Corticothalamic Responsive Neurostimulation for Focal Epilepsy: A Single-Center Experience.

PURPOSE: Owing to its extensive, reciprocal connectivity with the cortex and other subcortical structures, the thalamus is considered an important target for neuromodulation in drug-resistant focal epilepsy. Using corticothalamic stimulation, it is possible to modulate both the thalamus and the cortical seizure onset zone. Limited published clinical experience describes corticothalamic stimulation with depth leads targeting one of the anterior (ANT), centromedian (centromedian nucleus), or pulvinar (PUL) thalamic nuclei. However, it is not clear which of these nuclei is the "best" therapeutic target. METHODS: This study comprised a single-center experience with corticothalamic responsive neurostimulation using the RNS System to target these three thalamic nuclei. Presented here are the methods for target selection and device programming as well as clinical outcomes and a comparison of ictal and nonictal electrophysiological features. RESULTS: In this small retrospective study (N = 19), responsive corticothalamic neurostimulation was an effective therapy for 79% of patients (≥50% reduction in disabling seizure frequency), regardless of whether the thalamic lead was implanted in the ANT (N = 2), PUL (N = 6), or centromedian nucleus (N = 11). Twenty-six percent of patients reported a reduction in disabling seizure frequency ≥90%. Both high frequency (≥100 Hz) and low (≤20 Hz) frequency were used to stimulate the thalamus depending on the patient's response and ability to tolerate higher charge densities. In all patients, a longer burst duration (2000-5000 ms) was ultimately implemented on the thalamic leads. Across patients, peaks in the intracranial EEG were observed at theta, beta, gamma, and sleep spindle frequencies. Changes in frequency content and distribution were observed over time in all three nuclei. CONCLUSIONS: These results indicate that both high frequency and low frequency corticothalamic responsive neurostimulation can potentially be an effective adjunctive therapy in drug-resistant focal epilepsy. These data can also contribute to a broader understanding of thalamic electrophysiology in the context of focal epilepsy.

Laser Interstitial Thermal Therapy for the Treatment of a Pineal Region Glioma Through an Infratentorial Approach: A Case Report.

Laser interstitial thermal therapy (LITT) is a minimally invasive surgical option for the treatment of brain tumors introduced in 1983. The innovative technique was welcomed for its ability to access deep-seated supratentorial and posterior cranial fossa lesions. Surgical approaches to pineal region tumors are challenging and require a high degree of precision since the critical vasculature, such as the vein of Galen and precentral vein, in the area pose significant anatomical challenges to operating surgeons. To minimize the risk of damaging this key venous anatomy, an infratentorial approach may be more advantageous. We present a case where LITT was utilized through an infratentorial approach to a pineal region tumor. A 62-year-old male with no significant past medical history presented to his primary care physician complaining of ataxia and headaches for the past four weeks. An MRI was concerning for multicentric glioma within the cerebellar hemispheres, brainstem extending to the middle cerebellar peduncle, upper cervical spinal cord, and pineal region. An enhancing lesion of the midbrain tectum was concerning for a high-grade tumor. We decided to proceed with stereotactic biopsy and magnetic resonance-guided LITT via an infratentorial approach. Supratentorial trajectory planning did not allow for a safe corridor due to the venous anatomy; thus, it was decided to proceed with an infratentorial approach. The patient was positioned prone, had his bone fiducial CT fused with MRI, and the tumor was targeted using robotic guidance (ROSA, Zimmer Biomet, Warsaw, Indiana). Postoperatively, he suffered from transient diplopia due to cranial nerve VI palsy. Additionally, the postoperative MRI revealed a decrease in the size of the enhancing lesion and the hyperintense T2 signal within the brainstem. Open surgical approaches to tumors within the pineal region often pose an anatomic and neurovascular challenge. We describe the safe utilization of a novel, previously unreported infratentorial approach utilizing LITT with promising treatment, morbidity, and efficacy outcomes. A larger series will be necessary to ensure the safety and efficacy of this approach.

Magnetoencephalography-identified preictal spiking correlates to preictal spiking on stereotactic EEG.

