Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population. The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses. Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

The immune system and metabolic products in epilepsy and glioma-associated epilepsy: emerging therapeutic directions.

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.

Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management.

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug-drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials.

Patterns of Antiseizure Medication Use Following Meningioma Resection: A Single-Institution Experience.

OBJECTIVE: To investigate antiseizure medication (ASM) practice behavior for patients who present with seizures before meningioma resection and to review postoperative ASM management. METHODS: A retrospective study was performed of 112 consecutive patients with meningiomas who underwent resection at a single institution between October 2016 and January 2020. Data were collected through detailed chart review. RESULTS: Of 112 patients, 35 (31%) had a preoperative seizure, and 43 (38%) were prescribed a preoperative ASM. At discharge, 96 patients (86%) were prescribed an ASM, most often 1000 mg daily of levetiracetam (64%, 61/96) and less often higher doses of levetiracetam or other ASMs. By the 6-month postoperative visit, 55 patients (49%) were taking at least 1 ASM, most commonly levetiracetam monotherapy (65%) at 500 mg twice daily (47%). This number further decreased to 45 (40%) patients by 1-year follow-up and 36 (32%) patients by last-known follow-up. By last follow-up (median 27.3 months; range 5.4-57.4 months), 24 patients (21%) had experienced a postoperative seizure, and 36 patients (32%) were never able to discontinue ASMs. Of patients remaining on levetiracetam monotherapy, only 36% remained on levetiracetam 500 mg twice daily. CONCLUSIONS: Approximately two thirds (68%) of patients who underwent surgical resection of meningioma were eventually able to completely discontinue their postoperative ASM regimen. However, nearly one third (32%) of patients required long-term ASM management. Levetiracetam monotherapy was the most common ASM prescribed during the postoperative period, and the proportion of patients requiring either higher doses of levetiracetam or alternative ASMs increased over time.

Long-term antiseizure medication use in patients after meningioma resection: identifying predictors for successful weaning and failures.

OBJECTIVE: To define risk factors for meningioma-related seizures and predictors of successful weaning of antiseizure medications following meningioma resection. METHODS: This is a retrospective study of 95 patients who underwent meningioma resection at a single institution. Primary outcome analyzed was ability to achieve seizure freedom without the use of anti-seizure medication at 6-months, 1-year, and last known follow up. Secondary outcome was postoperative seizure freedom. RESULTS: Preoperative seizures (OR: 11.63, 95% CI [3.64, 37.17], p < 0.0001), non-skull base tumor location (OR: 3.01, 95% CI [1.29, 7.02], p = 0.0128), and modified STAMPE score of 3-5 (OR: 5.42, 95% CI [2.18, 13.52], p = 0.0003) were associated with greater likelihood of remaining on antiseizure medication at 6-month follow up. Preoperative seizures (OR: 4.93, 95% CI: [2.00, 12.16 ], p = 0.0008), intratumoral calcifications (OR: 4.19, 95% CI: [1.61, 14.46], p = 0.0055), modified STAMPE score of 3-5 (OR: 5.42, CI [2.18, 13.52], p = 0.0003), and Ki67 greater than 7% (OR: 5.68, CI [1.61, 20.10], p = 0.0060) were significant risk factors for inability to discontinue ASMs by last follow up. Preoperative seizures (OR: 4.33, 95% CI [1.59, 11.85], p = 0.0050) and modified STAMPE score of 3-5 (OR: 6.09, 95% CI [2.16, 17.20], p = 0.0007) were significant risk factors for postoperative seizures. CONCLUSIONS: Preoperative seizures, modified STAMPE2 score of 3-5, non-skull base tumor location, intratumoral calcifications, and Ki67 > 7% were significant risk factors for inability to achieve seizure freedom without ASMs. In addition, the modified STAMPE2 score successfully predicted increased seizure risk following meningioma resection for patients with a score of 3 or higher.

Postoperative risk of IDH-mutant glioma-associated seizures and their potential management with IDH-mutant inhibitors.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

High-Frequency Oscillations in Tumor-Related Epilepsy.

