Efficacy and safety of retigabine/ezogabine as adjunctive therapy in adult Asian patients with drug-resistant partial-onset seizures: A randomized, placebo-controlled Phase III study

AbstractPurposeThe purpose of this study was to evaluate the efficacy and safety of adjunctive retigabine/ezogabine (RTG/EZG) therapy in Asian adults with partial-onset seizures.MethodsA Phase III, randomized, double-blind, placebo-controlled, parallel-group study was conducted at 26 centers in Asia. Eligible patients were randomized in a 1:1:1 ratio to receive RTG/EZG 600mg/day (200mg 3 times daily), RTG/EZG 900mg/day (300mg 3 times daily), or placebo. The study consisted of an 8-week screening/baseline phase, followed by a 16-week treatment phase (4-week titration phase and 12-week maintenance phase).ResultsThe study was terminated early because of emerging safety information on RTG/EZG (i.e., retinal pigmentation and skin/mucosal discoloration) from long-term trials. Of 132 patients screened and 76 randomized, 75 (placebo, n=25; RTG/EZG 600mg/day, n=26; RTG/EZG 900mg/day, n=24) received at least 1 dose of the study drug and were included in the safety and intent-to-treat populations. The responder rate (≥50% reduction in 28-day total partial-onset seizure frequency) was 31% with RTG/EZG 600mg/day and 17% with RTG/EZG 900mg/day versus 0% with placebo. Median percent change from baseline in 28-day total partial-onset seizure frequency during the maintenance phase was −33.90% and −22.46% with RTG/EZG 600 and 900mg/day, respectively, versus −22.21% with placebo. No new safety concerns were identified.ConclusionsInsufficient data were obtained to permit definitive conclusions. However, the results appear to be broadly in line with those from previous studies that included primarily Caucasian patients

Chinese Public Attitudes Toward Epilepsy (PATE) scale: translation and psychometric evaluation

None of the quantitative scale for public attitudes toward epilepsy was translated to Chinese language. This study aimed to translate and test the validity and reliability of a Chinese version of the Public Attitudes Toward Epilepsy (PATE) scale. Methods: The translation was performed according to standard principles and tested in 140 Chinese-speaking adults aged more than 18 years for psychometric validation. Results: The items in each domain had similar standard deviations (equal item variance), ranged from 0.85-0.95 in personal domain and 0.75-1.04 in general domain. The correlation between an item and its domain was 0.4 and above for all, and higher than the correlation with the other domain. Multitrait analysis showed the Chinese PATE had a similar variance, floor and ceiling effects, and relative relationship between the domains, as the original PATE. The Chinese PATE scale showed a similar correlation with almost all demographic variable except age. Item means were generally clustered in the factor analysis as hypothesized. The Cronbach’s α values was within acceptable range (0.773) in the personal domain and satisfactory range (0.693) in the general domain. Conclusion: The Chinese PATE scale is a validated and reliable translated version in measuring the public attitudes toward epilepsy

Fused multivariate empirical mode decomposition (MEMD) and inverse solution method for EEG source localization

EEG source localization is determining possible cortical sources of brain activities with scalp EEG. Generally, every step of the data processing sequence affects the accuracy of EEG source localization. In this paper, we introduce a fused multivariate empirical mode decomposing (MEMD) and inverse solution algorithm with an embedded unsupervised eye blink remover in order to localize the epileptogenic zone accurately. For this purpose, we constructed realistic forward models using MRI and boundary element method (BEM) for each patient to obtain results that are more realistic. We also developed an unsupervised algorithm utilizing a wavelet method to remove eye blink artifacts. Additionally, we applied MEMD, which is one of the recent and suitable feature extraction methods for non-linear, non-stationary, and multivariate signals such as EEG, to extract the signal of interest. We examined the localization results using the two most reliable linear distributed inverse methods in the literature: weighted minimum norm estimation (wMN) and standardized low resolution tomography (sLORETA). Results affirm the success of the proposed algorithm with the highest agreement compared to MRI reference by a specialist. Fusion of MEMD and sLORETA results in approximately zero localization error in terms of spatial difference with the validated MRI reference. High accuracy results of proposed algorithm using non-invasive and low-resolution EEG provide the potential of using this work for pre-surgical evaluation towards epileptogenic zone localization in clinics