Magnetoencephalography (MEG) is a noninvasive diagnostic modality that directly measures neuronal signaling by recording the magnetic field created from dendritic, intracellular, electrical currents of the neuron at the surface of the head. In clinical practice, MEG is used in the epilepsy presurgical evaluation and most commonly is an "interictal" study that can provide source localization of spike-wave discharges. However, seizures may be recorded during MEG ("ictal MEG") and mapping of these discharges may provide more accurate localization of the seizure onset zone. In addition, spike-negative EEG with unique MEG spike-waves may be present in up to 1/3 of MEG studies and unique MEG seizures (EEG-negative seizures) have been reported. This case report describes a patient with unique MEG seizures that exhibited MEG pre-ictal spiking in a tight cluster consistent with the independent interictal epileptiform activity. Stereotactic EEG demonstrated pre-ictal spiking concordant with the MEG pre-ictal spiking.

Brain-responsive corticothalamic stimulation in the pulvinar nucleus for the treatment of regional neocortical epilepsy: A case series.

Drug-resistant focal epilepsy with regional neocortical seizure onsets originating from the posterior quadrant can be particularly difficult to treat with resective surgery due to the overlap with eloquent cortex. Published reports indicate that corticothalamic treatment targeting the anterior or centromedian nucleus of the thalamus with direct brain-responsive stimulation may be an effective approach to treat regional neocortical epilepsy. The pulvinar has remained largely unstudied as a neurostimulation target to treat refractory epilepsy. Because the pulvinar has connections with the posterior quadrant, neurostimulation may be effective if applied to seizures originating in this area. We performed a retrospective chart review of patients with regional neocortical seizure onsets in the posterior quadrant treated with the RNS System. Demographics, epilepsy history, clinical seizure frequencies, and neuropsychological testing results were obtained from the chart. Electrocorticogram (ECoG) records stored by the RNS System were reviewed to evaluate electrographic seizure onset patterns. Our patients were followed for 10, 12.5, and 15 months. All patients were responders (≥50% seizure reduction), and two of the three patients experienced a ≥90% reduction in seizures at the last follow-up. Pre- and postsurgical neuropsychological evaluations were compared for two of the patients, and there was no evidence of cognitive decline found in either patient. Interestingly, mild cognitive improvements were reported. The third patient had only postimplant neuropsychological testing data available. Findings for this patient suggested executive dysfunction that was present prior to the RNS System which did not worsen with surgery. A visual inspection of ECoGs revealed near-simultaneous seizure onsets in neocortical and pulvinar leads in two patients. Seizure onsets in the third patient were more variable. This is the first published report of brain-responsive neurostimulation targeting the pulvinar to treat refractory regional onset epilepsy of posterior quadrant origin.

Brain-Responsive Neurostimulation for the treatment of adults with epilepsy in tuberous sclerosis complex: A case series.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery. METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc). RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year. SIGNIFICANCE: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation.

Brain-responsive corticothalamic stimulation in the centromedian nucleus for the treatment of regional neocortical epilepsy.

OBJECTIVE: The aim of the study was to determine if corticothalamic responsive stimulation targeting the centromedian nucleus of the thalamus (CMT) is a potential treatment for neocortical epilepsies with regional onsets. METHODS: We assessed efficacy and safety of CMT and neocortical responsive stimulation, detection, and stimulation programming, methods for implantation, and location and patterns of electrographic seizure onset and spread in 7 patients with medically intractable focal seizures with a regional neocortical onset. RESULTS: The median follow-up duration was 17 months (average: 17 months, range: 8-28 months). The median % reduction in disabling seizures (excludes auras) in the 7 patients was 88% (mean: 80%, range: 55-100%). The median % reduction in all seizure types (disabling + auras) was 73% (mean: 67%, range: 15-94%). There were no adverse events related to implantation of the responsive neurostimulator and leads or related to the delivery of responsive stimulation. Stimulation-related contralateral paresthesias were addressed by adjusting stimulation parameters in the clinic during stimulation testing. Electrographic seizures were detected in the CMT and neocortex in all seven patients. Four patients had simultaneous or near simultaneous seizure onsets in the neocortex and CMT and three had onsets in the neocortex with spread to the CMT. CONCLUSION: In this small series of patients with medically intractable focal seizures and regional neocortical onset, responsive neurostimulation to the neocortex and CMT improved seizure control and was well tolerated. SIGNIFICANCE: Responsive corticothalamic neurostimulation of the CMT and neocortex is a potential treatment for patients with regional neocortical epilepsies.

