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Effects of daytime secondarily generalized epileptic seizures on sleep during the following night
Epilepsy & Behavior 25 (2012) 289–294
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Effects of daytime secondarily generalized epileptic seizures on sleep during the following night Therese Gutter ⁎, Al W. de Weerd Department of Clinical Neurophysiology and Sleep Centre SEIN Zwolle, The Netherlands
a r t i c l e
i n f o
Article history: Received 6 May 2012 Revised 22 June 2012 Accepted 28 June 2012 Available online 13 October 2012 Keywords: Seizures Sleep quality Sleep structure Sleep recordings Polysomnography Electroencephalography
a b s t r a c t Nocturnal seizures may disturb sleep, but the effect of an epileptic seizure during daytime on sleep during the next night has been under investigated. In this proof-of-principle study, the sleep of 425 patients with epilepsy, who underwent long-term video-electroencephalography recordings, was analyzed. The sleep recordings were retrospectively divided into two groups: Seizure Free, no seizure occurred at least 24 h before the start of the night sleep recording, and Daytime Seizure, at least one (secondarily) generalized seizure occurred during the day before. In Daytime Seizure, longer time in bed and latency to first REM and more NREM II were seen as well as a decrease of deep sleep and REM sleep compared to Seizure Free. As many participants underwent long-term recordings over a period longer than 48 h, we had the opportunity to compare in individual patients the sleep architecture during nights with and without seizures on the day before the recording. Time in bed and WASO were longer, and sleep efficiency was less in the nights after a seizure on the day before the recording. These differences were statistically significant, but their clinical relevance is doubtful. © 2012 Elsevier Inc. All rights reserved.
1. Introduction The post-ictal phase is different for each individual. The differences in severity and post-ictal signs can only partly be explained by the type and duration of the seizures. The timing of the seizure can also affect the duration of the recovery period. Nocturnal seizures disturb sleep [1,2]; hence, fatigue and daytime drowsiness are often seen. In theory, we might expect good recovery from post-ictal symptoms after a good night's sleep when seizures have occurred during the daytime, but in practice, things may be different. The influence of daytime seizures on sleep during the subsequent night has previously been investigated in small groups only or reported in case studies [3,4]. A reduction of deep sleep and REM sleep and an increase of light sleep were seen. Restriction of total sleep time and also deprivation of only NREM or REM sleep can cause an impairment of alertness, cognitive performance and mood, as measured in healthy subjects [5–7]. The changes in sleep architecture caused by a seizure the previous day could also result in neurobehavioral dysfunction [8]. Due to the fact that sleep architecture differs greatly between people [9], also in people with epilepsy, exploring the effects of daytime seizures on sleep in a larger cohort is worthwhile. Moreover, it is not known whether the effects of a daytime seizure on sleep during the next night differ for various types of epilepsy or whether the localization of the epileptogenic zone makes a difference. It has been reported ⁎ Corresponding author at: Stichting Epilepsie Instellingen Nederland, Dr. Denekampweg 20, 8025 BV Zwolle, The Netherlands. E-mail address: [email protected] (T. Gutter). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2012.06.021
that disturbed sleep is seen more frequently in epilepsy originating from the temporal lobe than in epilepsy from the frontal lobe [10]. After comparison of night sleep recordings after a daytime seizure with recordings after a seizure‐free period of at least 24 h before the night of interest, a decrease of deep sleep and REM sleep and an increase of light sleep can be expected. Also, more short or longer periods of being awake during the night can be expected, as found in previous studies [11–13]. The aim of this study was to investigate the effect of (secondarily) generalized seizures during the day on the objective architecture of sleep during the following night and its relation to the origin and type of the epileptic seizures. 2. Methods 2.1. Selection of recordings In this retrospective, observational cohort study, all 1090 longterm video-electro-encephalographic recordings performed in our tertiary epilepsy clinic in the period April 2006 to January 2010 were re-analyzed. These recordings were made in people with epilepsy aged 15 years or older. After exclusion of all EEGs (a) in which partial sleep deprivation was used as a provocation method, or the period between ‘lights off’ and ‘lights on’ was less than 6 h; (b) in which nocturnal seizures were recorded; (c) which were made in people with a severe intellectual disability; (d) which were incomplete or (e) which were recorded after unclassified seizures less than 24 h before the night of interest, a total of 425 recordings (339 people with epilepsy)
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were used for this study (Fig. 1). The recordings were divided into two groups: group Seizure Free (control group) with 331 recordings in 290 individuals who did not suffer a (secondarily) generalized seizure within the 24 h before the night of investigation and the group Daytime Seizure with 94 recordings in 74 individuals who suffered at least one such generalized seizure during the daytime or early evening before the night of investigation (Study I). A sub-analysis (Study II) of differences between sleep during nights after daytime seizures and nights after seizure-free days was done in all individuals, who during 3–5 days of monitoring had at least one EEG recorded in both situations. In people in whom more than one recording were made in either state, the recording after the most severe seizure was selected for the group Daytime Seizure and the recording after the longest seizure-free period was selected for the group Seizure Free.
etc.), number and type of recorded Daytime Seizures were also noted. All data were collected in accordance with the American Academy of Sleep Medicine (AASM) 2007 rules for measuring sleep (Table 1). 2.3. Semiology of the seizures All seizures were classified according to the International League Against Epilepsy (ILAE) seizure semiological terminology [14,15]. Generalized tonic‐clonic seizures (TCs), tonic seizures (Ts), and seizures that started as a complex partial seizure followed by a secondary generalization (CP+), all with a duration of at least 30 s, were included. The seizures were classified using the clinical signs on the video. Due to the short duration and or no apparent involvement of the brainstem, less severe or more subtle Daytime Seizures were assumed to have no influence on sleep architecture and were not taken into account in this study.
2.2. Database 2.4. Long-term video-EEG and sleep recordings In addition to demographic data, type of epilepsy, localization of the origin of the epilepsy and the different antiepileptic drugs (AEDs) used, the day the recording took place (first night or second, third,
Recordings were performed with 40‐channel Natus-Stellate (Canada) digital video-EEG monitoring systems following the guidelines for long-
Fig. 1. Flow chart with included and excluded recordings.
T. Gutter, A.W. de Weerd / Epilepsy & Behavior 25 (2012) 289–294 Table 1 Variables used to qualify sleep architecture. Sleep variables Objective sleep Time in bed quality Total sleep time Sleep efficiency Sleep latency
Sleep structure
Abbreviation
Measure
TIB TST
NREM I(%)
Light off to light on, in minutes NREM I + NREM II + NREM III+ REM, in minutes TST ∗ 100 / TIB Light off to first epoch of any sleep, in minutes Number of transitions from sleep to waking Stage wake during TIB minus sleep latency, in minutes Number of changes between sleep stages Sleep onset to start of first epoch REM sleep NREM I in minutes / TST ∗ 100
NREM II(%)
NREM II in minutes / TST ∗ 100
NREM III(%)
NREM III in minutes / TST ∗ 100
REM(%)
REM in minutes / TST ∗100
SE SOL
Awakenings
Awakenings
Wake after sleep onset Sleep (stage) changes REM latency
WASO
Percentage stage I Percentage stage II Percentage stage III Percentage stage REM
StCh REM latency
The bold printed variables are recommended by the AASM [10]. REM = rapid eye movement. NREM = non‐REM.
