Lifestyle factors associated with symptoms suggestive of restless legs syndrome in Korean adolescents.

OBJECTIVE: Restless legs syndrome (RLS) is a common sleep disorder among adolescents. This study aimed to investigate the lifestyle factors and sleep disturbances associated with the symptoms suggestive of RLS in Korean adolescents. METHODS: In this cross-sectional study, we investigated a total of 25,789 adolescents (mean age, 15.8 ± 1.7 years; male, 48.5 %). The presence of symptoms suggestive of RLS was assessed with a single question about RLS in the Global Sleep Assessment Questionnaire. We performed multiple logistic regression analysis to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of lifestyle factors and sleep disturbances that were independently associated with adolescent RLS. RESULTS: The prevalence of RLS-suggestive symptoms was 5.1 % among adolescents. After adjustment, lifestyle factors associated with symptoms suggestive of RLS were occasional alcohol consumption (OR, 1.245; 95 % CI, 1.006-1.540) and proneness to Internet addiction (OR, 1.027; 95 % CI, 1.021-1.033). Bedtime behaviors associated with RLS-suggestive symptoms were sleeping with a doll or pet (OR, 1.194; 95 % CI, 1.032-1.381) and sleeping with a TV or radio on (OR, 1.366; 95 % CI, 1.156-1.614). Male sex, frequent snoring and witnessed apnea, perceived sleep insufficiency, excessive daytime sleepiness were also associated with RLS-suggestive symptoms in adolescents. CONCLUSIONS: Adolescents with symptoms suggestive of RLS were associated with different lifestyle factors compared to adults with RLS. Further research is needed to determine the clinical implications of lifestyle factors in adolescent RLS.

Therapeutic Drug Monitoring of 6 New-Generation Antiseizure Medications Using a Mass Spectrometry Method: Analysis of 2-Year Experience in a Large Cohort of Korean Epilepsy Patients.

CONTEXT.­: New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. OBJECTIVE.­: To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. DESIGN.­: Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. RESULTS.­: The method was linear with limit of detection less than 0.05 µg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs. CONCLUSIONS.­: A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.

Psychotic Symptoms in Patients With Major Neurological Diseases.

Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.

The effect of cognitive behavioral therapy on depression of people with epilepsy.

BACKGROUND: Depression, a common mental problem frequently detected in people with epilepsy (PWE), is a major factor that decreases the quality of life of PWE. The cognitive behavioral therapy (CBT) is the most commonly used non-pharmacological treatment for depressive disorders. The CBT for PWE with depression has not yet been studied in Korea. This study aimed to evaluate the effects of the CBT on depression in PWE in Korea. METHOD: This study included 16 PWE with depression who received CBT and 30 control PWE with depression who did not receive CBT. The mean number of CBT sessions per patient was 7.2 in the CBT group. The Beck Depression Inventory-II (BDI-II) and Patient Health Questionnaire-9 (PHQ-9) were administered before and after CBT sessions in the CBT group, whereas PHQ-9 was performed at baseline and follow-up in the control group. The difference in PHQ-9 and BDI-II scores were analyzed between the pre- and post-CBT periods in the CBT group. The difference between baseline and follow-up PHQ-9 scores was compared in the control group. RESULTS: There was no significant difference in baseline variables between the CBT and control groups. The PHQ-9 score significantly decreased after the CBT sessions in the CBT group (pre-CBT PHQ-9 = 13.56 vs. post-CBT PHQ-9 = 8.56) but it did not change in the control group (Baseline PHQ-9 = 13.83 vs. follow-up PHQ-9 = 14.67). Twelve PWE had undergone four or more CBT sessions with pre-CBT and post-CBT BDI-II. The BDI-II score significantly decreased after CBT sessions (pre-CBT BDI-II = 30.75 vs. post-CBT BDI-II = 21.5). The CBT decreased the sub-field scores of cognitive and physical-emotional factors as well as suicidal ideation, but the score of sleep problems did not significantly improve. The CBT did not significantly change the seizure frequency. CONCLUSION: The CBT significantly improved depression in Korean PWE. Therefore, it can be considered a treatment tool for depression in PWE. However, a study with more patients and a fixed number of CBT sessions is recommended to generalize this effect.

