008; accepted 29 February 2008
KEYWORDS Epilepsy; Excessive daytime sleepiness; Obstructive sleep apnea; Insomnia; Quality of life
Summary The frequency of sleep disturbances in patients with epilepsy and their impact on quality of life (QoL) have been documented in a few reports, and the 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 (SASDQ), 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.
Introduction * Corresponding author. Tel.: +30 2551030491. E-mail addresses: [email protected], [email protected] (K. Vadikolias).
Poor sleep is a common complaint that can have a huge impact on patients’ quality of life (QoL) and
1059-1311/$ — see front matter # 2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2008.02.005
Influence of sleep disturbance on quality of life of patients with epilepsy ability to function.1 Several studies have confirmed that excessive daytime sleepiness (EDS) and sleep disturbances are common in epilepsy,2—4 with the exception of a recent study that revealed similar frequency of sleep disorders in a unselected population 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 awakenings, and increased duration of sleep stages 1 and 2.6 Furthermore, epilepsy coexists with obstructive sleep apnea (OSA), as has been documented in several case series.7—9 The sleep disorders in patients with epilepsy are commonly attributed to the effects of antiepileptic drugs (AEDs) or to seizures.6 In recent studies, the importance of sleep disturbance 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 patients with epilepsy the prevalence of EDS, insomnia, and OSA and their potential impact on QoL.
Methods Patients 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 patients from a wide region of Greece, so the sample 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 duration of disease. Seizure frequency was determined from a seizure diary completed by the patient, which was reviewed at routine clinical visit. Seizure frequency per month was determined as the mean seizure frequency during at least the last 12 months prior to enrollment. Patients were divided into three seizures 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 Classification of Epilepsies and Epileptic Syndromes12 into two groups: generalized seizures (GS), and partial seizures (PS) with or without secondary generalization. Duration of disease was defined by the present age and the age at diagnosis.
589
All patients were 18 years old, had been diagnosed with epilepsy (at least two unprovoked seizures) for at least 1 year, their epilepsy had been stable for the 6 months preceding their participation and had been taking AED at the time of recruitment. Exclusion criteria were any serious cognitive dysfunction (like dementia or learning disability), psychiatric 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 criteria. Of the excluded patients, twelve refused to 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.
Questionnaires We measured the patient’s QoL with the Quality of Life in Epilepsy Inventory (QOLIE-31), which is a selfcompleted questionnaire designed for epileptic patients that has recently been translated and validated in Greek language.13 The 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 diagnosis of insomnia.14 Patients 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),15 the most common measure of EDS used in the evaluation of patients with epilepsy. The ESS is a self-administered, eightitem questionnaire designed to ascertain sleep propensity in a variety of everyday situations.16 A score of 10 or higher is considered abnormal. We used the Sleep Apnea scale of the Sleep Disorders Questionnaire (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.17 In 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 for men and 26 for women, as has been suggested for epileptic patients by Weatherwax, which yielded a sensitivity of 75% and a specificity of 65% for men and 80% and 67%, for women.8
Statistics We established a database so that the accuracy of each parameter could be easily controlled. Consequently, we tested if normal distribution goodness accords with all quantitative variables by the
590 Kolmogorov—Smirnov test. All variables of the study were found to fit normal distribution. Means and standard deviation scores (m S.D.) were calculated for each variable. We also performed multiple regression analysis between dependent variable (EDS, OSA, insomnia; Fig. 1) and independent ones (age, sex, duration of disease, type and frequency of 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 correlation coefficients between quantitative variables. The Statistical Package for Social Sciences (SPSS for Windows) was used for all statistical analyses.
C. Piperidou et al. Values of p < 0.05 were considered statistically significant.
Results Patient characteristics Of 124 patients included, 55 (43.7%) were male. The mean age was 35.4 12.9 (18—70), and mean duration of epilepsy was 13 11.3 (1—51). Epileptic seizures were generalized in 35/122 (28.7%) of patients and localisation-related (including secondarily generalized) in 87/122 (71.3%). Two patients
Figure 1 Correlation between QOLIE-31 subscales and (A) OSA, (B) EDS and (C) Insomnia. OSA: Obstructive Sleep Apnea; EDS: Excessive Daytime Sleepiness; & with OSA, EDS, Insomnia; ~ without OSA, EDS, Insomnia; ~, & statistical significant.
Influence of sleep disturbance on quality of life of patients with epilepsy Table 1 Demographic and clinical characteristics Variable
N (%) or mean S.D.
Male sex Age Duration of epilepsy (years)
55 (43.7%) 35.4 12.9 13 11.3
Seizure type a Generalised seizures Localisation-related b
35/122 (28.7%) 87/122 (71.3%)
Seizure frequency in past year <1 pre month 92/124 (74.2%) 1—5 per month 20/124 (16.1%) >1 per month 12/124 (9.6%) Seizures during sleep c 50/120 (41.7%) a b c
591
There was no correlation between EDS and demographic 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 significant positive correlation between the presence of insomnia and seizure frequency ( p = 0.02) (Table 2).
Sleep disorders and quality of life
Two patients had unclassified epileptic seizures. Including secondarily generalized. Number of patients varies because of missing data.
had unclassified epileptic seizures. Ninety-two (74.2%) had <1 seizures per month, 16.1% 1—5 seizures 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 epileptic patients (12.8% in women and 20.6% in male).