term monitoring of epilepsy [16–18]. In addition to the electrodes of the 10–20 system [19], 4 electrodes were used over the left and right temporal regions according to the 10–10 system (F9, F10, P9 and P10) [20]. Polygraphy was also performed using 2 submental (EMG), 2 eyemovement (EOG), and 2 ECG electrodes and one respiration effort sensor (piezo-electrical crystal, abdominal movements) [21]. Video recordings took place continuously and were time locked to the EEG. The individuals spent the day in a living room where, as far as possible, a normal living situation was simulated. If necessary, patient-specific seizure provocations were used, such as cycling on the ergometer and performing attention tasks. The individuals had private bedrooms at night which were also equipped for video- and audio monitoring. 2.5. Reporting the results All recordings were made for clinical reasons (mainly to diagnose epilepsy), for classification of seizures or for assessment of the individuals for epilepsy surgery. As in common practice, reporting of all EEG phenomena and scoring of the sleep stages were performed by specialized technicians according to the guidelines of the International Federation of Clinical Neurophysiology (IFCN) and the AASM [21,22]. A board‐certified neurologist reviewed the EEG for a second time and made a conclusion with, if applicable, a seizure classification and the clinical relevance of the findings. In cases of discrepancy, reassessment was done by a third expert; this was the final verdict. To assess sleep quality, the sleep variables, time in bed (TIB), total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), awakenings, wake after sleep onset (WASO), stage changes (StCh) and REM latency, were used. The sleep structure was determined based on the distribution of the sleep stages over the night (Table 1). 2.6. Statistical analysis To compare the demographic data between the groups, we used independent-sample t-tests for normally distributed data and Mann– Whitney U tests where data were not normally distributed. The median was used to measure central tendency in the sleep variables which measure duration and frequency because by definition they show an asymptotic distribution (positive skew). These variables were (log-) transformed to a normalized distribution, and comparison between both groups in the main study was done using independent sample
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t-tests. For comparison of the sleep variables in the subgroup of individuals with recordings in both groups, paired sample t-tests were used. Linear regression analysis was used to correct for confounding by age, use of AEDs and the effect of the first night. A sub-analysis for the effects of type and number of seizures was performed using ANOVA with Bonferroni's correction. Differences were considered statistically different at p b 0.05. All statistical analyses were performed with SPSS 16.0 (SPSS Inc., Chicago, IL). 3. Results 3.1. A comparison of sleep architecture in the groups Seizure Free and Daytime Seizure 3.1.1. Subjects and recordings Table 2 shows the demographic data of the Seizure Free and Daytime Seizure groups. No significant difference was seen in age (p = 0.73), gender (p = 0.90), AED use (p = 0.26) and type of epilepsy (p = 0.66). There was a significant difference between the groups for the day of recording (p b 0.001). In the Seizure Free group, 82.5% of the recordings were first-night recordings. In the Daytime Seizure group, only half of the recordings were first-night recordings. In the Daytime Seizure group (94 recordings), 184 seizures were seen: 32 TCs in 23 recordings (19 individuals), 17 Ts in 8 recordings (8 individuals) and 135 CP+ in 63 recordings (47 individuals). 3.1.2. Sleep architecture In Table 3, the group comparisons are shown. People in the Seizure Free group had a shorter time in bed (TIB difference: − 15.5 min, CI95%: −31.00 to − 3.50, p = 0.001) and had a shorter REM latency (difference: − 17.8 min, CI95%: − 29.0 to −3.0, p = 0.01) when compared to those with Daytime Seizures. Significantly less light sleep Table 2 Demographic data of the participants at the time of recording.
Number of video-EEGs (subjects) Age (years) mean (SD) Gender Male Female Antiepileptic drugs None One AED Two AEDs Three AEDs Four AEDs Five AEDs Type of epilepsy Generalized Localization related Frontal Temporal Other localizations Unclear Not classified Day video-EEG of sequence 1st night 2nd night 3rd night 4th night >4th night
Group Seizure Free
Group Daytime Seizure
331 (290)
94 (74)
36.2 (16.3)
36.9 (16.7)
149 (45.0%) 182 (55.0%)
43 (45.7%) 51 (54.3%)
38 110 120 48 14 1
(11.5%) (33.2%) (35.6%) (14.5%) (4.2%) (0.3%)
11 20 45 18 – –
28 27 52 103 11 105 32
(8.5%) (81.9%) (15.7%) (31.1%) (3.3%) (31.7%) (9.7%)
5 (5.3%) 88 (93.6%) 20 (21.3%) 60 (63.8%) 6 (6.4%) 2 (2.1%) 1 (1.1%)
273 17 10 19 12
(82.5%) (5.1%) (3.0%) (5.7%) (3.6%)
46 (48.9%) 21 (22.3%) 8 (8.5%) 14 (14.9%) 5 (5.3%)
⁎t-Test/⁎⁎χ2
⁎⁎⁎
Mann–Whitney U
p = 0.73⁎ p = 0.90⁎⁎
p = 0.26⁎⁎⁎
(11.7%) (21.3%) (47.9%) (19.1%)
p = 0.66⁎⁎
p b 0.001⁎⁎⁎
Age, gender, number of AEDs taken and type of epilepsy of the people with epilepsy at the time of investigation. Group Seizure Free: video-EEGs in people with epilepsy who had been seizure free for at least 24 h before the night of interest. Group Daytime Seizure: video-EEGs in people who suffered a (secondary) generalized seizure on the day before the night of interest.
