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Corresponding author at: Third Department of Pediatrics, “Attikon” University Hospital, National & Kapodistrian University of Athens, Rimini 1, 12462, Haidari, Athens, Greece.
High load epileptic activity before treatment is not unfavorable concerning absences.
•
Persisting absence discharges may be deleterious for sleep architecture and stability.
•
Absolute control of absences is accompanied by a more continuous, efficacious sleep.
Abstract
Purpose
Childhood absence epilepsy (CAE) is an epileptic syndrome presenting between 2nd–10th years. The spells are elicited with hyperventilation (HV) while sleep seems to exacerbate the electrical activity. Our aim is to describe sleep architecture and its relationship with epileptic discharges (EDs) in patients with CAE, before treatment and one year later.
Methods
Twenty-eight, drug-naive children were recruited (21 girls), mean age 90.1 ± 32.6 months. Routine-EEG and overnight EEG-polygraphy were conducted upon diagnosis and one year later. Patients were separated in two groups of similar mean age, according to their clinical response at the second recording: group A: children with absolute control of absences and group B: children with partial control. Sleep parameters, EDs and arousals were measured. The effect of medication on sleep parameters was examined, according to 2 groups: valproic-treated and non valproic-treated.
Results
Group A showed significant improvement in total sleep time, REM-sleep latency, REM-sleep, arousals-number/hour and arousals-duration/hour between the two recordings. Comparing the two groups for each recording separately, group A initially demonstrated greater epileptic activity and worse sleep parameters, whereas in the second recording exhibited total elimination of the EDs and significantly less arousals. Group B demonstrated persisting EDs and slight deterioration in some sleep parameters during the second recording, despite the lower epileptic load initially. No significant difference was identified between valproic and non-valproic treated patients, regarding the effect on sleep parameters.
Conclusion
Absolute control of absences and normalization of the electroencephalogram are accompanied by more continuous, stable and efficacious sleep in children with CAE.
Typical absence seizures are the main and often the unique manifestation of several epileptic syndromes in idiopathic generalized epilepsy (IGE). Among them childhood absence epilepsy (CAE) is the most frequent IGE syndrome in children, with presentation between the 2nd and 10th year of life, most common in girls (2:1) of 5–6 years old, and responsible for 10% of childhood epilepsies. In the majority of the patients with CAE the absences will be abolished before the age of 12 years old and less than 10% will develop generalized tonic-clonic seizures (GTCS) [
]. The clinical manifestation of absences consist of behavioral and cognitive arrest, manifested during wakefulness, while the electroencephalographic (EEG) pattern includes prolonged complexes of generalized 2.5–4 Hz spike and slow-wave discharges (SWD).
Although wakefulness is mandatory for the electroclinical event, sleep seems to exacerbate the development of the electrical activity. Particularly, during non-REM sleep, there is an activation of the SWD, but their duration is shorter and their morphology fragmented compared to wake state [
]. Regarding sleep macrostructure in CAE patients the results are extrapolated either from studies in patients that received treatment or from studies with limited sleep recordings. These studies demonstrate an increase in sleep latency, REM latency from sleep onset, number of arousals, total time of waking after sleep onset (WASO) [
The aim of the particular study is to describe: sleep architecture in drug naïve patients with CAE, and the changes observed one year after treatment initiation, according to their clinical response.There are no reports in the literature with full EEG polysomnography during the whole night in drug naïve children with CAE exclusively, that address the mutual interaction between sleep and epileptic activity. Furthermore, there is no study to describe the EEG sleep characteristics and the way they are influenced after the antiepileptic treatment onset, and the differences between children that still show absences and those who are absence free. This is a prospective case controlled study with a routine and also a whole night EEG recordings before treatment and one year after treatment initiation, in a cohort of drug naïve patients with CAE.
2. Materials and methods
2.1 Subjects
Thirty normal and healthy children were recruited to participate in the study. Only children who met the inclusion and exclusion criteria of International League Against Epilepsy (ILAE) 1989 for Childhood Absence Epilepsy (CAE) were included. The study had approval from the Institutional Review Board (IRB) and the Ethics Committee and patients’ parents signed an informed consent.
The study enrolled children 4–12 years of age, with newly diagnosed absence seizures, normal neurodevelopment and no medical treatment at the time of the first recording. Two subjects were deleted from the roster: one due to parental denial for their child to undertake the night sleep recording and the other due to very poor quality of the EEG data.
