Coupling between slow waves and sharp-wave ripples engages distributed neural activity during sleep in humans.

Hippocampal-dependent memory consolidation during sleep is hypothesized to depend on the synchronization of distributed neuronal ensembles, organized by the hippocampal sharp-wave ripples (SWRs, 80 to 150 Hz), subcortical/cortical slow-wave activity (SWA, 0.5 to 4 Hz), and sleep spindles (SP, 7 to 15 Hz). However, the precise role of these interactions in synchronizing subcortical/cortical neuronal activity is unclear. Here, we leverage intracranial electrophysiological recordings from the human hippocampus, amygdala, and temporal and frontal cortices to examine activity modulation and cross-regional coordination during SWRs. Hippocampal SWRs are associated with widespread modulation of high-frequency activity (HFA, 70 to 200 Hz), a measure of local neuronal activation. This peri-SWR HFA modulation is predicted by the coupling between hippocampal SWRs and local subcortical/cortical SWA or SP. Finally, local cortical SWA phase offsets and SWR amplitudes predicted functional connectivity between the frontal and temporal cortex during individual SWRs. These findings suggest a selection mechanism wherein hippocampal SWR and cortical slow-wave synchronization governs the transient engagement of distributed neuronal populations supporting hippocampal-dependent memory consolidation.

Comparative Effectiveness of Stereotactic Electroencephalography Versus Subdural Grids in Epilepsy Surgery.

OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

Neurostimulation in people with drug-resistant epilepsy: Systematic review and meta-analysis from the ILAE Surgical Therapies Commission.

OBJECTIVE: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta-analysis. METHODS: We followed the Preferred Reporting Items of Systematic reviews and Meta-Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open-label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow-up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. RESULTS: We identified 30 eligible studies, six of which were RCTs. At long-term follow-up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: -5.1, 74.5). In the open-label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow-up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow-up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. SIGNIFICANCE: Neurostimulation modalities are an effective treatment option for drug-resistant epilepsy, with improving outcomes over time and few major complications. Seizure-reduction rates among the three therapies were similar during the initial blinded phase. Recent long-term follow-up studies are encouraging for RNS and DBS but are lacking for VNS.

Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.

The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.

Using electrocorticogram baseline seizure frequency to assess the efficacy of responsive neurostimulation.

BACKGROUND: The effect of direct brain responsive neurostimulation on the frequency of electrographic seizures in patients with medically refractory focal epilepsy has not been evaluated by chronic ambulatory electrocorticographic monitoring. METHODS: This was a retrospective study of 9 patients who underwent implantation of the responsive neurostimulator (RNS) system from 2015 to 2017 at the University of California, Irvine. Leads were placed at the ictal onset zone as determined by intracranial electroencephalography (EEG). The neurostimulator was programmed to detect and deliver stimulation following identification of the individual's epileptiform patterns. Electrographic seizures were determined by review of all detections. The electrocorticography (ECoG) seizure frequency baseline was the average of the first 2 months postimplantation. The patient-reported seizure frequency baseline was the average of the 2 most recent months prior to RNS implantation. Seizure control was assessed at 3 months, 6 months, and 12 months. RESULTS: Nine patients were included in the study. All 9 patients have been treated with responsive stimulation for at least 3 months, 7/9 for 6 months, and 4/9 for 12 months. The mean change in seizure frequency was -10%, -19%, and -56% at 3, 6, and 12 months, respectively, using a self-reported seizure frequency baseline compared with -85%, -71%, and -56% at 3, 6, and 12 months, respectively, using the ECoG seizure frequency baseline. CONCLUSION: Chronic ECoG may provide a more accurate estimate of seizure frequency and provide additional insight into the true efficacy of the RNS system.

Strategic hospital partnerships: improved access to care and increased epilepsy surgical volume.

