Citations

Neurostimulation for epilepsy refers to the application of electricity to affect the central nervous system, with the goal of reducing seizure frequency and severity. We review the available evidence for the use of neurostimulation to treat pediatric epilepsy, including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), deep brain stimulation (DBS), chronic subthreshold cortical stimulation (CSCS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We consider possible mechanisms of action and safety concerns, and we propose a methodology for selecting between available options. In general, we find neurostimulation is safe and effective, although any high quality evidence applying neurostimulation to pediatrics is lacking. Further research is needed to understand neuromodulatory systems, and to identify biomarkers of response in order to establish optimal stimulation paradigms.

Abstract Brain stimulation offers an alternative to focal resection for the treatment of focal drug-resistant epilepsy. Chronic subthreshold cortical stimulation is an individualized biomarker-informed open-loop continuous electrical stimulation approach targeting the seizure onset zone and surrounding areas. Before permanent implantation, trial stimulation is performed during invasive monitoring to assess stimulation efficacy as well as to optimize stimulation location and parameters by modifying interictal EEG biomarkers. We present clinical and neurophysiological results from a retrospective analysis of 21 patients, showing a median percent reduction in seizure frequency of 100% and responder rate of 89% with a median follow-up of 27 months. About 40% of patients were free of disabling seizures for a 12-month period or longer. We find that stimulation-induced decreases in delta (1–4 Hz) power and increases in alpha and beta (8–20 Hz) power during trial stimulation correlate with improved long-term clinical outcomes. These results suggest chronic subthreshold cortical stimulation may be an effective alternative approach to treating focal drug-resistant epilepsy and that short-term stimulation-related changes in spectral power may be a useful interictal biomarker and relate to long-term clinical outcome.

Abstract BACKGROUND Subdural grids and strip electrodes provide wide coverage of the cerebral cortex, precise delineation of the extent of the seizure onset zone, and improved spatial sampling to perform functional mapping for eloquent cortex. OBJECTIVE To describe a novel device that allows for a minimally invasive approach to implantation of subdural grid and strip electrodes. METHODS A skull mounted device was created to allow for implantation of subdural electrodes through a keyhole craniotomy with direct visualization using the aid of a flexible neurovideoscope. The initial studies in preparation for grid development performed on cadaveric skulls were analyzed to determine the size of craniotomy required for deployment, maximal distance of strip electrode deployment from center of craniotomy, and visual inspection of the cortex was performed for any underlying damage. RESULTS The device allowed for the placement of subdural electrodes through a 40-mm craniotomy. Subdural electrodes were deployed in multiple directions to a distance of a 70-mm radius from the center of the craniotomy. There was no visual damage to the underlying cortex after the procedures were completed. CONCLUSION Large craniotomies are typically desired to provide direct visualization of the implantation of subdural electrodes, but can increase the risk of subdural hemorrhages and infections. This study describes a novel minimally invasive endoscopically assisted device for the implantation of subdural strip electrodes under direct visualization. With this device, we are able to limit the size of the craniotomy, avoid incision through the temporalis muscle, and implant subdural electrodes with visualization of the cortex.

OBJECTIVE Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising therapy for refractory epilepsy. Unfortunately, the variability in outcomes from ANT DBS is not fully understood. In this pilot study, the authors assess potential differences in functional connectivity related to the volume of tissue activated (VTA) in ANT DBS responders and nonresponders as a means for better understanding the mechanism of action and potentially improving DBS targeting. METHODS This retrospective analysis consisted of 6 patients who underwent ANT DBS for refractory epilepsy. Patients were classified as responders (n = 3) if their seizure frequency decreased by at least 50%. The DBS electrodes were localized postoperatively and VTAs were computationally generated based on DBS programming settings. VTAs were used as seed points for resting-state functional MRI connectivity analysis performed using a control dataset. Differences in cortical connectivity to the VTA were assessed between the responder and nonresponder groups. RESULTS The ANT DBS responders showed greater positive connectivity with the default mode network compared to nonresponders, including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobule, and precuneus. Interestingly, there was also a consistent anticorrelation with the hippocampus seen in responders that was not present in nonresponders. CONCLUSIONS Based on their pilot study, the authors observed that successful ANT DBS in patients with epilepsy produces increased connectivity in the default mode network, which the authors hypothesize increases the threshold for seizure propagation. Additionally, an inhibitory effect on the hippocampus mediated through increased hippocampal γ-aminobutyric acid (GABA) concentration may contribute to seizure suppression. Future studies are planned to confirm these findings.

When medically intractable epilepsy is multifocal or focal but poorly localized, neuromodulation can be useful therapy. One such technique is deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT). Unfortunately, the ANT is difficult to visualize in standard MRI sequences and its indirect targeting is difficult because of thalamic variability and atrophy in patients with epilepsy. The following study describes the novel use of the fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence to delineate the mammillothalamic tract for direct targeting of the ANT through visualizing the termination of the mammillothalamic tract in the ANT. The day prior to surgery in a 19-year-old, right-handed woman with a 5-year history of epilepsy, MRI was performed on a 3-T Siemens Prisma scanner (Siemens AG, Healthcare Sector) using a 64-channel head and neck coil. As part of the imaging protocol, noncontrast magnetization-prepared rapid gradient echo (MP-RAGE) and diffusion tensor imaging (DTI) sequences were obtained for targeting purposes. The ANT was directly targeted using the FGATIR sequence, and bilateral Medtronic 3389 leads were placed. At the last follow-up (2 months), the patient reported an approximate 75% decrease in seizure frequency, as well as a decrease in seizure severity.

OBJECTIVEEpilepsy surgery is effective for lesional epilepsy, but it can be associated with significant morbidity when seizures originate from eloquent cortex that is resected. Here, the objective was to describe chronic subthreshold cortical stimulation and evaluate its early surgical safety profile in adult patients with epilepsy originating from seizure foci in cortex that is not amenable to resection.METHODSAdult patients with focal drug-resistant epilepsy underwent intracranial electroencephalography monitoring for evaluation of resection. Those with seizure foci in eloquent cortex were not candidates for resection and were offered a short therapeutic trial of continuous subthreshold cortical stimulation via intracranial monitoring electrodes. After a successful trial, electrodes were explanted and permanent stimulation hardware was implanted.RESULTSTen patients (6 males) who underwent chronic subthreshold cortical stimulation between 2014 and 2016 were included. Based on radiographic imaging, intracranial pathologies included cortical dysplasia (n = 3), encephalomalacia (n = 3), cortical tubers (n = 1), Rasmussen encephalitis (n = 1), and linear migrational anomaly (n = 1). The duration of intracranial monitoring ranged from 3 to 20 days. All patients experienced an uneventful postoperative course and were discharged home with a median length of stay of 10 days. No postoperative surgical complications developed (median follow-up length 7.7 months). Seizure severity and seizure frequency improved in all patients.CONCLUSIONSThe authors’ institutional experience with this small group shows that chronic subthreshold cortical stimulation can be safely and effectively performed in appropriately selected patients without postoperative complications. Future investigation will provide further insight to recently published results regarding mechanism and efficacy of this novel and promising intervention.