The study finally included 28 children, 21 girls and 7 boys (3:1), with mean age 90,1 months (±32,642) and median age 86,5 months. Nineteen children were treated with valproic acid (VPA) as monotherapy or in combination either with ethosuxomide (ESM) or lamotrigine (LTG) and the rest were treated with the last two medication. In particular, 13 children received VPA as monotherapy, 4 children were treated with VPA and ESM, 2 children with VPA and LTG, 7 children with ESM and one with LTG exclusively.
In order to evaluate the differences of the sleep parameters according to the antiepileptic treatment response, the cohort was divided in 2 groups: group A: children with absolute control of absences (absence free) and group B: children with partial control of absences at the second recording. Children in both response groups were treated with almost all possible medication. In group A, 12 children (70,59%) received VPA either as monotherapy or polytherapy and in group B 7 children (63,64%) respectively.
With respect to estimate the different effect of treatment on sleep parameters and epileptic activity, and taking into consideration the small size of our cohort, we stratified 2 groups: patients treated with valproic acid (VPA) either as monotherapy or as polytherapy and patients treated with other drugs not including VPA (non VPA).
2.2 Polygraphic recordings
A routine EEG of 10–15 min was conducted before the night recording that included testing of posterior dominant rhythm reaction, photic stimulation for the frequencies 1–30 Hz and hyperventilation until the first electroclinical absence.
Every subject had two nights of polysomnography in a standard sleep laboratory in “Attikon University Hospital”, 3rd Pediatrics Clinic. The first recording was before antiepileptic treatment onset and the second was 12 months later, while the children where under medication. Subjects were asked to restrain from sleep during the afternoon preceding the recording. Lights-off time for the recording was calculated based on children’s usual sleep habits. All children were allowed sleeping until their spontaneous awakening in the morning. The recording was terminated 30 min after awakening.
The sleep studies were conducted on a 44 channel polysomnographic digital system (Stellate Harmonie). Electrodes placement was according to the 10–20 international placement system. Other variables that were monitored include: electroculogram (EOG) of two electrodes placed 1 cm above the right outer cantus and 1 cm below the left outer cantus and referred to A1, two chin electromyography electrodes (EMG) placed 3 cm apart, two electrocardiography electrodes and finger pulse oximetry. Other respiratory variables and leg EMG were not recorded as they were out of interest and in order to assure best sleep.
2.3 Sleep scoring
The recordings were scored by 2 experienced sleep experts and one PhD candidate concurrently with any differences resolved by consensus, in Embla Remlogic 1.1 and according to the American Academy of Sleep Medicine (AASM) Manual of sleep scoring and Associated events 2007 [
Total duration of stages of NREM sleep (N1, N2, N3) and REM sleep and percentages of each to the total sleep time (TST) and the sleep period (SP).
2.
Total sleep time (TST): the time from sleep onset to the end of the final sleep epoch minus time awake.
3.
Sleep period (SP): the time from sleep onset to the end of the final sleep epoch.
4.
Arousal index (number per hour of sleep period), and arousal duration index (duration in seconds per hour of sleep period).
5.
Discharges index (number per hour of sleep period) and discharges duration index (duration in seconds per hour of sleep period) during the sleep period.
6.
REM sleep latency: the time between sleep onset and first appearance of REM sleep.
7.
Wake after sleep onset (WASO): the time spent awake from sleep onset to the final sleep epoch
8.
Presence of focal discharges
9.
Presence of polyspikes (polyspikes are defined as a close association of 3 or more biphasic spikes)
2.4 Statistical analysis
The statistical analysis was performed in the whole cohort for the data of both night polysomnographies. Descriptive statistics, including mean and standard deviation, was used for analysis. To evaluate the differences on sleep parameters between the first and the second recording for each response group (A and B) Paired Samples Test was performed. In order to evaluate the differences on sleep parameters of the first and second night recording among the two response groups Mann-Whitney Test was performed. Mann-Whitney Test was also conducted to estimate the differences on sleep parameters for each recording among children treated with VPA and children not treated with VPA.
In order to examine possible correlations between the therapeutic outcome and EEG characteristics, Pearson analysis was performed. For the descriptive and statistical analysis IBM SPSS Statistics 22.0 was used.