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Table 3 Central values of the sleep variables of all recordings in the Seizure Free and Daytime Seizure groups. Total recordings (N = 425)
Group Seizure Free (N = 331 recordings)
Group Daytime Seizure (N = 94 recordings)
Differences Seizure Free minus Daytime Seizure
t-Test (2-sided)
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
508.5a 415.5a 79.1b 19.5a 18.0a 59.0a 79.0a 93.0a 14.8b 39.7b 26.2b 19.3b
524.0a 433.8a 79.1b 19.8a 18.0a 62.0a 84.0a 110.8a 16.6b 42.5b 23.3b 17.6b
−15.5 −18.3 0 0.3 0 −3.0 −5.0 −17.8 −1.8 −2.8 2.9 1.7
p = 0.001 p = 0.068 p = 0.998 p = 0.499 p = 0.974 p = 0.700 p = 0.437 p = 0.010 p = 0.150 p = 0.023 p = 0.012 p = 0.037
(379.0–714.0) (138.5–644.0) (14.1) (1.5–255.0) (0–83) (8.0–333.0) (26–216) (8.0–373.5) (9.9) (10.2) (9.7) (6.8)
(439.0–755.5) (189.0–688.5) (14.2) (2.0–240.0) (1–71) (5.5–355.5) (20–206) (9.0–613.5) (12.9) (12.1) (9.8) (7.5)
The central values (with range or SD) of sleep variables of all recordings in people who were seizure free for at least 24 h before the night of interest and in those who suffered a (secondarily) generalized seizure on the day before the night of interest (Daytime Seizure). In addition, the differences between the central values of both groups and the p‐value obtained using the unpaired t-test are shown (log-transformation was used in non-normally distributed variables before statistical analysis). a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
(NREM II(%):− 2.8%, CI95%:− 5.2 to− 0.4, p = 0.023) and more deep sleep (NREM III(%): 2.9%, CI95%: 0.6 to 5.0, p = 0.012 and REM(%) (1.7%, CI95%: 0.1 to 3.3), p = 0.037) were seen in the Seizure Free group than in the Daytime Seizure group. For the other parameters, no significant differences were found between the groups. 3.1.3. Influence of age, AEDs and day of sequence Linear regression with age as a potential confounder did not show an effect on the differences between the sleep variables in the groups except for TST. The shorter period TST (difference: 18.3 min) was not significant before correction (beta coefficient (B) = 0.05, p = 0.068), but after correction for age, the difference met the statistical criterion (B = 0.054, p = 0.037). Multivariate analysis including the number of different AEDs taken did not change the findings. First-night effect as a potential confounder resulted only a change in NREM III(%). The difference in the percentage NREM III between both groups after correction for day of sequence of recording was no longer statistically significant (univariate: B=−2.833, p=0.012; multivariate: B=−2.241, p=0.059). 3.1.4. Influence of localization of the epileptogenic area Temporal and frontal epilepsies were the most common types seen in this study. After exclusion of recordings with an unclear localization (N = 107), those with generalized epilepsy (N = 33) and unclassified
epilepsy (N = 33), a total of 252 recordings remained (205 subjects). For those belonging to the group Daytime Seizure, the TIB, TST and REM latency were longer (TIB difference: − 12.0 min, p = 0.006; TST: − 18.0 min, p = 0.050; REM latency: 21.8 min, p = 0.011) than the recordings in the Seizure Free group. The differences between the sleep stages were no longer significant between the groups, and multivariate analysis with localization of the epileptogenic zone as a possible confounder did not change these findings. 3.1.5. Influence of the type and number of seizures Multiple comparisons were performed using one-way ANOVA to measure the differences between the central values of the sleep variables of the night sleep recordings after TCs, Ts and CP+ s. Significant differences between these groups are seen in TIB (pb 0.001), SE (p=0.017), SOL (p = 0.026), WASO (p = 0.017), NREM I(%) (p =0.037) and REM sleep (p= 0.002) (Table 4). Bonferroni's post hoc test showed more TIB and WASO and less REM sleep after TCs than after CP + s and a lower SE, longer SOL, more REM I and less REM sleep after Ts than after CP + s. One-way ANOVA suggested that the influence of the number of seizures during daytime was negligible. The assumption that simple partial and more subtle seizures during daytime did not change sleep architecture was also checked. The recordings (N= 39) after only short-term seizures during the day before
Table 4 Central values of the sleep variables of all recordings in individuals with a seizure during daytime. Total recordings (N = 94)
Tonic‐clonic seizure (N = 23 recordings)
Tonic seizure (N = 8 recordings)
Complex partial with secondarily generalization (N = 63 recordings)
One-way ANOVA
Bonferroni's post hoc test
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
571.0a 457.0a 76.0b 28.0a 20.0a 100.5a 95.0a 131.5a 16.9b 43.4b 25.7b 14.2b
558.3a 370.0a 68.0b 27.8a 12.0a 60.0a 80.0a 127.3a 27.4b 42.2b 17.5b 12.8b
506.0 431.5 81.6 17.0 18.0 48.5 81.0 105.5 15.1 42.2 23.2 19.43
p b 0.001 p = 0.064 p = 0.017 p = 0.026 p = 0.064 p = 0.016 p = 0.064 p = 0.317 p = 0.037 p = 0.908 p = 0.096 p = 0.002
TC > CP+; p b 0.001
(456.0–755.5) (238.0–688.5) (13.0) (3.5–82.5) (6–62) (17.5–321.0) (34–206) (9.0–613.5) (8.9) (9.5) (8.2) (7.4)
(439.0–702.0) (224.5–514.5) (21.3) (10.0–240.0) (1–71) (5.5–355.5) (20–195) (60.0–355.0) (25.6) (19.7) (10.7) (7.7)
(449.5–695.5) (189.0–606.5) (12.9) (2.0–99.5) (5–59) (5.5–355.0) (28–171) (51.0–499.0) (11.4) (10.8) (9.3) (6.9)
T b CP+; p = 0.029 T > CP+; p = 0.036 TC > CP+; p = 0.021
T > CP+; p = 0.032
TC b CP+; p= 0.009 T b CP+; p = 0.045
The central values (range and SD) of sleep variables in the recordings of individuals with a seizure during daytime. In addition, the p-values are shown when the differences of central values between seizure groups were significant. a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
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Table 5 Central values of the sleep variables of all recordings in individuals with one recording in each situation. Total recordings (N = 23)
Seizure Free
Daytime Seizure
Differences Seizure Free minus Daytime Seizure
Paired t-test (2-sided)
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
507.0a (440.0–584.0) 447.0a (317.5–529.5) 84.4b (8.95) 17.0a (5.0–97.5) 18.0a (7–34) 51.0a (11.0–126.5) 80.0a (35–123) 97.4a (8.0–261.5) 13.1b (8.5) 41.6b (9.7) 25.5b (9.7) 19.7b (5.7)
523.0a (470.5–743.5) 431.5a (238.0–688.5) 78.4b (17.26) 15.5a (3.5–45.0) 16.0a (6–40) 53.5a (11.5–355.5) 81.0a (33–127) 110.5a (9.0–485.0) 15.4b (9.5) 43.1b (12.1) 23.1b (7.0) 18.5b (8.6)
−26.0 10.0 6.0 0.5 1.0 −22.8 −2.0 −25.3 −2.3 −1.5 2.4 1.2
p = 0.021 p= 0.574 p = 0.008 p= 0.478 p= 0.725 p = 0.004 p= 0.962 p= 0.119 p= 0.183 p= 0.474 p= 0.176 p= 0.386
The central values (range or SD) of the sleep variables in the recordings in individuals with both one recording after a seizure-free period of at least 24 h and one recording during the night following a (secondarily) generalized seizure during the day. In addition, the differences between the central values of both groups [3,4] (with confidential interval) are shown. The p‐value was obtained using the paired t-test (log-transformation was used in non-normally distributed variables before statistical analysis). a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
were compared with the recordings after a seizure free period of at least 24 hours (N= 292). Between both groups, no significant differences were found. Comparison of the recordings after only short-term seizures (N=39) and the recordings of the Daytime Seizure group with more severe seizures (N=94) showed a longer TIB (18.5 min, p=0.026), more light sleep (NREM II(%): 4.95%, p=0.023), less deep sleep (NREM III(%): −4.10%, p =0.023) and less REM sleep (−3.45%, p=0.015) in the group with the severe seizures. REM latency was again longer after severe seizures but not significant anymore (21.25 min, p=0.331). The other sleep variables also did not differ significantly. 3.2. Comparison of the sleep architecture in people with recordings in both groups 3.2.1. Subjects and recordings In 23 individuals, with a mean age of 36.7 years (SD: 14.2), night sleep was recorded in both the Daytime Seizure and Seizure Free situations. These individuals all had partial epilepsy; the localization was temporal in 20, frontal in one and not classifiable in two. Three individuals did not use AEDs at all, 6 used only one AED, 12 used two AEDs and 2 used three AEDs. Forty seizures were recorded: 12 TCs (8 subjects) and 28 CP+ (15 subjects). 3.2.2. Architecture of sleep After a daytime seizure before the night of investigation (Daytime Seizure), TIB (p = 0.021) and WASO (p = 0.004) were longer and SE (p = 0.008) was lower when compared to the Seizure Free situation (Table 5). 3.2.3. Influence of potential confounders The differences in sleep between Seizure Free and Daytime Seizure were corrected for potential confounding. Neither age [23], number of AEDs, day of recording [24–26] nor type of seizure led to any bias. 4. Discussion In this study, the objective architecture of sleep in people with epilepsy who suffered a (secondarily) generalized seizure on the day before the night of interest was compared with the architecture of sleep in people with epilepsy who were seizure free for at least the previous 24 h. This resulted in differences which are discussed below, together with the findings in 23 subjects who had recordings in both situations.