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 Medication 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) (Table 3). 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
Table 2 Multiple regression analysis between demographic and clinical characteristics and EDS, OSA and insomnia EDS
OSA
Beta Age Sex Duration of epilepsy Frequency of seizures Type of seizures
p
0.207 0.222 0.002 0.038 0.083
Insomnia
Beta
0.168 0.115 0.988 0.780 0.548
0.620 0.212 0.070 0.023 0.020
p
Beta
p
0.000 0.009 0.426 0.772 0.804
0.053 0.022 0.127 0.237 0.015
0.633 0.831 0.253 0.020 0.882
Bold values mean statistical significance.
Table 3 Mean (S.D.) QOLIE-31 subscales score in relation to EDS, OSA, insomnia
Total score Seizure worry Overall QOL Emotional well-being Energy/fatigue Cognitive functioning Medical effects Social functioning
ESSa <10
ESS 10
Mean S.D.
Mean S.D.
79.00 69.71 72.36 70.77
63.60 43.87 59.58 51.92
15.21 24.78 15.03 18.22
20.51 34.36 17.58 29.11
p
Without OSA With OSA Mean
0.004 0.003 0.011 0.005
72.43 62.81 69.16 68.25
p
S.D. Mean S.D. 16.57 28.64 15.10 18.00
66.35 55.14 66.57 64.66
23.48 34.51 21.50 24.71
0.109 0.210 0.453 0.374
AISb <6
AIS 6
Mean S.D.
Mean S.D.
77.25 67.13 73.50 73.81
53.41 43.78 53.35 50.09
14.02 28.87 13.22 14.45
21.46 28.05 19.22 24.31
p 0.000 0.000 0.000 0.000
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 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 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 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. a ESS 10 indicates EDS. b Indicates insomnia.
592
C. Piperidou et al.
Table 4 Multiple regression analysis between demographic, clinical characteristics and sleep disturbances and QOLIE-31 subscales
Age Duration Frequency EDS OSA Insomnia
Total score
Seizure worry Overall QoL
Emotional well-being
Energy fatigue
Beta
Beta
Beta
Beta
0.279 0.138 0.166 0.011 0.239 0.516
p 0.049 0.223 0.153 0.919 0.072 0.000
0.403 0.176 0.228 0.063 0.134 0.169
p 0.022 0.207 0.110 0.644 0.407 0.274
Beta 0.312 0.113 0.214 0.079 0.177 0.440
p 0.041 0.353 0.088 0.505 0.213 0.002
0.115 0.048 0.156 0.074 0.033 0.524
p 0.447 0.692 0.211 0.535 0.813 0.000
0.189 0.038 0.082 0.083 0.078 0.645
p 0.157 0.725 0.454 0.430 0.531 0.000
Cognitive functioning
Medical effects
Beta
Beta
0.248 0.223 0.124 0.057 0.375 0.289
p 0.126 0.089 0.349 0.656 0.016 0.049
0.223 0.054 0.021 0.063 0.132 0.274
Social functioning p 0.237 0.720 0.893 0.668 0.458 0.106
Beta 0.179 0.091 0.137 0.111 0.144 0.332
p 0.308 0.519 0.344 0.421 0.383 0.038
Bold values mean statistical significance.
( p < 0.001), Cognitive functioning ( p = 0.04) and Social functioning ( p = 0.03), and OSA only for Cognitive functioning ( p = 0.01) (Table 4).
Discussion 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 independent negative factors of QOL in patients with epilepsy. The frequency of EDS in our epileptic patients was higher than in the general population, in accordance 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 studies, the frequency is higher than in controls, yet the difference is significant in some,3,18,19 but not in all.5,10,20,21 This discrepancy may be attributed to differences in patient samples (patients referred to a sleep center,8 medically refractory patients,7 unselected patients5) and possibly differences in treatment, given that a number of CNS drugs is positively associated with EDS.22 Data on predictors of EDS in patients with epilepsy is not clear. Seizures and AEDs affect sleep and may lead to EDS. However, EDS has been documented in patients with epilepsy before starting any medical treatment or after its discontinuation.23 Other 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.24 The 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.5 but in contrast to other studies.20,24 These data indicate that pathogenesis of EDS in epileptic patients is a complex phenomenon, which needs careful evaluation.