Trait impulsivity in Juvenile Myoclonic Epilepsy

Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs)

Sex-specific disease modifiers in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10−9) and 10p11.21 (P = 3.6 × 10−8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10−3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10−3) and increased seizure-like events (P = 6.8 × 10−7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10−3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease

Social stigma in epilepsy, a population-based study in Malaysia / Kheng-Seang Lim

This study aims to determine the magnitude of social stigma in epilepsy as measured by the public attitudes toward epilepsy, in the general as well as in a specific population, in Malaysia. The preliminary study showed that there is a significant impact of epilepsy on the employment in Malaysia, an indirect indicator to a need to study social stigma among Malaysian population. However, the systematic review revealed a need to develop a cross-culturally applicable quantitative scale measuring the public attitudes toward epilepsy, leading to the study on development and validation of a PATE (Public Attitudes Toward Epilepsy) scale, which is developed based on a stigmatization model. Factoring into personal and general domains led to a new concept of classifying the public attitudes toward epilepsy into personal and general attitudes. In order to be applied among Malaysian population, translation of the PATE scale Malay and Chinese languages was performed. Psychometric testing of this translated version showed that the Malay and Chinese translated PATE scales were valid and reliable. The study on students showed that the scale is easily applied among a homogenous group and can be used in a web-based design. In addition, attitudes of students were only better than the general population in the general domain but not in the personal domain, indicating that a significant discrepancy between the personal and general attitudes toward epilepsy. The study on teachers showed significant better attitudes among teachers as compared to the general population with tertiary education, suggesting that attitudes toward epilepsy may be job specific. Population studies showed that there was no significant difference in attitudes toward epilepsy between the Chinese and Malay populations. However, on subcategory analysis, Chinese had better attitudes toward social contact with people with epilepsy, indicating that Chinese patients with epilepsy might have less social restriction as compared with the Malay. In addition, the studies also demonstrated that each ethnic group had a unique urban-rural pattern of attitudes toward iii epilepsy, enable us to understand the cultural differences from the sociological perspectives

Attitudes toward epilepsy, a systematic review

<p>Surveys about attitudes towards those with epilepsy have been performed since 1949, in order to understand the social stigma toward epilepsy. This review aims to demonstrate the variation in public attitudes towards epilepsy and its associated factors, with a critical review of the methodology used to examine attitudes towards epilepsy. There was marked variation of attitudes between Western and non-Western populations, and these attitudes were positively correlated with the standard of living. Besides the general public, studies were also performed within specifi c groups, particularly teachers and students. However absence of a standardized questionnaire makes direct comparison diffi cult. A few quantitative methods were developed but these were limited by cultural variations and thus lack of global acceptance. Short-term intervention studies demonstrate an improvement of attitude with knowledge. Nonetheless, the cultural and social reasons underlying the attitudes, and how this affects the life of people with epilepsy, are understudied. Therefore, surveys on attitudes should continue to be carried out, particularly in populations prone to have negative attitudes with emphasis on underlying reasons, and such progress should be monitored longitudinally. Attitudes of people such as parents, teachers, school counselors, health care professionals, and employers, which have a direct impact on people with epilepsy, should be more extensively studied.</p

Traumatic vertebral artery dissection mimicking central pontine myelinolysis: A case report

A 27 year-old Chinese man, involved in a motor vehicle accident, presented with rapidly progressive pseudobulbar palsy and spastic tetraplegia. Magnetic resonance imaging (MRI) of the brain showed central pontine T2 hyperintensity with an unaffected outer rim, consistent with central pontine myelinolysis. There was no hyponatraemia before MRI and he was neither an alcoholic nor malnourished. Cerebral angiogram confirmed the diagnosis of right vertebral artery dissection. Vertebral artery dissection should be considered in a case with imaging suggestive of central pontine myelinolysis