INTRODUCTION: To define the patient characteristics, tumor characteristics, and clinical course of patients with primary brain tumors with high-frequency oscillations (HFOs) recorded on electrocorticography. Furthermore, we evaluated whether the presence of HFOs portends a greater risk of postoperative tumor-related epilepsy and whether the resection of HFO-generating tissue reduces likelihood of postoperative tumor-related epilepsy. METHODS: This was a retrospective study of 35 patients undergoing awake craniotomy for tumor resection, all of whom underwent intraoperative electrocorticography. Electrocorticography data were reviewed to assess the presence of HFOs and determine their contact locations. The data were analyzed to determine whether HFO-generating tissue was included in the resection and relationship to postoperative seizure outcome. RESULTS: Seventeen patients (48.5%) were found to have HFOs. Very few patients (4 of 35, 11.4%) had sharp waves. Patients with and without HFOs did not significantly differ in demographics, presentation, tumor characteristics, or tumor molecular genetics. A history of seizures prior to resection was not associated with the presence of HFOs ( P = 0.62), although when patients had seizures during the same hospitalization as the resection, HFOs were more likely to be present ( P = 0.045). Extent of HFO resection was not associated with the likelihood of postoperative seizure freedom. CONCLUSIONS: Approximately half (48.5%) of patients undergoing resection for a primary brain tumor had HFOs. Although HFO resection was not shown to lead to improved seizure freedom, this study was limited by a small sample size, and further investigation into HFO resection and patient outcomes in this population is warranted.

Impact of intraoperative direct cortical stimulation dynamics on perioperative seizures and afterdischarge frequency in patients undergoing awake craniotomy.

OBJECTIVE: Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients. METHODS: A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors' institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures. RESULTS: Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS. CONCLUSIONS: The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity.

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Tumor type, epilepsy burden, and seizure documentation: experiences at a single center neuro-oncology clinic.

BACKGROUND: Patients with both primary and metastatic brain tumors have significant seizure burden due to their tumor. The management of tumor-related epilepsy (TRE) and optimizing antiepileptic drug (AED) regimens requires collaboration between neurologists and seizure specialists, which is facilitated by seizure documentation in clinic notes. We aim to describe seizure incidence in patients seen in neuro-oncology clinical practice. Further, in the subset of those patients with TRE, we aim to analyze seizure documentation. METHODS: This is a retrospective review of patients with a primary or metastatic brain tumor seen in a neuro-oncology clinic in October 2019. Patients with TRE were included in the analysis of seizure documentation. These notes were analyzed for inclusion of seizure descriptors, terminology, AED regimens, and changes in management. RESULTS: Of the full cohort of 356 patients, 199 (55.9%) had TRE. Anaplastic astrocytomas had the highest percentage of patients with TRE. The analysis of seizure documentation in patients with TRE revealed that the majority of notes (90.9%) mentioned seizures. Fewer notes (39.6%) provided additional descriptions of the seizures or commented on AED regimens (58.3%). In notes for patients who had seizures within the previous 6 months, seizure descriptors were more likely. CONCLUSIONS: This study defines the TRE burden in a cohort of patients seen in neuro-oncology clinic. Among patients with TRE, our study shows that documentation of many aspects of the characteristics and management of patient seizures can be improved, which would facilitate further analysis of impact on patient care as well as future research.

HFOApp: A MATLAB Graphical User Interface for High-Frequency Oscillation Marking.

Epilepsy affects 3.4 million people in the United States, and, despite the availability of numerous antiepileptic drugs, 36% of patients have uncontrollable seizures, which severely impact quality of life. High-frequency oscillations (HFOs) are a potential biomarker of epileptogenic tissue that could be useful in surgical planning. As a result, research into the efficacy of HFOs as a clinical tool has increased over the last 2 decades. However, detection and identification of these transient rhythms in intracranial electroencephalographic recordings remain time-consuming and challenging. Although automated detection algorithms have been developed, their results are widely inconsistent, reducing reliability. Thus, manual marking of HFOs remains the gold standard, and manual review of automated results is required. However, manual marking and review are time consuming and can still produce variable results because of their subjective nature and the limitations in functionality of existing open-source software. Our goal was to develop a new software with broad application that improves on existing open-source HFO detection applications in usability, speed, and accuracy. Here, we present HFOApp: a free, open-source, easy-to-use MATLAB-based graphical user interface for HFO marking. This toolbox offers a high degree of intuitive and ergonomic usability and integrates interactive automation-assist options with manual marking, significantly reducing the time needed for review and manual marking of recordings, while increasing inter-rater reliability. The toolbox also features simultaneous multichannel detection and marking. HFOApp was designed as an easy-to-use toolbox for clinicians and researchers to quickly and accurately mark, quantify, and characterize HFOs within electrophysiological datasets.

Simulation-Based Assessments and Graduating Neurology Residents' Milestones: Status Epilepticus Milestones.