In this study, EDS was significantly associated with 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.11,10 Our findings regarding EDS are not comparable with the results of these two studies, because sleep disorders did not 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—27 Our results are in agreement with a previous study in unselected epileptic patients, which used the same cut-off score (30%)5 but lower than in studies on patients with refractory epilepsy (35%)7 and epilepsy patients referred to a sleep center (45% and 52%).28 In the study by Manni et al. the frequency of OSA was 14.1%, when patients were investigated with symptom checklist.9 The 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 view that the SASDQ is not a diagnostic tool and should only be used to screen individuals for OSA.8 In our patients, the frequency of OSA was positively correlated with age and male gender, as in the general population. There was no correlation between the presence of OSA and seizure frequency. 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.29 CPAP 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.29 multicenter randomized placebo-controlled studies are needed
Influence of sleep disturbance on quality of life of patients with epilepsy to further investigate the interaction between OSA and epilepsy. The presence of OSA had a significant negative correlation only with the Cognitive functioning subscale of QOLIE-31, which, indeed, remained an independent factor in multivariate analysis. Psychological studies in the general population have indicated that OSA is associated with many cognitive dysfunctions, regarding mainly verbal activity, attention, short memory, learning skills and logical reasoning.32 Moreover, 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.33 Many factors have been implicated in cognitive impairment among epileptic patients (seizures themselves, structural brain lesions, genetic background, and adverse effects of AEDs).34 This is, to the best of our knowledge, the first study to show that OSA correlated with cognitive impairment in epileptic patients. Comparative studies of OSA patients and healthy individuals indicate a significantly higher rate of anxiety and depressive disorders in the former.32,35 However, in a recent study patients with OSA did not differ from the control group in terms of emotional state.27 Similarly, 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 studies to establish the impact of OSA on QoL in epileptic patients. 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 awakenings and decreased sleep efficiency and sleep adequacy in epileptic patients.6,10 Additionally, Khatami et al.5 found 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 barbiturates) produce sedation and drowsiness as side effects. Furthermore, lamotrigine has been found to reduce arousals and stage shifts.36 We found that insomnia strongly correlated with frequency of seizures. Abad-Alegria et al.37 also demonstrated that early awakening, nocturnal awakening 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 analysis, insomnia was an independent negative factor
593
for Total score and all domains except Seizure worry and Medication effects. A recent epidemiologic survey in the general population revealed a negative impact of insomnia on QoL.38 We could not find any other study that specifically correlates insomnia with QoL in epileptic patients. In our results, frequency 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—42 Two studies43,44 did 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 disturbances 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. Nevertheless, we suggest that clinical recognition and treatment of sleep disturbances is important for the improvement of QoL in patients with epilepsy.
References 1. Soldatos RC, Allaert AF, Ohta T, Dikeos GD. How do individuals sleep around the world? Results from a single-day survey in ten countries. Sleep Med 2005;6:5—13. 2. Basil WC. Epilepsy and sleep disturbance. Epilepsy Behav 2003;S12:s39—s45. 3. Maganti R, Hausman N, Koehn M, Sandok E, Glurish I, Mukesh BN. Excessive daytime sleepiness and sleep complaints among children with epilepsy. Epilepsy Behav 2006;8(1):272—7. 4. Xu X, Brandenburg AN, McDermott MA, Basil WC. Sleep disturbances reported by refractory partial-onset epilepsy patients receiving polytherapy. Epilepsia 2006;47(7): 1176—83. 5. Khatami R, Zutter D, Siegel A, Mathis J, Donati F, Bassetti C. Sleep-wake habits and disorders in a series of 100 adult epilepsy patients–—a prospective study. Seizure 2006;15: 299—306. 6. Me ´ndez M, Radtke R. Interaction between sleep and epilepsy. J Clin Neurophysiol 2001;18(2):106—27. 7. Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002—7. 8. Weatherwax KJ, Lin X, Marzec ML, Malow BA. Obstructive sleep apnea in epilepsy patients: the sleep apnea scale of the sleep disorders questionnaire (SA-SDQ) is a useful screening instrument for obstructive sleep apnea in a disease-specific population. Sleep Med 2003;4:517—21. 9. Manni R, Terzaghi M, Arbasino C, Sartori I, Calimberti A, Tartara A. Obstructive sleep apnea in a clinical series of adult epilepsy patients: frequency and features of the comorbidity. Epilepsia 2003;44(6):836—40.
594 10. De Weerd A, De Haas S, Otte A, Kasteleijn Nolst- Trenite´ DK, van Erp G, Cohen A, et al. Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life. Epilepsia 2004;45(11):1397—404. 11. Alanis-Guevara I, Pen ˜a E, Corona T, Lo ´pez-Ayala T, Lo ´pezMeza E, Lo ´pez-Go ´mez M. Sleep disturbances, socioeconomic status, and seizures control as main predictors of quality of life in epilepsy. Epilepsy Behav 2005;7:481—5. 12. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989:389—99. 13. Piperidou H, Terzoudi A, Vorvolakos T, Devis E, Heliopoulos I, Vadikoliaw K, et al. The Greece version of the quality of life in epilepsy inventory (QOLIE-31). Qual Life Res 2006;15:833—9. 14. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res 2003;55(3):263—7. 15. Tsara V, Serasli E, Amfilochiou A, Costadinidis T, Christaki P. Greek version of the Epworth sleepiness scale. Sleep Breath 2004;8(2):91—5. 16. Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992;15:376—81. 17. Douglas AB, Bornstein R, Nino-Murcia G, et al. The sleep disorders questionnaire. I. Creation and multivariate structure of SDQ. Sleep 1994;17:160—7. 18. Foldvary-Schaefer N. Sleep complaints and epilepsy: the role of seizures, antiepil eptic drugs and sleep disorders. J Clin Neurophysiol 2002;19(6):514—21. 19. Sanchez de Leon I, Foldvary N, Marsilio D, Dinner DS. Effect of seizure frequency and antiepileptic drugs on daytime alertness as measured by Epworth Sleepiness Scale in patients with epilepsy. Epilepsia 1997;38:56. 20. Manni R, Politini L, Sartori I, Ratti MT, Galimberti CA, Tartara A. Daytime sleepiness in epilepsy patients: evaluation by means of the by Epworth Sleepiness Scale. J Neurol 2000;247:716—7. 21. Vignatelli L, Bisulli F, Naldi I, Ferioli S, Pittau F, Provini F, et al. Excessive daytime sleepiness and subjective sleep quality in patients with nocturnal frontal lobe epilepsy: a case-control study. Epilepsia 2006;47(Suppl. 5):73—7. 22. Jenssen S, Gracely E, Mahmood T, Tracy J, Sperling M. Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center. Epilepsy Behav 2006;9:632—5. 23. Manni R, Tartara A. Evaluation of sleepiness in epilepsy. Clin Neurophysiol 2000;2(Suppl.):111—4. 24. Malow BA, Bowees RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997;20:1105—10. 25. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-age adults. N Engl J Med 1993;328(17):1230—5. 26. Sharma S, Kumpawat S, Banga A, Goel A. Prevalence and risk factors of obstructive sleep apnea syndrome in a population of Delhi, India. Chest 2006;130:149—56. 27. Gle ˛bocka A, Kossowska A, Bednarek M. Obstructive sleep apnea and the quality of life. J Physiol Pharmacol 2006;57 (Supp4):111—4.