3. Results
3.1 Demographics
Twenty-one of the children were girls and seven were boys (3:1). Mean age of absences’ onset for the cohort was 90.1 ± 32.64 months. The latency from the onset of absences until the diagnosis was calculated at 6 ± 7.94 1–29 months.
Regarding the antiepileptic treatment response 12 months after the initiation, mean age in group A (absence free children) was 93.35 ± 25.11 months and in group B (children with partial control of absences) was 85.09 ± 42.69 months. All patients in group B were female, whereas in group A female were 10 out of 17 patients.
3.2 Epileptic activity data
All children showed complexes of generalized spike and wave activity during all stages of non REM sleep and some in REM sleep also (Fig. 1, Fig. 2, Fig. 3, Fig. 4) during the first night recording, before treatment initiation.
Fig. 1Generalized spike and wave complex during stage I of non REM sleep in 15 s EEG epoch.
Table 1 presents the results of the epileptic activity during sleep. Focal discharges during sleep EEG (Fig. 5) were present in 53,6% (15/28). The localization of the focal discharges was mainly frontal, yet it was also observed in some patients in central, temporal and occipital regions.
Table 1Polyspikes and focal discharges during sleep EEG.
There is a significant positive correlation between polyspikes and age, indicating that as age increases polyspikes are more often (p = 0,013). No other statistically significant correlation was identified.
3.3 Sleep/wake macrostructural parameters
Table 3 shows the mean (±SD) values of macrostructural sleep parameters observed in all 28 subjects in the first recording and in the second one year later, as well as the results of the statistical analysis.
Table 3Sleep/wake macrostructural parameters of the first and second night recordings for the whole cohort.
Variables/Sample N = 28
1st (before AED onset)
2nd (12 months after AED onset)
Statistical analysis (Paired Samples Test)
m ± SD
m ± SD
Sig. (2-tailed)
SP (min)
492.89 ± 85.06
498.36 ± 64.91
0.754
TST (min)
423.05 ± 79.82
445.71 ± 82.25
0.240
RSL (min)
120.23 ± 53.38
109.39 ± 50.22
0.435
WASO (min)
68.88 ± 48.41
53.79 ± 35.1
0.111
SE (%)
86.11 ± 8.79
88.97 ± 8.03
0.137
N1(%TST)
7.92 ± 4.26
8.32 ± 4.78
0.825
N2(%TST)
34.46 ± 11.12
30.67 ± 11.95
0.280
N3 (%TST)
39.13 ± 12.12
40.99 ± 12.97
0.613
REM (%TST)
18.47 ± 5.07
20.00 ± 4.34
0. 197
Arousal index (number/h)
10.80 ± 4.01
8.60 ± 3.40
0.007
Arousal duration index (sec/h)
87.79 ± 34.74
76.98 ± 34.30
0.095
Discharges index (number/h)
26.46 ± 23.36
2.98 ± 4.67
0.000
Discharges duration index (sec/h)
97.16 ± 64.96
12.36 ± 21.15
0.000
AED: antiepileptic drug; SP, sleep period; TST, total sleep time; RSL, REM sleep latency; WASO, wake after sleep onset; SE, sleep efficiency; N1, stage I of non REM sleep; N2, stage II of non REM sleep; N3, slow wave sleep,; REM, rapid eye movement sleep. Bold values indicate statistically significant (p < 0.05) differences.
In the second recording arousal index for number/hour (p = 0,007) and discharges index for both number/hour (p = 0,001) and duration/hour (p = 0,001) are decreased, reaching statistical significance. For the parameters SP, TST, SE, N3 and REM sleep there is a trend for increase, and for RSL and N2 a trend for decrease, not reaching a statistical significance.
Table 4, Table 5 demonstrate the mean (±SD) values of macrostructural sleep parameters and the statistical analysis performed in both groups between the two recordings. In group A: statistically significant increase is observed for TST (p = 0,05) and REM sleep (p = 0,004) and decrease for RSL (p = 0,007), arousal index for number/hour (p = 0,01), arousal index for duration/hour (p = 0,041), discharges index for number/hour (p = 0,002) and discharges index for duration/hour (p = 0,001). WASO, SE and N3 are increased (p > 0,05). In group B there is a statistically significant decrease for discharges index, for both number/hour (p = 0,001) and duration/hour (p = 0,001); REM sleep N3 are also decreased (p > 0,05).