BACKGROUND: The American Board of Psychiatry and Neurology and the Accreditation Council for Graduate Medical Education (ACGME) developed Milestones that provide a framework for residents' assessment. However, Milestones do not provide a description for how programs should perform assessments. OBJECTIVES: We evaluated graduating residents' status epilepticus (SE) identification and management skills and how they correlate with ACGME Milestones reported for epilepsy and management/treatment by their program's clinical competency committee (CCC). METHODS: We performed a cohort study of graduating neurology residents from 3 academic medical centers in Chicago in 2018. We evaluated residents' skills identifying and managing SE using a simulation-based assessment (26-item checklist). Simulation-based assessment scores were compared to experience (number of SE cases each resident reported identifying and managing during residency), self-confidence in identifying and managing these cases, and their end of residency Milestones assigned by a CCC based on end-of-rotation evaluations. RESULTS: Sixteen of 21 (76%) eligible residents participated in the study. Average SE checklist score was 15.6 of 26 checklist items correct (60%, SD 12.2%). There were no significant correlations between resident checklist performance and experience or self-confidence. The average participant's level of Milestone for epilepsy and management/treatment was high at 4.3 of 5 (SD 0.4) and 4.4 of 5 (SD 0.4), respectively. There were no significant associations between checklist skills performance and level of Milestone assigned. CONCLUSIONS: Simulated SE skills performance of graduating neurology residents was poor. Our study suggests that end-of-rotation evaluations alone are inadequate for assigning Milestones for high-stakes clinical skills such as identification and management of SE.

Efficacy of clobazam as add-on therapy in brain tumor-related epilepsy.

PURPOSE: Brain tumor-related epilepsy (TRE) is often resistant to currently available antiepileptic medications (AEDs). Clobazam was initially approved as adjunctive AED for patients with Lennox Gastaut syndrome but has been used in TRE, despite limited evidence in this context. This observational study aims to examine the effect of clobazam on seizure frequency on patients who have a primary CNS tumor and continued seizures despite their current AEDs. METHODS: A retrospective review of patients with histologically-confirmed primary brain tumors seen in the neuro-oncology interdisciplinary clinic from April 2016-2019 was completed, and patients on clobazam were identified. Response to clobazam was defined as a greater than 50% reduction in seizure frequency. Additional data including patient and tumor characteristics, treatment course, tolerability, AEDs used prior to addition of clobazam, and AEDs concomitantly used with clobazam were collected. RESULTS: A total of 35 patients with TRE on clobazam were identified, with 2 patients unable to tolerate the medication due to side effects. Of the 33 remaining patients, a total of 31 (93.9%) of patients were deemed responders. Ten patients (30.3%) were seizure free within 6 months of clobazam initiation and 21 (63.6%) reported a significant reduction in seizure frequency. This reduction also allowed several patients to modify concurrent AEDs. CONCLUSIONS: Clobazam is an effective agent to use as add-on AED in TRE, with 94% of patients showing a significant response within 6 months. Furthermore, the addition of clobazam may yield a reduction in polypharmacy, as concomitant AEDs can be reduced and potentially withdrawn.

True abdominal epilepsy is clonic jerking of the abdominal musculature.

Abdominal epilepsy (AE) has long been reported as a rare phenomenon in children with various episodic gastrointestinal sensory and painful symptoms suspected to be due to epileptic seizures. Originally, AE was diagnosed when abdominal sensory or painful symptoms were associated with pain, temporal lobe origin, an epileptiform or paroxysmal EEG pattern, and a clinical response to antiseizure medication. AE has also been associated with non-epileptic etiologies such as migraine. Reports of abdominal epilepsy based on an abnormal EEG or clinical response to antiseizure medication without diagnosis confirmation by video-EEG are at best speculative, and at worst, misdiagnoses. We describe three adult patients with focal aware motor seizures manifesting as recurrent, isolated prolonged painless rhythmic clonic jerking of the abdominal musculature including epilepsia partialis continua. All patients had a contralateral structural lesion on high-resolution brain MRI in the abdominal region of the motor homunculus. Standard EEG was unrevealing and only after extra EEG electrodes and video-EEG monitoring was the ictal origin confirmed. Historically, AE has been described as a disorder involving subjective sensory symptoms including vague abdominal pain, instead of epileptic motor signs of abdominal clonic jerking. We recommend replacing the use of vague terms such as AE with International League Against Epilepsy terminology along with diagnostic confirmation validated by video-EEG monitoring. [Published with video sequence].

The Representation of Finger Movement and Force in Human Motor and Premotor Cortices.