C. Piperidou et al. 28. Malow BA, Weatherwax KJ, Chervin RD, HobanTF. Marzec ML, Martin C, et al. Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: a prospective pilot study. Sleep Med 2003;4:509—15. 29. Ho ¨llinger P, Khatami R, Gugger M, Hess CW, Bassetti CL. Epilepsy and obstructive sleep apnea. Eur Neurol 2006;55: 74—9. 30. Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology 1994;44(11):2060—4. 31. Beran RG, Holland GJ, Yan KY. The use of CPAP in patients with refractory epilepsy. Seizure 1997;6:323—5. 32. Al-Barak M, Shepertycky MR, kryger MH. Morbidity and mortality in obstructive sleep apnea syndrome 2: Effect of treatment on neuropsychiatric morbidity and quality of life. Sleep Biol Rhythms 2003;1:65—74. 33. Cornaggia CM, Beghi M, Provenzi M, Beg E. Correlation between cognition and behavior in epilepsy. Epilepsia 2006;47(Suppl.2):34—9. 34. Hirsch E, Schmitz B, Carren ˜o M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurol Scand 2003;108(Suppl. 180):23—32. 35. Veale D, Poussin G, Benes F, Pepin J-L, Levy P. Identification of quality of life concerns of patients with obstructive sleep apnea at the time of initiation of continuous positive airway pressure: a discourse analysis. Qual Life Res 2002;11: 389—99. 36. Foldvary N, Perry M, Lee J, Dinner D, Morris H. The effects of lamotrgine on sleep in patients with epilepsy. Epilepsia 2001;42(12):1569—73. 37. Abad-Alegria F, Lopez-Mallen ME, de Francisco-Maqueda P. Insomnio y somnolencia en epilepsia. Rev Neurol 1997;25: 1171—2. 38. LeBlanc M, Beaulieu-Bonneau S, Me ´rette C, Savard J, Ivers H, Morin CM. Psychological and health-related quality of life factors associated with insomnia in a population-based sample. J Psychosom Res 2007;63:157—66. 39. Baker G, Gagnon D, McNulty P. The relationship between seizure frequency, seizure type and quality of life: Findings from three European countries. Epilepsy Res 1998;30: 231—40. ¨ ztu 40. Senol V, Soyuer F, Arman F, O ¨rk A. Influence of fatigue, depression, and demographic, socioeconomic, and clinical variables on quality of life of patients with epilepsy. Epilepsy Behav 2007;10:96—104. 41. Choi-Kwon S, Chung C, Kim H, Lee S, Yoon S, Kho H, et al. Factors affecting the quality of life in patients with epilepsy in Seoul, South Korea. Acta Neurol Scand 2003;108:428—34. 42. Guekht A, Mitrokhina T, Lebedeva A. Factors influencing on quality of life in people with epilepsy. Seizure 2007;16(2): 128—33. 43. Meldolesi G, Picardi A, Quarato P, Gramaldo LG, Esposito V, Marcia A, et al. Factors associated with generic and diseasespecific quality of life in temporal lobe epilepsy. Epilepsy Res 2006;69:135—46. 44. Boylan LS, Flint LA, Labovitz DL, Jackson SC, Stamer K, Devinsky O. Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy. Neurology 2004;62:258—61.
www.elsevier.com/locate/yseiz
Influence of sleep disturbance on quality of life of patients with epilepsy Charitomeni Piperidou a, Anna Karlovasitou b, Nikolaos Triantafyllou c, Aikaterini Terzoudi a, Theodoros Constantinidis d, Konstantinos Vadikolias a,*, Ioannis Heliopoulos a, Dimitrios Vassilopoulos c, Stavros Balogiannis b a
Department of Neurology, Democritus University of Thrace, University - General Hospital, Alexandroupolis, Greece b 1st Department of Neurology, Aristotle University of Thessaloniki, AHEPA Hospital, Greece c Department of Neurology, Athens National University, Aeginition Hospital, Greece d Department of Epidemiology, Democritus University of Thrace, Greece Received 14 September 2007; received in revised form 17 January 2008; accepted 29 February 2008
KEYWORDS Epilepsy; Excessive daytime sleepiness; Obstructive sleep apnea; Insomnia; Quality of life
Summary The frequency of sleep disturbances in patients with epilepsy and their impact on quality of life (QoL) have been documented in a few reports, and the 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 (SASDQ), 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.
