Severity of sleep apnea as a prognostic factor for mortality in patients with multiple system atrophy.

BACKGROUND: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis. RESULTS: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069). CONCLUSION: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor.

Improving Diagnostic Performance of MRI for Temporal Lobe Epilepsy With Deep Learning-Based Image Reconstruction in Patients With Suspected Focal Epilepsy.

OBJECTIVE: To evaluate the diagnostic performance and image quality of 1.5-mm slice thickness MRI with deep learning-based image reconstruction (1.5-mm MRI + DLR) compared to routine 3-mm slice thickness MRI (routine MRI) and 1.5-mm slice thickness MRI without DLR (1.5-mm MRI without DLR) for evaluating temporal lobe epilepsy (TLE). MATERIALS AND METHODS: This retrospective study included 117 MR image sets comprising 1.5-mm MRI + DLR, 1.5-mm MRI without DLR, and routine MRI from 117 consecutive patients (mean age, 41 years; 61 female; 34 patients with TLE and 83 without TLE). Two neuroradiologists evaluated the presence of hippocampal or temporal lobe lesions, volume loss, signal abnormalities, loss of internal structure of the hippocampus, and lesion conspicuity in the temporal lobe. Reference standards for TLE were independently constructed by neurologists using clinical and radiological findings. Subjective image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed. Performance in diagnosing TLE, lesion findings, and image quality were compared among the three protocols. RESULTS: The pooled sensitivity of 1.5-mm MRI + DLR (91.2%) for diagnosing TLE was higher than that of routine MRI (72.1%, P < 0.001). In the subgroup analysis, 1.5-mm MRI + DLR showed higher sensitivity for hippocampal lesions than routine MRI (92.7% vs. 75.0%, P = 0.001), with improved depiction of hippocampal T2 high signal intensity change (P = 0.016) and loss of internal structure (P < 0.001). However, the pooled specificity of 1.5-mm MRI + DLR (76.5%) was lower than that of routine MRI (89.2%, P = 0.004). Compared with 1.5-mm MRI without DLR, 1.5-mm MRI + DLR resulted in significantly improved pooled accuracy (91.2% vs. 73.1%, P = 0.010), image quality, SNR, and CNR (all, P < 0.001). CONCLUSION: The use of 1.5-mm MRI + DLR enhanced the performance of MRI in diagnosing TLE, particularly in hippocampal evaluation, because of improved depiction of hippocampal abnormalities and enhanced image quality.

Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness.

OBJECTIVE: To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). METHODS: Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. RESULTS: In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. CONCLUSIONS: RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.

Attention-deficit hyperactivity disorder in adults with epilepsy: An indirect relationship with suicide risk.

PURPOSE: Studies on attention-deficit hyperactivity disorder (ADHD) are scarce in adults with epilepsy. This study aimed to investigate the risk factors for ADHD and determine whether ADHD is directly associated with the risk of suicide in adults with epilepsy. METHODS: ADHD was assessed using the Structured Clinical Interview for the DSM-5 Disorders Clinical Version. The Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0, Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and Generalized Anxiety Disorder-7 (GAD-7) were also used. Suicide risk was defined as a MINI suicidality score of ≥ 1. Stepwise logistic regression and mediation analyses were conducted. RESULTS: Of the 157 adults with epilepsy, 19 (12.1 %) were diagnosed with ADHD, including inattentive (5.7 %), hyperactive (3.8 %), and combined (2.5 %) types. Thirty-two subjects (20.4 %) had a risk of suicide. ADHD was insignificantly associated with any epilepsy-related factors. The diagnosis of ADHD was not associated with suicide risk independent of NDDIE ≥ 14 and GAD-7 ≥ 7. Mediation effects of ADHD on suicidality using NDDIE ≥ 14 (odds ratio [OR] 2.850, 95 % confidence interval [CI] 1.398-5.811, p = 0.004) or GAD-7 ≥ 7 (OR 3.240, 95 % CI 1.537-6.828, p = 0.002) were statistically significant, with the proportion mediated being 84.5 % or 92.0 % of the total ADHD effect, respectively. These models were adjusted for age, sex, and composite epilepsy severity scores. CONCLUSIONS: ADHD was diagnosed in 12.1% of adults with epilepsy and was not associated with any epilepsy-related factors. ADHD was indirectly associated with the risk of suicide resulting from depression and anxiety in adults with epilepsy.