4.1. Comparison of the groups Seizure Free and Daytime Seizure 4.1.1. Architecture of sleep Comparison of the groups Seizure Free and Daytime Seizure showed an increase of TIB and REM latency after daytime seizures. This corresponds to findings in two previous studies where the night sleep in people with partial epilepsy was compared to the night sleep in controls [12,26]. The differences in our study were small and are of dubious value in discrimination of a possible sleep disorder. During the night following a daytime seizure, more NREM II, less NREM III and less REM sleep were found than in the night after a seizure-free period longer than 24 h. The decrease in NREM III and REM sleep corresponds with an often cited case study of a 52-year-old woman with status epilepticus during the daytime [4]. In this case, the reported decrease of light sleep (NREM II) on the first night was in contrast with the increase of NREM II(%) we found in our study. Our finding of a decrease of REM sleep is in accordance with the results of another study which found a 6% decrease in REM sleep after complex partial seizures on the day before in people with temporal lobe epilepsy [3]. In our study, all types of epilepsy were included. 4.1.2. Influence of localization of the epileptogenic zone The comparison of only the night sleep recordings of people with partial epilepsy showed, both before and after correction for the localization of the epileptic‐onset zone, an increase of TIB, TST and REM latency in the Daytime Seizure group compared with those who were Seizure Free. Thus, the onset zone has no influence on sleep quality. Previous studies in people with generalized epilepsy showed an increase of time in light sleep and a decrease of deep sleep and REM sleep compared to the sleep structure in healthy volunteers [12,13,27]. We had insufficient data on this type of epilepsy to comment further. 4.1.3. Influence of type of seizure Tonic‐clonic seizures (TCs) had more impact on total TIB, WASO and percentage REM than complex partial seizures with secondary generalization (CP+) (Table 5). In another study, the sleep structure was assessed after differentiation for type of seizure. Rapid eye movement sleep was more suppressed after a complex partial seizure with temporal origin and secondary generalization than after a seizure without secondary generalization [13]. Our findings confirm a decrease of REM sleep after a (secondarily) generalized seizure during the day. The longer TIB and WASO after a TC have not been described previously. Tonic‐clonic seizures are the most severe seizures with most impact
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and longest duration. After this type of seizure, the patient is often tired and goes to bed, and no seizure‐provocative activities are performed to avoid seizure clustering or even status epilepticus. In general, sleep starts early after these severe seizures. The often long duration of the ictal phenomena in TCs may result in a prolonged disturbance of the brainstem and deeper brain structures. This phenomenon might explain the major effects on REM sleep.
4.2. Subjects with days with and without seizures 4.2.1. Architecture of sleep In this group of 23 individuals who – in the same long‐term monitoring – underwent recordings after days with and without seizures, TIB was longer during the night after a seizure on the day before when compared to the night in the other condition. Its background is discussed above. Our finding of longer WASO after one or more seizures, resulting in a lower SE, has also been described in previous studies [12,27]. In contrast with these studies, in our study, nocturnal seizures were a reason for exclusion. The clinical relevance of the longer WASO and lower SE as a result of a daytime seizure may be doubtful. The differences between both groups, with the same persons in both groups Seizure Free and Daytime Seizure, are small, while the variability of these sleep variables is still large. The distribution of sleep stage was similar in the recordings with and without seizures on the day before. This is in contrast to the findings in the cohort study. Apart from differences in the number of individuals studied, we have no explanation for this finding. Correction for confounding by age, number of AEDs taken, and type of seizure or localization of its origin did not change the results in this group of 23 individuals. The reduction of REM sleep in temporal lobe epilepsy, as expected from an earlier study, could not be confirmed in our study [3].
4.2.2. Limitations The study took place in a tertiary-care epilepsy clinic. This may introduce bias in patient selection, for example more people with localization-related epilepsy. Exclusion of mental retardation as comorbidity may also have influenced the findings. Although the influence of the number of different AEDs was controlled, change of medication used as provocation procedure during consecutive recordings was not included as an additional variable in this study. Furthermore, the retrospective character of our study prohibits judgments on the quality of sleep by the individuals themselves.
4.2.3. Conclusion In a cohort of 425 people with epilepsy, longer TIB and REM latency, more NREM II and less NREM III and REM sleep were seen after a (secondarily) generalized seizure on the day before the recording. In the 23 people with recordings after days with and without seizures, more WASO, resulting in a lower SE, was seen during the night after a daytime seizure. These significant differences in both studies are from objective measurements. The relationship with the subjective perception of their sleep in these individuals is unknown and will be investigated in further research.
Acknowledgment This work was supported by the 'Christelijke Vereniging van Lijders aan Epilepsie' an a grant from UCB Pharma B.V. References [1] Hofstra WA, Grootemarsink BE, Dieker R, van der Palen J, de Weerd AW. Temporal distribution of clinical seizures over the 24 hour day: a retrospective observational study in a tertiary epilepsy clinic. Epilepsia 2009;50(9):2019-26. [2] Herman S, Walczak T, Bazil C. Distribution of the partial seizures during the sleep– wake cycle. Neurology 2001;56:1453-9. [3] Bazil C, Castro L, Walczak T. Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy. Arch Neurol 2000;57:363-8. [4] Bazil C, Andersen C. Sleep structure following status epilepticus. Sleep Med 2001;2: 447-9. [5] Dongen van HPA, Maislin G, Mullington JM, Dinges DF. The cumulative cost of addition wakefulness: dose–response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 2003;2(26):117-26. [6] Endo T, Roth C, Landolt HP, et al. Selective REM sleep deprivation in humans: effects on sleep and sleep EEG. Am J Physiol Regul Integr Comp Physiol 1998;274:R1186-94. [7] Kunz D, Mahlberg R, Müller C, Tilmanne A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab 2004;89(1):128-34. [8] Bazil CW. Effects of sleep on the postictal state. Epilepsy Behav 2010;19:146-50. [9] Ohayon M, Carskadon M, Guilleminault C, Vitiello M. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human. Sleep 2004;27(7):1255-73. [10] Crespel A, Coubes P, Baldy-Moulinier M. Sleep influence on seizures and epilepsy effect on sleep in partial frontal and temporal lobe epilepsies. J Clin Neurophysiol 2000;111(S2):S54-9. [11] Hamel AR, Sterman MB. Sleep and epilepsy abnormalities during sleep. In: Sterman MB, Shouse MN, Passouant P, editors. Sleep and Epilepsy. Orlando, Fla: Academic Press Inc; 1982. p. 361-77. [12] Besset A. Influence of generalized seizures on sleep organization. In: Sterman MB, Shouse MN, Passouant P, editors. Sleep and epilepsy. Orlando, Fla: Academic Press Inc; 1982. p. 339-46. [13] Declerck AC, Wauquier A, Sijben-Kiggen R, Martens W. A normative study of sleep in different forms of epilepsy. In: Sterman MB, Shouse MN, Passouant P, editors. Sleep and Epilepsy. Orlando, Fla: Academic Press Inc; 1982. p. 329-38. [14] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501. [15] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99. [16] Flink R. Guidelines for the use of EEG methodology in the diagnosis of epilepsy. Acta Neurol Scand 2002;106:1-7. [17] American Electroencephalographic Society. Guideline fourteen: guidelines for recording clinical EEG on digital media. J Clin Neurophysiol 1994;11(1):114-5. [18] American Electroencephalographic Society. Guideline twelve: guidelines for long-term monitoring for epilepsy. J Clin Neurophysiol 1994;11(1):88–110. [19] Jasper HH. The ten-twenty electrode system of the International Federation. Electroencephalogr Clin Neurophysiol 1958;10:371-5. [20] American Electroencephalographic Society. Guideline thirteen: guidelines for standard electrode position nomenclature. J Clin Neurophysiol 1994;11:111-3. [21] Iber C, Ancoli-Israel S, Chesson A, Quan S, for the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. 