Responsive neurostimulation as a therapy for epilepsy following new-onset refractory status epilepticus: Case series and review of the literature.

OBJECTIVE: To report clinical outcomes of patients who presented with new-onset refractory status epilepticus (NORSE), developed drug-resistant epilepsy (DRE), and were treated with responsive neurostimulation (RNS). METHODS: We performed a retrospective review of patients implanted with RNS at our institution and identified three who originally presented with NORSE. Through chart review, we retrieved objective and subjective information related to their presentation, workup, and outcomes including patient-reported seizure frequency. We reviewed electrocorticography (ECoG) data to estimate seizure burden at 3, 6, 12, and 24 months following RNS implantation. We performed a review of literature concerning neurostimulation in NORSE. RESULTS: Use of RNS to treat DRE following NORSE was associated with reduced seizure burden and informed care by differentiating epileptic from non-epileptic events. CONCLUSIONS: Our single-center experience of three cases suggests that RNS is a safe and potentially effective treatment for DRE following NORSE. SIGNIFICANCE: This article reports outcomes of the largest case series of NORSE patients treated with RNS. Since patients with NORSE are at high risk of adverse neuropsychiatric and cognitive sequelae beyond seizures, a unique strength of RNS over other surgical options is the ability to distinguish ictal or peri-ictal from non-epileptic events.

Intraoperative application and early experience with novel high-resolution, high-channel-count thin-film electrodes for human microelectrocorticography.

OBJECTIVE: The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS: A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS: Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS: High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

Rapid Passive Gamma Mapping as an Adjunct to Electrical Stimulation Mapping for Functional Localization in Resection of Primary Brain Neoplasms.

OBJECTIVE: We examined the utility of passive high gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM. METHODS: This was a retrospective cohort study of 75 patients who underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of a U.S. Food and Drug Administration-approved high-gamma mapping tool in July 2017. RESULTS: The preimplementation and postimplementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, P = 0.250) and extent of resection (97.14% vs. 98.19%, P = 0.481) were comparable between cohorts. Median Karnofsky performance status at initial follow-up was similar between cohorts (P = 0.650). Multivariable Cox regression models demonstrated an adjusted hazard ratio for overall survival of 0.10 (95% confidence interval: 0.02-0.43, P = 0.002) for the postimplementation cohort relative to the preimplementation cohort. Progression-free survival adjusted for insular involvement showed an adjusted hazard ratio of 1.00 (95% confidence interval: 0.49-2.06, P = 0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7% vs. 25%, P = 0.150). CONCLUSIONS: Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a nonsignificant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

Mismatch repair-deficient glioma with spatially distinct IDH-mutant and IDH-wild type components arising in the setting of Lynch syndrome.

Pathogenic mutations in MLH1, MSH2, PMS2, and MSH6 compromise DNA mismatch repair mechanisms and in the heterozygous state result in Lynch syndrome, which is typified by a predisposition to endometrial, ovarian, colorectal, gastric, breast, hematologic, and soft tissue cancers. Rarely, germline pathogenic aberrations in these genes are associated with the development of primary central nervous system tumors. We present a report of an adult female with no prior cancer history who presented with a multicentric, infiltrative supratentorial glioma involving both the left anterior temporal horn and left precentral gyrus. Surgical treatment and neuropathological/molecular evaluation of these lesions revealed discordant isocitrate dehydrogenase (IDH) status and histologic grade at these spatially distinct disease sites. A frameshift alteration within the MLH1 gene (p.R217fs*12, c.648delT) was identified in both lesions and subsequently identified in germline testing of a blood sample, consistent with Lynch syndrome. Despite distinct histopathologic features and divergent IDH status of the patient's tumors, the molecular findings suggest that both sites of intracranial neoplasia may have developed as a consequence of underlying monoallelic germline mismatch repair deficiency. This case illustrates the importance of characterizing the genetic profile of multicentric gliomas and highlights the oncogenic potential of germline mismatch repair gene pathogenic alterations within central nervous system gliomas.

Survival, Functional, and Seizure Control Outcomes After Resection of Perirolandic World Health Organization Grade II and III Gliomas: A Single-Center Retrospective Review.

