Eco-anxiety: An adaptive behavior or a mental disorder? Results of a psychometric study.

OBJECTIVE: Eco-anxiety is a complex construct that has been created to grasp the psychological impact of the consequences of global warming. The concept needs a reliably valid questionnaire to better evaluate its impact on the risk of anxiety and depressive disorders. The Eco-Anxiety Questionnaire (EAQ-22) evaluates two dimensions: 'habitual ecological anxiety' and 'distress related to eco-anxiety'. However, a version in French, one of the world's widely spoken languages, was until now lacking. We aimed to translate and validate the French EAQ-22 and to evaluate the prevalence of the level of the two dimensions of eco-anxiety and the relationship with anxiety and depressive symptoms in a representative adult sample of the French general population. METHODS: This study was performed under the auspices of the Institut national du sommeil et de la vigilance (INSV). Participants (18-65 years) were recruited by an institute specialized in conducting online surveys of representative population samples (quota sampling). Two native French speakers and two native English speakers performed a forward-backward translation of the questionnaire. The Hospital Anxiety and Depression scale (HAD) was administered to assess anxiety (HAD-A) and depressive (HAD-D) symptoms and for external validity. Internal structural validity and external validity were analysed. RESULTS: Evaluation was performed on 1004 participants: mean age 43.47 years (SD=13.41, range: [19-66]); 54.1% (n=543) women. Using the HAD, 312 (31.1%) patients had current clinically significant anxiety symptoms (HAD-A>10) and 150 (14.9%) had current clinically significant depressive symptoms (HAD-D>10). Cronbach's alpha coefficient was 0.934, indicating very good internal consistency. Correlation between EAQ-22 and HAD scores was low (r[1004]=0.209, P<0.001), 'habitual ecological anxiety' was correlated less with HAD-A and HAD-D than 'distress related to eco-anxiety', indicating good external validity. CONCLUSION: This study validates the French EAQ-22 and paves the way for using the EAQ-22 as a global tool for assessing eco-anxiety. Further prospective studies are now required to better evaluate the impact of eco-anxiety on the occurrence of anxiety and depressive disorder.

Better characterizing sleep beliefs for personalized sleep health promotion: the French sleep beliefs scale validation study.

Background: The Sleep Beliefs Scale (SBS) is a well-known tool to design and monitor personalized sleep health promotion at an individual and population level. The lack of an established French version limits the development of effective interventions targeting these populations. Thus, the aim of this study was to validate the French version of the SBS in a representative sample of the general population. Methods: Quota sampling was used to recruit 1,004 participants (18-65 years, mean age: 43 years, 54% of female) who underwent an online survey to complete the SBS, and to assess sleep schedules, sleep quality and disorders, and mental health. Cronbach's α coefficient, confirmatory factor analysis, item-internal consistency (IIC), and item discriminant validity (IDV) of the SBS were computed to assess internal validity while bivariate associations with sleep schedules, sleep quality and disorders, and mental health were used to assess external convergent and discriminant validity. Results: The mean score on the SBS was 12.3 ± 4.9. Item 19 ("Quiet & Dark") showed the highest rate of correct answers (n = 801, 79.8%), while item 20 ("Recovering sleep") showed the lowest rate of correct answers (n = 246, 24.5%). Overall, the SBS showed satisfactory internal consistency (α = 0.87) and confirmed the three-factor structure proposed by the original study. All items were found consistent (IIC > 0.4) and discriminant (IIC > IDV) except for item 20 ("recovering lost sleep by sleeping for a long time"). Females, older participants, and subjects with short time-in-bed, poor sleep quality, insomnia, and circadian rhythm disorder had higher SBS scores while participants with depressive symptoms had lower SBS scores. Conclusion: We successfully translated and validated the French version of the SBS in a representative sample, making it a reliable instrument for researchers and clinicians to assess and target sleep beliefs. Correct answers vary from 25 to 80% which underlines the importance of continuing sleep health promotion campaigns by targeting poorly understood behaviors. Our findings also shed light on the fickleness of beliefs that are prone to vary within individuals across time, in step with societal changes. Several associated factors were identified, thus contributing to our understanding of sleep beliefs and offering insights for personalized approaches to enhance sleep health and overall well-being.