Introduction * Corresponding author. Tel.: +30 2551030491. E-mail addresses: [email protected], [email protected] (K. Vadikolias).
Poor sleep is a common complaint that can have a huge impact on patients’ quality of life (QoL) and
1059-1311/$ — see front matter # 2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2008.02.005
Influence of sleep disturbance on quality of life of patients with epilepsy ability to function.1 Several studies have confirmed that excessive daytime sleepiness (EDS) and sleep disturbances are common in epilepsy,2—4 with the exception of a recent study that revealed similar frequency of sleep disorders in a unselected population 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 awakenings, and increased duration of sleep stages 1 and 2.6 Furthermore, epilepsy coexists with obstructive sleep apnea (OSA), as has been documented in several case series.7—9 The sleep disorders in patients with epilepsy are commonly attributed to the effects of antiepileptic drugs (AEDs) or to seizures.6 In recent studies, the importance of sleep disturbance 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 patients with epilepsy the prevalence of EDS, insomnia, and OSA and their potential impact on QoL.
Methods Patients 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 patients from a wide region of Greece, so the sample 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 duration of disease. Seizure frequency was determined from a seizure diary completed by the patient, which was reviewed at routine clinical visit. Seizure frequency per month was determined as the mean seizure frequency during at least the last 12 months prior to enrollment. Patients were divided into three seizures 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 Classification of Epilepsies and Epileptic Syndromes12 into two groups: generalized seizures (GS), and partial seizures (PS) with or without secondary generalization. Duration of disease was defined by the present age and the age at diagnosis.
589
All patients were 18 years old, had been diagnosed with epilepsy (at least two unprovoked seizures) for at least 1 year, their epilepsy had been stable for the 6 months preceding their participation and had been taking AED at the time of recruitment. Exclusion criteria were any serious cognitive dysfunction (like dementia or learning disability), psychiatric 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 criteria. Of the excluded patients, twelve refused to 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.
Questionnaires We measured the patient’s QoL with the Quality of Life in Epilepsy Inventory (QOLIE-31), which is a selfcompleted questionnaire designed for epileptic patients that has recently been translated and validated in Greek language.13 The 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 diagnosis of insomnia.14 Patients 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),15 the most common measure of EDS used in the evaluation of patients with epilepsy. The ESS is a self-administered, eightitem questionnaire designed to ascertain sleep propensity in a variety of everyday situations.16 A score of 10 or higher is considered abnormal. We used the Sleep Apnea scale of the Sleep Disorders Questionnaire (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.17 In 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 for men and 26 for women, as has been suggested for epileptic patients by Weatherwax, which yielded a sensitivity of 75% and a specificity of 65% for men and 80% and 67%, for women.8
Statistics We established a database so that the accuracy of each parameter could be easily controlled. Consequently, we tested if normal distribution goodness accords with all quantitative variables by the
590 Kolmogorov—Smirnov test. All variables of the study were found to fit normal distribution. Means and standard deviation scores (m S.D.) were calculated for each variable. We also performed multiple regression analysis between dependent variable (EDS, OSA, insomnia; Fig. 1) and independent ones (age, sex, duration of disease, type and frequency of 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 correlation coefficients between quantitative variables. The Statistical Package for Social Sciences (SPSS for Windows) was used for all statistical analyses.
C. Piperidou et al. Values of p < 0.05 were considered statistically significant.
Results Patient characteristics Of 124 patients included, 55 (43.7%) were male. The mean age was 35.4 12.9 (18—70), and mean duration of epilepsy was 13 11.3 (1—51). Epileptic seizures were generalized in 35/122 (28.7%) of patients and localisation-related (including secondarily generalized) in 87/122 (71.3%). Two patients
Figure 1 Correlation between QOLIE-31 subscales and (A) OSA, (B) EDS and (C) Insomnia. OSA: Obstructive Sleep Apnea; EDS: Excessive Daytime Sleepiness; & with OSA, EDS, Insomnia; ~ without OSA, EDS, Insomnia; ~, & statistical significant.
Influence of sleep disturbance on quality of life of patients with epilepsy Table 1 Demographic and clinical characteristics Variable
N (%) or mean S.D.
Male sex Age Duration of epilepsy (years)
55 (43.7%) 35.4 12.9 13 11.3
Seizure type a Generalised seizures Localisation-related b
35/122 (28.7%) 87/122 (71.3%)
Seizure frequency in past year <1 pre month 92/124 (74.2%) 1—5 per month 20/124 (16.1%) >1 per month 12/124 (9.6%) Seizures during sleep c 50/120 (41.7%) a b c
591
There was no correlation between EDS and demographic 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 significant positive correlation between the presence of insomnia and seizure frequency ( p = 0.02) (Table 2).