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.

OBJECTIVE: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System. METHODS: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. RESULTS: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. SIGNIFICANCE: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.

Human Left Anterior Cingulate Stimulation Elicits a Reproducible Micturition Response.

Electrical stimulation of a brain region producing a micturition response has never previously been described in the human. This report identifies the anterior cingulate gyrus as a brain region important in the micturition response. Stereo electroencephalography was performed in a 38-year-old female with medically refractory epilepsy. The response of the left anterior cingulate from low- to high-frequency brain stimulation was tested. Stimulation within the left anterior cingulate resulted in a reproducible micturition response. The response was dependent on the frequency of stimulation (present with stimulation at 50-150 Hz and not present at 5 or 350 Hz). These results provide evidence for the presence of a region within the human left anterior cingulate gyrus involved in producing the micturition response. This may have implications in the understanding of the physiological mechanisms of willful micturition and in the treatment of bladder disorders.

External Ventricular Drain Placement Accuracy and Safety When Done by Midlevel Practitioners.

BACKGROUND: External ventricular drains (EVDs) measure intracranial pressure, divert cerebrospinal fluid, and allow for orthotropic administration of pharmacologic agents. Currently, neurosurgeons and neurosurgery residents are the primary practitioners placing EVDs. Due to the urgency of neurosurgical pathologies and the lack of qualified residents at most hospitals, midlevel practitioner (MLP) placement of EVDs would be advantageous. OBJECTIVE: To assess the accuracy and complication rates of MLP and neurosurgeon EVD placement. METHODS: This was a retrospective cohort of all patients with an EVD placed between January 2012 and September 2016 at a level 1 trauma center. We compared safety and accuracy of EVD placement between neurosurgeons and MLPs. RESULTS: MLP first attempted EVD placement in 238 patients and senior neurosurgeon first attempted EVD placement in 70 subjects. There was no significant difference between accuracy of placement within the ventricle (87.4% vs 90.0%, P = .5557), hemorrhage rate (5.9% vs 4.3%, P = .77), or infection rate (0.8% vs 1.4%, P = .5399) for placement attempted by an MLP compared with a neurosurgeon, respectively. CONCLUSION: MLPs perform EVD placement safely with no significant difference in accuracy of placement or complication rates compared with placement by senior neurosurgeons. This may allow for earlier management of elevated intracranial pressure and access to care where previously unavailable; leading to improved patient outcomes.

A Comparison of Vagal Nerve Stimulation and Responsive Neurostimulation for the Treatment of Medically Refractory Complex Partial Epilepsy.

BACKGROUND: Neuromodulatory applications such as vagus nerve stimulation (VNS) and responsive neurostimulation (RNS) are safe and effective strategies for medically intractable epilepsy secondary to complex partial seizures, but researchers have yet to compare their efficacies. OBJECTIVE: The goal of this study is to compare VNS and RNS efficacy at reducing seizure frequency and complication rates in subjects with medically intractable epilepsy secondary to complex partial seizures. METHODS: This is a retrospective chart review of 30 patients with medically intractable complex partial epilepsy, who underwent either VNS or RNS placement at a single institution between June 2012 and January 2016. There was a mean follow-up of 19 months. Seizure frequency reduction and complications were identified. RESULTS: The median seizure frequency reduction was similar for VNS (66%) and RNS (58%). There was no major morbidity or mortality, and the frequency of minor complications was similar between VNS (15%) and RNS (18%). CONCLUSION: We found that VNS and RNS reduced the median seizure frequency similarly with no difference in morbidity or mortality. Further prospective studies are warranted as VNS and RNS therapy improves over time.

Influence of age and location of ictal onset on postoperative outcome in patients with localization-related epilepsy.

