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.

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.

Efficacy, safety, and tolerability of perampanel in Asian and non-Asian patients with epilepsy.

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non-Asian populations with refractory focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo-controlled, phase-3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6-week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure-freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (-31.1% and -38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (-21.1% [P = 0.0001], -26.3% [P < 0.0001], and -27.7% [P = 0.0001] change, respectively) in the non-Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non-Asian population. Seizure-freedom rate among all patients was 4.9%-11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment-emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk-benefit profile in both Asian and non-Asian populations with refractory focal seizures.

The Role of Anterior Thalamic Deep Brain Stimulation as an Alternative Therapy in Patients with Previously Failed Vagus Nerve Stimulation for Refractory Epilepsy.

Deep brain stimulation (DBS) has provided new treatment options for refractory epilepsy; however, treatment outcomes of DBS in refractory epilepsy patients previously treated with vagus nerve stimulation (VNS) have not been clarified. Herein, treatment outcomes of DBS of the anterior nucleus of the thalamus (ANT-DBS) in patients who had previously experienced VNS failure are reported. Seven patients who had previously experienced VNS failure underwent ANT-DBS device implantation. VNS was turned off before DBS device implantation. Monthly seizure counts starting from baseline to 12-18 months after DBS were analyzed. Five (71.3%) of the 7 patients experienced a >50% reduction of seizure counts after DBS; 1 responder reached a seizure-free status after DBS therapy. Of the 2 nonresponders, 1 subject showed improvement in seizure strength and duration, which lessened the impact of the seizures on the patient's quality of life. This is the first study in which favorable outcomes of ANT-DBS surgery were observed in individual patients with refractory epilepsy who had not responded to prior VNS. Further studies with a larger number of subjects and longer follow-up period are needed to confirm the feasibility of ANT-DBS in patients who have previously experienced VNS failure.

SPECT perfusion changes during ictal automatisms with preserved responsiveness in patients with right temporal lobe epilepsy.

Ictal automatism with preserved responsiveness (APR) has been reported, particularly in nondominant temporal lobe epilepsy (TLE), but its pathophysiology remains poorly understood. This study sought to investigate the relationship between APRs and increased cerebral blood flow (CBF) using ictal single photon emission computed tomography (SPECT) in TLE. Forty-seven subjects with right mesial TLE (15 with and 32 without APR) were enrolled. Patients with APR (APR+) were subdivided into four groups according to degree of responsiveness during seizures. Cerebral blood flow changes during these seizures were semiquantitatively assessed by subtraction ictal SPECT coregistered to MRI (SISCOM). Hyperperfusion in temporal regions did not vary significantly between the APR+ and APR- groups. Cerebral blood flow changes in the frontal area, insula, cingulum, and occipital area were also nonsignificant. However, hyperperfusion in the ipsilateral parietal areas was more frequent in the APR- group than in the APR+ group. Furthermore, hyperperfusion of the contralateral basal ganglia showed an inclination to be more common in the APR- group, but without statistical significance. The study suggested that the involvement of the parietal association cortex during seizure may play an important role in ictal loss of consciousness in TLE. Further studies will be needed to elucidate the pathophysiology of changes in consciousness during temporal lobe seizures.

BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study with an open-label extension.

OBJECTIVES: To evaluate dose-response relationship of BGG492 as add-on therapy to 1-3 antiepileptic drugs in patients with partial-onset seizures and to investigate safety and tolerability of BGG492. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study (core study) with a 30-week, flexible-dose, open-label extension. In the core study, patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. On completion of the core study, eligible patients entered the extension study. Primary outcome measures were total partial seizure frequency per 28 days (core study) and safety and tolerability (extension study). RESULTS: Overall, 93 patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]), and 81 (87.1%) completed the core study. Fifty-one patients entered and 43 (84.3%) completed the extension study. In the core study, no statistically significant dose-response trend among the BGG492 treatment groups (100 and 150 mg) was observed at the 4-week double-blind maintenance period (weeks 7-10); however, there was higher percent reduction in total partial seizure frequency in the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI] -18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse events (AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%] vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9 [17.6%]). SIGNIFICANCE: There was no significant dose-response trend in the BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over placebo was observed in the BGG492 150 mg group. Safety and tolerability data were consistent with the known safety profile for BGG492, and no new safety risks were identified.

Comparison of levetiracetam and oxcarbazepine monotherapy among Korean patients with newly diagnosed focal epilepsy: A long-term, randomized, open-label trial.