Sleep disorders and quality of life
Two patients had unclassified epileptic seizures. Including secondarily generalized. Number of patients varies because of missing data.
had unclassified epileptic seizures. Ninety-two (74.2%) had <1 seizures per month, 16.1% 1—5 seizures 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 epileptic patients (12.8% in women and 20.6% in male).
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 Medication 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) (Table 3). 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
Table 2 Multiple regression analysis between demographic and clinical characteristics and EDS, OSA and insomnia EDS
OSA
Beta Age Sex Duration of epilepsy Frequency of seizures Type of seizures
p
0.207 0.222 0.002 0.038 0.083
Insomnia
Beta
0.168 0.115 0.988 0.780 0.548
0.620 0.212 0.070 0.023 0.020
p
Beta
p
0.000 0.009 0.426 0.772 0.804
0.053 0.022 0.127 0.237 0.015
0.633 0.831 0.253 0.020 0.882
Bold values mean statistical significance.
Table 3 Mean (S.D.) QOLIE-31 subscales score in relation to EDS, OSA, insomnia
Total score Seizure worry Overall QOL Emotional well-being Energy/fatigue Cognitive functioning Medical effects Social functioning
ESSa <10
ESS 10
Mean S.D.
Mean S.D.
79.00 69.71 72.36 70.77
63.60 43.87 59.58 51.92
15.21 24.78 15.03 18.22
20.51 34.36 17.58 29.11
p
Without OSA With OSA Mean
0.004 0.003 0.011 0.005
72.43 62.81 69.16 68.25
p
S.D. Mean S.D. 16.57 28.64 15.10 18.00
66.35 55.14 66.57 64.66
23.48 34.51 21.50 24.71
0.109 0.210 0.453 0.374
AISb <6
AIS 6
Mean S.D.
Mean S.D.
77.25 67.13 73.50 73.81
53.41 43.78 53.35 50.09
14.02 28.87 13.22 14.45
21.46 28.05 19.22 24.31
p 0.000 0.000 0.000 0.000
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 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 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 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. a ESS 10 indicates EDS. b Indicates insomnia.
592
C. Piperidou et al.
Table 4 Multiple regression analysis between demographic, clinical characteristics and sleep disturbances and QOLIE-31 subscales
Age Duration Frequency EDS OSA Insomnia
Total score
Seizure worry Overall QoL
Emotional well-being
Energy fatigue
Beta
Beta
Beta
Beta
0.279 0.138 0.166 0.011 0.239 0.516
p 0.049 0.223 0.153 0.919 0.072 0.000
0.403 0.176 0.228 0.063 0.134 0.169
p 0.022 0.207 0.110 0.644 0.407 0.274
Beta 0.312 0.113 0.214 0.079 0.177 0.440
p 0.041 0.353 0.088 0.505 0.213 0.002
0.115 0.048 0.156 0.074 0.033 0.524
p 0.447 0.692 0.211 0.535 0.813 0.000
0.189 0.038 0.082 0.083 0.078 0.645
p 0.157 0.725 0.454 0.430 0.531 0.000
Cognitive functioning
Medical effects
Beta
Beta
0.248 0.223 0.124 0.057 0.375 0.289
p 0.126 0.089 0.349 0.656 0.016 0.049
0.223 0.054 0.021 0.063 0.132 0.274
Social functioning p 0.237 0.720 0.893 0.668 0.458 0.106
Beta 0.179 0.091 0.137 0.111 0.144 0.332
p 0.308 0.519 0.344 0.421 0.383 0.038
Bold values mean statistical significance.
( p < 0.001), Cognitive functioning ( p = 0.04) and Social functioning ( p = 0.03), and OSA only for Cognitive functioning ( p = 0.01) (Table 4).
Discussion 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 independent negative factors of QOL in patients with epilepsy. The frequency of EDS in our epileptic patients was higher than in the general population, in accordance 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 studies, the frequency is higher than in controls, yet the difference is significant in some,3,18,19 but not in all.5,10,20,21 This discrepancy may be attributed to differences in patient samples (patients referred to a sleep center,8 medically refractory patients,7 unselected patients5) and possibly differences in treatment, given that a number of CNS drugs is positively associated with EDS.22 Data on predictors of EDS in patients with epilepsy is not clear. Seizures and AEDs affect sleep and may lead to EDS. However, EDS has been documented in patients with epilepsy before starting any medical treatment or after its discontinuation.23 Other 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.24 The 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.5 but in contrast to other studies.20,24 These data indicate that pathogenesis of EDS in epileptic patients is a complex phenomenon, which needs careful evaluation.
In this study, EDS was significantly associated with 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.11,10 Our findings regarding EDS are not comparable with the results of these two studies, because sleep disorders did not 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—27 Our results are in agreement with a previous study in unselected epileptic patients, which used the same cut-off score (30%)5 but lower than in studies on patients with refractory epilepsy (35%)7 and epilepsy patients referred to a sleep center (45% and 52%).28 In the study by Manni et al. the frequency of OSA was 14.1%, when patients were investigated with symptom checklist.9 The 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 view that the SASDQ is not a diagnostic tool and should only be used to screen individuals for OSA.8 In our patients, the frequency of OSA was positively correlated with age and male gender, as in the general population. There was no correlation between the presence of OSA and seizure frequency. 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.29 CPAP 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.29 multicenter randomized placebo-controlled studies are needed
Influence of sleep disturbance on quality of life of patients with epilepsy to further investigate the interaction between OSA and epilepsy. The presence of OSA had a significant negative correlation only with the Cognitive functioning subscale of QOLIE-31, which, indeed, remained an independent factor in multivariate analysis. Psychological studies in the general population have indicated that OSA is associated with many cognitive dysfunctions, regarding mainly verbal activity, attention, short memory, learning skills and logical reasoning.32 Moreover, 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.33 Many factors have been implicated in cognitive impairment among epileptic patients (seizures themselves, structural brain lesions, genetic background, and adverse effects of AEDs).34 This is, to the best of our knowledge, the first study to show that OSA correlated with cognitive impairment in epileptic patients. Comparative studies of OSA patients and healthy individuals indicate a significantly higher rate of anxiety and depressive disorders in the former.32,35 However, in a recent study patients with OSA did not differ from the control group in terms of emotional state.27 Similarly, 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 studies to establish the impact of OSA on QoL in epileptic patients. 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 awakenings and decreased sleep efficiency and sleep adequacy in epileptic patients.6,10 Additionally, Khatami et al.5 found 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 barbiturates) produce sedation and drowsiness as side effects. Furthermore, lamotrigine has been found to reduce arousals and stage shifts.36 We found that insomnia strongly correlated with frequency of seizures. Abad-Alegria et al.37 also demonstrated that early awakening, nocturnal awakening 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 analysis, insomnia was an independent negative factor
593
for Total score and all domains except Seizure worry and Medication effects. A recent epidemiologic survey in the general population revealed a negative impact of insomnia on QoL.38 We could not find any other study that specifically correlates insomnia with QoL in epileptic patients. In our results, frequency 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—42 Two studies43,44 did 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 disturbances 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. Nevertheless, we suggest that clinical recognition and treatment of sleep disturbances is important for the improvement of QoL in patients with epilepsy.
References 1. Soldatos RC, Allaert AF, Ohta T, Dikeos GD. How do individuals sleep around the world? Results from a single-day survey in ten countries. Sleep Med 2005;6:5—13. 2. Basil WC. Epilepsy and sleep disturbance. Epilepsy Behav 2003;S12:s39—s45. 3. Maganti R, Hausman N, Koehn M, Sandok E, Glurish I, Mukesh BN. Excessive daytime sleepiness and sleep complaints among children with epilepsy. Epilepsy Behav 2006;8(1):272—7. 4. Xu X, Brandenburg AN, McDermott MA, Basil WC. Sleep disturbances reported by refractory partial-onset epilepsy patients receiving polytherapy. Epilepsia 2006;47(7): 1176—83. 5. Khatami R, Zutter D, Siegel A, Mathis J, Donati F, Bassetti C. Sleep-wake habits and disorders in a series of 100 adult epilepsy patients–—a prospective study. Seizure 2006;15: 299—306. 6. Me ´ndez M, Radtke R. Interaction between sleep and epilepsy. J Clin Neurophysiol 2001;18(2):106—27. 7. Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002—7. 8. Weatherwax KJ, Lin X, Marzec ML, Malow BA. Obstructive sleep apnea in epilepsy patients: the sleep apnea scale of the sleep disorders questionnaire (SA-SDQ) is a useful screening instrument for obstructive sleep apnea in a disease-specific population. Sleep Med 2003;4:517—21. 9. Manni R, Terzaghi M, Arbasino C, Sartori I, Calimberti A, Tartara A. Obstructive sleep apnea in a clinical series of adult epilepsy patients: frequency and features of the comorbidity. Epilepsia 2003;44(6):836—40.