OBJECTIVE Surgical treatment of patients with medically refractory focal epilepsy is underutilized. Patients may lack access to surgically proficient centers. The University of California, Irvine (UCI) entered strategic partnerships with 2 epilepsy centers with limited surgical capabilities. A formal memorandum of understanding (MOU) was created to provide epilepsy surgery to patients from these centers. METHODS The authors analyzed UCI surgical and financial data associated with patients undergoing epilepsy surgery between September 2012 and June 2016, before and after institution of the MOU. Variables collected included the length of stay, patient age, seizure semiology, use of invasive monitoring, and site of surgery as well as the monthly number of single-surgery cases, complex cases (i.e., staged surgeries), and overall number of surgery cases. RESULTS Over the 46 months of the study, a total of 104 patients underwent a total of 200 operations; 71 operations were performed in 39 patients during the pre-MOU period (28 months) and 129 operations were performed in 200 patients during the post-MOU period (18 months). There was a significant difference in the use of invasive monitoring, the site of surgery, the final therapy, and the type of insurance. The number of single-surgery cases, complex-surgery cases, and the overall number of cases increased significantly. CONCLUSIONS Partnerships with outside epilepsy centers are a means to increase access to surgical care. These partnerships are likely reproducible, can be mutually beneficial to all centers involved, and ultimately improve patient access to care.

Length of stay for patients undergoing invasive electrode monitoring with stereoelectroencephalography and subdural grids correlates positively with increased institutional profitability.

OBJECTIVE: Lowering the length of stay (LOS) is thought to potentially decrease hospital costs and is a metric commonly used to manage capacity. Patients with epilepsy undergoing intracranial electrode monitoring may have longer LOS because the time to seizure is difficult to predict or control. This study investigates the effect of economic implications of increased LOS in patients undergoing invasive electrode monitoring for epilepsy. METHODS: We retrospectively collected and analyzed patient data for 76 patients who underwent invasive monitoring with either subdural grid (SDG) implantation or stereoelectroencephalography (SEEG) over 2 years at our institution. Data points collected included invasive electrode type, LOS, profit margin, contribution margins, insurance type, and complication rates. RESULTS: LOS correlated positively with both profit and contribution margins, meaning that as LOS increased, both the profit and contribution margins rose, and there was a low rate of complications in this patient group. This relationship was seen across a variety of insurance providers. SIGNIFICANCE: These data suggest that LOS may not be the best metric to assess invasive monitoring patients (i.e., SEEG or SDG), and increased LOS does not necessarily equate with lower or negative institutional financial gain. Further research into LOS should focus on specific specialties, as each may differ in terms of financial implications.

Stereotactic robot-assisted MRI-guided laser thermal ablation of radiation necrosis in the posterior cranial fossa: technical note.

Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a variety of intracranial lesions. Utilization of robotic assistance with stereotactic procedures has gained attention due to potential for advantages over conventional techniques. The authors report the first case in which robot-assisted MRI-guided LITT was used to treat radiation necrosis in the posterior fossa, specifically within the cerebellar peduncle. The use of a stereotactic robot allowed the surgeon to perform LITT using a trajectory that would be extremely difficult with conventional arc-based techniques. A 60-year-old man presented with facial weakness and brainstem symptoms consistent with radiation necrosis. He had a history of anaplastic astrocytoma that was treated with CyberKnife radiosurgery 1 year prior to presentation, and he did well for 11 months until his symptoms recurred. The location and form of the lesion precluded excision but made the patient a suitable candidate for LITT. The location and configuration of the lesion required a trajectory for LITT that was too low for arc-based stereotactic navigation, and thus the ROSA robot (Medtech) was used. Using preoperative MRI acquisitions, the lesion in the posterior fossa was targeted. Bone fiducials were used to improve accuracy in registration, and the authors obtained an intraoperative CT image that was then fused with the MR image by the ROSA robot. They placed the laser applicator and then ablated the lesion under real-time MR thermometry. There were no complications, and the patient tolerated the procedure well. Postoperative 2-month MRI showed complete resolution of the lesion, and the patient had some improvement in symptoms.

A new Elixhauser-based comorbidity summary measure to predict in-hospital mortality.

BACKGROUND: Recently, van Walraven developed a weighted summary score (VW) based on the 30 comorbidities from the Elixhauser comorbidity system. One of the 30 comorbidities, cardiac arrhythmia, is currently excluded as a comorbidity indicator in administrative datasets such as the Nationwide Inpatient Sample (NIS), prompting us to examine the validity of the VW score and its use in the NIS. METHODS: Using data from the 2009 Maryland State Inpatient Database, we derived weighted summary scores to predict in-hospital mortality based on the full (30) and reduced (29) set of comorbidities and compared model performance of these and other comorbidity summaries in 2009 NIS data. RESULTS: Weights of our derived scores were not sensitive to the exclusion of cardiac arrhythmia. When applied to NIS data, models containing derived summary scores performed nearly identically (c statistics for 30 and 29 variable-derived summary scores: 0.804 and 0.802, respectively) to the model using all 29 comorbidity indicators (c=0.809), and slightly better than the VW score (c=0.793). Each of these models performed substantially better than those based on a simple count of Elixhauser comorbidities (c=0.745) or a categorized count (0, 1, 2, or ≥ 3 comorbidities; c=0.737). CONCLUSIONS: The VW score and our derived scores are valid in the NIS and are statistically superior to summaries using simple comorbidity counts. Researchers wishing to summarize the Elixhauser comorbidities with a single value should use the VW score or those derived in this study.