INTRODUCTION: Localization-related epilepsy is a significant concern for the middle-aged and older population given the lesser cognitive reserve and the greater likelihood of adverse systemic antiepileptic drug effects. Epilepsy surgery for this age group has the potential for greater postoperative morbidity and mortality, a protracted rehabilitation with its associated economic burden, progressive cognitive and memory decline and a lesser chance of becoming seizure-free after the procedure. METHODS: A retrospective institutional archival review of 120 patients with medically refractory partial epilepsy of both temporal and extratemporal epilepsy was performed. Comparative assessments for seizure cessation and neuropsychological effects were made for those younger and older than 50 years and those with epilepsy durations of greater and less than 20 years. RESULTS: A comparison of surgical outcomes by age group identified that Engel Class I outcomes were attained in 26 of 35 (74%) patients in the older group compared with 49 of 85 (58%) patients in the younger group (p = 0.087). Of the 11 patients aged 60 years or older, 91% attained an Engel Class I outcome, significantly higher than those under 60 years (60%; p = 0.041). Stratification by age of the entire group, otherwise, demonstrated no significant differences by Engel class outcome. Considering both transient and permanent disabilities, the overall complication rate was 14.2% and was similar in patients less than 50 years of age (15.3%) and those aged 50 years or greater (11.4%; p = 0.58). Verbal memory decline was more notable in the older population and for those with epilepsy duration of greater than 20 years. CONCLUSION: This study demonstrates that epilepsy surgery in the older population has similar seizure-free outcomes and complications when compared with younger patients for both mesial temporal and extratemporal origins. Caution regarding postoperative memory decline in the older population must be stressed.

Ictal barking as a manifestation of temporal lobe epilepsy.

Ictal nonspeech vocalizations have been described as manifestations of either frontal or temporal epileptogenicity originating mainly from the dominant hemisphere. Ictal barking, particularly, has been considered a manifestation of mesial frontal epilepsy. A 42-year-old right-handed male with posttraumatic drug-resistant complex partial epilepsy manifested ictal barking near electrographic onset. Extraoperative electrocorticography with subdural electrode coverage of the right frontoparietal and temporal and left frontal surfaces provided surveillance of ictal origin and propagation. Ictal origin was identified in the right mesial temporal lobe with barking vocalization manifesting within 3s of electrographic onset. No subsequent spread of activity was noted beyond the temporal lobe. Resection of the mesial temporal structure resulted in seizure freedom. Pathology identified hippocampal sclerosis. This case supports the notion that an intrinsic, intralobar epileptogenic neural network in either hemisphere can act as a conduit into the limbic and memory circuits without a laterality bias to manifest as barking.

Longitudinal metabolic and cognitive changes in mild cognitive impairment patients.

Advancements in clinical therapies have identified the need for biomarkers of early Alzheimer disease that distinguish the earliest stages of pathology and target those patients who are likely to gain the most benefit. The aim of this study was to characterize the longitudinal metabolic changes measured by 1H magnetic resonance spectroscopy in correlation to neuropsychologic indices of episodic memory, attention and mental processing speed, language facility, and executive function in subjects with mild cognitive impairment (MCI). Quantitative 1H magnetic resonance spectroscopy of the posterior cingulate gyrus was performed and repeated at 11.56+/-4.3 months. N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), myo-inositol (mI), and glutamate/glutamine (Glx) metabolite levels were measured, corrected for cerebrospinal fluid dilution, and ratios calculated in MCI and cognitively normal subjects. In the first study, MCI subjects showed lower NAA levels, NAA/Cho, and NAA/mI ratios and increased Cho/Cr and mI/Cr compared with controls. In the follow-up study, 36% of the MCI subjects [atypical MCI (atMCI)] showed interval increases in NAA, Cr, and Glx levels compared with 64% of MCI subjects (typical MCI) who showed an interval decrease in NAA, Cr, and Glx. Both MCI subgroups had higher Clinical Dementia Rating scores and lower scores on episodic memory, phonemic, and semantic word fluency tasks, compared with controls. The annualized rate of change in metabolic and cognitive status did not differ between normal aging and MCI subjects. atMCI subjects showed significant negative correlations between metabolite levels and executive function task scores, with NAA/mI showing a significant positive correlation with phonemic and semantic word fluency. There were no significant correlations between metabolite levels and cognitive performance in tMCI subjects; however, NAA/mI and mI/Cr were negatively correlated with executive function tasks. These results indicate 2 distinct evolving metabolite profiles that correlate with changes in executive function and can be used to differentiate MCI from normal aging.