Combined Depth and Subdural Electrodes for Lateralization of the Ictal Onset Zone in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization.

Seizure outcome in medically treated patients with adult-onset epilepsy and cerebral cavernous malformation.

PURPOSE: We evaluated long-term seizure outcomes of antiseizure medications (ASMs) and risk factors for drug resistance in patients with adult-onset epilepsy associated with cerebral cavernous malformation (CCM). MATERIALS AND METHODS: This retrospective observational study included patients newly diagnosed with adult-onset focal epilepsy associated with CCM. Patients received individualized treatments with ASMs. All patients were followed-up for at least 2 years. The main outcome measure was terminal 2 year seizure freedom (2-YSF). RESULTS: Forty eight subjects (28 men and 20 women) were included. Thirty-one (64.6%) subjects achieved a terminal 2-YSF (range 2.0-17.0 years). After treatment with the first drug regimen, 31 (64.6%) subjects achieved 2-YSF, with 23 remaining seizure-free until final follow-up visit. Of the 23 subjects treated with the second drug regimen and the six treated with the third drug regimen, ten (43.5%) and one (16.7%), respectively, achieved a terminal 2-YSF. Stepwise logistic regression analyses showed that terminal 2-YSF was negatively associated with epileptiform discharge on EEG at the time of diagnosis (odds ratio = 0.214, p = 0.047) and tended to be associated with age ≥ 45 years at seizure onset (odds ratio = 4.260, p = 0.056). CONCLUSION: The present study found that 64.6% of CCM patients with adult-onset epilepsy achieved terminal 2-YSF after ASM initiation. Interictal epileptiform discharge on EEG at the time of diagnosis was associated with poor prognosis. Failure to achieve sustained seizure freedom after two ASMs may indicate the need for surgical treatment.

Accuracy of predicting surgical outcomes using interictal electrical source imaging in patients with MRI-negative intractable epilepsy.

OBJECTIVE: We investigated the accuracy of interictal electrical source imaging (II-ESI) in localizing the epileptogenic zone in MRI-negative epilepsy patients who underwent epilepsy surgery. We also aimed to compare II-ESI's utility with other presurgical investigations and its role in guiding intracranial electroencephalography (iEEG) planning. METHODS: We retrospectively reviewed the medical records of patients with operated MRI-negative intractable epilepsy at our center between 2010 and 2016. All patients underwent video electroencephalography (EEG) monitoring, high-resolution MRI, 18 fluorodeoxyglucose positron emission tomography (FDG-PET) scans, ictal single-photon emission computed tomography (SPECT) and intracranial EEG (iEEG) monitoring. We computed II-ESI following the visual identification of interictal spikes, and outcomes were determined using Engel's classification at 6 months after surgery. RESULTS: Among 21 operated MRI-negative intractable epilepsy patients, 15 had sufficient data for II-ESI analysis. Of these, nine patients (60%) showed favorable outcomes corresponding to Engle's classification I and II. The localization accuracy of II-ESI was 53%, which was not significantly different from those of FDG-PET and ictal SPECT (47% and 45%, respectively). Among the patients, iEEG did not cover the areas suggested by II-ESIs in seven cases (47%). In two of those patients (29%), the regions indicated by II-ESIs were not resected, resulting in poor surgical outcomes. CONCLUSION: This study demonstrates that the localization accuracy of II-ESI was comparable to ictal SPECT and the brain FDG-PET scan. II-ESI is a simple, noninvasive method for evaluating the epileptogenic zone and guiding iEEG planning in patients with MRI-negative epilepsy.

Effects of Continuous Positive Airway Pressure on Sleep State Misperception in Patients With Obstructive Sleep Apnea.

