State-dependent effects of responsive neurostimulation depend on seizure localization.

Brain-responsive neurostimulation is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS System do not experience meaningful seizure reduction. Initial titration of RNS therapy is typically similar for all patients, raising the possibility that treatment response might be enhanced by consideration of patient-specific variables. Indeed, small, single-center studies have yielded preliminary evidence that RNS System effectiveness depends on the brain state during which stimulation is applied.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown.

Expert and deep learning model identification of iEEG seizures and seizure onset times.

Hundreds of 90-s iEEG records are typically captured from each NeuroPace RNS System patient between clinic visits. While these records provide invaluable information about the patient's electrographic seizure and interictal activity patterns, manually classifying them into electrographic seizure/non-seizure activity, and manually identifying the seizure onset channels and times is an extremely time-consuming process. A convolutional neural network based Electrographic Seizure Classifier (ESC) model was developed in an earlier study.

Vascular anomaly, lipoma, and polymicrogyria associated with schizencephaly: developmental and diagnostic insights. Illustrative case.

Background: Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain "tumors.

Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity.

The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experiences.

Non-linear Embedding Methods for Identifying Similar Brain Activity in 1 Million iEEG Records Captured From 256 RNS System Patients.

Finding electrophysiological features that are similar across patients with epilepsy may facilitate identifying treatment options for one patient that worked in patients with similar brain activity patterns. Three non-linear iEEG (intracranial electroencephalogram) embedding methods of finding similar cross-patient iEEG records in a large iEEG dataset were developed and compared. About 1 million iEEG records from 256 patients with drug-resistant focal onset seizures who were treated in prospective trials of the RNS System were used for analyses.

Neuromodulation in 2035: The Neurology Future Forecasting Series.

Neuromodulation devices are approved in the United States for the treatment of movement disorders, epilepsy, pain, and depression, and are used off-label for other neurologic indications. By 2035, advances in our understanding of neuroanatomical networks and in the mechanism of action of stimulation, coupled with developments in material science, miniaturization, energy storage, and delivery, will expand the use of neuromodulation devices. Neuromodulation approaches are flexible and modifiable.

A High Accuracy Electrographic Seizure Classifier Trained Using Semi-Supervised Labeling Applied to a Large Spectrogram Dataset.

The objective of this study was to explore using ECoG spectrogram images for training reliable cross-patient electrographic seizure classifiers, and to characterize the classifiers' test accuracy as a function of amount of training data. ECoG channels in ∼138,000 time-series ECoG records from 113 patients were converted to RGB spectrogram images. Using an unsupervised spectrogram image clustering technique, manual labeling of 138,000 ECoG records (each with up to 4 ECoG channels) was completed in 320 h, which is an estimated 5 times faster than manual labeling without ECoG clustering.

Acute effects of brain-responsive neurostimulation in drug-resistant partial onset epilepsy.

Objective: Understanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings.

Methods: In patients implanted with the NeuroPace® RNS® System, acute changes in iEEG spectral power following active and sham stimulation periods were quantified and compared within individual iEEG channels. Additionally, acute stimulation-induced acute iEEG changes were compared within iEEG channels before and after patients experienced substantial reductions in clinical seizure frequency.

Mood and quality of life in patients treated with brain-responsive neurostimulation: The value of earlier intervention.

Objective: To establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention.

Methods: Data were retrospectively analyzed from prospective clinical trials of a direct brain-responsive neurostimulator (RNS® System) for treatment of adults with medically intractable focal-onset epilepsy. Participants completed the Quality of Life in Epilepsy Inventory (QOLIE-31) yearly through 9 years of follow-up and the Beck Depression Inventory-II (BDI-II) through 2 years of follow-up.

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy.

: Epilepsy affects more than 1% of the US population, and over 30% of adults with epilepsy do not respond to antiseizure medications without life-impacting medication-related side effects. Resection of the seizure focus is not an option for many patients because it would cause unacceptable neurological or cognitive harm. For these patients, neuromodulation has emerged as a nondestructive, effective, and safe alternative.

Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.

Background: Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Electrocorticographic events from long-term ambulatory brain recordings can potentially supplement seizure diaries.

Purpose: To determine the feasibility of using epileptiform events detected by continuous electrocorticographic monitoring via a brain-responsive neurostimulation system to supplement patient-maintained seizure diaries.

Methods: Data were retrospectively analyzed from a randomized controlled trial of brain-responsive neurostimulation (RNS® System) for adjunctive treatment of medically intractable focal onset seizures in 191 subjects. The long-term (≥3 months) correspondence between daily counts of diary-reported seizures and device-recorded "long epileptiform events" (LEs), a proxy for electrographic seizures (ESs), was assessed using cross-correlation and logistic generalized estimating equation models.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

Objective: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system.

Methods: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings.

Quantitative electrocorticographic biomarkers of clinical outcomes in mesial temporal lobe epileptic patients treated with the RNS® system.

Objectives: Find interictal electrocorticographic (ECoG) biomarkers of clinical outcomes in mesiotemporal lobe (MTL) epilepsy patients.

Methods: In the NeuroPace® RNS® System clinical trials with 256 patients, 20 MTL patients with the most reduction in clinical seizures at Year 7 compared to baseline (upper response quartile; -96.5% median change) and 20 with the least reduction in clinical seizures (lower response quartile; -17.

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings.

Objectives: Describe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).

Methods: Clinical seizures from eight patients (mean follow-up of 10.

Brain-responsive neurostimulation for epilepsy (RNS System).

Controlled clinical trials in adults with medically intractable focal seizures treated with the RNS System demonstrate that closed-loop responsive neurostimulation to the seizure focus reduces the frequency of disabling seizures, is well tolerated, and is acceptably safe. Seizure reductions begin with initiation of treatment and continue over time, reaching median reductions of 75% after 9 years of treatment. Treatment with responsive cortical stimulation is also associated with improvement in quality of life and cognitive function related to the functional area being treated.

Clinical and electrocorticographic response to antiepileptic drugs in patients treated with responsive stimulation.

Objective: The objective of this study was to explore whether chronic electrocorticographic (ECoG) data recorded by a responsive neurostimulation system could be used to assess clinical responses to antiepileptic drugs (AEDs).

Methods: Antiepileptic drugs initiated and maintained for ≥3 months by patients participating in clinical trials of the RNS System were identified. Such "AED Starts" that produced an additional ≥50% reduction in patient-reported clinical seizure frequency were categorized as clinically beneficial, and the remaining as not beneficial.

Changes in the electrocorticogram after implantation of intracranial electrodes in humans: The implant effect.

Objective: Subacute and long-term electrocorticographic (ECoG) changes in ambulatory patients with depth and cortical strip electrodes were evaluated in order to determine the length of the implant effect.

Methods: ECoG records were assessed in patients with medically intractable epilepsy who had depth and/or strip leads implanted in order to be treated with brain-responsive stimulation. Changes in total spectral power, band-limited spectral power, and spike rate were assessed.

Infection and Erosion Rates in Trials of a Cranially Implanted Neurostimulator Do Not Increase with Subsequent Neurostimulator Placements.

Background/aims: The RNS® System utilizes a cranially implanted neurostimulator attached to leads placed at the seizure focus to provide brain responsive stimulation for the treatment of medically intractable partial onset epilepsy. Infection and erosion rates related to the cranial implant site were assessed overall and by neurostimulator procedure to determine whether rates increased with additional procedures.

Methods: Infection and erosion rates were calculated as (1) chance per neurostimulator procedure, (2) incidence per patient implant year, and (3) rates for initial and each subsequent neurostimulator implant (generalized estimating equation).

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.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Objective: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.

Methods: Patients with partial seizures of neocortical origin 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.