Table 4Sleep/wake macrostructural parameters of the first and second night recordings for children that were absence free 12 months after AED onset (group A).
Variables/ Sample N = 17
1st (before AED onset)
2nd (12 months after AED onset)
Statistical analysis (Paired Samples Test)
m ± SD
m ± SD
Sig. (2-tailed)
SP (min)
490.56 ± 74.51
500.13 ± 72.05
0.584
TST (min)
409.31 ± 62.65
445.84 ± 89.05
0.050
RSL (min)
132.71 ± 48.06
94.24 ± 35.19
0.007
WASO (min)
81.26 ± 55.15
60.00 ± 33.41
0.139
SE (%)
84.06 ± 10.41
89.72 ± 8.00
0.093
N1(%TST)
8.14 ± 4.04
6.79 ± 4.32
0.363
N2(%TST)
37.16 ± 10.79
30.61 ± 11.30
0.150
N3 (%TST)
37.03 ± 11.97
41.99 ± 12.13
0.317
REM (%TST)
17.64 ± 4.08
20.60 ± 4.20
0.004
Arousal index (number/h)
10.17 ± 4.07
7.52 ± 2.94
0.010
Arousal duration index (sec/h)
88.56 ± 36.84
68.57 ± 37.33
0.041
Discharges index (number/h)
29.14 ± 30.90
0.05 ± 0.11
0.002
Discharges duration index (sec/h)
101.92 ± 82.57
0.12 ± 0.27
0.000
AED: antiepileptic drug; SP, sleep period; TST, total sleep time; RSL, REM sleep latency; WASO, wake after sleep onset; SE, sleep efficiency; N1, stage I of non REM sleep; N2, stage II of non REM sleep; N3, slow wave sleep,; REM, rapid eye movement sleep. Bold values indicate statistically significant (p < 0.05) differences.
Table 5Sleep/wake macrostructural parameters of the first and second night recordings for children that still had absences and abnormalities in the EEG 12 months after AED onset (group B).
Variables/Sample N = 11
1st (before AED onset)
2nd (12 months after AED onset)
Statistical analysis (Paired Samples Test)
m ± SD
m ± SD
Sig. (2-tailed)
SP (min)
493.18 ± 108.05
486.85 ± 52.04
0.875
TST (min)
442.38 ± 105.75
445.50 ± 73.80
0.946
RSL (min)
97.65 ± 59.66
135.15 ± 62.56
0.108
WASO (min)
50.80 ± 23.38
51.35 ± 35.11
0.559
SE (%)
89.44 ± 4.31
91.11 ± 8.02
0.639
N1(%TST)
7.86 ± 4.74
10.91 ± 4.59
0.213
N2(%TST)
30.23 ± 10.22
30.77 ± 13.63
0.932
N3 (%TST)
42.17 ± 11.72
39.31 ± 14.80
0.704
REM (%TST)
19.73 ± 6.25
18.99 ± 4.60
0.798
Arousal index (number/h)
11.92 ± 3.87
10.33 ± 3.52
0.298
Arousal duration index (sec/h)
88.68 ± 34.88
90.43 ± 24.88
0.849
Discharges index (number/h)
23.6564 ± 3.19
7.65 ± 4.57
0.000
Discharges duration index (sec/h)
88.82 ± 33.28
31.96 ± 23.44
0.001
AED: antiepileptic drug; SP, sleep period; TST, total sleep time; RSL, REM sleep latency; WASO, wake after sleep onset; SE, sleep efficiency; N1, stage I of non REM sleep; N2, stage II of non REM sleep; N3, slow wave sleep,; REM, rapid eye movement sleep. Bold values indicate statistically significant (p < 0.05) differences.
Table 6 shows the data for the differences in macrostructural sleep parameters between group A and group B in the first recording and between group A and group B in the second recording. During the first recording there was statistically significant difference with more RSL (p = 0.035) and N2 (p = 0,035) in group A; WASO is more and TST, SE, N3 and REM sleep are less (p > 5%). During the second recording group A shows greater decrease in discharges for number/hour (p = 0,001), discharges for duration/hour (p = 0,001), arousal index for number/hour (p = 0,041), arousal index for duration/hour (p = 0,020) and N1 (p = 0,018); N3 and REM sleep are greater in group A and RSL is less (p > 5%).