BACKGROUND: Little is known regarding the effects of continuous positive airway pressure (CPAP) on sleep misperception in obstructive sleep apnea (OSA). METHODS: Sleep state perception was measured by subtracting the objective total sleep time from the subjective sleep duration. Sleep underestimation and overestimation were defined as ± 60 minutes sleep perception. Insomnia and depressive symptoms were assessed using questionnaires. Finally, nonparametric statistical analyses were performed. RESULTS: Of the 339 patients with OSA included in the study, 90 (26.5%) and 45 (13.3%) showed sleep underestimation and overestimation, respectively. Overall, a significant underestimation of sleep was noted during CPAP titration comparing to a diagnostic PSG (P < 0.001). OSA patients with insomnia or depressive symptoms did not show any changes in sleep perception between diagnostic and CPAP titration studies, whereas those without insomnia or depressed mood showed significantly underestimated sleep duration during CPAP titration. Patients with OSA and either underestimated or overestimated misperception showed perceptual improvements during CPAP titration regardless of the presence of insomnia or depressive symptoms. However, of 204 patients with normal sleep perception, 138 (67.6%) and 10 (4.9%) had underestimation and overestimation of sleep during CPAP titration. CONCLUSION: CPAP titration may improve sleep perception with moderate to severe OSA who have sleep misperception. However, CPAP titration may result in sleep misperception especially underestimation of sleep in those who have normal sleep perception.

Sex differences in the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy.

PURPOSE: To determine whether sex affects the relationship between aggression and symptoms of depression and anxiety in adults with refractory focal epilepsy. METHODS: This cross-sectional study was conducted in 85 adults with refractory focal seizures, which are defined as one or more seizures recurring per month even when the patient is treated with two or more antiseizure medications. We used the Buss-Perry Aggression Questionnaire (AQ) and the Hospital Anxiety and Depression Scale (HADS) to evaluate aggression and symptoms of depression and anxiety, respectively. We performed multivariate linear regression and analysis of covariance with interaction terms. HADS-depression and HADS-anxiety scores were separately evaluated to avoid multicollinearity between both of them. RESULTS: The HADS-depression and HADS-anxiety scores, male sex, an antiseizure medication load of ≥3, and the use of pregabalin were independently correlated with at least one of the AQ total and subscale scores. These models for depressive and anxiety symptoms explained 34.2% and 32.5%, respectively, of the variance of the AQ total score. Although the AQ total scores did not differ between the sexes, sex significantly affected the relationships between aggression and symptoms of depression and anxiety. Specifically, HADS-depression and HADS-anxiety scores were positively associated with the AQ total scores, especially scores of verbal aggression and anger subtypes, in men but not in women. CONCLUSIONS: These findings support the importance of including anger management and other strategies targeted toward aggression in the development of psychological interventions to reduce anxiety and depression in adults with refractory focal epilepsy. Tailoring those interventions to the needs of males and females will be important to consider. .

General self-efficacy differentially moderates depressive symptoms in adults with epilepsy depending on seizure severity.

PURPOSE: We evaluated whether the relationship between general self-efficacy and depressive symptoms in patients with epilepsy differed depending on age, sex, and seizure status. METHODS: This multicenter, cross-sectional study was conducted on 299 adults with epilepsy, using the Beck Depression Inventory (BDI) and the General Self-efficacy Scale (GSES). We performed stepwise linear regression analysis and analysis of covariance with interaction terms. RESULTS: The stepwise linear regression analysis showed that BDI scores were negatively correlated with GSES scores and positively correlated with age ≥ 40 years, unemployed status, recurrence of generalized or focal to bilateral tonic-clonic seizures (GTCS or FBTCS), and antiseizure medication polytherapy. The final model explained 38.9% of the variance in BDI scores. The analysis of covariance revealed that the moderating effect of GSES scores on BDI scores was less in subjects who had seizure freedom for at least 1 year than in those who did not. In contrast, the moderating effect of GSES scores on BDI scores was greater in subjects who had an age ≥ 40 years and those who experienced GTCS or FBTCS during the previous year than in those who did not. The negative relationship between GSES and BDI scores tended to be stronger in men than in women, but it did not reach statistical significance (p = 0.098). All models were adjusted by significant factors in the linear regression analysis of BDI scores. CONCLUSIONS: The negative relationship between general self-efficacy and depressive symptoms may be stronger in older patients and patients with poorer seizure outcomes.

Emotional and behavioral profiles of adolescents with epilepsy: Associations with parental perception of epilepsy-related stigma.