Identifying important factors for successful surgery in patients with lateral temporal lobe epilepsy.

OBJECTIVE: Lateral temporal lobe epilepsy (LTLE) has been diagnosed in only a small number of patients; therefore, its surgical outcome is not as well-known as that of mesial temporal lobe epilepsy. We aimed to evaluate the long-term (5 years) and short-term (2 years) surgical outcomes and identify possible prognostic factors in patients with LTLE. METHODS: This retrospective cohort study was conducted between January 1995 and December 2018 among patients who underwent resective surgery in a university-affiliated hospital. Patients were classified as LTLE if ictal onset zone was in lateral temporal area. Surgical outcomes were evaluated at 2 and 5 years. We subdivided based on outcomes and compared clinical and neuroimaging data including cortical thickness between two groups. RESULTS: Sixty-four patients were included in the study. The mean follow-up duration after the surgery was 8.4 years. Five years after surgery, 45 of the 63 (71.4%) patients achieved seizure freedom. Clinically and statistically significant prognostic factors for postsurgical outcomes were the duration of epilepsy before surgery and focal cortical dysplasia on postoperative histopathology at the 5-year follow-up. Optimal cut-off point for epilepsy duration was eight years after the seizure onset (odds ratio 4.375, p-value = 0.0214). Furthermore, we propose a model for predicting seizure outcomes 5 years after surgery using the receiver operating characteristic curve and nomogram (area under the curve = 0.733; 95% confidence interval, 0.588-0.879). Cortical thinning was observed in ipsilateral cingulate gyrus and contralateral parietal lobe in poor surgical group compared to good surgical group (p-value < 0.01, uncorrected). CONCLUSIONS: The identified predictors of unfavorable surgical outcomes may help in selecting optimal candidates and identifying the optimal timing for surgery among patients with LTLE. Additionally, cortical thinning was more extensive in the poor surgical group.

Multidimensional Early Prediction Score for Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Achieving favorable postoperative outcomes in patients with drug-resistant epilepsy (DRE) requires early referrals for preoperative examinations. The purpose of this study was to investigate the possibility of a user-friendly early DRE prediction model that is easy for nonexperts to utilize. METHODS: A two-step genotype analysis was performed, by applying 1) whole-exome sequencing (WES) to the initial test set (n=243) and 2) target sequencing to the validation set (n=311). Based on a multicenter case-control study design using the WES data set, 11 genetic and 2 clinical predictors were selected to develop the DRE risk prediction model. The early prediction scores for DRE (EPS-DRE) was calculated for each group of the selected genetic predictors (EPS-DREgen), clinical predictors (EPS-DREcln), and two types of predictor mix (EPS-DREmix) in both the initial test set and the validation set. RESULTS: The multidimensional EPS-DREmix of the predictor mix group provided a better match to the outcome data than did the unidimensional EPS-DREgen or EPS-DREcln. Unlike previous studies, the EPS-DREmix model was developed using only 11 genetic and 2 clinical predictors, but it exhibited good discrimination ability in distinguishing DRE from drug-responsive epilepsy. These results were verified using an unrelated validation set. CONCLUSIONS: Our results suggest that EPS-DREmix has good performance in early DRE prediction and is a user-friendly tool that is easy to apply in real clinical trials, especially by nonexperts who do not have detailed knowledge or equipment for assessing DRE. Further studies are needed to improve the performance of the EPS-DREmix model.

Prediction of the Responsiveness to Vagus-Nerve Stimulation in Patients with Drug-Resistant Epilepsy via Directed-Transfer-Function Analysis of Their Perioperative Scalp EEGs.

This study aims to compare directed transfer function (DTF), which is an effective connectivity analysis, derived from scalp EEGs between responder and nonresponder groups implanted with vagus-nerve stimulation (VNS). Twelve patients with drug-resistant epilepsy (six responders and six nonresponders) and ten controls were recruited. A good response to VNS was defined as a reduction of ≥50% in seizure frequency compared with the presurgical baseline. DTF was calculated in five frequency bands (delta, theta, alpha, beta, and broadband) and seven grouped electrode regions (left and right frontal, temporal, parieto-occipital, and midline) in three different states (presurgical, stimulation-on, and stimulation-off states). Responders showed presurgical nodal strength close to the control group in both inflow and outflow, whereas nonresponders exhibited increased inward and outward connectivity measures. Nonresponders also had increased inward and outward connectivity measures in the various brain regions and various frequency bands assessed compared with the control group when the stimulation was on or off. Our study demonstrated that the presurgical DTF profiles of responders were different from those of nonresponders. Moreover, a presurgical normal DTF profile may predict good responsiveness to VNS.