1st ed. Westchester, Illinois: American Academy of Sleep Medicine; 2007. [22] Rechtschaffen A, Kales A, editors. A manual of standardized terminology, techniques and scoring system of sleep stages in human subjects. Los Angeles: Brain Information Service/Brain Research Institute, University of California. 1968. [23] Hirshkowitz M, Moore CA, Hamilton III CR, Rando KC, Karacan I. Polysomnography of adults and elderly: sleep architecture, respiration, and leg movement. J Clin Neurophysiol 1992;9(1):56-62. [24] Montplaisir J, Laverdière M, Sant-Hilaire JM, Rouleau I. Nocturnal sleep recording in partial epilepsy: a study with depth electrodes. J Clin Neurophysiol 1987;4(4):383-8. [25] Marzec ML, Selwa LM, Malow BA. Analysis of the first night effect and sleep parameters in medically refractory epilepsy patients. Sleep Med 2004;6:277-80. [26] Selwa LM, Marzec ML, Chervin RD, et al. Sleep staging and respiratory events in refractory epilepsy patients: is there a first night effect? Epilepsia 2008;49(12):2063-8. [27] Baldy-Moulinier M. 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Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Effects of daytime secondarily generalized epileptic seizures on sleep during the following night Therese Gutter ⁎, Al W. de Weerd Department of Clinical Neurophysiology and Sleep Centre SEIN Zwolle, The Netherlands
a r t i c l e
i n f o
Article history: Received 6 May 2012 Revised 22 June 2012 Accepted 28 June 2012 Available online 13 October 2012 Keywords: Seizures Sleep quality Sleep structure Sleep recordings Polysomnography Electroencephalography
a b s t r a c t Nocturnal seizures may disturb sleep, but the effect of an epileptic seizure during daytime on sleep during the next night has been under investigated. In this proof-of-principle study, the sleep of 425 patients with epilepsy, who underwent long-term video-electroencephalography recordings, was analyzed. The sleep recordings were retrospectively divided into two groups: Seizure Free, no seizure occurred at least 24 h before the start of the night sleep recording, and Daytime Seizure, at least one (secondarily) generalized seizure occurred during the day before. In Daytime Seizure, longer time in bed and latency to first REM and more NREM II were seen as well as a decrease of deep sleep and REM sleep compared to Seizure Free. As many participants underwent long-term recordings over a period longer than 48 h, we had the opportunity to compare in individual patients the sleep architecture during nights with and without seizures on the day before the recording. Time in bed and WASO were longer, and sleep efficiency was less in the nights after a seizure on the day before the recording. These differences were statistically significant, but their clinical relevance is doubtful. © 2012 Elsevier Inc. All rights reserved.
1. Introduction The post-ictal phase is different for each individual. The differences in severity and post-ictal signs can only partly be explained by the type and duration of the seizures. The timing of the seizure can also affect the duration of the recovery period. Nocturnal seizures disturb sleep [1,2]; hence, fatigue and daytime drowsiness are often seen. In theory, we might expect good recovery from post-ictal symptoms after a good night's sleep when seizures have occurred during the daytime, but in practice, things may be different. The influence of daytime seizures on sleep during the subsequent night has previously been investigated in small groups only or reported in case studies [3,4]. A reduction of deep sleep and REM sleep and an increase of light sleep were seen. Restriction of total sleep time and also deprivation of only NREM or REM sleep can cause an impairment of alertness, cognitive performance and mood, as measured in healthy subjects [5–7]. The changes in sleep architecture caused by a seizure the previous day could also result in neurobehavioral dysfunction [8]. Due to the fact that sleep architecture differs greatly between people [9], also in people with epilepsy, exploring the effects of daytime seizures on sleep in a larger cohort is worthwhile. Moreover, it is not known whether the effects of a daytime seizure on sleep during the next night differ for various types of epilepsy or whether the localization of the epileptogenic zone makes a difference. It has been reported ⁎ Corresponding author at: Stichting Epilepsie Instellingen Nederland, Dr. Denekampweg 20, 8025 BV Zwolle, The Netherlands. E-mail address: [email protected] (T. Gutter). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2012.06.021
that disturbed sleep is seen more frequently in epilepsy originating from the temporal lobe than in epilepsy from the frontal lobe [10]. After comparison of night sleep recordings after a daytime seizure with recordings after a seizure‐free period of at least 24 h before the night of interest, a decrease of deep sleep and REM sleep and an increase of light sleep can be expected. Also, more short or longer periods of being awake during the night can be expected, as found in previous studies [11–13]. The aim of this study was to investigate the effect of (secondarily) generalized seizures during the day on the objective architecture of sleep during the following night and its relation to the origin and type of the epileptic seizures. 2. Methods 2.1. Selection of recordings In this retrospective, observational cohort study, all 1090 longterm video-electro-encephalographic recordings performed in our tertiary epilepsy clinic in the period April 2006 to January 2010 were re-analyzed. These recordings were made in people with epilepsy aged 15 years or older. After exclusion of all EEGs (a) in which partial sleep deprivation was used as a provocation method, or the period between ‘lights off’ and ‘lights on’ was less than 6 h; (b) in which nocturnal seizures were recorded; (c) which were made in people with a severe intellectual disability; (d) which were incomplete or (e) which were recorded after unclassified seizures less than 24 h before the night of interest, a total of 425 recordings (339 people with epilepsy)
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were used for this study (Fig. 1). The recordings were divided into two groups: group Seizure Free (control group) with 331 recordings in 290 individuals who did not suffer a (secondarily) generalized seizure within the 24 h before the night of investigation and the group Daytime Seizure with 94 recordings in 74 individuals who suffered at least one such generalized seizure during the daytime or early evening before the night of investigation (Study I). A sub-analysis (Study II) of differences between sleep during nights after daytime seizures and nights after seizure-free days was done in all individuals, who during 3–5 days of monitoring had at least one EEG recorded in both situations. In people in whom more than one recording were made in either state, the recording after the most severe seizure was selected for the group Daytime Seizure and the recording after the longest seizure-free period was selected for the group Seizure Free.
etc.), number and type of recorded Daytime Seizures were also noted. All data were collected in accordance with the American Academy of Sleep Medicine (AASM) 2007 rules for measuring sleep (Table 1). 2.3. Semiology of the seizures All seizures were classified according to the International League Against Epilepsy (ILAE) seizure semiological terminology [14,15]. Generalized tonic‐clonic seizures (TCs), tonic seizures (Ts), and seizures that started as a complex partial seizure followed by a secondary generalization (CP+), all with a duration of at least 30 s, were included. The seizures were classified using the clinical signs on the video. Due to the short duration and or no apparent involvement of the brainstem, less severe or more subtle Daytime Seizures were assumed to have no influence on sleep architecture and were not taken into account in this study.