PURPOSE: We evaluated self-reported psychopathology in adolescents with epilepsy (AWE) and determined which types of psychopathology were associated with the parental perception of stigma towards AWE. METHODS: This was a cross-sectional, multicenter study of 289 adolescents aged 11 to 18 years. Psychopathology was evaluated using the Youth Self-Report scale, which consists of eight narrowband and three broadband syndrome scales. We analyzed the raw score and T-score of each syndrome scale. The parental perception of stigma was assessed using the modified three-item Epilepsy Stigma Scale. RESULTS: Of the 289 AWE (180 boys and 109 girls), 18.3% had at least one emotional or behavioral problem in the clinical range. Social problems were the most common (10.0%), followed by attention problems (6.9%) and aggressive behaviors (4.2%). Externalizing problems (11.8%) were two times more common than internalizing problems (6.2%). Females and older AWE had a higher level of internalizing problems. Social problems were more common in girls (15.6%) than in boys (6.7%), whereas thought problems were more common in boys (3.9%) than in girls (0%). Epilepsy-related factors, especially antiseizure medication polytherapy, were significantly associated with various emotional and behavioral problems. A quarter of parents felt stigma towards their children with epilepsy. Male sex, antiseizure medication polytherapy, and longer duration of epilepsy were more likely to be associated with the parental perception of stigma. Parental perception of stigma was significantly associated with psychopathology in AWE, particularly externalizing problems and social problems. CONCLUSIONS: Emotional and behavioral problems in AWE are common and vary depending on demographic, clinical, and parental factors. Early identification and proper management of these problems are crucial for decreasing comorbid psychopathology in AWE.

Obstructive sleep apnea may reduce a diagnostic accuracy of video-polysomnography for idiopathic REM sleep behavior disorder.

BACKGROUND: Severe obstructive sleep apnea (OSA) in patients with rapid eye movement (REM) sleep behavior disorder (RBD) may result in frequent fragmentation of REM sleep and consequently lead to a false negative diagnosis of RBD on a video-polysomnography (video-PSG). Thus, we determined whether OSA has the negative impact on video-PSG diagnostic accuracy for RBD. METHODS: Patients with clinically diagnosed idiopathic RBD were included. RBD was confirmed if a video-PSG demonstrated complex motor behavior during REM sleep or REM sleep without atonia (RWA). Motor behavior was measured using the RBD Severity Scale. Cohen's kappa coefficient was calculated for qualitative assessment of RWA. A stepwise logistic regression analysis was performed. RESULTS: Of a total 254 patients included, a diagnosis of RBD was confirmed by a video-PSG in 221 patients (87.0%). RWA, vocalization, and axial or proximal muscle movements in REM sleep were noted in 86.6%, 58.3%, and 35.9%, respectively. A video-PSG diagnosis of RBD was less likely associated with severe OSA (odds ratio [OR] 0.284, p = 0.010) and moderate OSA (OR 0.404, p = 0.071) whereas was more likely associated with longer REM sleep time (OR 1.036, p < 0.001). In 43 patients who underwent a continuous positive airway pressure (CPAP) titration study, a diagnosis of RBD was more common on a CPAP titration study (88.4%) than on a first video-PSG (65.1%) (p = 0.013). Twelve (27.9%) of 43 CPAP patients were diagnosed with RBD according only to CPAP titration study. CONCLUSIONS: OSA that requires CPAP may reduce a diagnostic accuracy for RBD by a video-PSG. False negative results were probably due to frequent electromyographic artifacts and/or severe sleep disruption from apneic events during REM sleep.

Association between sleep apnea severity and symptoms of depression and anxiety among individuals with obstructive sleep apnea.

OBJECTIVE: We determined whether the severity of sleep apnea is associated with symptoms of depression and anxiety in patients with obstructive sleep apnea (OSA) and whether symptoms of OSA, other than respiratory events, are associated with depression and anxiety symptoms. METHODS: Depressive and anxiety symptoms were defined as a Patient Health Questionnaire-9 score of ≥10 and a Generalized Anxiety Disorder-7 score of ≥8, respectively. Sleep apnea severity and rapid eye movement-related OSA were evaluated using the apnea-hypopnea index (AHI). Subjective symptoms of OSA were assessed using the Sleep Apnea Severity Questionnaire (SASQ). We conducted multivariate logistic regression analyses. RESULTS: We included 1390 adult patients with OSA (80.4% men) and 125 control subjects with primary snoring. Symptoms of depression and anxiety were present in 15.5% and 14.4% of patients with OSA, respectively. The prevalence of depressive and anxiety symptoms did not differ between OSA and control subjects after controlling for age and sex. Severe OSA, defined as an AHI score of ≥30, was significantly less likely than mild OSA to be associated with the presence of depression and anxiety symptoms in both the unadjusted and adjusted models (models were adjusted by age, sex, medical comorbidities, history of psychiatric disorders, and daytime sleepiness). By contrast, OSA symptoms assessed using the SASQ were positively correlated with the presence of depression and anxiety symptoms in both the unadjusted and adjusted models. Specifically, nocturnal awakening and morning waking symptoms, but not nocturnal breathing difficulties, were positively correlated with the presence of depression and anxiety symptoms. Subjects with rapid eye movement-related OSA were more likely to have depressive symptoms, but not anxiety, than those without. CONCLUSIONS: Symptoms of depression and anxiety were negatively correlated with the severity of sleep apnea but positively correlated with nocturnal awakening and early morning symptoms of OSA.

