Tracing topics and trends in drug-resistant epilepsy research using a natural language processing-based topic modeling approach.

Epilepsy is a common neurological disorder affecting over 70 million people worldwide. Although many patients achieve seizure control with anti-epileptic drugs (AEDs), 30%-40% develop drug-resistant epilepsy (DRE), where seizures persist despite adequate trials of AEDs. DRE is associated with reduced quality of life, increased mortality and morbidity, and greater socioeconomic challenges. The continued intractability of DRE has fueled exponential growth in research that aims to understand and treat this serious condition. However, synthesizing this vast and continuously expanding DRE literature to derive insights poses considerable difficulties for investigators and clinicians. Conventional review methods are often prolonged, hampering the timely application of findings. More-efficient approaches to analyze the voluminous research are needed. In this study, we utilize a natural language processing (NLP)-based topic modeling approach to examine the DRE publication landscape, uncovering key topics and trends. Documents were retrieved from Scopus, preprocessed, and modeled using BERTopic. This technique employs transformer models like BERT (Bidirectional Encoder Representations from Transformers) for contextual understanding, thereby enabling accurate topic categorization. Analysis revealed 18 distinct topics spanning various DRE research areas. The 10 most common topics, including "AEDs," "Neuromodulation Therapy," and "Genomics," were examined further. "Cannabidiol," "Functional Brain Mapping," and "Autoimmune Encephalitis" emerged as the hottest topics of the current decade, and were examined further. This NLP methodology provided valuable insights into the evolving DRE research landscape, revealing shifting priorities and declining interests. Moreover, we demonstrate an efficient approach to synthesizing and visualizing patterns within extensive literature that could be applied to other research fields.

Complications of Implanted Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

INTRODUCTION: Vagus Nerve Stimulation (VNS) has emerged as a promising tool in ischemic stroke rehabilitation. However, there has been no systematic review summarizing its adverse effects, critical information for patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis reports the adverse effects of VNS. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify common complications after VNS therapy. The search was executed in: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. RESULTS: After title-and-abstract screening of 4933 studies, 21 were selected for final inclusion. Across these studies, 1474 patients received VNS implantation. VNS was used as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). CONCLUSIONS: Complications from VNS are mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. In prior studies, VNS has served as treatment option in several instances of treatment-resistant conditions, such as epilepsy and psychiatric conditions, and its use in stroke recovery and rehabilitation should continue to be explored.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Neurosurgical treatment of spasticity: a potential return to the cerebellum.

OBJECTIVE: Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders. METHODS: In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity. RESULTS: Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity. CONCLUSIONS: Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

Vagal Nerve Stimulation: A Bibliometric Analysis of Current Research Trends.

BACKGROUND: Vagal nerve stimulation (VNS) has become established as an effective tool for the management of various neurologic disorders. Consequently, a growing number of VNS studies have been published over the past four decades. This study presents a bibliometric analysis investigating the current trends in VNS literature. MATERIALS AND METHODS: Using the Web of Science collection data base, a search was performed to identify literature that discussed applications of VNS from 2000 to 2021. Analysis and visualization of the included literature were completed with VOSviewer. RESULTS: A total of 2895 publications were identified. The number of articles published in this area has increased over the past two decades, with the most citations (7098) occurring in 2021 and the most publications (270) in 2020. The h-index, i-10, and i-100 were 97, 994, and 91, respectively, with 17.0 citations per publication on average. The highest-producing country and institution of VNS literature were the United States and the University of Texas, respectively. The most productive journal was Epilepsia. Epilepsy was the predominant focus of VNS research, with the keyword "epilepsy" having the greatest total link strength (749) in the keyword analysis. The keyword analysis also revealed two major avenues of VNS research: 1) the mechanisms by which VNS modulates neural circuitry, and 2) therapeutic applications of VNS in a variety of diseases beyond neurology. It also showed a significant prevalence of noninvasive VNS research. Although epilepsy research appears more linked to implanted VNS, headache and depression specialists were more closely associated with noninvasive VNS. CONCLUSION: VNS may serve as a promising intervention for rehabilitation beyond neurologic applications, with an expanding base of literature over the past two decades. Although epilepsy researchers have produced most current literature, other fields have begun to explore VNS as a potential treatment, likely owing to the rise of noninvasive forms of VNS.