2.2. Database 2.4. Long-term video-EEG and sleep recordings In addition to demographic data, type of epilepsy, localization of the origin of the epilepsy and the different antiepileptic drugs (AEDs) used, the day the recording took place (first night or second, third,
Recordings were performed with 40‐channel Natus-Stellate (Canada) digital video-EEG monitoring systems following the guidelines for long-
Fig. 1. Flow chart with included and excluded recordings.
T. Gutter, A.W. de Weerd / Epilepsy & Behavior 25 (2012) 289–294 Table 1 Variables used to qualify sleep architecture. Sleep variables Objective sleep Time in bed quality Total sleep time Sleep efficiency Sleep latency
Sleep structure
Abbreviation
Measure
TIB TST
NREM I(%)
Light off to light on, in minutes NREM I + NREM II + NREM III+ REM, in minutes TST ∗ 100 / TIB Light off to first epoch of any sleep, in minutes Number of transitions from sleep to waking Stage wake during TIB minus sleep latency, in minutes Number of changes between sleep stages Sleep onset to start of first epoch REM sleep NREM I in minutes / TST ∗ 100
NREM II(%)
NREM II in minutes / TST ∗ 100
NREM III(%)
NREM III in minutes / TST ∗ 100
REM(%)
REM in minutes / TST ∗100
SE SOL
Awakenings
Awakenings
Wake after sleep onset Sleep (stage) changes REM latency
WASO
Percentage stage I Percentage stage II Percentage stage III Percentage stage REM
StCh REM latency
The bold printed variables are recommended by the AASM [10]. REM = rapid eye movement. NREM = non‐REM.
term monitoring of epilepsy [16–18]. In addition to the electrodes of the 10–20 system [19], 4 electrodes were used over the left and right temporal regions according to the 10–10 system (F9, F10, P9 and P10) [20]. Polygraphy was also performed using 2 submental (EMG), 2 eyemovement (EOG), and 2 ECG electrodes and one respiration effort sensor (piezo-electrical crystal, abdominal movements) [21]. Video recordings took place continuously and were time locked to the EEG. The individuals spent the day in a living room where, as far as possible, a normal living situation was simulated. If necessary, patient-specific seizure provocations were used, such as cycling on the ergometer and performing attention tasks. The individuals had private bedrooms at night which were also equipped for video- and audio monitoring. 2.5. Reporting the results All recordings were made for clinical reasons (mainly to diagnose epilepsy), for classification of seizures or for assessment of the individuals for epilepsy surgery. As in common practice, reporting of all EEG phenomena and scoring of the sleep stages were performed by specialized technicians according to the guidelines of the International Federation of Clinical Neurophysiology (IFCN) and the AASM [21,22]. A board‐certified neurologist reviewed the EEG for a second time and made a conclusion with, if applicable, a seizure classification and the clinical relevance of the findings. In cases of discrepancy, reassessment was done by a third expert; this was the final verdict. To assess sleep quality, the sleep variables, time in bed (TIB), total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), awakenings, wake after sleep onset (WASO), stage changes (StCh) and REM latency, were used. The sleep structure was determined based on the distribution of the sleep stages over the night (Table 1). 2.6. Statistical analysis To compare the demographic data between the groups, we used independent-sample t-tests for normally distributed data and Mann– Whitney U tests where data were not normally distributed. The median was used to measure central tendency in the sleep variables which measure duration and frequency because by definition they show an asymptotic distribution (positive skew). These variables were (log-) transformed to a normalized distribution, and comparison between both groups in the main study was done using independent sample
291
t-tests. For comparison of the sleep variables in the subgroup of individuals with recordings in both groups, paired sample t-tests were used. Linear regression analysis was used to correct for confounding by age, use of AEDs and the effect of the first night. A sub-analysis for the effects of type and number of seizures was performed using ANOVA with Bonferroni's correction. Differences were considered statistically different at p b 0.05. All statistical analyses were performed with SPSS 16.0 (SPSS Inc., Chicago, IL). 3. Results 3.1. A comparison of sleep architecture in the groups Seizure Free and Daytime Seizure 3.1.1. Subjects and recordings Table 2 shows the demographic data of the Seizure Free and Daytime Seizure groups. No significant difference was seen in age (p = 0.73), gender (p = 0.90), AED use (p = 0.26) and type of epilepsy (p = 0.66). There was a significant difference between the groups for the day of recording (p b 0.001). In the Seizure Free group, 82.5% of the recordings were first-night recordings. In the Daytime Seizure group, only half of the recordings were first-night recordings. In the Daytime Seizure group (94 recordings), 184 seizures were seen: 32 TCs in 23 recordings (19 individuals), 17 Ts in 8 recordings (8 individuals) and 135 CP+ in 63 recordings (47 individuals). 3.1.2. Sleep architecture In Table 3, the group comparisons are shown. People in the Seizure Free group had a shorter time in bed (TIB difference: − 15.5 min, CI95%: −31.00 to − 3.50, p = 0.001) and had a shorter REM latency (difference: − 17.8 min, CI95%: − 29.0 to −3.0, p = 0.01) when compared to those with Daytime Seizures. Significantly less light sleep Table 2 Demographic data of the participants at the time of recording.
Number of video-EEGs (subjects) Age (years) mean (SD) Gender Male Female Antiepileptic drugs None One AED Two AEDs Three AEDs Four AEDs Five AEDs Type of epilepsy Generalized Localization related Frontal Temporal Other localizations Unclear Not classified Day video-EEG of sequence 1st night 2nd night 3rd night 4th night >4th night
Group Seizure Free
Group Daytime Seizure
331 (290)
94 (74)
36.2 (16.3)
36.9 (16.7)
149 (45.0%) 182 (55.0%)
43 (45.7%) 51 (54.3%)
38 110 120 48 14 1
(11.5%) (33.2%) (35.6%) (14.5%) (4.2%) (0.3%)
11 20 45 18 – –
28 27 52 103 11 105 32
(8.5%) (81.9%) (15.7%) (31.1%) (3.3%) (31.7%) (9.7%)
5 (5.3%) 88 (93.6%) 20 (21.3%) 60 (63.8%) 6 (6.4%) 2 (2.1%) 1 (1.1%)
273 17 10 19 12
(82.5%) (5.1%) (3.0%) (5.7%) (3.6%)
46 (48.9%) 21 (22.3%) 8 (8.5%) 14 (14.9%) 5 (5.3%)
⁎t-Test/⁎⁎χ2
⁎⁎⁎
Mann–Whitney U
p = 0.73⁎ p = 0.90⁎⁎
p = 0.26⁎⁎⁎
(11.7%) (21.3%) (47.9%) (19.1%)
p = 0.66⁎⁎
p b 0.001⁎⁎⁎
Age, gender, number of AEDs taken and type of epilepsy of the people with epilepsy at the time of investigation. Group Seizure Free: video-EEGs in people with epilepsy who had been seizure free for at least 24 h before the night of interest. Group Daytime Seizure: video-EEGs in people who suffered a (secondary) generalized seizure on the day before the night of interest.
