The single nucleotide variant n.60G>C in the microRNA-146a associated with susceptibility to drug-resistant epilepsy.

OBJECTIVE: The aim of this study was to evaluate single nucleotide variants (SNVs) n.-411A > G (rs57095329) and n.60 G > C (rs2910164) in microRNA (miR)-146a, related to suppressing of TRAF6 with risk for epilepsy, as well as miR-146a and TRAF6 levels. METHODS: DNAs were extracted from epileptogenic tissues and blood leukocytes from drug-resistant epilepsy patients and healthy-individuals, respectively. Genotypes were identified by real-time PCR. Hardy-Weinberg equilibrium (HWE) and Fisher or X2 tests evaluated the difference between groups. The disease risk was assessed by odds ratio (OR) with 95 % confidence interval (95 %CI). The prognostic impact on probability seizure-free survival (PSF) was evaluated by Kaplan-Meier and log-rank tests. RESULTS: For rs57095329 both control and patient samples were not in HWE (p < 0.05) and the genotypes prevalence was similar in patients and controls (p>0.05). For rs2910164, control samples were in HWE (p = 0.61), contrasting with patients (p = 0.03), and similar frequencies of wild-type homozygous (GG) (43.4 % vs. 34.4 %, p = 0.2) and variant (CC) genotypes (8.0 % vs. 6.6 %, p = 0.6) were observed in patients and controls, respectively. However, increased frequency of heterozygous (GC) was observed in patients compared to controls (59.0 % vs. 42.7 %, p = 0.04) with 1.98 (95 %CI=1.09-3.57) risk for epilepsy. The miR-146a expression level in the epileptogenic tissues was lower in the GC (p = 0.02) and CC (p = 0.09) compared to GG genotype. TRAF6 expression level was higher in CC than in GG genotype (p = 0.09). Interestingly, there was an increased frequency of patients harboring GC genotype and less time until surgery compared to patients harboring GG or CC (36.06 % vs. 11.5 %, p = 0.01), confirmed by PSF (p = 0.04). CONCLUSIONS: The GC genotype for SNV rs2910164 appears associated with susceptibility to drug-resistant epilepsy due to the decreased MIR146a expression, favoring NF-kB pathway through TRAF6.

Unruptured Brain Arteriovenous Malformations: Primary ONYX Embolization in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients.

BACKGROUND AND PURPOSE: In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX). METHODS: Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration. RESULTS: Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients). CONCLUSIONS: In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial.