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.

Unexpected median SEPs fluctuations during brain cavernous malformation resection with no post-operative deficit.

Median nerve somatosensory evoked potentials (SEPs) may present changes during cavernous malformation (CM) resection unrelated to new post-operative sensory deficits. We performed intraoperative neurophysiological monitoring of median SEPs (m-SEPs) in three patients who underwent CM resection (surgery) near the sensory-motor cortex. The only preoperative clinical manifestations in all patients were seizures. All patients presented m-SEPs alterations on the side of the lesion during the procedure. Two patients presented permanent changes in the cortical potentials. In the third patient, the cortical and subcortical components suffered temporal fluctuations to return to baselines at the end of the surgery. None of these patients developed new post-operative clinical deficits. During brain cavernous malformation resection, significant fluctuations in the amplitude of different components of m-SEPs may occur. These changes may be due to excitability variations on m-SEP generators and do not translate into new post-operative neurological deficits.

Preventing Poor Outcomes for Neurosurgical Patients.

Ensuring that patients with neurosurgical conditions have the best possible outcome requires early diagnosis, monitoring, and interventions to prevent complications and optimize care. Here, we review several neurosurgical conditions and the measures taken to prevent complications and optimize outcomes. We hope that the practical tips provided herein prove helpful in caring for neurosurgical patients.

A Review on Variability in Treatment Protocols With Posterior Cranial Vault Distraction.

BACKGROUND: Prior studies have confirmed the ability of posterior cranial vault distraction osteogenesis (PVDO) to expand the intracranial volume in patients with craniosynostosis. To date, there is scant literature on the optimal distraction protocol for PVDO. The authors sought to review the literature and define a common protocol for posterior cranial vault distraction. METHODS: The authors performed a systematic review for published PVDO protocols. The data collected from these studies included age at the time of PVDO, number of distraction devices placed, time for latency, rate and rhythm of distraction, distraction length, time for consolidation, and surgical outcomes. RESULTS: A total of 286 patients were identified within 24 studies from 2011 to 2019. The mean age of patients identified was 25.34 months. After application of distractors, latency period ranged between 1 and 7 days, with most patients undergoing 5 to 7 days of latency. Once distraction was begun, the majority of patients (77.4%) underwent 1 mm of distraction daily. Total lengths of distraction ranged between 13 and 35 mm, with the largest cohort of patients undergoing 26 to 30 mm of total distraction. A total of 60 complications were reported for a total of 212 patients, yielding an overall complication rate of 28.3%. CONCLUSIONS: Although there is variability in reported PVDO protocols, the majority are similar to distraction osteogenesis protocols described for long bone sites. Increased patient age correlates with selection of a greater latency period and total distraction length, while frequency of complications is also increased.

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.

Responsive neurostimulation of the frontal lobe for the detection and treatment of seizures in intractable epilepsy due to tuberous sclerosis complex: illustrative case.

BACKGROUND: Responsive neurostimulation (RNS) is often considered to be a palliative therapy for drug-resistant epilepsy (DRE) and is generally not considered to be a treatment for patients with tuberous sclerosis complex (TSC). Here, the authors present the case of a 24-year-old male with TSC who obtained seizure freedom following RNS device implantation. OBSERVATIONS: Prior to RNS device implantation, the patient underwent tuberectomies, subependymal giant cell astrocytoma resection, vagus nerve stimulator placement, and left frontal lobe resection but continued to have frequent seizures. An RNS device was implanted, which initially led to a decrease in seizures, but he continued to have 12 seizures per month. He then underwent lead revision for stimulation via a different electrode. After that lead change, he had no seizures for almost 3 years. In the following 3 years, he had two episodes of breakthrough seizures, both of which occurred with medication weans. Although the patient still requires antiseizure medication, he has had years of seizure freedom with RNS therapy. LESSONS: This study exhibits the potential effectiveness of RNS therapy for patients with TSC and DRE. RNS should be considered for patients with TSC when other therapies have not sufficiently treated their epilepsy. https://thejns.org/doi/10.3171/CASE23411.

Surgical Management of Thoracic Dorsal Arachnoid Webs: A Ten-Year Single-Institution Experience.

OBJECTIVE: Thoracic dorsal arachnoid webs are intradural membranes that may cause obstruction of CSF flow and spinal cord compression. While well-recognized, they are rare and there is a paucity of long-term data on their natural history and prognosis. We reviewed radiographic features, surgical indications, and pathologic specimens of patients diagnosed with focal thoracic dorsal arachnoid webs. METHODS: A radiology database and surgical case logs were queried for thoracic arachnoid webs at a single hospital system for a ten-year period. A retrospective chart review was performed on identified cases. RESULTS: We identified 127 patients with dorsal thoracic arachnoid webs. Arachnoid webs were radiographically classified into three morphologic types: Type 1 (54%) causing spinal cord deformity only, Type 2 (32%) producing cord deformity with myelomalacia, and Type 3 (14%) with cord deformity, myelomalacia, and syringomyelia. These arachnoid webs were commonly centered at the upper thoracic T4 segmental level. Forty-one cases (32%) required surgery, generally for thoracic myelopathy with gait instability (46%) and lower extremity numbness and pain (39%). In patients who underwent surgery, 79% experienced symptomatic improvement and 21% remained stable, after an average of 21 months follow-up evaluation. Surgical pathology revealed fibrous connective tissue (100%) with calcifications (26%) or inflammation (7%). CONCLUSIONS: The majority in a large series of patients with dorsal arachnoid webs did not undergo surgical intervention, but those with myelomalacia and syrinx experienced radiographic and clinical deterioration without surgery. Surgery to treat symptomatic arachnoid webs results in significant clinical improvement with low surgical morbidity.