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Table 3 Central values of the sleep variables of all recordings in the Seizure Free and Daytime Seizure groups. Total recordings (N = 425)
Group Seizure Free (N = 331 recordings)
Group Daytime Seizure (N = 94 recordings)
Differences Seizure Free minus Daytime Seizure
t-Test (2-sided)
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
508.5a 415.5a 79.1b 19.5a 18.0a 59.0a 79.0a 93.0a 14.8b 39.7b 26.2b 19.3b
524.0a 433.8a 79.1b 19.8a 18.0a 62.0a 84.0a 110.8a 16.6b 42.5b 23.3b 17.6b
−15.5 −18.3 0 0.3 0 −3.0 −5.0 −17.8 −1.8 −2.8 2.9 1.7
p = 0.001 p = 0.068 p = 0.998 p = 0.499 p = 0.974 p = 0.700 p = 0.437 p = 0.010 p = 0.150 p = 0.023 p = 0.012 p = 0.037
(379.0–714.0) (138.5–644.0) (14.1) (1.5–255.0) (0–83) (8.0–333.0) (26–216) (8.0–373.5) (9.9) (10.2) (9.7) (6.8)
(439.0–755.5) (189.0–688.5) (14.2) (2.0–240.0) (1–71) (5.5–355.5) (20–206) (9.0–613.5) (12.9) (12.1) (9.8) (7.5)
The central values (with range or SD) of sleep variables of all recordings in people who were seizure free for at least 24 h before the night of interest and in those who suffered a (secondarily) generalized seizure on the day before the night of interest (Daytime Seizure). In addition, the differences between the central values of both groups and the p‐value obtained using the unpaired t-test are shown (log-transformation was used in non-normally distributed variables before statistical analysis). a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
(NREM II(%):− 2.8%, CI95%:− 5.2 to− 0.4, p = 0.023) and more deep sleep (NREM III(%): 2.9%, CI95%: 0.6 to 5.0, p = 0.012 and REM(%) (1.7%, CI95%: 0.1 to 3.3), p = 0.037) were seen in the Seizure Free group than in the Daytime Seizure group. For the other parameters, no significant differences were found between the groups. 3.1.3. Influence of age, AEDs and day of sequence Linear regression with age as a potential confounder did not show an effect on the differences between the sleep variables in the groups except for TST. The shorter period TST (difference: 18.3 min) was not significant before correction (beta coefficient (B) = 0.05, p = 0.068), but after correction for age, the difference met the statistical criterion (B = 0.054, p = 0.037). Multivariate analysis including the number of different AEDs taken did not change the findings. First-night effect as a potential confounder resulted only a change in NREM III(%). The difference in the percentage NREM III between both groups after correction for day of sequence of recording was no longer statistically significant (univariate: B=−2.833, p=0.012; multivariate: B=−2.241, p=0.059). 3.1.4. Influence of localization of the epileptogenic area Temporal and frontal epilepsies were the most common types seen in this study. After exclusion of recordings with an unclear localization (N = 107), those with generalized epilepsy (N = 33) and unclassified
epilepsy (N = 33), a total of 252 recordings remained (205 subjects). For those belonging to the group Daytime Seizure, the TIB, TST and REM latency were longer (TIB difference: − 12.0 min, p = 0.006; TST: − 18.0 min, p = 0.050; REM latency: 21.8 min, p = 0.011) than the recordings in the Seizure Free group. The differences between the sleep stages were no longer significant between the groups, and multivariate analysis with localization of the epileptogenic zone as a possible confounder did not change these findings. 3.1.5. Influence of the type and number of seizures Multiple comparisons were performed using one-way ANOVA to measure the differences between the central values of the sleep variables of the night sleep recordings after TCs, Ts and CP+ s. Significant differences between these groups are seen in TIB (pb 0.001), SE (p=0.017), SOL (p = 0.026), WASO (p = 0.017), NREM I(%) (p =0.037) and REM sleep (p= 0.002) (Table 4). Bonferroni's post hoc test showed more TIB and WASO and less REM sleep after TCs than after CP + s and a lower SE, longer SOL, more REM I and less REM sleep after Ts than after CP + s. One-way ANOVA suggested that the influence of the number of seizures during daytime was negligible. The assumption that simple partial and more subtle seizures during daytime did not change sleep architecture was also checked. The recordings (N= 39) after only short-term seizures during the day before
Table 4 Central values of the sleep variables of all recordings in individuals with a seizure during daytime. Total recordings (N = 94)
Tonic‐clonic seizure (N = 23 recordings)
Tonic seizure (N = 8 recordings)
Complex partial with secondarily generalization (N = 63 recordings)
One-way ANOVA
Bonferroni's post hoc test
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
571.0a 457.0a 76.0b 28.0a 20.0a 100.5a 95.0a 131.5a 16.9b 43.4b 25.7b 14.2b
558.3a 370.0a 68.0b 27.8a 12.0a 60.0a 80.0a 127.3a 27.4b 42.2b 17.5b 12.8b
506.0 431.5 81.6 17.0 18.0 48.5 81.0 105.5 15.1 42.2 23.2 19.43
p b 0.001 p = 0.064 p = 0.017 p = 0.026 p = 0.064 p = 0.016 p = 0.064 p = 0.317 p = 0.037 p = 0.908 p = 0.096 p = 0.002
TC > CP+; p b 0.001
(456.0–755.5) (238.0–688.5) (13.0) (3.5–82.5) (6–62) (17.5–321.0) (34–206) (9.0–613.5) (8.9) (9.5) (8.2) (7.4)
(439.0–702.0) (224.5–514.5) (21.3) (10.0–240.0) (1–71) (5.5–355.5) (20–195) (60.0–355.0) (25.6) (19.7) (10.7) (7.7)
(449.5–695.5) (189.0–606.5) (12.9) (2.0–99.5) (5–59) (5.5–355.0) (28–171) (51.0–499.0) (11.4) (10.8) (9.3) (6.9)
T b CP+; p = 0.029 T > CP+; p = 0.036 TC > CP+; p = 0.021
T > CP+; p = 0.032
TC b CP+; p= 0.009 T b CP+; p = 0.045
The central values (range and SD) of sleep variables in the recordings of individuals with a seizure during daytime. In addition, the p-values are shown when the differences of central values between seizure groups were significant. a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
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Table 5 Central values of the sleep variables of all recordings in individuals with one recording in each situation. Total recordings (N = 23)
Seizure Free
Daytime Seizure
Differences Seizure Free minus Daytime Seizure
Paired t-test (2-sided)
TIB (min) TST (min) SE (%) SOL (min) Awakenings WASO (min) StCh REM latency (min) NREM I(%) NREM II(%) NREM III(%) REM(%)
507.0a (440.0–584.0) 447.0a (317.5–529.5) 84.4b (8.95) 17.0a (5.0–97.5) 18.0a (7–34) 51.0a (11.0–126.5) 80.0a (35–123) 97.4a (8.0–261.5) 13.1b (8.5) 41.6b (9.7) 25.5b (9.7) 19.7b (5.7)
523.0a (470.5–743.5) 431.5a (238.0–688.5) 78.4b (17.26) 15.5a (3.5–45.0) 16.0a (6–40) 53.5a (11.5–355.5) 81.0a (33–127) 110.5a (9.0–485.0) 15.4b (9.5) 43.1b (12.1) 23.1b (7.0) 18.5b (8.6)
−26.0 10.0 6.0 0.5 1.0 −22.8 −2.0 −25.3 −2.3 −1.5 2.4 1.2
p = 0.021 p= 0.574 p = 0.008 p= 0.478 p= 0.725 p = 0.004 p= 0.962 p= 0.119 p= 0.183 p= 0.474 p= 0.176 p= 0.386
The central values (range or SD) of the sleep variables in the recordings in individuals with both one recording after a seizure-free period of at least 24 h and one recording during the night following a (secondarily) generalized seizure during the day. In addition, the differences between the central values of both groups [3,4] (with confidential interval) are shown. The p‐value was obtained using the paired t-test (log-transformation was used in non-normally distributed variables before statistical analysis). a Central value = median (minimum − maximum). b Central value = mean (standard deviation).
were compared with the recordings after a seizure free period of at least 24 hours (N= 292). Between both groups, no significant differences were found. Comparison of the recordings after only short-term seizures (N=39) and the recordings of the Daytime Seizure group with more severe seizures (N=94) showed a longer TIB (18.5 min, p=0.026), more light sleep (NREM II(%): 4.95%, p=0.023), less deep sleep (NREM III(%): −4.10%, p =0.023) and less REM sleep (−3.45%, p=0.015) in the group with the severe seizures. REM latency was again longer after severe seizures but not significant anymore (21.25 min, p=0.331). The other sleep variables also did not differ significantly. 3.2. Comparison of the sleep architecture in people with recordings in both groups 3.2.1. Subjects and recordings In 23 individuals, with a mean age of 36.7 years (SD: 14.2), night sleep was recorded in both the Daytime Seizure and Seizure Free situations. These individuals all had partial epilepsy; the localization was temporal in 20, frontal in one and not classifiable in two. Three individuals did not use AEDs at all, 6 used only one AED, 12 used two AEDs and 2 used three AEDs. Forty seizures were recorded: 12 TCs (8 subjects) and 28 CP+ (15 subjects). 3.2.2. Architecture of sleep After a daytime seizure before the night of investigation (Daytime Seizure), TIB (p = 0.021) and WASO (p = 0.004) were longer and SE (p = 0.008) was lower when compared to the Seizure Free situation (Table 5). 3.2.3. Influence of potential confounders The differences in sleep between Seizure Free and Daytime Seizure were corrected for potential confounding. Neither age [23], number of AEDs, day of recording [24–26] nor type of seizure led to any bias. 4. Discussion In this study, the objective architecture of sleep in people with epilepsy who suffered a (secondarily) generalized seizure on the day before the night of interest was compared with the architecture of sleep in people with epilepsy who were seizure free for at least the previous 24 h. This resulted in differences which are discussed below, together with the findings in 23 subjects who had recordings in both situations.
4.1. Comparison of the groups Seizure Free and Daytime Seizure 4.1.1. Architecture of sleep Comparison of the groups Seizure Free and Daytime Seizure showed an increase of TIB and REM latency after daytime seizures. This corresponds to findings in two previous studies where the night sleep in people with partial epilepsy was compared to the night sleep in controls [12,26]. The differences in our study were small and are of dubious value in discrimination of a possible sleep disorder. During the night following a daytime seizure, more NREM II, less NREM III and less REM sleep were found than in the night after a seizure-free period longer than 24 h. The decrease in NREM III and REM sleep corresponds with an often cited case study of a 52-year-old woman with status epilepticus during the daytime [4]. In this case, the reported decrease of light sleep (NREM II) on the first night was in contrast with the increase of NREM II(%) we found in our study. Our finding of a decrease of REM sleep is in accordance with the results of another study which found a 6% decrease in REM sleep after complex partial seizures on the day before in people with temporal lobe epilepsy [3]. In our study, all types of epilepsy were included. 4.1.2. Influence of localization of the epileptogenic zone The comparison of only the night sleep recordings of people with partial epilepsy showed, both before and after correction for the localization of the epileptic‐onset zone, an increase of TIB, TST and REM latency in the Daytime Seizure group compared with those who were Seizure Free. Thus, the onset zone has no influence on sleep quality. Previous studies in people with generalized epilepsy showed an increase of time in light sleep and a decrease of deep sleep and REM sleep compared to the sleep structure in healthy volunteers [12,13,27]. We had insufficient data on this type of epilepsy to comment further. 4.1.3. Influence of type of seizure Tonic‐clonic seizures (TCs) had more impact on total TIB, WASO and percentage REM than complex partial seizures with secondary generalization (CP+) (Table 5). In another study, the sleep structure was assessed after differentiation for type of seizure. Rapid eye movement sleep was more suppressed after a complex partial seizure with temporal origin and secondary generalization than after a seizure without secondary generalization [13]. Our findings confirm a decrease of REM sleep after a (secondarily) generalized seizure during the day. The longer TIB and WASO after a TC have not been described previously. Tonic‐clonic seizures are the most severe seizures with most impact
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and longest duration. After this type of seizure, the patient is often tired and goes to bed, and no seizure‐provocative activities are performed to avoid seizure clustering or even status epilepticus. In general, sleep starts early after these severe seizures. The often long duration of the ictal phenomena in TCs may result in a prolonged disturbance of the brainstem and deeper brain structures. This phenomenon might explain the major effects on REM sleep.
4.2. Subjects with days with and without seizures 4.2.1. Architecture of sleep In this group of 23 individuals who – in the same long‐term monitoring – underwent recordings after days with and without seizures, TIB was longer during the night after a seizure on the day before when compared to the night in the other condition. Its background is discussed above. Our finding of longer WASO after one or more seizures, resulting in a lower SE, has also been described in previous studies [12,27]. In contrast with these studies, in our study, nocturnal seizures were a reason for exclusion. The clinical relevance of the longer WASO and lower SE as a result of a daytime seizure may be doubtful. The differences between both groups, with the same persons in both groups Seizure Free and Daytime Seizure, are small, while the variability of these sleep variables is still large. The distribution of sleep stage was similar in the recordings with and without seizures on the day before. This is in contrast to the findings in the cohort study. Apart from differences in the number of individuals studied, we have no explanation for this finding. Correction for confounding by age, number of AEDs taken, and type of seizure or localization of its origin did not change the results in this group of 23 individuals. The reduction of REM sleep in temporal lobe epilepsy, as expected from an earlier study, could not be confirmed in our study [3].
4.2.2. Limitations The study took place in a tertiary-care epilepsy clinic. This may introduce bias in patient selection, for example more people with localization-related epilepsy. Exclusion of mental retardation as comorbidity may also have influenced the findings. Although the influence of the number of different AEDs was controlled, change of medication used as provocation procedure during consecutive recordings was not included as an additional variable in this study. Furthermore, the retrospective character of our study prohibits judgments on the quality of sleep by the individuals themselves.
4.2.3. Conclusion In a cohort of 425 people with epilepsy, longer TIB and REM latency, more NREM II and less NREM III and REM sleep were seen after a (secondarily) generalized seizure on the day before the recording. In the 23 people with recordings after days with and without seizures, more WASO, resulting in a lower SE, was seen during the night after a daytime seizure. These significant differences in both studies are from objective measurements. The relationship with the subjective perception of their sleep in these individuals is unknown and will be investigated in further research.
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