The generation and propagation of the human alpha rhythm.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Theta Bursts Precede, and Spindles Follow, Cortical and Thalamic Downstates in Human NREM Sleep.

Since their discovery, slow oscillations have been observed to group spindles during non-REM sleep. Previous studies assert that the slow-oscillation downstate (DS) is preceded by slow spindles (10-12 Hz) and followed by fast spindles (12-16 Hz). Here, using both direct transcortical recordings in patients with intractable epilepsy (n = 10, 8 female), as well as scalp EEG recordings from a healthy cohort (n = 3, 1 female), we find in multiple cortical areas that both slow and fast spindles follow the DS. Although discrete oscillations do precede DSs, they are theta bursts (TBs) centered at 5-8 Hz. TBs were more pronounced for DSs in NREM stage 2 (N2) sleep compared with N3. TB with similar properties occur in the thalamus, but unlike spindles they have no clear temporal relationship with cortical TB. These differences in corticothalamic dynamics, as well as differences between spindles and theta in coupling high-frequency content, are consistent with NREM theta having separate generative mechanisms from spindles. The final inhibitory cycle of the TB coincides with the DS peak, suggesting that in N2, TB may help trigger the DS. Since the transition to N1 is marked by the appearance of theta, and the transition to N2 by the appearance of DS and thus spindles, a role of TB in triggering DS could help explain the sequence of electrophysiological events characterizing sleep. Finally, the coordinated appearance of spindles and DSs are implicated in memory consolidation processes, and the current findings redefine their temporal coupling with theta during NREM sleep.SIGNIFICANCE STATEMENT Sleep is characterized by large slow waves which modulate brain activity. Prominent among these are downstates (DSs), periods of a few tenths of a second when most cells stop firing, and spindles, oscillations at ∼12 times a second lasting for ∼a second. In this study, we provide the first detailed description of another kind of sleep wave: theta bursts (TBs), a brief oscillation at ∼six cycles per second. We show, recording during natural sleep directly from the human cortex and thalamus, as well as on the scalp, that TBs precede, and spindles follow DSs. TBs may help trigger DSs in some circumstances, and could organize cortical and thalamic activity so that memories can be consolidated during sleep.

Frequency of Past and Current Psychiatric Disorders in Patients Referred for Polysomnography: A Pilot Study.

STUDY OBJECTIVES: The aim of this study was to assess the frequency of past and current psychiatric disorders among patients referred to a sleep unit for polysomnography. METHODS: A total of 152 patients referred to the Sleep Center of Timone Hospital in Marseille were included from January 12 to March 31, 2015. Clinical data were collected using the Mini International Neuropsychiatric Interview. RESULTS: The final sample consisted of 102 patients. Polysomnography helped diagnose the following common sleep disorders: obstructive sleep apnea, restless legs syndrome, insomnia, and non-rapid eye movement sleep arousal disorder. Ninety patients (88%) had psychiatric disorders. All patients (27) without a common sleep disorder diagnosis had psychiatric disorders and among patients with a common sleep disorder diagnosis 84% had psychiatric disorders. Among the psychiatric disorders a past major depressive episode was the most frequent pathology. CONCLUSIONS: This study shows that patients referred to a sleep unit have a high prevalence of psychiatric disorders. This may be explained by residual symptoms of psychiatric illnesses, a diagnostic misdirection, a denial of psychiatric diagnosis, or an undiagnosed somatic symptom disorder. Finally, this study shows the importance of cross-disciplinary communication considering the diagnostic heterogeneity that may represent a sleep complaint.

Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation.

Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer's disease, the analysis of networks altered by medication would be particularly interesting. Eleven healthy subjects were recruited in the context of the European Innovative Medicines Initiative 'PharmaCog'. Each underwent five sessions of simultaneous EEG-fMRI in order to investigate the effects of donepezil and memantine before and after sleep deprivation (SD). The SD approach has been previously proposed as a model for cognitive impairment in healthy subjects. By applying network based statistics (NBS), we observed altered brain networks significantly linked to donepezil intake and sleep deprivation. Taking into account the sleep stages extracted from the EEG data we revealed that a network linked to sleep is interacting with sleep deprivation but not with medication intake. We successfully extracted the functional resting-state networks modified by donepezil intake, sleep and SD. We observed donepezil induced whole brain connectivity alterations forming a network separated from the changes induced by sleep and SD, a result which shows the utility of this approach to check for the validity of pharmacological resting-state analysis of the tested medications without the need of taking into account the subject specific vigilance.