Minimally invasive surgical approaches for temporal lobe epilepsy.

Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60-80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease.

Improved outcomes with earlier surgery for intractable frontal lobe epilepsy.

OBJECTIVE: To explore the prognostic implications of epilepsy duration and age at surgery for seizure outcomes after frontal lobe epilepsy (FLE) surgery. METHODS: We reviewed 158 patients who underwent FLE surgery from 1995 to 2010. The primary outcome was seizure freedom at last follow-up (Engel class IA). Analyses employed Cox proportional and multiphase hazard modeling. RESULTS: The mean age at surgery was 20.4 years, and mean epilepsy duration was 12.0 years. The estimated chance of seizure freedom was 66% (95% confidence interval [CI] = 62-68) at 1 postoperative year, 52% (95% CI = 48-56) at 2 years, and 44% (95% CI = 39-49) at 5 years and beyond. Seventy-five percent of recurrences occurred within 6 postoperative months. Both younger age at surgery (<18 years) and shorter epilepsy duration (<5 years) correlated with better seizure outcomes on univariate analysis, but only epilepsy duration remained statistically significant after multivariate modeling. Independent poor prognostic indicators included left-sided resections and acute postoperative seizures (APOSs; whole model log-rank test p < 0.0001). APOSs were particularly predictive of early epilepsy recurrence, starting within 6 postoperative months (adjusted risk ratio [RR] = 4.42, p < 0.0001), whereas long epilepsy duration correlated with late recurrences (RR = 6.25, p < 0.0001). Worse outcomes were seen with longer epilepsy duration for duration cutoffs of 2, 5, and 10 years independently for adults and children, although statistical significance was only achieved in children (66% seizure free at 5 postoperative years if operated on within 5 years of epilepsy onset vs 31% if later; p = 0.01). INTERPRETATION: Early resection may improve seizure outcomes of FLE surgery, particularly in children.

"Mail-slot" Technique for Minimally Invasive Placement of Subdural Grid Electrodes: A Single-institution Experience.

BACKGROUND: In the management of multi-drug-resistant focal epilepsies, intracranial electrode implantation is used for precise localization of the ictal onset zone. In select patients, subdural grid electrode implantation is utilized. Subdural grid placement traditionally requires large craniotomies to visualize the cortex prior to mapping. However, smaller craniotomies may enable shorter operations and reduced risks. We aimed to compare surgical outcomes between patients undergoing traditional large craniotomies with those undergoing tailored "mini" craniotomies (the "mail-slot" technique) for subdural grid placement. METHODS: This retrospective cohort study included 23 patients who underwent subdural electrode implantation for epilepsy monitoring between 2014 and 2020. Patients were categorized into mini-craniotomies (n = 9) and traditional large craniotomies (n = 14) groups. Demographics, operative details, and outcomes were reviewed. Craniotomy size and number of electrodes were determined via post hoc radiographs. RESULTS: Of the 23 patients studied, the mini group had smaller craniotomy sizes (mean: 22.71 cm2 vs. 65.17 cm2, P < 0.001) and higher electrode-to-size ratios (mean: 4.25 vs. 1.71, P < 0.0001). The mini group had slightly fewer total electrodes (mean: 88.67 vs. 107.43, P = 0.047). No significant differences were found in operative duration, blood loss, invasive electroencephalography duration, complications, or Engel scores between the groups. One patient per group required further invasive epilepsy monitoring for localization; all patients underwent therapeutic surgery. CONCLUSIONS: Our findings suggest that mini-craniotomies for subdural grid placement in epilepsy monitoring offer significant advantages, including smaller craniotomy sizes and shorter operation durations, without compromising safety or efficacy. These results support the trend towards minimally invasive, patient-tailored surgical approaches in epilepsy treatment.

Stereoelectroencephalography for continuous two-dimensional cursor control in a brain-machine interface.