Effects of Vagus Nerve Stimulation on Sleep-Disordered Breathing, Daytime Sleepiness, and Sleep Quality in Patients With Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) on sleep-disordered breathing (SDB), daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy (DRE). It also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. METHODS: Twenty-four patients were recruited. Paired t-tests and multiple linear regression analyses were performed to determine how the demographic and clinical characteristics of the patients influenced the variables that changed significantly after VNS treatment. RESULTS: After VNS, the patients showed significant increases in the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), apnea index, hypopnea index, and oxygen desaturation index (ODI), as well as a significant decrease in the lowest arterial oxygen saturation (SaO2 nadir) (p<0.05). The multiple linear regression analyses demonstrated that the predictor of larger increases in AHI and RDI was being older at baseline, and that the predictor of a larger increase in apnea index was a longer epilepsy duration. The strongest predictor of a larger increase in ODI was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. The strongest predictor of a larger decrease in SaO2 nadir was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. CONCLUSIONS: This study has confirmed that VNS improves seizure control in patients with DRE, whereas it increases obstructive sleep apnea (OSA). Furthermore, the increase in OSA is affected by age and the duration of epilepsy. Therefore, careful observation and monitoring of SDB is recommended in patients who undergo VNS.

Association between Self-Perceived Periodic Limb Movement during Sleep and Excessive Daytime Sleepiness Depend on Restless Leg Symptoms in Korean Adolescents.

Although periodic limb movement during sleep (PLMS) and restless legs syndrome (RLS) are common in children and adolescents, they are relatively overlooked as a target of treatment. PLMS has been evaluated as having a lower clinical significance than RLS. This study examined the relationship of socio-behavioral factors of PLMS in Korean adolescents and checked whether PLMS is associated with excessive daytime sleepiness (EDS), depending on whether restless legs symptoms accompany it. In a cross-sectional study, 25,789 adolescents between 12 and 18 years of age (15.76 ± 1.73 years; female 51.49%) were evaluated using an online survey. Various self-report questionnaires were used to assess PLMS and RLS symptoms, EDS, sleep habits, and various socio-behavioral factors. The prevalence of self-perceived PLMS and restless legs symptoms were 903 (3.50%) and 1311 (5.08%), respectively. Of the 1311 participants, 399 had self-perceived PLMS. The odds ratios (ORs) for self-perceived PLMS in participants with restless legs symptoms were: males (OR = 1.528; 95% CI: 1.145-2.040), usually/always experienced apnea apnea (OR, 3.006; 95% CI, 1.954-4.624), increased proneness to Internet addiction (OR = 1.013; 95% CI: 1.001-1.025), sometimes/often consuming coffee (OR = 1.312; 95% CI: 1.015-1.695), EDS (OR = 0.826; 95% CI: 0.488-1.398), and perceived insufficient sleep (OR = 1.143; 95% CI: 0.835-1.565). The male gender, witness apnea, consuming coffee, and being prone to Internet addiction were identified as factors significantly associated with self-perceived PLMS in participants with restless legs symptoms. However, EDS and insufficient sleep were associated with self-perceived PLMS in the absence of restless legs symptoms.

Levetiracetam Therapeutic Drug Monitoring in a Large Cohort of Korean Epileptic Patients.

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography-tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20-5000) mg and 25.5 (3.03-133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8-95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

Regional Ictal Hyperperfusion in the Contralateral Occipital Area May Be a Poor Prognostic Marker of Anterior Temporal Lobectomy: A SISCOM Analysis of MTLE Cases.