Coordination of cortical and thalamic activity during non-REM sleep in humans.

Every night, the human brain produces thousands of downstates and spindles during non-REM sleep. Previous studies indicate that spindles originate thalamically and downstates cortically, loosely grouping spindle occurrence. However, the mechanisms whereby the thalamus and cortex interact in generating these sleep phenomena remain poorly understood. Using bipolar depth recordings, we report here a sequence wherein: (1) convergent cortical downstates lead thalamic downstates; (2) thalamic downstates hyperpolarize thalamic cells, thus triggering spindles; and (3) thalamic spindles are focally projected back to cortex, arriving during the down-to-upstate transition when the cortex replays memories. Thalamic intrinsic currents, therefore, may not be continuously available during non-REM sleep, permitting the cortex to control thalamic spindling by inducing downstates. This archetypical cortico-thalamo-cortical sequence could provide the global physiological context for memory consolidation during non-REM sleep.

Distribution, Amplitude, Incidence, Co-Occurrence, and Propagation of Human K-Complexes in Focal Transcortical Recordings

K-complexes (KCs) are thought to play a key role in sleep homeostasis and memory consolidation; however, their generation and propagation remain unclear. The commonly held view from scalp EEG findings is that KCs are primarily generated in medial frontal cortex and propagate parietally, whereas an electrocorticography (ECOG) study suggested dorsolateral prefrontal generators and an absence of KCs in many areas. In order to resolve these differing views, we used unambiguously focal bipolar depth electrode recordings in patients with intractable epilepsy to investigate spatiotemporal relationships of human KCs. KCs were marked manually on each channel, and local generation was confirmed with decreased gamma power. In most cases (76%), KCs occurred in a single location, and rarely (1%) in all locations. However, if automatically detected KC-like phenomena were included, only 15% occurred in a single location, and 27% occurred in all recorded locations. Locally generated KCs were found in all sampled areas, including cingulate, ventral temporal, and occipital cortices. Surprisingly, KCs were smallest and occurred least frequently in anterior prefrontal channels. When KCs occur on two channels, their peak order is consistent in only 13% of cases, usually from prefrontal to lateral temporal. Overall, the anterior-posterior separation of electrode pairs explained only 2% of the variance in their latencies. KCs in stages 2 and 3 had similar characteristics. These results open a novel view where KCs overall are universal cortical phenomena, but each KC may variably involve small or large cortical regions and spread in variable directions, allowing flexible and heterogeneous contributions to sleep homeostasis and memory consolidation.

Sleep disorders among French anaesthesiologists and intensivists working in public hospitals: a self-reported electronic survey.

BACKGROUND: Sleep disorders can affect the health of physicians and patient outcomes. OBJECTIVES: To determine the prevalence of sleep disorders among French anaesthesiologists and intensivists working in a public hospital. DESIGN: A cross-sectional survey. SETTING: Anaesthesiologists and intensivists working in French public hospitals. MAIN OUTCOME MEASURES: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) was used to assess the degree of excessive daytime sleepiness. RESULTS: Among 1504 responders, 677 (45%) physicians reported sleep disorders. The independent factors associated with sleep disorders were reporting of sleep disorders [odds ratio (OR) 12.04, 95% CI (95% confidence interval) 8.89 to 16.46], sleep time less than 7 h (OR 8.86, 95% CI 6.50 to 12.20), work stress (OR 2.04, 95% CI 1.49 to 2.83), stress at home (OR 1.77, 95% CI 1.24 to 2.53), anxiolytic use (OR 3.69, 95% CI 2.23 to 6.25), psychotropic drug use (OR 3.91, 95% CI 1.51 to 11.52) and excessive daytime sleepiness (OR 1.81, 95% CI 1.34 to 2.45). Six hundred and seventy-six (44%) responders reported excessive daytime sleepiness during their professional activity. The independent factors associated with excessive daytime sleepiness were female sex (OR 1.86, 95% CI 1.49 to 2.34), tea consumption (OR 1.47, 95% CI 1.14 to 1.91), regular practice of nap (OR 1.68, 95% CI 1.34 to 2.09), stress at home (OR 1.31, 95% CI 1.02 to 1.68), more than four extended work shifts monthly (OR 1.25, 95% CI 1.01 to 1.56) and sleep disorders (OR 1.73, 95% CI 1.31 to 2.29). Reporting sleep disorder duration and a sleep time less than 7 h were the two major risk factors for sleep disorders. Female sex was the major risk factor for excessive daytime sleepiness. CONCLUSION: French anaesthesiologists did not report more sleep disorders than the general population, but their alertness is impaired by a factor of two.

Synchronization of isolated downstates (K-complexes) may be caused by cortically-induced disruption of thalamic spindling.

Sleep spindles and K-complexes (KCs) define stage 2 NREM sleep (N2) in humans. We recently showed that KCs are isolated downstates characterized by widespread cortical silence. We demonstrate here that KCs can be quasi-synchronous across scalp EEG and across much of the cortex using electrocorticography (ECOG) and localized transcortical recordings (bipolar SEEG). We examine the mechanism of synchronous KC production by creating the first conductance based thalamocortical network model of N2 sleep to generate both spontaneous spindles and KCs. Spontaneous KCs are only observed when the model includes diffuse projections from restricted prefrontal areas to the thalamic reticular nucleus (RE), consistent with recent anatomical findings in rhesus monkeys. Modeled KCs begin with a spontaneous focal depolarization of the prefrontal neurons, followed by depolarization of the RE. Surprisingly, the RE depolarization leads to decreased firing due to disrupted spindling, which in turn is due to depolarization-induced inactivation of the low-threshold Ca2+ current (IT). Further, although the RE inhibits thalamocortical (TC) neurons, decreased RE firing causes decreased TC cell firing, again because of disrupted spindling. The resulting abrupt removal of excitatory input to cortical pyramidal neurons then leads to the downstate. Empirically, KCs may also be evoked by sensory stimuli while maintaining sleep. We reproduce this phenomenon in the model by depolarization of either the RE or the widely-projecting prefrontal neurons. Again, disruption of thalamic spindling plays a key role. Higher levels of RE stimulation also cause downstates, but by directly inhibiting the TC neurons. SEEG recordings from the thalamus and cortex in a single patient demonstrated the model prediction that thalamic spindling significantly decreases before KC onset. In conclusion, we show empirically that KCs can be widespread quasi-synchronous cortical downstates, and demonstrate with the first model of stage 2 NREM sleep a possible mechanism whereby this widespread synchrony may arise.

Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.

Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans.

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep.

Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects.

AIMS: To assess the sleepiness induced by pramipexole, a D2/D3-dopamine receptor agonist commonly used in Parkinson's disease and restless legs syndrome, without the problem of the confounding factors related to the disease. METHODS: Placebo, bromocriptine (2.5 mg), L-dopa (100 mg) and pramipexole (0.5 mg) were administered in a single oral dose on four separate days, with at least a 2-week wash-out period in a randomized cross-over design. Induced somnolence was assessed using Multiple Sleep Latency Test (MSLT) and subjective scaling of vigilance. Twelve male subjects (26.3 +/- 5.5 years old) without anxiety, mood, sleep or sedation disorders were enrolled. RESULTS: Pramipexole significantly reduced mean sleep latency compared with placebo 3 h 30 min [-6.1 min (-9.8, -2.4), P = 0.002] and 5 h 30 min [-5.6 min (-7.7, -3.5), P = 0.003] after administration. In addition, the total duration of sleep during the tests was higher with pramipexole than with placebo [+6.0 min (2.3, 9.7), P < 0.001]. These differences were not observed with L-dopa and bromocriptine in comparison with placebo. The induced sleepiness was not associated with an increase in subjective somnolence scaling, indicating that this adverse event may occur without prior warning. CONCLUSIONS: These results show that a single oral dose of pramipexole induces sleepiness as assessed by MSLT in healthy young subjects, independent of disease-related sleep dysfunction.

Human thalamic and cortical activities assessed by dimension of activation and spectral edge frequency during sleep wake cycles.

STUDY OBJECTIVES: Using spectral edge frequency (SEF95) and dimension of activation (DA), a new tool derived from the dimension of correlation, we assessed the activation of thalamus and cortex in the different vigilance states. PATIENTS: Results were gathered from intracerebral recordings performed in 12 drug-resistant epileptic patients during video-stereoelectroencephalographic (SEEG) monitoring. RESULTS: In the cortex, we observed a progressive decrease of DA from wake to sleep, with minimal DA values characterizing the deep slow wave sleep (dSWS) stage. During paradoxical sleep (PS), cortical level of activity returned to DA values similar to those obtained during wakefulness. In the thalamus, DA values during wakefulness were higher than the values observed during light SWS (ISWS), deep SWS (dSWS) and PS; there were no significant differences between the 3 sleep stages. Similar variations were observed with SEF95. CONCLUSION: DA analysis proved reliable for quantification of cortical activity, in agreement with data issued from classical vigilance states scoring and spectral analysis. At the thalamic level, only 2 levels of activity within a sleep wake cycle were observed, pointing to dissociated levels of activation between the thalamus and the neocortex during ISWS and PS.

Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia.

BACKGROUND: Dynamic action of anesthetic agents was compared at cortical and subcortical levels during induction of anesthesia. Unconsciousness involved the cortical brain but suppression of movement in response to noxious stimuli was mediated through subcortical structures. METHODS: Twenty-five patients with Parkinson disease, previously implanted with a deep-brain stimulation electrode, were enrolled during the implantation of the definitive pulse generator. During induction of anesthesia with propofol (n = 13) or sevoflurane (n = 12) alone, cortical (EEG) and subcortical (ESCoG) electrogenesis were obtained, respectively, from a frontal montage (F3-C3) and through the deep-brain electrode (p0-p3). In EEG and ESCoG spectral analysis, spectral edge (90%) frequency, median power frequency, and nonlinear analysis dimensional activation calculations were determined. RESULTS: Sevoflurane and propofol decreased EEG and ESCoG activity in a dose-related fashion. EEG values decreased dramatically at loss of consciousness, whereas there was little change in ESCoG values. Quantitative parameters derived from EEG but not from ESCoG were able to predict consciousness versus unconsciousness. Conversely, quantitative parameters derived from ESCoG but not from EEG were able to predict movement in response to laryngoscopy. CONCLUSION: These data suggest that in humans, unconsciousness mainly involves the cortical brain, but that suppression of movement in response to noxious stimuli is mediated through the effect of anesthetic agents on subcortical structures.

Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study.

PURPOSE: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug-resistant epilepsies of mesial temporal lobe origin. METHODS: From July 1996 to March 2000, three European centers selected 21 patients with mesial temporal lobe epilepsy (MTLE) for a temporal lobectomy. The preoperative investigations included video-EEG with foramen ovale electrodes, magnetic resonance imaging, neuropsychological testing, and the ESI-55 quality-of-life questionnaire. In place of a cortectomy, radiosurgical treatment was performed by using the Leksell Gamma Knife (LGK) at a dose of 24 +/- 1 Gy at the margin. The target included the anterior parahippocampal cortex and the basal and lateral part of the amygdala and anterior hippocampus (head and body). One patient (a heavy smoker) died of a myocardial infarction. Twenty patients were available for prospective evaluation. A minimum 2-year follow-up period included clinical, neuropsychological, and radiologic evaluations. RESULTS: At each 6-month follow-up evaluation, the frequency of seizures was significantly smaller than that at the previous visit. The median seizure frequency of 6.16 the month before treatment was reduced to 0.33 at 2 years after treatment. At 2 years, 65% of the patients (13 of 20) were seizure free. Five patients had transient side effects, including depression, headache, nausea, vomiting, and imbalance. There was no permanent neurological deficit reported except nine visual field deficits. No neuropsychological deterioration was observed 2 years after treatment. The quality of life was significantly better than that before surgery. CONCLUSIONS: The safety and efficacy of the radiosurgical treatment of MTLEs appears good in this group of patient over short-to-middle term. Delay of the seizure cessation was the major disadvantage of GKS. A longer follow-up period is required for confirmation of these results.