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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 39
| Issue : 4 | Page : 195-199 |
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Comparison of awake electroencephalography, electroencephalography after sleep deprivation, and melatonin-induced sleep electroencephalography sensitivity in the diagnosis of epilepsy in adults
Burcu Selbest Demirtas, İrem Fatma Uludag, Ufuk Şener, Yaşar Zorlu
Department of Neurology, Faculty of Medicine, University of Health Sciences Izmir, İzmir, Turkey
| Date of Submission | 26-May-2022 |
| Date of Decision | 26-Jul-2022 |
| Date of Acceptance | 01-Aug-2022 |
| Date of Web Publication | 19-Dec-2022 |
Correspondence Address:
İrem Fatma Uludag
Yali Mahallesi 6500/1 Sokak Mavisehir Modern 2 Sitesi 10F Daire 1 35550 Karşıyaka Izmir
Turkey
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/nsn.nsn_101_22
Introduction: The aim of this study was to compare routine awake electroencephalography (r-EEG), melatonin-induced sleep EEG (m-EEG) and EEG (d-EEG) after sleep deprivation studies in terms of epileptiform anomalies (EA), and to compare d-EEG and m-EEG studies in terms of sleep induction in patients requiring differential diagnosis of epileptic seizure/nonepileptic seizure. Methods: The study included 45 patients aged 18–45 years who had at least one seizure suspected to be epileptic but could not be diagnosed with epilepsy with clinical and laboratory findings. Each patient underwent r-EEG on the 1st day, d-EEG on the 2nd day after 24 h of sleeplessness, and m-EEG on the 3rd day after the administration of 6 mg melatonin following 7 h night sleep. Three separate EEG tracings of the patients were compared for EA. The d-EEG and m-EEG methods were examined for their ability to achieve sleep, total sleep time (ST), and sleep latency (SL). Results: When the detection rate of EA in d-EEG and m-EEG was compared with that of r-EEG, it was found to be significantly higher (P < 0.001) (73.3% with d-EEG, 75.6% with m-EEG, and 35.6% with r-EEG). Sleep was achieved at a rate of 100% after receiving melatonin and at a rate of 97.8% with sleep deprivation. There was no significant difference between d-EEG and m-EEG in terms of mean ST and SL (ST = 58.6 ± 12.6 min and 59.7 ± 8.3 min, respectively; SL = 287.6 ± 484.3 s and 152.2 ± 178.7 s after the start of the EEG, respectively). Conclusions: Sleep EEG is superior to awake EEG in terms of detecting EA. In an EEG study, where melatonin was used to induce sleep, the sleep rate and SL were similar to those of d-EEG, and melatonin did not have an EA increasing or suppressing effect on EEG. Given the ease of application and low side effect profile, it is thought that m-EEG may be an applicable method in the diagnosis of epilepsy.
Keywords: Deprivation electroencephalography, epilepsy, epileptiform discharge, melatonin, sleep electroencephalography
How to cite this article:
Demirtas BS, Uludag &F, Şener U, Zorlu Y. Comparison of awake electroencephalography, electroencephalography after sleep deprivation, and melatonin-induced sleep electroencephalography sensitivity in the diagnosis of epilepsy in adults. Neurol Sci Neurophysiol 2022;39:195-9 |
How to cite this URL:
Demirtas BS, Uludag &F, Şener U, Zorlu Y. Comparison of awake electroencephalography, electroencephalography after sleep deprivation, and melatonin-induced sleep electroencephalography sensitivity in the diagnosis of epilepsy in adults. Neurol Sci Neurophysiol [serial online] 2022 [cited 2023 Mar 28];39:195-9. Available from: http://www.nsnjournal.org/text.asp?2022/39/4/195/364417 |
| Introduction | |  |
Sleep electroencephalography (EEG) studies have a higher sensitivity than routine EEG (r-EEG) in the diagnosis of epilepsy (50% vs. 80%).[1] Sleep deprivation or sleep-inducing drugs can be utilized to induce sleep during EEG studies.[1] There are EEG studies demonstrating that drugs can increase or decrease background brain and epileptiform activity (EA).[2],[3],[4] Although carrying out the study during spontaneous night sleep is the most physiological method with the least likelihood of complications for sleep-induced EEG studies, difficulties arise while performing the study this way due to the length of the examination, and assessment process and cost. A result can be achieved in a shorter time and is less costly with sleep EEG studies after sleep deprivation. However, EEG (d-EEG) after sleep deprivation is not an easy method to use since sleep deprivation triggers epilepsy seizures, and staying up all night is difficult for the patient.[1]
Melatonin, also known as N-acetyl-5-methoxytryptamine, is an effective hormone in circadian rhythm. It is secreted at night by the pineal gland, which is activated by darkness. As the levels of melatonin increase, fewer stimuli are perceived, and the feeling of sleep increases. Many researchers report that exogenous administration of melatonin increases the rate of falling asleep and sleep quality.[5],[6],[7],[8] There are a limited number of studies regarding the effect of melatonin on sleep EEG.[8]
In this study, r-EEG, melatonin-induced sleep EEG (m-EEG), and d-EEG studies were compared in terms of EA, and d-EEG and m-EEG studies were compared in terms of sleep induction in patients with suspected clinical epileptic seizures.