594 10. De Weerd A, De Haas S, Otte A, Kasteleijn Nolst- Trenite´ DK, van Erp G, Cohen A, et al. Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life. Epilepsia 2004;45(11):1397—404. 11. Alanis-Guevara I, Pen ˜a E, Corona T, Lo ´pez-Ayala T, Lo ´pezMeza E, Lo ´pez-Go ´mez M. Sleep disturbances, socioeconomic status, and seizures control as main predictors of quality of life in epilepsy. Epilepsy Behav 2005;7:481—5. 12. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989:389—99. 13. Piperidou H, Terzoudi A, Vorvolakos T, Devis E, Heliopoulos I, Vadikoliaw K, et al. The Greece version of the quality of life in epilepsy inventory (QOLIE-31). Qual Life Res 2006;15:833—9. 14. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res 2003;55(3):263—7. 15. Tsara V, Serasli E, Amfilochiou A, Costadinidis T, Christaki P. Greek version of the Epworth sleepiness scale. Sleep Breath 2004;8(2):91—5. 16. Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992;15:376—81. 17. Douglas AB, Bornstein R, Nino-Murcia G, et al. The sleep disorders questionnaire. I. Creation and multivariate structure of SDQ. Sleep 1994;17:160—7. 18. Foldvary-Schaefer N. Sleep complaints and epilepsy: the role of seizures, antiepil eptic drugs and sleep disorders. J Clin Neurophysiol 2002;19(6):514—21. 19. Sanchez de Leon I, Foldvary N, Marsilio D, Dinner DS. Effect of seizure frequency and antiepileptic drugs on daytime alertness as measured by Epworth Sleepiness Scale in patients with epilepsy. Epilepsia 1997;38:56. 20. Manni R, Politini L, Sartori I, Ratti MT, Galimberti CA, Tartara A. Daytime sleepiness in epilepsy patients: evaluation by means of the by Epworth Sleepiness Scale. J Neurol 2000;247:716—7. 21. Vignatelli L, Bisulli F, Naldi I, Ferioli S, Pittau F, Provini F, et al. Excessive daytime sleepiness and subjective sleep quality in patients with nocturnal frontal lobe epilepsy: a case-control study. Epilepsia 2006;47(Suppl. 5):73—7. 22. Jenssen S, Gracely E, Mahmood T, Tracy J, Sperling M. Subjective somnolence relates mainly to depression among patients in a tertiary care epilepsy center. Epilepsy Behav 2006;9:632—5. 23. Manni R, Tartara A. Evaluation of sleepiness in epilepsy. Clin Neurophysiol 2000;2(Suppl.):111—4. 24. Malow BA, Bowees RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997;20:1105—10. 25. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-age adults. N Engl J Med 1993;328(17):1230—5. 26. Sharma S, Kumpawat S, Banga A, Goel A. Prevalence and risk factors of obstructive sleep apnea syndrome in a population of Delhi, India. Chest 2006;130:149—56. 27. Gle ˛bocka A, Kossowska A, Bednarek M. Obstructive sleep apnea and the quality of life. J Physiol Pharmacol 2006;57 (Supp4):111—4.
C. Piperidou et al. 28. Malow BA, Weatherwax KJ, Chervin RD, HobanTF. Marzec ML, Martin C, et al. Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: a prospective pilot study. Sleep Med 2003;4:509—15. 29. Ho ¨llinger P, Khatami R, Gugger M, Hess CW, Bassetti CL. Epilepsy and obstructive sleep apnea. Eur Neurol 2006;55: 74—9. 30. Devinsky O, Ehrenberg B, Barthlen GM, Abramson HS, Luciano D. Epilepsy and sleep apnea syndrome. Neurology 1994;44(11):2060—4. 31. Beran RG, Holland GJ, Yan KY. The use of CPAP in patients with refractory epilepsy. Seizure 1997;6:323—5. 32. Al-Barak M, Shepertycky MR, kryger MH. Morbidity and mortality in obstructive sleep apnea syndrome 2: Effect of treatment on neuropsychiatric morbidity and quality of life. Sleep Biol Rhythms 2003;1:65—74. 33. Cornaggia CM, Beghi M, Provenzi M, Beg E. Correlation between cognition and behavior in epilepsy. Epilepsia 2006;47(Suppl.2):34—9. 34. Hirsch E, Schmitz B, Carren ˜o M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurol Scand 2003;108(Suppl. 180):23—32. 35. Veale D, Poussin G, Benes F, Pepin J-L, Levy P. Identification of quality of life concerns of patients with obstructive sleep apnea at the time of initiation of continuous positive airway pressure: a discourse analysis. Qual Life Res 2002;11: 389—99. 36. Foldvary N, Perry M, Lee J, Dinner D, Morris H. The effects of lamotrgine on sleep in patients with epilepsy. Epilepsia 2001;42(12):1569—73. 37. Abad-Alegria F, Lopez-Mallen ME, de Francisco-Maqueda P. Insomnio y somnolencia en epilepsia. Rev Neurol 1997;25: 1171—2. 38. LeBlanc M, Beaulieu-Bonneau S, Me ´rette C, Savard J, Ivers H, Morin CM. Psychological and health-related quality of life factors associated with insomnia in a population-based sample. J Psychosom Res 2007;63:157—66. 39. Baker G, Gagnon D, McNulty P. The relationship between seizure frequency, seizure type and quality of life: Findings from three European countries. Epilepsy Res 1998;30: 231—40. ¨ ztu 40. Senol V, Soyuer F, Arman F, O ¨rk A. Influence of fatigue, depression, and demographic, socioeconomic, and clinical variables on quality of life of patients with epilepsy. Epilepsy Behav 2007;10:96—104. 41. Choi-Kwon S, Chung C, Kim H, Lee S, Yoon S, Kho H, et al. Factors affecting the quality of life in patients with epilepsy in Seoul, South Korea. Acta Neurol Scand 2003;108:428—34. 42. Guekht A, Mitrokhina T, Lebedeva A. Factors influencing on quality of life in people with epilepsy. Seizure 2007;16(2): 128—33. 43. Meldolesi G, Picardi A, Quarato P, Gramaldo LG, Esposito V, Marcia A, et al. Factors associated with generic and diseasespecific quality of life in temporal lobe epilepsy. Epilepsy Res 2006;69:135—46. 44. Boylan LS, Flint LA, Labovitz DL, Jackson SC, Stamer K, Devinsky O. Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy. Neurology 2004;62:258—61.