Objective: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the realworld safety and effectiveness of the RNS System. Methods: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. Results: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

SUMMARYPurpose: To identify and describe thalamic dysfunction in patients with temporal as well as extratemporal status epilepticus (SE) and to also analyze the specific clinical, radiological, and electroencephalography (EEG) characteristics of patients with acute thalamic involvement. Methods: We retrospectively identified patients who presented with clinical and electrographic evidence of partial SE and had thalamic abnormalities on diffusion-weighted imaging (DWI) within 5 days of documentation of lateralized epileptiform discharges (group 1). The spatial and temporal characteristics of the periodic lateralized epileptiform discharges (PLEDs) and the recorded electrographic seizures were analyzed and correlated with magnetic resonance imaging (MRI)-DWI hyperintense lesions. The findings of group 1 patients were compared with those of patients with partial SE without thalamic abnormalities on DWI (group 2).Results: The two groups were similar with regard to clinical presentation and morphology of epileptiform discharges. Group 1 patients had thalamic hyperintense lesions on DWI that appeared in the region of the pulvinar nucleus, ipsilateral to the epileptiform activity. Statistically significant relationship was noted between the presence of thalamic lesions and ipsilateral cortical laminar involvement (p ¼ 0.039) as well as seizure origin in the posterior quadrants (p ¼ 0.038). A trend towards PLEDs originating in the posterior quadrants was also noted (p ¼ 0.077). Discussion: Thalamic DWI hyperintense lesions may be observed after prolonged partial SE and are likely the result of excessive activity in thalamic nuclei having reciprocal connections with the involved cortex. The thalamus likely participates in the evolution and propagation of partial seizures in SE.

Drug‐resistant focal epilepsy with regional neocortical seizure onsets originating from the posterior quadrant can be particularly difficult to treat with resective surgery due to the overlap with eloquent cortex. Published reports indicate that corticothalamic treatment targeting the anterior or centromedian nucleus of the thalamus with direct brain‐responsive stimulation may be an effective approach to treat regional neocortical epilepsy. The pulvinar has remained largely unstudied as a neurostimulation target to treat refractory epilepsy. Because the pulvinar has connections with the posterior quadrant, neurostimulation may be effective if applied to seizures originating in this area. We performed a retrospective chart review of patients with regional neocortical seizure onsets in the posterior quadrant treated with the RNS System. Demographics, epilepsy history, clinical seizure frequencies, and neuropsychological testing results were obtained from the chart. Electrocorticogram (ECoG) records stored by the RNS System were reviewed to evaluate electrographic seizure onset patterns. Our patients were followed for 10, 12.5, and 15 months. All patients were responders (≥50% seizure reduction), and two of the three patients experienced a ≥90% reduction in seizures at the last follow‐up. Pre‐ and postsurgical neuropsychological evaluations were compared for two of the patients, and there was no evidence of cognitive decline found in either patient. Interestingly, mild cognitive improvements were reported. The third patient had only postimplant neuropsychological testing data available. Findings for this patient suggested executive dysfunction that was present prior to the RNS System which did not worsen with surgery. A visual inspection of ECoGs revealed near‐simultaneous seizure onsets in neocortical and pulvinar leads in two patients. Seizure onsets in the third patient were more variable. This is the first published report of brain‐responsive neurostimulation targeting the pulvinar to treat refractory regional onset epilepsy of posterior quadrant origin.

PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiography on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.