| Methods | | |
Forty-five patients aged between 18 and 45 years (33 females, 12 males, mean age 32.84 ± 10.44 years) admitted to the epilepsy outpatient clinic whose epileptic seizure diagnosis could not be confirmed with anamnesis and clinical findings were included in the present study. Patients suspected of having acute symptomatic seizures, diagnosed with sleep disturbances, having another comorbid neurological disease, and history of malignancy, active systemic bacterial, viral, or fungal infection, chronic drug use other than antiepileptic therapy, and pregnant patients were not included in the study. All patients were examined after a single suspicious seizure history, and this seizure was thought to be a generalized convulsive epileptic seizure in terms of prediagnosis. For each patient, the first EEG was carried out as soon as possible after presenting with a single seizure.
The study was approved by the ethics committee of the hospital, and all patients signed the informed consent form.
A detailed seizure history and personal and family histories were obtained from the patients. Neurological examination and cranial magnetic resonance imaging were performed.
A 24-channel Grass-Telefactor Beehive Millennium EEG unit (Astro-Med, 2005, West Warwick, RI, USA) was used for interictal EEG recording, and superficial electrodes were placed in line with the international 10–20 system. Bipolar and reference electrode montages were used. All studies were performed in the same room in a dark and quiet environment starting at 10:30 a.m. R-EEG was performed on the 1st day, d-EEG on the 2nd day after a sleepless night, and on the 3rd day, m-EEG was done after 7 h of a normal night's sleep by administering 6 mg melatonin and waiting 30 min. r-EEG, d-EEG, and m-EEGs were evaluated by double-blinded researchers in terms of EA (epileptiform transients such as spikes and sharp waves), number of generalized epileptiform discharges (GEDs), and focal epileptiform discharges (FEDs).
For better documentation of sleep, additional chin electrodes and electrooculogram electrodes were used. The recordings were analyzed in terms of sleep with the Neuron-Spectrum-PSG system. After all, electrodes were connected to the patient, and the time from the start of the study (light off) until the end of the recording (light on) was determined as the total recording time (TRT). TRT was 1 h for each patient. Total sleep time (TST) and sleep latency (SL) were calculated in sleep studies.
The statistical analysis of the data was performed using SPSS version 20.0 software (IBM Corp., Armonk, NY). Descriptive tests were used for the descriptive analyses, and ANOVA, t-tests, and Chi-square tests were used for the comparative analyses. A P < 0.05 was considered statistically significant.
| Results | | |
Of the 45 patients included in the study, 33 were females and 12 were males. The mean age of the participants was 32.84 ± 10.44 years [Table 1].
Of the patients studied, 16 (35.6%) were found to have EA with r-EEG, 33 (73.3%) with d-EEG, and 34 (75.6%) with m-EEG. The detection rate of EA in d-EEG and m-EEG was significantly higher (P < 0.001) than that in r-EEG. The mean number of GEDs was 2.0 ± 8.8 and the mean number of FEDs was 4.6 ± 16.5 in the r-EEGs of the patients. The mean number of GEDs was 6.4 ± 17.8 and the mean number of FEDs was 9.6 ± 33.8 in the d-EEGs. The mean number of GEDs was 5.2 ± 14.5 and the mean number of FEDs was 8.9 ± 32.6 in the m-EEGs. There was no statistically significant difference between the mean number of GEDs and FEDs obtained from the r-EEG, d-EEG, and m-EEG examinations [Table 2].
There were no periods of drowsiness or sleep on the r-EEG. The administration of melatonin induced sleep within 30 min in all 45 patients. After sleep deprivation, 44 (97.8%) of the patients were able to sleep. The mean SL was 152.2 ± 178.7 s for m-EEG and 287.6 ± 484.3 s for d-EEG. The mean TST was 59.7 ± 8.3 min after melatonin treatment and 58.6 ± 12.6 min after sleep deprivation [Table 3]. There was no difference between d-EEG and m-EEG in terms of achieving sleep, SL, and TST.
| Discussion | | |
The primary aim of our study was to test whether melatonin-induced sleep EEG provides as much information as sleep EEG after sleep deprivation in terms of detecting EA. Our results showed that there was no difference between d-EEG and m-EEG in terms of EA. When EAs on EEGs in our study were evaluated separately as GED and FED, there was also no difference between m-EEG and d-EEG.
In some previous studies, similar to our study, whether melatonin could be equivalent to sleep deprivation in terms of sleep acquisition and detecting EA was investigated. In these studies, as in our study, it was concluded that melatonin was as effective as sleep deprivation in inducing sleep and had no effect on the occurrence of EA or the macrostructure of sleep.[9],[10],[11] However, these studies were conducted in pediatric patient groups, and it was noted that melatonin might not be as effective in the adult age group in terms of inducing sleep.[9],[10],[11] A similar study has not yet been conducted in adult patients, and there are not enough data in the literature on the usefulness of melatonin in obtaining sleep EEG in patients suspected to have epilepsy. Therefore, we think that our study makes a valuable contribution.
Different views have been reported as to whether the effect of d-EEG demonstrating epileptic activity is based on sleep induction or sleep deprivation or the cumulative effect of both.[12],[13],[14] Fountain et al. suggested that the effect of d-EEG was mostly related to sleep deprivation since it was observed an EA rate similar to during sleep in EEG studies after sleep deprivation, even patient was still awake.[14] In contrast, in a 2-h sleep EEG study after partial sleep deprivation in patients with suspected epileptic seizures, Peraita-Adrados et al. suggested that the activation of epileptic discharges was probably particularly sleep-related since none of their patients had epileptic abnormalities on routine EEGs before sleep recordings.[15] In our study, melatonin-induced sleep in each patient gave as much information as d-EEG in terms of m-EEG EA From this perspective, our study suggests that the emergence of EA is associated with sleep itself, not sleep deprivation, and therefore melatonin-induced sleep may provide as much information as d-EEG for EA. However, we would like to emphasize a limitation of the present study. In our study, m-EEG was taken 24 h after d-EEG. For this reason, it is possible that the previous day's sleep deprivation may have an effect on the emergence of EAs seen in m-EEG. Although it is known that the effect of sleep deprivation on EEG is evident on the first recovery night, this effect is minimal on the second recovery night. It has also been reported that there may be changes in memory performance tests lasting longer than 24 h after sleep deprivation.[16],[17] The reason we used the present study design was that our participants were patients with suspected epileptic seizures whose r-EEG did not yield definitive results. We wanted to perform d-EEG as soon as possible after the seizure to avoid changing the diagnostic process and to maintain the high possibility of EA on EEG after the seizure. In addition, because we wanted m-EEG and d-EEG to be at approximately the same time from the suspected epileptic seizure, we performed m-EEG the day after the d-EEG. Although the time between the 3 EEGs was kept within a short window of 24 h, the difference in the time elapsed after the seizures for the 3 EEGs is also a limitation. Furthermore, we think that the fact that the patients were not asked about their previous basic sleep habits and their sleep anamnesis was not taken is a deficiency in our study. In addition to our current study design, it would be appropriate to repeat all 3 EEGs, on nonconsecutive days, in patients who did not have a seizure for a certain period and kept a sleep diary during this period.
Different drugs have also been used for sleep EEG studies, but these drugs have been found to cause changes in EEG. It was found that the rate of EA detected when using barbiturates and benzodiazepines for sleep EEG studies was lower than that of d-EEG. In contrast, the rate of EA in EEG studies using chlorpromazine to induce sleep was significantly higher than that of d-EEG.[2],[3],[4] It seems that melatonin did not have such a suppressor or activator effect on EA in our study. Moreover, the side effect profile of melatonin is also very low compared to other sleep-inducing drugs. In one study, the feeling of drowsiness was reported as a side effect after melatonin intake.[18] In our study, no such side effects were observed.
In a previous study, daily use of melatonin in children with sleep disturbances and neurological disabilities increased the frequency of seizures at the beginning of treatment, and the frequency of seizures returned to the pretreatment level in the following days.[19] In another study, no increase was observed in the seizure frequency of children with epilepsy and sleep disturbances during daily melatonin treatment.[20] Some authors report that melatonin might have antiepileptic properties in children with different types of epileptic seizures.[21],[22],[23] In a recent review, it has been suggested that both melatonin and its analogs act as antiseizure and neuroprotective agents.[24] With this data, the use of melatonin may be considered safe to use in epilepsy patients.
It has been reported that the sleep rate in children aged 1–4 years given melatonin was higher than that of children aged 5–12 years, and this was attributed to not giving appropriate doses based on children's weight.[9] In another study, it was found that melatonin had similar effects at doses of 0.5 and 5 mg in the prevention and treatment of jet lag but that a dose of 5 mg provided faster sleep than a dose of 0.5 mg.[25] Based on these results, it can be assumed that the administration of a fixed 6 mg dose was appropriate in our study.
| Conclusions | | |
An EEG study performed after melatonin use provides the same level of information as d-EEG in terms of EA according to our data. Melatonin did not have any suppressor or activator effect on EA in the EEG study. Sleep can be achieved at a very high rate with melatonin. Almost no side effects arise, and the use of melatonin in epilepsy patients does not pose any risk. It can be concluded that melatonin can be used safely before sleep EEG studies.
Melatonin-induced sleep EEG can be used more frequently in clinical practice in epilepsy patients or in patients with suspected seizures who require sleep EEG since the examination can be performed immediately, the patient does not experience the discomfort of sleep deprivation, and there are no risks or side effects.
Despite the limitations we have mentioned, we think that our study will contribute to the current literature, as it is the first study to provide information about the effectiveness of melatonin-induced sleep EEG in the adult patient group and will be a resource for both daily clinical applications and future studies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]
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