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.

Comparisons of impulsivity among patients with different subtypes of epilepsy.

PURPOSE: This study assessed whether patients with epilepsy have a higher level of impulsivity than healthy controls, and compared impulsivity among patients with different subtypes of epilepsy. METHODS: The multicenter study included 108 subjects with epilepsy and 56 healthy volunteers. Subjects were evaluated by the Barratt Impulsiveness Scale-11 (BIS-11) and Patient Health Questionnaire-9, with BIS-11 scores analyzed as both dichotomized and continuous variables. High impulsivity was defined as a total BIS-11 score ≥ 67. RESULTS: Of the 108 subjects with epilepsy, 36 had idiopathic generalized epilepsy (IGE), 47 had temporal lobe epilepsy (TLE), and 25 had frontal lobe epilepsy (FLE). A significantly higher percentage of subjects with epilepsy (22.2%) than controls (1.8%) had BIS-11 scores ≥ 67 (p = 0.001), although mean BIS-11 scores were similar in subjects with epilepsy (59.5 ± 10.0) and controls (58.8 ± 4.6). Higher percentages of subjects with IGE and FLE had BIS-11 scores ≥ 67 than subjects with TLE and controls. Mean total BIS-11 scores did not differ between controls and subjects with IGE and FLE, but were lower in subjects with TLE than in controls. Differences in impulsivity among controls and subjects with epilepsy subtypes varied depending on BIS-11 subscale. CONCLUSIONS: Patients with epilepsy, particularly IGE and FLE, were more likely to have high impulsivity scores, defined by a certain cutoff on the BIS-11, than controls and subjects with TLE. However, mean impulsivity scores did not differ among controls and subjects with IGE and FLE. Dichotomizing BIS-11 scores may be necessary to avoid false negative results in subjects with epilepsy.

Perampanel as First Add-On Therapy in Patients with Focal-Onset Seizures in the FAME Trial: Post hoc Analyses of Efficacy and Safety Related to Maintenance Dose and Background Antiepileptic Drug Therapy.

Background and Purpose: FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel. Methods: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs). Results: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p<0.001) and when added to first- versus second-line ASM monotherapy (83.5% vs. 33.3%; p=0.013). By concomitant background ASM and perampanel maintenance dose, 50% responder rates were 100% for perampanel 4 mg/day added to carbamazepine, oxcarbazepine, lamotrigine, or valproic acid, and 85% when added to levetiracetam. Add-on perampanel improved 75% and seizure-free responder rates, and median percent changes from baseline seizure frequency per 28 days. Perampanel was well tolerated when added to ASM monotherapy, with dizziness being the most common TEAE. Conclusions: Post hoc analyses of FAME provide supportive data for the use of perampanel as an effective and well-tolerated first add-on treatment to a broad spectrum of ASM monotherapies in patients with FOS.

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response.

Background and Purpose: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel. Methods: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed. Results: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%). Conclusions: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Dual burdens of felt stigma and depressive symptoms in patients with epilepsy: Their association with social anxiety, marriage, and employment.

PURPOSE: The present study evaluated whether patients with epilepsy with dual conditions of felt stigma and depressive symptoms are more strongly associated with social anxiety, being unmarried, and being unemployed than those with depressive symptoms or felt stigma alone. METHODS: This multicenter, cross-sectional study evaluated subjects using the Stigma Scale-Revised, the Patient Health Questionnaire-9, and the six-item versions of the Social Interaction Anxiety Scale, and the companion Social Phobia Scale. Subjects were grouped by depressive symptoms and felt stigma into four groups. Multivariate logistic regression analyses were performed. RESULTS: The 298 subjects included 173 men and 125 women. Of these subjects, 35 (11.7%) had depressive symptoms alone, 33 (11.1%) had stigma alone, and 27 (9.1%) had both depressive symptoms and felt stigma. Multivariate logistic regression analyses showed that, compared with the control group having neither depressive symptoms nor felt stigma, the odds ratios (ORs) for social interaction anxiety and social phobia were highest in the group of dual conditions (OR 18.7 and 13.5, respectively), followed by the depression-alone (OR 7.7 and 4.6, respectively) and stigma-alone (OR 5.0 and 2.8, respectively) groups. Similarly, the ORs for being unmarried (OR 29.2) and unemployed (OR 3.1) were significant only in the group of dual conditions. In addition, male sex and younger age were independently associated with being unmarried whereas seizures recurring ≥1 per month were independently associated with being unemployed. CONCLUSIONS: Dual conditions of felt stigma and depressive symptoms may be more strongly associated with social anxiety, being unmarried, and being unemployed than depressive symptoms or felt stigma alone in patients with epilepsy.

Felt stigma may potentiate the relationship between perceived stress and depressive symptoms in persons with epilepsy.

PURPOSE: This study assessed the strengths of association among perceived stress, felt stigma, and depression in adults with epilepsy, and evaluated whether felt stigma altered the association between perceived stress and depression. METHODS: This multicenter, cross-sectional study included adults with epilepsy. Depression was assessed using the Beck Depression Inventory (BDI), and perceived stress was evaluated using the 10-item Perceived Stress Scale. Felt stigma was determined using the three-item Stigma Scale for Epilepsy, with individuals categorized as positive for felt stigma if they answered "yes" to at least one of these items. A hierarchical linear regression analysis and an analysis of covariance with interaction terms were performed. RESULTS: The 316 adults with epilepsy included 171 men and 145 women; of these, 109 (34.5%) reported felt stigma. A hierarchical linear regression analysis showed that perceived stress was the most important correlate of depressive symptoms, followed by felt stigma, being unemployed, recurrence of generalized or focal to bilateral tonic-clonic seizures, and being married. The model explained 54.0% of the variance of BDI scores. Significant interactions between felt stigma and perceived stress on BDI scores was identified in both crude and adjusted models (p < 0.05 each). Specifically, in an adjusted model, BDI scores were more strongly associated with perceived stress in persons with (p < 0.001, partial eta2 = 0.225) than without (p < 0.001, partial eta2 = 0.205) felt stigma. CONCLUSIONS: Perceived stress was the most significant correlate of depressive symptoms in adults with epilepsy, followed by felt stigma. The interaction between perceived stress and felt stigma on depressive symptoms was significant. These findings may help in developing cognitive behavioral therapy for stigma and stress management in persons with epilepsy.

Validation of items on the NDDIE and PHQ-9 associated with suicidal ideation during suicidality screening in patients with epilepsy.

PURPOSE: This study was performed to validate individual items on the Neurological Disorders Depression Inventory for Epilepsy (NDDIE) and the Patient Health Questionnaire-9 (PHQ-9), as well as their total scores, during suicidality screening of patients with epilepsy (PWE). METHODS: PWE were assessed with the Mini International Neuropsychiatric Interview (MINI), the NDDIE, and the PHQ-9. Moderate to high suicidality, as assessed by the Suicidality Module of the MINI, was considered the standard measurement. Each item and overall scores for the NDDIE and PHQ-9 were evaluated by receiver operating characteristic (ROC) curve analyses. The optimal cutoff criteria were identified as those with the highest Youden index. RESULTS: Of the 213 participants, 20 (9.4%) had moderate to high suicidality. Item 4 on the NIDDE and item 9 on the PHQ-9, representing suicidal ideation, showed the best psychometric properties for suicidality. A cutoff of >1 for item 4 on the NDDIE showed an area under the ROC curve (AUC) of 0.853, a sensitivity of 90.0%, and a specificity of 72.0%. A cutoff >0 for item 9 on the PHQ-9 showed an AUC of 0.851, a sensitivity of 90.0%, and a specificity of 74.6%. The specificities and positive predictive values of item 4 on the NDDIE and item 9 on the PHQ-9 were higher in patients with depression than those in the overall patient population. CONCLUSION: Item 4 of NDDIE and Item 9 of PHQ-9 showed value in screening for suicidality. Use of these items may rapidly identify suicidality among PWE.