Readmission after neurosurgical intervention in epilepsy: A nationwide cohort analysis.

OBJECTIVE: Hospital readmissions result in increased health care costs and are associated with worse outcomes after neurosurgical intervention. Understanding factors associated with readmissions will inform future studies aimed at improving quality of care in those with epilepsy. METHODS: Patients of all ages with epilepsy who underwent a neurosurgical intervention were identified in the 2014 Nationwide Readmissions Database, a nationally representative dataset containing data from roughly 17 million US hospital discharges. Diagnosis of epilepsy was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based case definitions. Neurosurgical interventions for epilepsy: resective/disconnective surgery, responsive neurostimulation/deep brain stimulation, vagus nerve stimulation, radiosurgery, and intracranial electroencephalography were identified using ICD-9-CM procedure codes. Primary outcome was all-cause 30-day readmission following discharge from the index hospitalization. RESULTS: There were a total of 2284 index surgical admissions. Overall, 10.83% (n = 251) of patients following an index epilepsy surgery admission were readmitted within 30 days. Factors independently associated with 30-day readmission for all epilepsy surgery admissions were: Medicare insurance (P < .01), discharge disposition that was not home (P < .01), higher Elixhauser comorbidity indexes (P < .01), longer length of stay (P < .01), and adverse events of surgical and medical care during index stay (P = .04). In the multivariate model, Medicare insurance (hazard ratio [HR] 1.81 [1.29-2.53], P < .01) and length of stay (HR 1.02 [1.01-1.04], P < .01) remained significant independent predictors for 30-day readmission. The most common primary reason for readmissions was epilepsy/convulsions accounting for 22.85%. SIGNIFICANCE: Our results suggest that careful management of postoperative seizures and discharge planning after epilepsy surgery may be important to optimize outcomes and reduce the risk of readmission, particularly for patients on Medicare.

Theta band network supporting human episodic memory is not activated in the seizure onset zone.

Episodic memory, everyday memory for events, is frequently impaired in patients with epilepsy. We tested patients undergoing intracranial electroencephalography (intracranial EEG) monitoring for the treatment of medically-refractory epilepsy on a well-characterized paradigm that requires episodic memory. We report that an anatomically diffuse network characterized by theta-band (4-7 Hz) coherence is activated at the time of target selection in a task that requires episodic memory. This distinct network of oscillatory activity is absent when episodic memory is not required. Further, the theta band synchronous network was absent in electrodes within the patient's seizure onset zone (SOZ). Our data provide novel empirical evidence for a set of brain areas that supports episodic memory in humans, and it provides a pathophysiologic mechanism for the memory deficits observed in patients with epilepsy.

Language mapping using electrocorticography versus stereoelectroencephalography: A case series.

Direct electrical stimulation (DES) is sometimes used in epilepsy surgery to identify areas that may result in language deficits if resected. Extraoperative language mapping is usually performed using electrocorticography (ECOG) - grids and strip electrodes; however, given the better safety profile of stereoelectroencephalogaphy (SEEG), it would be desirable to determine if mapping using SEEG is also effective. We report a case series of fifteen patients that underwent language mapping with either ECOG (5), SEEG (9), or both (1). Six patients in the SEEG group underwent resection or ablation with only mapping via SEEG. No patients in the SEEG group that underwent resective or ablative surgery experienced persistent language deficits. These results suggest that language mapping with SEEG may be considered as a clinically useful alternative to language mapping with ECOG.

Epilepsy with temporal encephalocele: Characteristics of electrocorticography and surgical outcome.

