Ryder P. Gwinn

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

In Vivo Modulation of Hippocampal Epileptiform Activity with Radial Electric Fields

Summary:  Purpose: Electric field stimulation can interact with brain activity in a subthreshold manner. Electric fields have been previously adaptively applied to control seizures in vitro. We report the first results from establishing suitable electrode geometries and trajectories, as well as stimulation and recording electronics, to apply this technology in vivo.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.

Laterality and temporal distribution of seizures in patients with bitemporal independent seizures during a trial of responsive neurostimulation

We describe seizure laterality and temporal seizure patterns in six subjects with bilateral temporal lobe epilepsy (bTLE) implanted with bilateral hippocampal depth electrodes and the NeuroPace RNS™ system over 84 consecutive days. Seizures were disproportionate in laterality in three subjects and disproportionate in time for two subjects. Clustering of seizures did not clearly affect laterality. Some but not all subjects with bTLE displayed nonrandom temporal or lateral clustering of seizures.

132 A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease.

INTRODUCTION Traditional stereotactic radiofrequency thalamotomy has been used with success in medication-refractory tremor-dominant Parkinson disease (PD). Recently, transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been used to successfully perform thalamotomy for essential tremor. We designed a double-blinded, randomized controlled trial to investigate the effectiveness of MRgFUS thalamotomy in tremor-dominant PD. METHODS Patients with medication-refractory, tremor-dominant PD were enrolled in the 2-center study and randomly assigned 1:2 to receive either a sham procedure or treatment. After the 3-month blinded phase, the sham group was offered treatment. Outcome was measured with blinded Clinical Rating Scale for Tremor (CRST) and Unified Parkinsons Disease Rating Scale (UPDRS) ratings. The primary outcome compared improvement in hand tremor between the treatment and sham procedure at 3 months. Secondary outcomes were measured with UPDRS and hand tremor at 12 months. Safety was assessed with MRI, adverse events, and comprehensive neurocognitive assessment. RESULTS Twenty-seven patients were enrolled and 6 were randomly assigned to a sham procedure. For the primary outcome assessment, there was a mean 50% improvement in hand tremor from MRgFUS thalamotomy at 3 months compared with a 22% improvement from the sham procedures (P = .088). The 1-year tremor scores for all 19 patients treated with 1-year follow-up data (blinded and unblinded) showed a reduction in tremor scores of 40.6% (P = .0154) and a mean reduction in medicated UPDRS motor scores of 3.7 (32%, P = .033). Sham patients had a notable placebo effect with a mean 21.5% improvement in tremor scores at 3 months. Twenty-seven patients completed the primary analysis, 19 patients completed the 12-month assessment, 3 patients opted for deep brain stimulation, 3 were lost to follow-up, 1 patient opted for no treatment, and 1 is pending a 12-month evaluation. CONCLUSION Transcranial MRgFUS demonstrates a trend toward improvement in hand tremor, and a clinically significant reduction in mean UPDRS. A significant placebo response was noted in the randomized trial.cause of intractable epilepsy in children. Seizure freedom following resection of FCD is determined by complete resection of the dysplastic cortical tissue.However, difficulty with intraoperative identification of the FCD lesion may limit the ability to achieve the surgical objective of complete extirpation of these lesions. The use of intraoperative magnetic resonance imaging (iMRI) may aid in real-time detection of these lesions and improve seizure control outcomes compared with traditional resective surgery.

Atmospheric Pressure and Seizure Frequency in the Epilepsy Unit: Preliminary Observations

Summary:  Objective: To demonstrate that seizure frequency in patients undergoing video EEG telemetry does not correlate with atmospheric pressure (AP) changes.

Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease: A Randomized Clinical Trial

Importance Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown. Objective To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. Design, Setting, and Participants Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. Interventions Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. Main Outcomes and Measures The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson’s Disease Rating Scale (UPDRS) scores and quality of life measures. Results Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, −11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, −5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]). Conclusions and Relevance Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. Trial Registration ClinicalTrials.gov identifier NCT01772693

Local spatial effect of 50 Hz cortical stimulation in humans

Purpose: Cortical stimulation to abort seizures is under human investigation. Ideal electrode placement and stimulating parameters are unknown with poor understanding of tissue volume affected by stimulation or duration and nature of its effect on cortical activity. To help characterize this effect, we analyzed electrocorticography (ECoG) recorded adjacent to stimulated contacts during and after bipolar stimulation in patients undergoing functional cortical mapping with subdural electrodes.

Individualizing therapies with responsive epilepsy neurostimulation — A mirtazapine case study of hippocampal excitability

Objectives This study aimed to investigate mirtazapine-induced changes in responsive neurostimulator (RNS) recordings in a patient with epilepsy. Materials and methods Cortical detection/stimulation counts from an RNS implanted in a patient with bitemporal epilepsy were matched to mirtazapine use to see if that drug altered hippocampal excitability. Results Mirtazapine decreased hippocampal stability; when mirtazapine was held after a washout period, DSC counts declined, but when it was retrialed, DSC counts increased. Responsive epilepsy neurostimulator system data helped design an optimal and individualized medication regimen for our patient with drug-resistant focal epilepsy. Conclusions Responsive neurostimulator systems in epilepsy may assess a medications effect on hippocampal excitability. Mirtazapine worsened hippocampal excitability in a patient with bitemporal epilepsy.