BACKGROUND AND OBJECTIVE: Subtraction of ictal SPECT coregistered to MRI (SISCOM) provides complementary information for detecting the ictal onset zone, especially in patients with MRI-negative focal epilepsy, and provides additional useful information for predicting long-term postresection outcomes. This study sought to investigate the relationship between surgical failure and increased cerebral blood flow (CBF) pattern using SPECT in patients with mesial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS). METHODS: Among 42 subjects who underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) for MTLE-HS, 29 (69.0%) were seizure-free (SF group). Hyperperfusion was compared in 14 ipsilateral and contralateral brain regions in SISCOM images between the two groups. RESULTS: The pattern of ictal hyperperfusion in temporal regions did not vary significantly between the SF and non-seizure-free (NSF) groups. However, CBF increases in the contralateral occipital area was more frequent in the NSF group than in the SF group. Furthermore, ictal hyperperfusion of the ipsilateral occipital and contralateral parietal areas tended to be more frequent in the NSF group. CONCLUSION: The results indicate that poor ATL-AH surgical outcome is associated with a tendency of ictal hyperperfusion of the contralateral occipital cortex based on SISCOM analysis. The pattern of early ictal CBF changes implicating the propagation from temporal to occipital cortices can be considered a marker of poor surgical outcomes of ATL-AH in MTLE-HS patients.

Effect of Long-Term Treatment with Vagus Nerve Stimulation on Mood and Quality of Life in Korean Patients with Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: This study aimed to determine the long-term effects of vagus nerve stimulation (VNS) treatment on suicidality, mood-related symptoms, and quality of life (QOL) in patients with drug-resistant epilepsy (DRE). We also investigated the relationships among these main effects, clinical characteristics, and VNS parameters. METHODS: Among 35 epilepsy patients who underwent VNS implantation consecutively in our epilepsy center, 25 patients were recruited to this study for assessing the effects of VNS on suicidality, mood-related symptoms, and QOL. The differences in these variables between before and after VNS treatment were analyzed statistically using paired t-tests. Multiple linear regression analyses were also performed to determine how the patients' demographic and clinical characteristics influenced the variables that showed statistically significant changes after long-term VNS treatment. RESULTS: After VNS, our patients showed significant improvements not only in the mean seizure frequency but also in suicidality, depression, and QOL. The reduction in depression was associated with the improvement in QOL and more-severe depression at baseline. The reduction in suicidality was associated with higher suicidality at baseline, smaller changes in depression, and less-severe depression at baseline. Improved QOL was associated with lower suicidality at baseline. CONCLUSIONS: This study found that VNS decreased the mean seizure frequency in patients with DRE, and also improved their depression, suicidality, and QOL. These results provide further evidence for therapeutic effect of VNS on psychological comorbidities of patients with DRE.

Surgical outcome and prognostic factors in epilepsy patients with MR-negative focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data. METHODS: We retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD. RESULTS: Finally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD. CONCLUSION: In this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD.

Association between eveningness preference, socio-behavioral factors, and insomnia symptoms in Korean adolescents.

OBJECTIVE/BACKGROUND: Studies focusing on insomnia in adolescents are relatively scarce compared to those on excessive daytime sleepiness. We aimed to investigate the prevalence of insomnia symptoms and associated factors in Korean high school students. PATIENTS/METHODS: A total of 8565 students (girls: 4104) were investigated nationwide, across 15 South Korean districts using an online self-report questionnaire. Insomnia symptoms were evaluated using the Global Sleep Assessment Questionnaire. The participants' mean age was 16.77 ± 0.85 years. RESULTS: The prevalence of insomnia symptoms was 39.43% (n = 3377). Logistic regression was used to estimate the odds ratio (OR) of insomnia symptoms associated with sleep characteristics and social behaviors after adjusting for the relevant covariates. Evening preference (OR, 2.51, 95% CI, 2.20-2.86), perception of insufficient sleep (OR, 3.55, 95% CI, 3.11-4.06), snoring usually/always (OR, 1.25; 95% CI, 1.00-1.55), witnessed sleep apnea usually/always (OR, 1.70; 95% CI, 1.17-2.46), increased internet addiction (OR, 1.02; 95% CI, 1.02-1.03), bad sleep environment (OR, 1.77; 95% CI, 1.50-2.10), ≥3 private extra classes (OR, 1.23; 95% CI, 1.01-1.49), often coffee consumption (OR, 1.31; 95% CI, 1.10-1.56), and often nocturnal eating (OR, 1.24; 95% CI, 1.06-1.45) were associated with insomnia symptoms. Evening preference (OR, 3.48; 95% CI, 2.52-4.82) was also associated with insomnia symptoms in the perceived sufficient sleep subgroup. CONCLUSION: Insomnia symptoms were common in Korean high school students. Evening preference was the major factor associated with insomnia symptoms. Various socio-behavioral factors were also associated with insomnia symptoms.