Temporal lobe encephaloceles (TEs) are increasingly identified in patients with epilepsy due to advances in neuroimaging. Select patients become seizure-free with lesionectomy. In practice, however, many of these patients will undergo standard anterior temporal lobectomy. Herein we report on the first series of patients with refractory temporal lobe epilepsy (TLE) with encephalocele to undergo chronic or intraoperative electrocorticography (ECoG) in order to characterize the putative epileptogenic nature of these lesions and help guide surgical planning. This retrospective study includes nine adult patients with magnetic resonance imaging/computed tomography (MRI/CT)-defined temporal encephalocele treated between 2007 and 2014 at University of California San Francisco (UCSF). Clinical features, ECoG, imaging, and surgical outcomes are reviewed. Six patients underwent resective epilepsy surgery. Each case demonstrated abnormal epileptiform discharges around the cortical area of the encephalocele. Two underwent tailored lesionectomy and four underwent lesionectomy plus anterior medial temporal resection. Postoperatively, five patients, including both with lesionectomy only, had Engel class Ia surgical outcome, and one had a class IIb surgical outcome. The role of TE in the pathogenesis of epilepsy is uncertain. ECoG can confirm the presence of interictal epileptiform discharges and seizures arising from these lesions. Patients overall had a very good surgical prognosis, even with selective surgical approaches.

Predicting 30-Day Non-Seizure Outcomes Following Temporal Lobectomy with Personalized Machine Learning Models.

BACKGROUND: Temporal lobe epilepsy is the most common reason behind drug-resistant seizures and temporal lobectomy (TL) is performed after all other efforts have been taken for a Temporal lobe epilepsy. Our study aims to develop multiple machine learning (ML) models capable of predicting postoperative outcomes following TL surgery. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program database identified patients who underwent TL surgery. We focused on 3 outcomes: prolonged length of stay (LOS), nonhome discharges, and 30-day readmissions. Six ML algorithms, TabPFN, XGBoost, LightGBM, Support Vector Machine, Random Forest, and Logistic Regression, coupled with the Optuna optimization library for hyperparameter tuning, were tested. Models with the highest area under the receiver operating characteristic (AUROC) values were included in the web application. SHapley Additive exPlanations was used to evaluate importance of predictor variables. RESULTS: Our analysis included 423 patients. Of these patients, 111 (26.2%) experienced prolonged LOS, 33 (7.8%) had nonhome discharges, and 29 (6.9%) encountered 30-day readmissions. The top-performing models for each outcome were those built with the Random Forest algorithm. The Random Forest models yielded AUROCs of 0.868, 0.804, and 0.742 in predicting prolonged LOS, nonhome discharges, and 30-day readmissions, respectively. CONCLUSIONS: Our study uses ML to forecast adverse postoperative outcomes following TL. We developed accessible predictive models that enhance prognosis prediction for TL surgery. Making ML models available for this purpose represents a significant advancement in shifting toward a more patient-centric, data-driven paradigm.

What is the cognitive footprint of insular glioma?

Cognitive impairment has a profound deleterious impact on long-term outcomes of glioma surgery. The human insula, a deep cortical structure covered by the operculum, plays a role in a wide range of cognitive functions including interceptive thoughts and salience processing. Both low-grade (LGG) and high-grade gliomas (HGG) involve the insula, representing up to 25% of LGG and 10% of HGG. Surgical series from the past 30 years support the role of primary cytoreductive surgery for insular glioma patients; however, reported cognitive outcomes are often limited to speech and language function. The breath of recent neuroscience literature demonstrates that the insula plays a broader role in cognition including interoceptive thoughts and salience processing. This article summarizes the vast functional role of the healthy human insula highlighting how this knowledge can be leveraged to improve the care of patients with insular gliomas.

Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case.

BACKGROUND: Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke. OBSERVATIONS: Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE). LESSONS: VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

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.

A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation.

Introduction: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. Methods: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. Results: Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. Discussion: Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

Pallidal deep brain stimulation for DYT6 dystonia.