Stereoelectroencephalography (SEEG) is becoming more prevalent as a planning tool for surgical treatment of intractable epilepsy. Stereoelectroencephalography uses long, thin, cylindrical "depth" electrodes containing multiple recording contacts along each electrode's length. Each lead is inserted into the brain percutaneously. The advantage of SEEG is that the electrodes can easily target deeper brain structures that are inaccessible with subdural grid electrodes, and SEEG does not require a craniotomy. Brain-machine interface (BMI) research is also becoming more common in the Epilepsy Monitoring Unit. A brain-machine interface decodes a person's desired movement or action from the recorded brain activity and then uses the decoded brain activity to control an assistive device in real time. Although BMIs are primarily being developed for use by severely paralyzed individuals, epilepsy patients undergoing invasive brain monitoring provide an opportunity to test the effectiveness of different invasive recording electrodes for use in BMI systems. This study investigated the ability to use SEEG electrodes for control of 2D cursor velocity in a BMI. Two patients who were undergoing SEEG for intractable epilepsy participated in this study. Participants were instructed to wiggle or rest the hand contralateral to their SEEG electrodes to control the horizontal velocity of a cursor on a screen. Simultaneously they were instructed to wiggle or rest their feet to control the vertical component of cursor velocity. The BMI system was designed to detect power spectral changes associated with hand and foot activity and translate those spectral changes into horizontal and vertical cursor movements in real time. During testing, participants used their decoded SEEG signals to move the brain-controlled cursor to radial targets that appeared on the screen. Although power spectral information from 28 to 32 electrode contacts were used for cursor control during the experiment, post hoc analysis indicated that better control may have been possible using only a single SEEG depth electrode containing multiple recording contacts in both hand and foot cortical areas. These results suggest that the advantages of using SEEG for epilepsy monitoring may also apply to using SEEG electrodes in BMI systems. Specifically, SEEG electrodes can target deeper brain structures, such as foot motor cortex, and both hand and foot areas can be targeted with a single SEEG electrode implanted percutaneously. Therefore, SEEG electrodes may be an attractive option for simple BMI systems that use power spectral modulation in hand and foot cortex for independent control of 2 degrees of freedom.

Correlation between magnetoencephalography-based "clusterectomy" and postoperative seizure freedom.

OBJECT: During the presurgical evaluation of patients with medically intractable focal epilepsy, a variety of noninvasive studies are performed to localize the hypothetical epileptogenic zone and guide the resection. Magnetoencephalography (MEG) is becoming increasingly used in the clinical realm for this purpose. No investigators have previously reported on coregisteration of MEG clusters with postoperative resection cavities to evaluate whether complete "clusterectomy" (resection of the area associated with MEG clusters) was performed or to compare these findings with postoperative seizure-free outcomes. METHODS: The authors retrospectively reviewed the charts and imaging studies of 65 patients undergoing MEG followed by resective epilepsy surgery from 2009 until 2012 at the Cleveland Clinic. Preoperative MEG studies were fused with postoperative MRI studies to evaluate whether clusters were within the resected area. These data were then correlated with postoperative seizure freedom. RESULTS: Sixty-five patients were included in this study. The average duration of follow-up was 13.9 months, the mean age at surgery was 23.1 years, and the mean duration of epilepsy was 13.7 years. In 30 patients, the main cluster was located completely within the resection cavity, in 28 it was completely outside the resection cavity, and in 7 it was partially within the resection cavity. Seventy-four percent of patients were seizure free at 12 months after surgery, and this rate decreased to 60% at 24 months. Improved likelihood of seizure freedom was seen with complete clusterectomy in patients with localization outside the temporal lobe (extra-temporal lobe epilepsy) (p = 0.04). CONCLUSIONS: In patients with preoperative MEG studies that show clusters in surgically accessible areas outside the temporal lobe, we suggest aggressive resection to improve the chances for seizure freedom. When the cluster is found within the temporal lobe, further diagnostic testing may be required to better localize the epileptogenic zone.

Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

Levetiracetam may favorably affect seizure outcome after temporal lobectomy.

PURPOSE: To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy. METHODS: Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome. KEY FINDINGS: Records of 312 patients were analyzed (mean ± standard deviation follow-up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66-72%), and 48% at 36 months (95% CI 45-52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1-4), dropping to 1.02 at last follow-up (range 0-4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43-0.89, and RR = 0.57, 95% CI 0.39-0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15-2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole-model log-rank test p-value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15-20% survival advantage by 5 years. No similar outcome correlations were identified with another AED. SIGNIFICANCE: AED use may be a potential new modifiable seizure-outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.