Table 6Differences in sleep/wake macrostructural parameters changes of the first and second night recordings between absence free children and those that still had absences 12 months after AED onset.
Variables
1st (before AED onset)
2nd (12 months after AED onset)
Statistical analysis (Mann-Whitney) Asymp. Sig. (2-tailed)
SP (min)
0.981
0.414
TST (min)
0.494
0.941
RSL (min)
0.035
0.127
WASO (min)
0.146
0.083
SE (min)
0.208
0.141
N1 (%TST)
0.869
0.018
N2 (%TST)
0.035
0.786
N3 (%TST)
0.286
0.824
REM (%TST)
0.464
0.334
Arousal index (number/h)
0.286
0.041
Arousal duration index (sec/h)
0.906
0.020
Discharges index (number/h)
0.286
0.000
Discharges duration index (sec/h)
0.832
0.000
AED: antiepileptic drug; SP, sleep period; TST, total sleep time; RSL, REM sleep latency; WASO, wake after sleep onset; SE, sleep efficiency; N1, stage I of non REM sleep; N2, stage II of non REM sleep; N3, slow wave sleep,; REM, rapid eye movement sleep. Bold values indicate statistically significant (p < 0.05) differences.
The analysis to identify the differences in macrostructural sleep parameters between children treated with VPA and children not treated with VPA for the first and second recording did not demonstrate any statistically significant result (p < 5%).
4. Discussion
In this study we describe that the elimination of epileptic activity improves sleep macrostructural parameters in drug naïve patients with CAE; this outcome is more evident, and therefore more beneficial for patients with absolute control of absences.
4.1 Focal discharges during sleep
Although generalized epileptic activity is the hallmark in CAE, focal epileptic discharges are not that rare and have been previously described in the literature [
Focal and generalized EEG paroxysms in childhood absence epilepsy: topographic associations and distinctive behaviors during the first cycle of non-REM sleep.
]. Previous studies suggest that in absence epilepsy the generalization of the epileptic activity is the result of a bilateral synchronization of prefrontal areas [
Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009.
]. In our study, more than 50% of the children exhibited interictal focal spikes, more evident during sleep, with a frontal, occipital and temporal topography. We did not identify any positive and significant correlation between the existence of focal discharges and the therapeutic outcome one year after the antiepileptic treatment onset, a finding that is in concordance with the existing literature [
Another EEG characteristic observed during sleep is polyspikes which are characteristic consequence of the fragmentation of the epileptic activity during non REM sleep [
Contribucion al estudio de las ausencias epilepticas. Evolucion clinica y EEG de 109 casos de ausencias, seguidas a traves de un periodo de tiempo que oscila entre 10 y 20 anos de observacion personal [thesis].
], no association with poor prognosis is mentioned. In our study polyspike were found in 32% of the children and their presence was more common in patients of older ages (p = 0,013). However, no prognostic correlation was identified between the polyspikes and the therapeutic outcome.
4.3 Sleep macrostructure parameters
Regarding the sleep macrostructure, previous publications with limited sleep recordings have reported decreased REM sleep, decreased N3, increased N2 and increased WASO, in poorly controlled CAE patients compared to those with good prognosis [
]. We found a statistically significant improvement for the whole cohort between the first and the second recording only for arousal index (Table 3) and a trend of improvement for the rest parameters. This improvement in sleep, especially concerning arousals, may be attributed to the significant decrease in epileptic activity (p = 0,001), which has been accused as the cause of arousing during sleep [
Regarding the two therapeutic outcome groups, group A demonstrated statistically significant improvement in several parameters (Table 4). This improvement coincides with the complete abolishment of the epileptic activity in these patients. The persisting epileptic discharges in group B, even though decreased, seems to be deleterious for sleep architecture, as shown by a slight deterioration in some parameters (Table 5). We could suggest that the remaining epileptic activity in children of group B affects sleep and leads to its instability and discontinuity.
We studied further the differences in sleep parameters and epileptic activity between groups A and B, for each recording separately. Surprisingly, during the first recording, children of group A demonstrated greater epileptic activity and worse sleep parameters compared to children of group B (Table 6). Despite the initially higher epileptic load observed in children of group A, this does not predispose them with greater resistance to treatment. The review of the literature did not reveal any correlation between resistance of absences and the amount of the epileptic activity. Commonly known factors predicting prognosis in CAE are the age at which seizures first started, an abnormal background rhythm on EEG, polyspikes, focal abnormalities, photosensitivity, the development of myoclonic seizures, a history of absence status, late onset of absence seizures, earlier age of onset of GTCS, a history of febrile convulsions, mental retardation and a positive family history [
]. All of these observations related to syndrome evolution remain controversial. However, it is not unusual in epilepsy the high epileptic load not to go along with bad prognosis and grand resistance. An explanation to this “easy come and easy go” character of Childhood Absence Epilepsy in our cohort could not be clear and determined. Still, it remains certainly an arithmetically proven observation which needs more enlightening and follow up through time.
Concerning the second recording, group A exhibits a total elimination of the epileptic activity, while in group B the epileptic activity, although reduced, still exists. This persistence of epileptic discharges in group B could explain the significantly higher arousal index observed when compared to group A. Yet, when compared to itself group B, despite the marked reduction of epileptic activity, exhibits a very slight reduction of the arousals. Although there was no significant modification on arousal index for group B, we cannot exclude that there could be indeed a change if Cycling Alternating Pattern (CAP) scoring is applied. There are recent studies [
] which clearly report that epileptic discharges may lead to arousals, increased CAP rate and they can even awake the patient. Therefore, we could suggest that it is not the amount of epileptic activity, but its existence and persistence in group B that seems to be deleterious, leading to sleep instability and discontinuity.
In view to the impact of the various antiepileptic treatment on sleep parameters, our results are quiet safe. In the literature VPA has been reported to beneficially modulate arousal instability in JME patients, and hence promote sleep quality and continuity [
]. Our study did not identify any significant difference in sleep parameters between patients that are treated with VPA (monotherapy/polytherapy) and those treated with other drugs. Moreover, the percentages of VPA patients in the two response groups were similar, and thus, if there was any impact at all, that was applied respectively.
The above findings support the hypothesis that epileptic activity could be responsible for sleep instability and alteration of sleep continuity and they are in concordance with studies in patients with idiopathic generalized epilepsy [
]. The cohort is representative for CAE concerning age of onset, gender and electroclinical and electroclinical caharacteristics before treatment onset [
], fact that strengthens the credibility of our results. We performed full night recordings before treatment and after one year, which has never before been described in previous publications.
Limitations of the study include first the number of patients enrolled, which is probably the reason that several parameters, although they exhibite a trend for improvement, do not reach statistical significance and second the lack of normal controls. A multivariate analysis of 13 parameters in a small cohort consists a limitation Another limiting point is the duration of the follow up of the cohort that does not allow us to extrapolate more definite, electroclinical, prognostic factors.
5. Conclusions
This is the first whole night full EEG recording study in a big drug naïve cohort of children with CAE. Regarding the EEG characteristics of the epileptic activity during sleep, we did not identify any prognostic correlation with the therapeutic outcome. Although the presence of polyspikes is and ominous feature for adults with IGE and absences, this does not apply in children with CAE. The high load of epileptic activity and sleep disorganization before treatment do not stand as an unfavorable prognostic factor for the therapeutic outcome. Only the absolute control of absences and normalization of the EEG could ensure a more continuous, stable and efficacious sleep in children with CAE. We expect that the sleep microstructure parameters may provide us more insight regarding sleep architecture and accurate prognostic factors.
Disclosure
None of the authors has any conflict of interest to disclose.
Acknowledgements
We would like to express our gratitude to our young patients and their parents, who even though not necessary agreed with pleasure to spend two nights in our EEG laboratory. Staff and colleagues involved in different aspects of collecting these data are gratefully acknowledged.
This study was funded by grants from Special Account for Research Grants (SARG) of National and Kapodistrian University of Athens.
We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with these guidelines.
Focal and generalized EEG paroxysms in childhood absence epilepsy: topographic associations and distinctive behaviors during the first cycle of non-REM sleep.
Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009.
Contribucion al estudio de las ausencias epilepticas. Evolucion clinica y EEG de 109 casos de ausencias, seguidas a traves de un periodo de tiempo que oscila entre 10 y 20 anos de observacion personal [thesis].
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