BACKGROUND: Mutations of the THAP1 gene were recently shown to underlie DYT6 torsion dystonia. Little is known about the response of this dystonia subtype to deep brain stimulation (DBS) at the internal globus pallidus (GPi). METHODS: Retrospective analysis of the medical records of three DYT6 patients who underwent pallidal DBS by one surgical team. The Burke-Fahn-Marsden Dystonia Rating scale served as the primary outcome measure. Comparison is made to 23 patients with DYT1 dystonia also treated with GPi-DBS by the same team. RESULTS: In contrast with the DYT1 patients who exhibited a robust and sustained clinical response to DBS, the DYT6 patients exhibited more modest gains during the first 2 years of therapy, and some symptom regression between years 2 and 3 despite adjustments to the stimulation parameters and repositioning of one stimulating lead. Microelectrode recordings made during the DBS procedures demonstrated no differences in the firing patterns of GPi neurons from DYT1 and DYT6 patients. DISCUSSION: Discovery of the genetic mutations responsible for the DYT6 phenotype allows for screening and analysis of a new homogeneous group of dystonia patients. DYT6 patients appear to respond less robustly to GPi-DBS than their DYT1 counterparts, most likely reflecting differences in the underlying pathophysiology of these distinct genetic disorders. CONCLUSIONS: While early results of pallidal DBS for DYT6 dystonia are encouraging, further research and additional subjects are needed both to optimise stimulation parameters for this population and to elucidate more accurately their response to surgical treatment.

Ictal head roll: a seizure semiology from the anterior prefrontal lobe.

Longstanding epilepsy can lead to modulation of cortical networks over time and unexpected seizure onset zones. Frontal lobe seizures, in particular, can have diverse semiologies and evolution patterns. We present a male patient with drug-resistant epilepsy secondary to severe traumatic brain injury who underwent bilateral stereo electroencephalography (SEEG) for surgical planning. SEEG localized an ictal circular head roll to the right anterior prefrontal region. This was followed by spread to the left orbitofrontal region and later the left amygdala and hippocampus, at which point a different semiology with behavioral arrest, lip smacking and oral automatisms began. This case, in which an ictal circular head roll was localized to the anterior prefrontal region, demonstrates the complexity of broad seizure networks that develop over time, leading to remote seizure spread.

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's 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 <25% 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.

The Sensitivity of Scalp EEG at Detecting Seizures-A Simultaneous Scalp and Stereo EEG Study.

PURPOSE: Compare the detection rate of seizures on scalp EEG with simultaneous intracranial stereo EEG (SEEG) recordings. METHODS: Twenty-seven drug-resistant epilepsy patients undergoing SEEG with simultaneous scalp EEG as part of their surgical work-up were included. A total of 172 seizures were captured. RESULTS: Of the 172 seizures detected on SEEG, 100 demonstrated scalp ictal patterns. Focal aware and subclinical seizures were less likely to be seen on scalp, with 33% of each observed when compared with focal impaired aware (97%) and focal to bilateral tonic-clonic seizures (100%) (P < 0.001). Of the 72 seizures without ictal scalp correlate, 32 demonstrated an abnormality during the SEEG seizure that was identical to an interictal abnormality. Seizures from patients with MRI lesions were statistically less likely to be seen on scalp than seizures from nonlesional patients (P = 0.0162). Stereo EEG seizures not seen on scalp were shorter in duration (49 seconds) compared with SEEG seizures seen on scalp (108.6 seconds) (P < 0.001). CONCLUSIONS: Scalp EEG is not a sensitive tool for the detection of focal aware and subclinical seizures but is highly sensitive for the detection of focal impaired aware and focal to bilateral tonic-clonic seizures. Longer duration of seizure and seizures from patients without MRI lesions were more likely to be apparent on scalp. Abnormalities seen interictally may at times represent an underlying seizure. The cognitive, affective, and behavioral long-term effects of ongoing difficult-to-detect seizures are not known.

High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy.

The pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN-), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN-) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy.