Lundstrom, Brian N.

BACKGROUND AND OBJECTIVES: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. Our study aims to analyze the national trends in different treatment modalities for individuals with drug-resistant epilepsy and investigate the outcomes associated with these procedural trends in the United States. METHODS: Using the National Inpatient Sample database from 2010 to 2020, patients with drug-resistant focal epilepsy who underwent laser interstitial thermal therapy (LITT), open surgical resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS) were identified. Trend analysis was performed using piecewise joinpoint regression. Propensity score matching was used to compare outcomes between 10 years prepandemic before 2020 and the first peak of the COVID-19 pandemic. RESULTS: This study analyzed a total of 33 969 patients with a diagnosis of drug-resistant epilepsy, with 3343 patients receiving surgical resection (78%), VNS (8.21%), RNS (8%), and LITT (6%). Between 2010 and 2020, there was an increase in the use of invasive electroencephalography monitoring for seizure zone localization ( P = .003). There was an increase in the use of LITT and RNS ( P < .001), while the use of surgical resection and VNS decreased over time ( P < .001). Most of these patients (89%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (11%) underwent treatment during the COVID pandemic (2020). After propensity score matching, the rate of pulmonary complications, postprocedural hematoma formation, and mortality were slightly higher during the pandemic compared with the prepandemic period ( P = .045, P = .033, and P = .026, respectively). CONCLUSION: This study indicates a relative decrease in the use of surgical resections, as a treatment for drug-resistant focal epilepsy. By contrast, newer, minimally invasive surgical approaches including LITT and RNS showed gradual increases in usage.

BACKGROUND AND OBJECTIVES: The anterior nucleus of the thalamus (ANT) is a common target for deep brain stimulation (DBS) for drug-resistant epilepsy (DRE). However, the surgical approach to the ANT remains challenging because of its unique anatomy. This study aims to summarize our experience with the posterior temporo-parietal extraventricular (TPEV) approach targeting the ANT for DBS in DRE. METHODS: We performed a retrospective analysis of patients with DRE who underwent ANT-DBS using the TPEV approach between January 2011 and February 2021. Subjects with at least 6-month follow-up were eligible. The final lead position and number of active contacts targeting the anteroventral nucleus (AV) of the ANT were assessed using Lead-DBS. Mean seizure frequency reduction percentage and responder rate (≥50% decrease in seizure frequency) were determined. RESULTS: Thirty-one patients (mean age: 32.9 years; 52% female patients) were included. The mean follow-up period was 27.6 months ± 13.9 (29, 16-36). The mean seizure frequency reduction percentage was 65% ± 26 (75, 50-82). Twenty-six of 31 participants (83%) were responders, P < .001. Two subjects (6%) were seizure-free for at least 6 months at the last evaluation. Antiepileptic drugs dose and/or number decreased in 17/31 subjects (55%). The success rate for placing at least 1 contact at AV was 87% (27/31 patients) bilaterally. The number of active contacts at the AV was significantly greater in the responder group, 3.1 ± 1.3 (3, 2-4) vs 1.8 ± 1.1 (2, 1-2.5); P = .041 with a positive correlation between the number of active contacts and seizure reduction percentage; r = 0.445, R 2 = 0.198, P = .012. CONCLUSION: The TPEV trajectory is a safe and effective approach to target the ANT for DBS. Future studies are needed to compare the clinical outcomes and target accuracy with the standard approaches.

AbstractDirect cortical stimulation has been applied in epilepsy for nearly a century and has experienced a renaissance, given unprecedented opportunities to probe, excite, and inhibit the human brain. Evidence suggests stimulation can increase diagnostic and therapeutic utility in patients with drug‐resistant epilepsies. However, choosing appropriate stimulation parameters is not a trivial issue, and is further complicated by epilepsy being characterized by complex brain state dynamics. In this article derived from discussions at the ICTALS 2022 Conference (International Conference on Technology and Analysis for Seizures), we succinctly review the literature on cortical stimulation applied acutely and chronically to the epileptic brain for localization, monitoring, and therapeutic purposes. In particular, we discuss how stimulation is used to probe brain excitability, discuss evidence on the usefulness of stimulation to trigger and stop seizures, review therapeutic applications of stimulation, and finally discuss how stimulation parameters are impacted by brain dynamics. Although research has advanced considerably over the past decade, there are still significant hurdles to optimizing use of this technique. For example, it remains unclear to what extent short timescale diagnostic biomarkers can predict long‐term outcomes and to what extent these biomarkers add information to already existing biomarkers from passive electroencephalographic recordings. Further questions include the extent to which closed loop stimulation offers advantages over open loop stimulation, what the optimal closed loop timescales may be, and whether biomarker‐informed stimulation can lead to seizure freedom. The ultimate goal of bioelectronic medicine remains not just to stop seizures but rather to cure epilepsy and its comorbidities.

Purpose of review Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation. Recent findings Invasive stimulation for treatment of focal epilepsy includes vagus nerve stimulation, responsive neurostimulation of the cortex and deep brain stimulation of the anterior nucleus of the thalamus. A wide range of other targets have been considered, including centromedian, central lateral and pulvinar thalamic nuclei; medial septum, nucleus accumbens, subthalamic nucleus, cerebellum, fornicodorsocommissure and piriform cortex. Stimulation for generalized onset seizures and mixed epilepsies as well as increased efforts focusing on paediatric populations have emerged. Hardware with more permanently implanted lead options and sensing capabilities is emerging. A wider variety of programming approaches than typically used may improve patient outcomes. Finally, noninvasive brain stimulation with its favourable risk profile offers the potential to treat increasingly diverse epilepsy patients. Summary Neurostimulation for the treatment of epilepsy is surprisingly varied. Flexibility and reversibility of neurostimulation allows for rapid innovation. There remains a continued need for excitability biomarkers to guide treatment and innovation. Neurostimulation, a part of bioelectronic medicine, offers distinctive benefits as well as unique challenges.

Abstract Deep brain stimulation and responsive neurostimulation (RNS) use high‐frequency stimulation (HFS) per the pivotal trials and manufacturer‐recommended therapy protocols. However, not all patients respond to HFS. In this retrospective case series, 10 patients implanted with the RNS System were programmed with low‐frequency stimulation (LFS) to treat their seizures; nine of these patients were previously treated with HFS (100 Hz or greater). LFS was defined as frequency < 10 Hz. Burst duration was increased to at least 1000 ms. With HFS, patients had a median seizure reduction (MSR) of 13% (interquartile range [IQR] = −67 to 54) after a median of 19 months (IQR = 8–49). In contrast, LFS was associated with a 67% MSR (IQR = 13–95) when compared to HFS and 76% MSR (IQR = 43–91) when compared to baseline prior to implantation. Charge delivered per hour and pulses per day were not significantly different between HFS and LFS, although time stimulated per day was longer for LFS (228 min) than for HFS (7 min). There were no LFS‐specific adverse effects reported by any of the patients. LFS could represent an alternative, effective method for delivering stimulation in focal drug‐resistant epilepsy patients treated with the RNS System.

Abstract Neuromodulation is a key therapeutic tool for clinicians managing patients with drug‐resistant epilepsy. Multiple devices are available with long‐term follow‐up and real‐world experience. The aim of this review is to give a practical summary of available neuromodulation techniques to guide the selection of modalities, focusing on patient selection for devices, common approaches and techniques for initiation of programming, and outpatient management issues. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (DBS‐ANT), and responsive neurostimulation (RNS) are all supported by randomized controlled trials that show safety and a significant impact on seizure reduction, as well as a suggestion of reduction in the risk of sudden unexplained death in epilepsy (SUDEP). Significant seizure reductions are observed after 3 months for DBS, RNS, and VNS in randomized controlled trials, and efficacy appears to improve with time out to 7 to 10 years of follow‐up for all modalities, albeit in uncontrolled follow‐up or retrospective studies. A significant number of patients experience seizure‐free intervals of 6 months or more with all three modalities. Number and location of epileptogenic foci are important factors affecting efficacy, and together with comorbidities such as severe mood or sleep disorders, may influence the choice of modality. Programming has evolved—DBS is typically initiated at lower current/voltage than used in the pivotal trial, whereas target charge density is lower with RNS, however generalizable optimal parameters are yet to be defined. Noninvasive brain stimulation is an emerging stimulation modality, although it is currently not used widely. In summary, clinical practice has evolved from those established in pivotal trials. Guidance is now available for clinicians who wish to expand their approach, and choice of neuromodulation technique may be tailored to individual patients based on their epilepsy characteristics, risk tolerance, and preferences.

Abstract Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

OBJECTIVE Epilepsy originating from the central lobule (i.e., the primary sensorimotor cortex) is a challenging entity to treat given its involvement of eloquent cortex. The objective of this study was to review available evidence on treatment options for central lobule epilepsy. METHODS A comprehensive literature search (PubMed/Medline, EMBASE, and Scopus) was conducted for studies (1990 to date) investigating postoperative outcomes for central lobule epilepsy. The primary and secondary endpoints were seizure freedom at last follow-up and postoperative neurological deficit, respectively. The following procedures were included: open resection, multiple subpial transections (MSTs), laser and radiofrequency ablation, deep brain stimulation (DBS), responsive neurostimulation (RNS), and continuous subthreshold cortical stimulation (CSCS). RESULTS A total of 52 studies and 504 patients were analyzed. Most evidence was based on open resection, yielding a total of 400 patients (24 studies), of whom 62% achieved seizure freedom at a mean follow-up of 48 months. A new or worsened motor deficit occurred in 44% (permanent in 19%). Forty-six patients underwent MSTs, of whom 16% achieved seizure freedom and 30% had a neurological deficit (permanent in 12%). There were 6 laser ablation cases (cavernomas in 50%) with seizure freedom in 4 patients and 1 patient with temporary motor deficit. There were 5 radiofrequency ablation cases, with 1 patient achieving seizure freedom, 2 patients each with Engel class III and IV outcomes, and 2 patients with motor deficit. The mean seizure frequency reduction at the last follow-up was 79% for RNS (28 patients), 90% for CSCS (15 patients), and 73% for DBS (4 patients). There were no cases of temporary or permanent neurological deficit in the CSCS or DBS group. CONCLUSIONS This review highlights the safety and efficacy profile of resection, ablation, and stimulation for refractory central lobe epilepsy. Resection of localized regions of epilepsy onset zones results in good rates of seizure freedom (62%); however, nearly 20% of patients had permanent motor deficits. The authors hope that this review will be useful to providers and patients when tailoring decision-making for this intricate pathology.