Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Long-term outcomes after responsive neurostimulation for treatment of refractory epilepsy: a single-center experience of 100 cases

OBJECTIVE: Despite antiepileptic drugs, more than 30% of people with epilepsy continue to have seizures. Patients with such drug-resistant epilepsy (DRE) may undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation, but many are not candidates for epilepsy surgery or fail to respond to such interventions. Responsive neurostimulation (RNS) provides a neuromodulatory option. In this study, the authors present a single-center experience with the use of RNS over the last 5 years to provide long-term control of seizures in patients with DRE with at least 1 year of follow-up. METHODS: The authors performed a retrospective analysis of a prospectively collected single-center database of consecutive DRE patients who underwent RNS system implantation from September 2015 to December 2020. Patients were followed-up postoperatively to evaluate seizure freedom and complications. RESULTS: One hundred patients underwent RNS placement. Seven patients developed infections: 2 responded to intravenous antibiotic therapy, 3 required partial removal and salvaging of the system, and 2 required complete removal of the RNS device. No postoperative tract hemorrhages, strokes, device migrations, or malfunctions were documented in this cohort. The average follow-up period was 26.3 months (range 1-5.2 years). In terms of seizure reduction, 8 patients had 0%-24% improvement, 14 had 25%-49% improvement, 29 experienced 50%-74% improvement, 30 had 75%-99% improvement, and 19 achieved seizure freedom. RNS showed significantly better outcomes over time: patients with more than 3 years of RNS therapy had 1.8 higher odds of achieving 75% or more seizure reduction (95% CI 1.07-3.09, p = 0.02). Also, patients who had undergone resective or ablative surgery prior to RNS implantation had 8.25 higher odds of experiencing 50% or more seizure reduction (95% CI 1.05-65.1, p = 0.04). CONCLUSIONS: Responsive neurostimulator implantation achieved 50% or more seizure reduction in approximately 80% of patients. Even in patients who did not achieve seizure freedom, significant improvement in seizure duration, severity, or postictal state was reported in more than 68% of cases. Infection (7%) was the most common complication. Patients with prior resective or ablative procedures and those who had been treated with RNS for more than 3 years achieved better outcomes

Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy

INTRODUCTION: One-third of patients with epilepsy continue to have seizures despite antiepileptic medications. Some of these refractory patients may not be candidates for surgical resection primarily because the seizure onset zones (SOZs) involve both hemispheres or are located in eloquent areas. The NeuroPace Responsive Neurostimulation System (RNS) is a closed-loop device that uses programmable detection and stimulation to tailor therapy to a patient\u27s individual neurophysiology. Here, we present our single-center experience with the use of RNS in thalamic nuclei to provide long-term seizure control in patients with refractory epilepsy. METHODS: We performed a prospective single-center study of consecutive refractory epilepsy patients who underwent RNS system implantation in the anterior (ANT) and centromedian (CM) thalamic nuclei from September 2015 to December 2020. Patients were followed postoperatively to evaluate seizure freedom and complications. RESULTS: Twenty-three patients underwent placement of 36 RNS thalamic leads (CM = 27 leads, ANT = 9 leads). Mean age at implant was 18.8 ± 11.2 years (range 7.8-62 years-old). Two patients (8.7%) developed infections: 1 improved with antibiotic treatments alone, and 1 required removal with eventual replacement of the system to recover the therapeutic benefit. Mean time from RNS implantation to last follow-up was 22.3 months. Based on overall reduction of seizure frequency, 2 patients (8.7%) had no- to \u3c25% improvement, 6 patients (26.1%) had 25-49% improvement, 14 patients (60.9%) had 50-99% improvement, and 1 patient (4.3%) became seizure-free. All patients reported significant improvement in seizure duration and severity, and 17 patients (74%) reported improved post-ictal state. There was a trend for subjects with SOZs located in the temporal lobe to achieve better outcomes after thalamic RNS compared to those with extratemporal SOZs. Of note, seizure etiology was syndromic in 12 cases (52.2%), and 7 patients (30.4%) had undergone resection/disconnection surgery prior to thalamic RNS therapy. CONCLUSION: Thalamic RNS achieved ≥50% seizure control in ~65% of patients. Infections were the most common complication. This therapeutic modality may be particularly useful for patients affected by aggressive epilepsy syndromes since a young age, those whose seizure foci are located in the mesial temporal lobe, and those who have failed prior surgical interventions

Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome

The fat mass and obesity-associated gene ( FTO ) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.287G>C, p.Arg96Pro/R96P) outside the catalytic site, causing numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function. Biochemical assays of cells with the patient’s variant were performed to further quantify the effect of the variant on function. Loss-of-function resulting from the patient’s R96P missense variant was demonstrated with in vitro biochemical characterization of demethylase activity, resulting in a 90% reduction in function of the fat mass and obesity-associated protein compared to wild-type. Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies