METHODS: Articles were retrieved from EMBASE, Medline and Cochrane Library from inception to January 2016. Treatment outcomes were analysed based on responder, seizure-free, withdrawal and adverse event rates. Quality of each study was also assessed.
RESULTS: Twelve articles fulfilled the inclusion criteria. Heterogeneity and quality of the included studies were considered acceptable. Overall, newer AEDs as adjunct therapy in children with inadequate control of focal seizure showed a trend of better seizure outcomes. The pooled ORs for responder, seizure-free and withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69 (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively higher than placebo (OR:1.64, 95%CI:1.13, 2.39).
CONCLUSION: In our updated review, newer AEDs as adjunct therapy for focal epilepsy in children have trends of better effectiveness compared to placebo. Newer AEDs are associated with statistically more children with >50% seizure reduction, and a trend of better seizure freedom. Their tolerability would also be considered acceptable with the observed low withdrawal rate. However, the relative lack of well-conducted RCTs evaluating their effectiveness against other active AED treatment in children would not facilitate evidence-based practice. This highlights the knowledge gap and the need for more well-conducted RCTs against active treatments to ascertain the long term effectiveness and the role of newer AEDs in managing epilepsy in children.
MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing.
RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene.
DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.
METHOD: A total of 2218 PWE were recruited retrospectively into this study. Deceased cases from 2009-2018 were identified from the National Registry Department of Malaysia. Age-, gender-, and ethnic-specific SMR were calculated.
RESULT: There was a total of 163 deaths, of which 111 (68.1%) were male. The overall case-fatality rate (CFR) was 7.3%. Male PWE had higher CFR (9.2%) compared to females (5.1%, p<0.001). The annual death rate of PWE was 867 per 100, 000 persons. The overall all-cause SMR was 1.6 (CI 95% 1.3-1.8). The SMR for younger age groups (15-19 and 20-29 years) were higher (5.4-5.5) compared to other age groups (0.4-2.5). Overall SMR for male PWE (1.8, 95% CI 1.5-2.1) was higher than females (1.2, 95% CI 0.9-1.6). However, the SMR for female PWE in the younger age groups (15-19, 20-29 and 30-39 years) was higher. SMR among the Indian PWE was the highest (1.6, 95% CI 1.2-2.0) compared to the Chinese (1.5, 95% CI 1.2-1.9) and the Malays (1.4, 95% 1.0-1.9). The CFR was higher in those with focal epilepsy (8.5% vs. 2.5-3.7% in genetic and other generalized epilepsies, p=0.003), epilepsy with structural cause (9.5% vs. 5.9% in others, p=0.005) and uncontrolled seizures (7.9% vs. 5.2% in seizure-free group, p<0.001).
CONCLUSION: The mortality rate of PWE in Malaysia is higher than that of the general population but lower compared to other Asian countries. Specifically, the rates are higher in the younger age group, male gender, and Indian ethnicity. Those with focal epilepsy, structural causes and uncontrolled seizures have higher mortality rates.