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.

Use of a mini balloon microcatheter to facilitate penetration of fine vascular networks and curative embolization in vein of Galen malformations.

Background Patients with vein of Galen malformations (VOGMs) can develop fine angiogenic networks with fistulous connections to the precursor of the vein of Galen. In these cases, transarterial embolization (TAE) with liquid embolic agents (LEAs) is challenging due to reflux in the pedicle leading to the network, causing poor penetration. Transvenous approaches carry a risk of hemorrhage from pathologic vasculature. Dual-lumen balloon microcatheters like the Scepter Mini (Microvention, Aliso Viejo, CA) improve distal pedicle access, preventing reflux.Objective Here, we report on the use of the Scepter Mini for TAE of angiogenic VOGM.Methods A single-institution retrospective chart review identified all VOGMs treated with Scepter Mini microcatheters. Clinical data, angioarchitecture, and technical parameters were reviewed.Results 17 Scepter Mini catheters were used in 12 embolization procedures of 7 patients with VOGM at a median age of 2.1 years. Patients presented with hydrocephalus (100%) and gross motor and speech delays (57.1%). Networks developed extra-axially into the subependymal zone fed by posterior choroidal, posterior cerebral, and thalamoperforator arteries. Posterior choroidal branches (n=7/17, 41.2%) were most frequently catheterized to achieve distal access to the network. Embolization with Onyx-18 and significant network penetration occurred in 17/17 uses. Near tip entrapment with LEA cast displacement occurred in 1/17 uses. Another patient experienced postprocedural intraventricular hemorrhage requiring a third ventriculostomy without permanent neurologic deficit.Conclusion The Scepter Mini provided excellent distal access with penetration to the fistula and extra-axial network reduction with few complications. The Scepter Mini provides a means for successful treatment of technically challenging angiogenic VOGM.

The Effect of Multiple Scopus Profiles on the Perceived Academic Productivity of Neurosurgeons in the United States.

OBJECTIVE: Bibliometrics assessing academic productivity plays a significant role in neurosurgeons' career advancement. This study aimed to evaluate the influence of multiple author profiles on Scopus on neurosurgeon author-level metrics (h-index, document number, citation number). METHODS: A list of 1671 academic neurosurgeons was compiled through public searches of hospital and faculty websites for 115 neurosurgical residency training programs. The h-index, document number, and citation number for each neurosurgeon were collected using the Scopus algorithm. For surgeons with multiple profiles, total document number and citation number were calculated by summing results of each profile. Cumulative h-indices were calculated manually. Comparisons were made between surgeons with a single Scopus profile and surgeons with multiple profiles. RESULTS: A total of 124 neurosurgeons with multiple profiles were identified. Gender distribution (P = 0.47), years in practice (P = 0.06), subspecialty (P = 0.32), and academic rank (P = 0.16) between neurosurgeons with a single profile versus multiple profiles were similar. Primary profile h-index median was 16 (interquartile range [IQR]: 8-34), combined profiles median was 20 (IQR: 11-36), and percent loss median was 17.3% (IQR: 3%-33%) (P < 0.001). For document number, primary profile median was 46 (IQR: 16-127), combined profiles median was 55 (IQR: 22-148), and percent loss median was 16.2% (IQR: 7%-36%) (P < 0.001). For citation number, primary profile median was 1030 (IQR: 333-4082), combined profiles median was 1319 (IQR: 546-4439), and percent loss median was 14.1% (IQR: 4%-32%) (P < 0.001). CONCLUSIONS: U.S. academic neurosurgeons with multiple existing profiles on Scopus experience a 17.3% loss in h-index, a 16.2% loss in document number, and a 14.1% loss in citations, heavily undercounting their perceived academic productivity.

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.

A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma.

Purpose: The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy. Patient and Methods: Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells. Results: A total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival. Conclusions: Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease. Significance: Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

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.

Hemorrhage Rates After Implantation and Explantation of Stereotactic Electroencephalography: Reevaluating Patients' Risk.

OBJECTIVE: Stereoelectroencephalography (sEEG), despite its established usefulness, has not been thoroughly evaluated for its adverse events profile. In this study, hemorrhage rates were evaluated both per patient and per lead placed not only in the immediate postoperative period, but also over the course of admission and after explantation when available. METHODS: This is a single-center retrospective study of pediatric and adult patients undergoing sEEG lead placement at a large urban hospital. All available postoperative imaging was reviewed for the presence of hemorrhage, including any imaging occurring throughout admission as well as within 1 month of lead explantation. Age and number of leads placed per procedure were compared using an unpaired t test assuming unequal variance. RESULTS: A total of 1855 leads were placed in 147 cases. The mean age was 30.4 ±15.0 and the male/female ratio was 47:53. 9 leads (0.49%) in 9 cases (6.12%) were involved with postimplantation hemorrhage occurring on postoperative day 0.44 on average. Postexplantation imaging was available for 45 cases. Seven leads (1.40%) in 7 cases (15.56%) were involved with postexplantation hemorrhage occurring on average on postoperative day 1.42. There was a significant difference in mean age between patients with postexplantation hemorrhage versus control (45.0 vs. 32.2; P = 0.0277). No cases of hemorrhage required surgical intervention and no patients had permanent neurologic deficit. CONCLUSIONS: Hemorrhage after sEEG lead implantation and explantation may be more common than previously reported. Consistent postexplantation imaging may be of clinical benefit in detecting hemorrhage that precludes patients from immediate discharge, particularly in older patients.