Surgeon-Led Initiatives to Increase Access to Surgical Treatment of Epilepsy at an Academic Level 4 Epilepsy Center: An Observational Cohort Study.

BACKGROUND: Underutilization of surgical treatment for epilepsy is multifactorial, and the multidisciplinary nature of caring for these patients represents a significant hurdle in expanding surgical treatment of epilepsy. OBJECTIVE: To develop internal and external surgical referral relationships for patients with medically refractory epilepsy with the goal of improving access to care. METHODS: To expand access to surgical epilepsy treatment at University of California (UC)-Irvine, 4 broad approaches focused on developing referral relationships and process improvement of surgical evaluation were undertaken in 2015 and 2016. The authors performed a retrospective review of all surgical epilepsy case referrals of the senior author from 2014 through 2020. RESULTS: Epilepsy surgical volume at UC-Irvine increased from an average of 5.2 cases annually to 32 cases in the first year (2015) of implementation. There was continued case volume growth from 2015 through 2020 to 52 procedures in the most recent year (P = .03). Hospital payments for epilepsy procedures increased from $1.09M in 2015 to $2.02M and $1.8M in 2019 and 2020 (P < .01), respectively, while maintaining a diverse payer mix. 79.4% of these patients did not have a previously established option for surgical epilepsy care. CONCLUSION: We outline strategies that level 4 epilepsy centers may use to strengthen collaborations and improve patient access for surgical epilepsy treatment. Increased collaboration can both improve the number of patients with epilepsy with access to specialized surgical care and produce reimbursement benefits for the centers caring for these patients, regardless of insurance source.

Application of Responsive Neurostimulation as both a Diagnostic Tool for Seizure Localization and a Supplementary Tool for Surgical Management in Patients with Multiple Epileptogenic Foci: A Case Series.

AIM: To present a series of medically refractory focal epilepsy patients with multiple or eloquent epileptogenic zones (EZs) in whom a responsive neurostimulation (RNS) system was used as a complementary modality to surgical resection. RNS was also used as a diagnostic tool to monitor long-term epileptogenic activity for enhanced localization, especially in patients with bilateral temporal seizures. MATERIAL AND METHODS: Ten consecutive patients who underwent RNS system placement and surgical resection at a single institution were assessed. RESULTS: The RNS system, with its capacity for chronic ambulatory electrocorticography (ECoG), provided important diagnostic information that helped to modify the plan of surgical resection in one patient with bitemporal epilepsy in order to improve seizure outcomes. In addition, the RNS facilitated the surgical management of patients with multiple or eloquent EZs. CONCLUSION: The authors report a population of 10 patients in which the RNS system was used as a diagnostic tool for improved localization of EZs over a long interval or as a complementary therapeutic tool in patients with multiple or eloquent EZs.

Elective versus nonelective brain tumor resections: a 5-year propensity score matching cost comparison analysis.

OBJECTIVE: Elective surgical cases generally have lower costs, higher profit margins, and better outcomes than nonelective cases. Investigating the differences in cost and profit between elective and nonelective cases would help hospitals in planning strategies to withstand financial losses due to potential pandemics. The authors sought to evaluate the exact cost and profit margin differences between elective and nonelective supratentorial tumor resections at a single institution. METHODS: The authors collected economic analysis data in all patients who underwent supratentorial tumor resection at their institution between January 2014 and December 2018. The patients were grouped into elective and nonelective cases. Propensity score matching was used to adjust for heterogeneity of baseline characteristics between the two groups. RESULTS: There were 143 elective cases and 232 nonelective cases over the 5 years. Patients in the majority of elective cases had private insurance and in the majority of nonelective cases the patients had Medicare/Medicaid (p < 0.01). The total charges were significantly lower for elective cases ($168,800.12) compared to nonelective cases ($254,839.30, p < 0.01). The profit margins were almost 6 times higher for elective than for nonelective cases ($13,025.28 vs $2,128.01, p = 0.04). After propensity score matching, there was still a significant difference between total charges and total cost. CONCLUSIONS: Elective supratentorial tumor resections were associated with significantly lower costs with shorter lengths of stay while also being roughly 6 times more profitable than nonelective cases. These findings may help future planning for hospital strategies to survive financial losses during future pandemics that require widespread cancellation of elective cases.