Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Visual automated fluorescence electrophoresis provides simultaneous quality, quantity, and molecular weight spectra for genomic DNA from archived neonatal blood spots.

The Guthrie 903 card archived dried blood spots (DBSs) are a unique but terminal resource amenable for individual and population-wide genomic profiling. The limited amounts of DBS-derived genomic DNA (gDNA) can be whole genome amplified, producing sufficient gDNA for genomic applications, albeit with variable success; optimizing the isolation of high-quality DNA from these finite, low-yield specimens is essential. Agarose gel electrophoresis and spectrophotometry are established postextraction quality control (QC) methods but lack the power to disclose detailed structural, qualitative, or quantitative aspects that underlie gDNA failure in downstream applications. Visual automated fluorescence electrophoresis (VAFE) is a novel QC technology that affords precise quality, quantity, and molecular weight of double-stranded DNA from a single microliter of sample. We extracted DNA from 3-mm DBSs archived in the Swedish Neonatal Repository for >30 years and performed the first quantitative and qualitative analyses of DBS-derived DNA on VAFE, before and after whole genome amplified, in parallel with traditional QC methods. The VAFE QC data were correlated with subsequent sample performance in PCR, sequencing, and high-density comparative genome hybridization array. We observed improved standardization of nucleic acid quantity, quality and integrity, and high performance in the downstream genomic technologies. Addition of VAFE measures in QC increases confidence in the validity of genetic data and allows cost-effective downstream analysis of gDNA for investigational and diagnostic applications.