The ability to grasp and manipulate objects requires controlling both finger movement kinematics and isometric force in rapid succession. Previous work suggests that these behavioral modes are controlled separately, but it is unknown whether the cerebral cortex represents them differently. Here, we asked the question of how movement and force were represented cortically, when executed sequentially with the same finger. We recorded high-density electrocorticography (ECoG) from the motor and premotor cortices of seven human subjects performing a movement-force motor task. We decoded finger movement [0.7 ± 0.3 fractional variance accounted for (FVAF)] and force (0.7 ± 0.2 FVAF) with high accuracy, yet found different spatial representations. In addition, we used a state-of-the-art deep learning method to uncover smooth, repeatable trajectories through ECoG state space during the movement-force task. We also summarized ECoG across trials and participants by developing a new metric, the neural vector angle (NVA). Thus, state-space techniques can help to investigate broad cortical networks. Finally, we were able to classify the behavioral mode from neural signals with high accuracy (90 ± 6%). Thus, finger movement and force appear to have distinct representations in motor/premotor cortices. These results inform our understanding of the neural control of movement, as well as the design of grasp brain-machine interfaces (BMIs).

Lacosamide-associated second-degree atrioventricular block in a healthy, young athlete.

Lacosamide enhances slow inactivation of voltage-gated sodium channels and can lead to dose-dependent PR interval prolongation. Previously, lacosamide has been associated with second-degree atrioventricular (AV) heart block in the context of multiple medical comorbidities and/or in the elderly with multimorbidity on other dromotropic agents. We report a case of second-degree AV block occurring in a healthy, athletic young adult. The patient had baseline bradycardia with no known cardiac comorbidities. He was exquisitely sensitive to lacosamide with EKG and telemetry changes developing on the order of hours after receiving intravenous lacosamide. Lacosamide was subsequently stopped, the second-degree AV block was no longer present and EKG returned to baseline. We hypothesize that his sensitivity to lacosamide-induced AV block was possibly secondary to his baseline bradycardia with early repolarization changes. The case underscores the importance of surveillance cardiac monitoring. While medical comorbidities and an older age may portend a greater risk of PR prolongation, routine EKGs should be considered in all patients receiving lacosamide.

Use of a simulation-based mastery learning curriculum for neurology residents to improve the identification and management of status epilepticus.

BACKGROUND: Appropriate and timely treatment of status epilepticus (SE) decreases morbidity and mortality. Therefore, skill-based training in the identification and management of SE is crucial for clinicians. OBJECTIVE: The objective of the study was to develop and evaluate the impact of a simulation-based mastery learning (SBML) curriculum to train neurology residents on the identification and management of SE. METHODS: We used pretest-posttest design with a retention test on SE skills for this study. Neurology residents in the second postgraduate year (PGY-2) were eligible to participate in the SE SBML curriculum. Learners completed a baseline-simulated SE skills assessment (pretest) using a 26-item dichotomous skills checklist. Next, they participated in a didactic session about the identification and management of SE, followed by deliberate skills practice. Subsequently, participants completed another skills assessment (posttest) using the same 26-item checklist. All participants were required to meet or exceed a minimum passing standard (MPS) determined by a panel of 14 SE experts using the Mastery Angoff standard setting method. After meeting the MPS at posttest, participants were reassessed during an unannounced in situ simulation session on the medical wards. We compared pretest with posttest simulated SE skills performance and posttest with reassessment in situ performance. RESULTS: The MPS was set at 88% (23/26) checklist items correct. Sixteen neurology residents participated in the intervention. Participant performance improved from a median of 44.23% (Interquartile range (IQR): 34.62-55.77) at pretest to 94.23% (IQR: 92.13-100) at the posttest after SBML (p < .001). There was no significant difference in scores between the posttest and in situ test up to 8 months later (94.23%; IQR: 92.31-100 vs. 92.31%; IQR: 88.46-96.15; p = .13). CONCLUSIONS: Our SBML curriculum significantly improved residents' SE identification and management skills that were largely retained during an unannounced simulated encounter in the hospital setting.

Analysis of risk factors and clinical sequelae of direct electrical cortical stimulation-induced seizures and afterdischarges in patients undergoing awake mapping.

OBJECTIVE: Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events. METHODS: A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I-IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables. RESULTS: A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2-7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures. CONCLUSIONS: ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.

Hippocampal theta coordinates memory processing during visual exploration.

The hippocampus supports memory encoding and retrieval, which may occur at distinct phases of the theta cycle. These processes dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate encoding and retrieval. Here, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Phase-locking at the peak of theta preceded fixations to retrieved locations, indicating that the hippocampus coordinates memory-guided eye movements. In contrast, phase-locking at the trough of theta followed fixations to novel object-locations and predicted intact memory of the original location. Theta-gamma phase amplitude coupling increased during fixations to conflicting visual content, but predicted memory updating. Hippocampal theta thus supports learning through two interleaved processes: strengthening encoding of novel information and guiding exploration based on prior experience.