Asian accreditation of sleep medicine physicians and technologists: practice guidelines by the Asian Society of Sleep Medicine.

Due to the rapid growth in sleep medicine's professional content, several countries have recognized sleep medicine as an independent specialty. The practice of sleep medicine and the demand for this service in Asian countries are expanding. At this point of growth, the accreditation of sleep medicine specialists is paramount to patient care and the training of physicians and technologists. The Asian Society of Sleep Medicine (ASSM) mandated a taskforce committee for the accreditation of sleep medicine practice. This taskforce developed Asian accreditation practice guidelines for sleep medicine physicians and technologists. This paper presents the newly approved Asian accreditation practice guidelines for sleep medicine physicians and technologists by the ASSM.

Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial.

This long-term open-label extension (OLE) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses in patients with epilepsy and focal (partial-onset) or generalized onset seizures, or Unverricht-Lundborg disease (ULD). A secondary objective was to evaluate efficacy of BRV in the subgroups of patients with focal or generalized onset seizures. Patients with epilepsy were eligible to enroll in this OLE (N01125; NCT00175916) and were analyzed if they had completed a previous double-blind BRV trial (N01114 [NCT00175929], N01252 [NCT00490035], N01254 [NCT00504881], N01187 [NCT00357669], and N01236 [NCT00368251]), and were expected to obtain a reasonable benefit from long-term BRV treatment. Patients entered the OLE at the BRV dose recommended at the end of the previous trial, with dose adjustments of BRV and concomitant antiseizure medications permitted. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables in patients with focal seizures were percent reduction in focal seizure frequency, 50 % responder rates, and 6- and 12-month seizure-freedom. Eight hundred and fifty-three patients (729 [85.5 %] with focal seizures, 30 [3.5 %] with generalized onset seizures, and 94 [11.0 %] with ULD) were enrolled and included in the Safety Set. Overall, 619 (72.6 %) patients discontinued the trial, mainly due to lack of efficacy (354 [41.5 %]), adverse events (100 [11.7 %]), and patient choice (98 [11.5 %]). During the OLE, 588 (68.9 %) patients received BRV for ≥12 months, 403 (47.2 %) for ≥36 months, and 223 (26.1 %) for ≥96 months. The most common modal dose of BRV was 150 mg/day (415 [48.7 %] patients). In the ULD subgroup, the most common modal BRV dose was 100 mg/day (44/94 [46.8 %] patients), and 37/94 (39.4 %) patients had ≥96 months of BRV exposure. Overall, 720/853 (84.4 %) patients reported TEAEs, 451 (52.9 %) had a drug-related TEAE, and 95 (11.1 %) discontinued BRV due to a TEAE. In the ULD subgroup, 87/94 (92.6 %) patients reported TEAEs, 60 (63.8 %) had a drug-related TEAE, and 16 (17.0 %) discontinued due to a TEAE. In patients with focal seizures, the median reduction in focal seizure frequency from Baseline was 43.1 % (n = 728), the 50 % responder rate was 43.6 % (n = 729), and 6- and 12-month seizure freedom rates were 22.2 % and 15.8 %, respectively (n = 595). Overall, BRV was well-tolerated as long-term adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease, with improvements in focal seizure frequency maintained over time.

Association between morningness-eveningness, sleep duration, weekend catch-up sleep and depression among Korean high-school students.