OBJECTIVE: We aimed to assess, in patients with perirolandic gliomas and gliomas originating from other regions, survival, functional outcomes, and seizure control and, in addition, to identify any clinical characteristics predictive of progression-free survival, overall survival, and seizure control. METHODS: We retrospectively analyzed 87 patients who underwent resection of World Health Organization grade II or III gliomas at a single institution between 2009 and 2021. Tumors were classified by topographic involvement. One-year postoperative functional status was quantified with Karnofsky Performance Status. One-year seizure control was defined by Engel seizure classification. Dichotomous and categorical variables were reported as counts and percentages and compared using Fisher exact test. A Cox regression model was used to identify covariates that affect progression-free survival and overall survival. RESULTS: Patients with perirolandic gliomas had similar survival and functional outcomes to patients with gliomas from other regions and a low rate of lasting neurologic deficits. Patients with perirolandic gliomas had comparatively worse long-term seizure outcomes (approached statistical significance). Perirolandic involvement (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.02-0.46; P = 0.005) and preoperative seizures (HR, 0.14; 95% CI, 0.02-0.62; P = 0.017) conferred a lower likelihood of durable seizure control, whereas increased extent of resection (HR, 1.07; 95% CI, 1.03-1.12; P = 0.003) enhanced the likelihood of seizure freedom. CONCLUSIONS: Despite proximity to or presence in eloquent structures, perirolandic gliomas can largely be resected without incurring worse functional outcomes. Patients with perirolandic gliomas should be considered for maximal safe resection to optimize survival outcomes and improve seizure control.

Neurosurgical Ablation for Pain: A Technology Review.

Neurosurgical ablative procedures for pain have dramatically transformed over the years. Compared to their precursors, present day techniques are less invasive and more precise as a result of advances in both device engineering and imaging technology. From a clinical perspective, understanding the strengths and drawbacks of modern techniques is necessary to optimize patient outcomes. In this review, we provide an overview of the major contemporary neuroablative modalities/technologies used for treating pain. We will compare and contrast these modalities from one another with respect to their intraoperative monitoring needs, invasiveness, range of access, and lesion generation. Finally, we will provide a brief commentary on the future of neuroablation given the advent of neuromodulation options for pain control.

Stereo-EEG recordings extend known distributions of canonical movement-related oscillations.

Objective.Previous electrophysiological research has characterized canonical oscillatory patterns associated with movement mostly from recordings of primary sensorimotor cortex. Less work has attempted to decode movement based on electrophysiological recordings from a broader array of brain areas such as those sampled by stereoelectroencephalography (sEEG), especially in humans. We aimed to identify and characterize different movement-related oscillations across a relatively broad sampling of brain areas in humans and if they extended beyond brain areas previously associated with movement.Approach.We used a linear support vector machine to decode time-frequency spectrograms time-locked to movement, and we validated our results with cluster permutation testing and common spatial pattern decoding.Main results.We were able to accurately classify sEEG spectrograms during a keypress movement task versus the inter-trial interval. Specifically, we found these previously-described patterns: beta (13-30 Hz) desynchronization, beta synchronization (rebound), pre-movement alpha (8-15 Hz) modulation, a post-movement broadband gamma (60-90 Hz) increase and an event-related potential. These oscillatory patterns were newly observed in a wide range of brain areas accessible with sEEG that are not accessible with other electrophysiology recording methods. For example, the presence of beta desynchronization in the frontal lobe was more widespread than previously described, extending outside primary and secondary motor cortices.Significance.Our classification revealed prominent time-frequency patterns which were also observed in previous studies that used non-invasive electroencephalography and electrocorticography, but here we identified these patterns in brain regions that had not yet been associated with movement. This provides new evidence for the anatomical extent of the system of putative motor networks that exhibit each of these oscillatory patterns.

Effects of 24-hour versus night-float call schedules on the clinical and operative experiences of postgraduate year 2 and 3 neurosurgical residents.

OBJECTIVE: To comply with the removal of the 88-hour week exemption and to support additional operative experience during junior residency, Oregon Health & Science University (OHSU) switched from a night-float call schedule to a modified 24-hour call schedule on July 1, 2019. This study compared the volumes of clinical, procedural, and operative cases experienced by postgraduate year 2 (PGY-2) and PGY-3 residents under these systems. METHODS: The authors retrospectively studied billing and related clinical records, call schedules, and Accreditation Council for Graduate Medical Education case logs for PGY-2 and PGY-3 residents at OHSU, a tertiary academic health center, for the first 4 months of the academic years from 2017 to 2020. The authors analyzed the volumes of new patient consultations, bedside procedures, and operative procedures performed by each PGY-2 and PGY-3 resident during these years, comparing the volumes experienced under each call system. RESULTS: Changing from a PGY-2 resident-focused night-float call system to a 24-hour call system that was more evenly distributed between PGY-2 and PGY-3 residents resulted in decreased volume of new patient consultations, increased volume of operative procedures, and no change in volume of bedside procedures for PGY-2 residents. PGY-3 residents experienced a decrease in operative procedure volume under the 24-hour call system. CONCLUSIONS: Transition from a night-float system to a 24-hour call system altered the distribution of clinical and procedural experiences between PGY-2 and PGY-3 residents. Further research is necessary to understand the impact of these changes on educational outcomes, quality and safety of patient care, and resident satisfaction.

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors.

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures. Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor. Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients. Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.