This open-label, multicenter, randomized phase IV trial (NCT01498822) of noninferiority design compared the long-term effectiveness, safety, and tolerability of levetiracetam (LEV) monotherapy with those of oxcarbazepine (OXC) monotherapy in adults with newly diagnosed focal epilepsy. Korean patients (16-80 years), with ≥2 unprovoked focal seizures in the year preceding the trial, who had not taken any antiepileptic drugs (AEDs) in the last 6 months, were randomized to receive LEV or OXC (1:1). Effectiveness, safety, and tolerability were assessed over a 50-week period. Treatment failure rates (per protocol set) were 15/118 (12.7%) in the LEV-treated group and 30/128 (23.4%) in the OXC-treated group, an absolute difference of -10.7% (95% confidence interval [CI] -20.2, -1.2). Because the upper 95% CI limit was less than the pre-specified noninferiority margin of 15%, LEV was considered noninferior to OXC. Twenty-four-week and 48-week seizure freedom rates were 53.8% and 34.7% for LEV vs. 58.5% and 40.9% for OXC. Both LEV and OXC were well tolerated, with 8.7% and 8.6% of patients reporting serious treatment-emergent adverse events, respectively. By comparing LEV with OXC, another newer AED, LEV can be considered a useful option as initial monotherapy for patients with newly diagnosed focal epilepsy.

Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome.

We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of nonpermanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA.

Correlation between headaches and affective symptoms in patients with epilepsy.

Headaches are a neglected entity in patients with epilepsy (PWE), although PWE have a high chance of suffering from seizure-related as well as seizure-unrelated headaches. We aimed to identify the prevalence and characteristics of headaches and investigate the correlation between headaches and affective symptoms in PWE. Consecutive PWE who visited our tertiary outpatient clinic were interviewed about headaches and epilepsy. Affective symptoms were evaluated using the Korean version of the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and suicidality portion of the Mini-International Neuropsychiatric Interview. We classified headaches as interictal or seizure-related headaches (SRHs; pre- and postictal). Tension-type headache and migraine were defined based on International Classification of Headache Disorders criteria. From the initial cohort of 177 patients (92 men, mean age: 37.1years), 73 (41.2%) reported suffering from interictal (N=34, 19.2%), preictal (N=3, 1.7%), and postictal (N=48, 27.1%) headaches. Univariate analysis revealed significantly higher BDI and BAI scores in the headache group. Tension-type headaches were the most frequent, and half of the interictal headaches and most of the SRHs were untreated. Spearman's partial correlation analyses showed that headaches overall were significantly related with depression and anxiety. Interictal headaches were correlated with depression only, and postictal headaches were correlated with depression as well as suicidality, separately. These results show that investigating and controlling headaches may relieve affective symptoms and ultimately improve the quality of life of PWE.

Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. METHODS: This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. RESULTS: Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. SIGNIFICANCE: Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used.

Can an exercise bicycle be safely used in the epilepsy monitoring unit?: An exercise method to provoke epileptic seizures and the related safety issues.

BACKGROUND AND PURPOSE: Long-term videoelectroencephalogram (video-EEG) monitoring is performed to diagnose an epileptic seizure and to investigate the differential diagnosis of paroxysmal events. To provoke an epileptic seizure, an exercise method is performed in some cases during long-term video-EEG recording in the epilepsy monitoring unit (EMU). The purpose of this study was two-fold: to assess the frequency and severity of adverse events associated with the use of an exercise bicycle and to find a way to safely use it in the EMU. METHODS: A retrospective survey was performed on all epileptic seizure videos recorded in the EMU from January 2012 to December 2013. Three hundred and fifty patients were included in this study. RESULTS: Eleven patients experienced an epileptic seizure while riding the exercise bicycle in the EMU. One patient's foot got stuck between the cycling pedal and its strap, and one patient fell off the exercise bicycle during the epileptic seizure. However, there were no serious adverse events over two years. CONCLUSION: Epileptic seizures were not frequent while riding the exercise bicycle, and serious injuries did not occur. But, there is a need to improve the safety in the EMU to control the potentially dangerous factors associated with the use of the exercise bicycle and to continuously monitor the patients with help from the staff.

Resection of individually identified high-rate high-frequency oscillations region is associated with favorable outcome in neocortical epilepsy.

OBJECTIVES: High-frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO-generating areas necessary to include in the resection. Here, we evaluated the potential of a patient-individualized approach of identifying high-rate HFO regions to plan the neocortical resection. METHODS: Fifteen patients with neocortical seizure-onset zones (SOZs) underwent intracranial electroencephalographic monitoring. To identify interictal HFOs, we applied an automated, hypersensitive HFO-detection algorithm followed by post hoc processing steps to reject false detections. The spatial relationship between HFO distribution and the SOZ was evaluated. To address high interpatient variability in HFO properties, we evaluated the high-rate HFO region, an unbiased statistical parameter, in each patient. The relationship between resection of the high-rate HFO region and postoperative outcome was examined. RESULTS: Grouped data demonstrated that the rate of ripple (60-200 Hz) and fast ripple (200-500 Hz) was increased in the SOZ (both p < 0.01). Intrapatient analysis of the HFO distribution localized the SOZ in 11 patients. High-rate HFO regions were determined in all patients by an individually adjusted threshold. Resection of high-rate HFO regions was significantly associated with a seizure-free outcome (p < 0.01). The extent/ratio of SOZ or spiking region resection did not differ between seizure-free and seizure-persistent groups. SIGNIFICANCE: Intrapatient analysis of high-rate HFOs provides more detailed description of HFO-generating areas and can mark the areas of clinically significant epileptogenicity--a crucial component of the neocortical epileptic network that should be removed to achieve a good outcome. Validating and adopting an unbiased quantitative HFO parameter has the potential to propel wider and prospective utilization of HFOs in the surgical treatment of neocortical epilepsy and to improve its outcome.

Proposal: different types of alteration and loss of consciousness in epilepsy.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

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.

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.

Long-term effects of adjunctive eslicarbazepine acetate in adult Asian patients with refractory focal seizures: Post hoc analysis of a phase III trial.

A post hoc analysis of data from Asian patients included in the study BIA-2093-304 was conducted to evaluate the long-term safety/tolerability and efficacy of adjunctive eslicarbazepine acetate (ESL) in adult Asian patients with refractory focal seizures. Part I was a randomized controlled trial, in which patients received ESL (800 or 1200 mg once daily [QD]) or placebo, assessed over a 12-week maintenance period. Patients completing Part I could enter two open-label extension periods (Part II, 1 year; Part III, ≥2 years), during which all received ESL (400-1600 mg QD). Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs). Efficacy assessments included responder and seizure freedom rates. The safety population included 125, 92, and 23 Asian patients in Parts I, II, and III, respectively. Incidence of ESL-related TEAEs was 61.3%, 45.7%, and 17.4% during Parts I, II, and III, respectively. ESL-related TEAEs (most commonly, dizziness, somnolence, and headache) were consistent with ESL's known safety profile. During Part I, responder rates were higher with ESL 800 (41.7%) and 1200 mg QD (44.4%) versus placebo (32.6%), although not statistically significant. Seizure freedom rates with ESL 800 (5.5%) and 1200 mg QD (11.1%) were also higher versus placebo (0%) (p < 0.05 for ESL 1200 mg QD versus placebo). At the end of Part II, responder and seizure freedom rates were 60.3% and 14.7%, respectively. In summary, adult Asian patients with refractory focal seizures were responsive to treatment with ESL as adjunctive therapy and generally showed treatment tolerance well for up to 3 years. No new/unexpected safety findings were observed.

Mapping the landscape of sleep medicine training across Asia.

STUDY OBJECTIVES: This study assessed the current state of sleep medicine accreditation and training in Asia by conducting a comprehensive survey across 29 Asian countries and regions facilitated by the Asian Society of Sleep Medicine (ASSM) to identify existing gaps and provide recommendations for future enhancements. METHODS: The ASSM Education Task Force Committee designed a survey to gather data on accreditation, education, and training standards in sleep medicine, including information on challenges in enhancing education in the field. RESULTS: With an 86% (25 countries/regions) response rate, the survey showed that sleep medicine is recognized as an independent specialty in just nine countries/regions (36% of the countries/regions surveyed). Ten countries/regions have established sleep medicine training programs, with Japan and Saudi Arabia offering it as a distinct specialty. Significant disparities in training and accreditation standards were identified, with many countries/regions lacking formalized training and practice guidelines. The survey also revealed that most local sleep societies across Asia support the development of an Asian Sleep Medicine Training Curriculum led by the ASSM. However, several barriers significantly impede the establishment and development of sleep medicine training programs, including the scarcity of trained specialists and technologists and the absence of national accreditation for sleep medicine. CONCLUSIONS: The survey highlights the need for standardized sleep medicine training and accreditation across Asia. Developing an Asian Sleep Medicine Training Curriculum and promoting ASSM accreditation guidelines are key recommendations. Implementing these strategies is essential for advancing sleep medicine as a widely recognized discipline throughout Asia.

Interaction between the electrical stimulation of a face-selective area and the perception of face stimuli.

We electrically stimulated the face-selective area in epileptic patients while they were performing a face-categorization task. Face categorization was interfered by electrical stimulation but was restored by increasing the visual signal. More importantly, face-categorization interference by electrical stimulation was confined to face-selective electrodes, and the amount of interference was positively correlated with the sensitivity of the face-selective electrodes. These results strongly support the hypothesis that the face-selective area has a direct causal link to face perception.

Is an epilepsy presurgical evaluation necessary for mid-grade and high-grade brain tumors presenting with seizures?

Patients with epilepsy caused by mid-grade and high-grade tumors do not usually undergo formal presurgical epilepsy evaluations before tumor resection. However, a minority of these patients may benefit significantly from just such a structured presurgical evaluation especially when seizure freedom or seizure reduction is a surgical aim in addition to total tumor resection. Typical cases comprise patients with multifocal tumors, tumors with bilateral extension, tumors over eloquent cortex, and the need for differentiation of spells of an uncertain nature, for example, epileptic versus psychogenic nonepileptic seizures. If they are epileptic, the definition of the epileptic lesion versus the epileptogenic zone and eloquent cortex can be another reason for monitoring. In addition to noninvasive recordings, invasive studies that use subdural or depths electrodes can be of special importance in these patients, leading to an exact delineation of the epileptogenic zone, usually extending beyond the epileptic lesion, and allow safe differentiation of epileptic from eloquent cortex.