The present study aimed to examine the association between morningness-eveningness preferences, sleep duration, weekend catch-up sleep duration and depression among Korean high-school students. A total of 8,655 high-school students participated from 15 districts in South Korea and completed an online self-report questionnaire. The following sleep characteristics were assessed: weekday and weekend sleep duration, weekend catch-up sleep duration, morningness-eveningness preference, perceived sufficiency of sleep, self-reported snoring and sleep apnea, daytime sleepiness, and sleep environment. Age, gender, body mass index, number of private classes, proneness to internet addiction, and depressive mood were also evaluated. A logistic regression analysis was conducted to compute odds ratios for the association between depression and sleep characteristics, after controlling for relevant covariates. Eveningness preference was a significant predictor of depressive mood (adjusted OR, 1.71; 95% CI, 1.47-1.99). Weekend CUS durations that were ≥2 hr and enrollment in numerous private classes were associated with a lower risk for depression (0.68, 0.55-0.85; 0.76, 0.60-0.95; respectively). Female gender, underweight and obese body weight, short weekday sleep durations, excessive daytime sleepiness, perceived excessiveness and insufficiency of sleep, self-reported snoring and sleep apnea, proneness to internet addiction and a non-optimal sleep environment were associated with an increased risk for depression. Eveningness preference and insufficient weekday sleep duration were associated with an increased risk for depression. Weekend CUS duration ≥2 hr reduced the risk for depression. Diverse aspects, including sleeping habits and sleep-related environmental factors, should be considered to reduce depressive symptoms in late adolescents.

Correlations between interictal extratemporal spikes and clinical features, imaging characteristics, and surgical outcomes in patients with mesial temporal lobe epilepsy.

PURPOSE: The significance of interictal epileptiform discharges (IEDs) observed in the extratemporal lobe has not been fully evaluated in patients with mesial temporal lobe epilepsy (MTLE). This study aimed to evaluate the surgical outcomes, clinical features, and functional neuroimaging characteristics of patients in relation to the presence or absence of extratemporal IED in MTLE with hippocampal sclerosis (HS). METHODS: A total of 165 patients with HS-induced MTLE who had undergone anterior temporal lobectomy were enrolled and stratified into the extratemporal interictal epileptiform discharges (ETD) and the temporal lobe discharges (TD) groups. We analyzed the differentiating features of pre- and postsurgical evaluation data between the two groups. For outcome assessment, only patients with a follow-up of at least 2 years were enrolled, and the outcomes were classified based on Engel classification. RESULTS: The ETD group showed extensive glucose hypometabolism involving the temporal lobe and extratemporal regions (p < 0.001), and IEDs were observed bilaterally or contralateral to the ictal focus (p = 0.02). However, there was no difference in the surgical outcomes between the two groups. On multivariate analysis, statistically significant variables related to ETD occurrence including seizure onset age were not identified nevertheless. CONCLUSION: Our results indicate that ETD had a surgical outcome comparable to that of TD. Therefore, a surgical intervention need not be delayed even if extratemporal IED may be found in presurgical long-term scalp EEG monitoring.

Defining the optimal target for anterior thalamic deep brain stimulation in patients with drug-refractory epilepsy.

OBJECTIVE: The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS. METHODS: From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space. RESULTS: Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up. CONCLUSIONS: Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

Sleep duration rather than sleep timing is associated with obesity in adolescents.

OBJECTIVE: In this study, we investigated differences in sleep patterns between obese and non-obese adolescents, and determined which sleep-related parameters were associated with a risk of adolescent obesity. METHODS: In this cross-sectional study, we evaluated 22,906 adolescents between 12 and 18 years of age (mean 15.2 ± 1.7 years; male 50.9%). Self-report questionnaires were used to assess body mass index (BMI) and sleep habits. Obesity was defined as a BMI-for-age ≥ 95th percentile. Weekend catch-up sleep (CUS) duration was calculated as the sleep duration on free days minus sleep duration on school days. We estimated mid-sleep time on free days corrected for oversleep on free days (MSFsc) and social jet lag. Then, we performed multivariate analysis for adolescent obesity and BMI, respectively. RESULTS: The prevalence of obesity was 6.0%. The average sleep duration (P = 0.017) and weekend CUS duration (P < 0.001) of obese adolescents were shorter than those of non-obese adolescents. However, there was no significant difference in MSFsc or social jet lag by the obesity status. After adjustment, obesity was significantly associated with short average sleep duration (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96) and short weekend CUS duration (OR 0.92, 95% CI 0.89-0.95). Similarly, BMI was inversely correlated with average sleep duration (B = -0.15, 95% CI -0.19 to -0.11) and weekend CUS duration (B = -0.09, 95% CI -0.11 to -0.06). CONCLUSIONS: Our observations suggest that short sleep duration, rather than late MSFsc or social jet lag, was associated with adolescent obesity.